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Author Topic: http://natap.org/  (Read 70383 times)

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #100 on: April 09, 2010, 01:48:53 PM »
Researchers discover a new way HIV infects women: inflammatory response causes infection



"The mechanism of this breakdown appears to be due to inflammatory factors produced by epithelial cells themselves, in response to HIV-1 exposure, that destroy the tight junctions between epithelial cells, thereby allowing microbes access to the inside of the body......The crossing of the bacteria by similar mechanism can lead to chronic inflammation and activation of immune cells of the body."


"In conclusion, the current study provides evidence for the first time that HIV-1 exposure at the mucosal surface leads to direct response by the mucosal epithelium, seen by production of inflammatory cytokines. This response is rapid, independent of viral infection and likely plays a key role in initiation of mucosal damage. This information will be critical for strategies to target control of mucosal damage......We further determined that exposure of the epithelial monolayers to HIV-1 led to enhanced production of a number of inflammatory cytokines, including TNF-α, by both intestinal and genital epithelial cells. When epithelial cells were exposed to HIV-1 in presence of anti-TNF antibody, there was no significant decrease in TER, indicating that TNF played a major role in impairing the barrier functions.....we found evidence for small but significant bacterial and viral translocation across epithelial monolayers following HIV-1 exposure......A recent study showed impairment of barrier function in intestinal biopsies of HAART-naïve patients compared to those on HAART treatment [14]. Increased production of cytokines IL-2, IL-4, IL-5 and TNF-α was found in supernatants of cultured intestinal biopsies in this study. Their conclusion was that following infection, HIV replication in target cells leads to local increase of inflammatory cytokines in the intestinal mucosa, which induce barrier impairment. This supports previous studies where PBMCs co-cultured with HIV-infected macrophages resulted in increased production of a number of cytokines, including TNF-α, IL-1β, IFN-α and IFN-γ which were shown to compromise epithelial barrier function [34]. The prevailing opinion from these studies is that the effect on epithelial barrier is likely mediated via immune cell activation due to viral replication"

http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #101 on: April 16, 2010, 02:05:14 PM »
EDITORIAL COMMENTARY

HIV Drug Resistance over the Long Haul




Clinical Infectious Diseases May 1 2010



P. Richard Harrigan




BC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada




      (See the article by The UK Collaborative Group on HIV Drug Resistance and UK CHIC Study Group, on pages 1275–1285.)










In this issue, The UK Collaborative Group on HIV Drug Resistance and UK CHIC Study Group present data from a large, long‐term study of human immunodeficiency virus (HIV) drug resistance [1]. Their data are derived from a clinic‐based collaborative study (the UK Collaborative Group on HIV Drug Resistance), which includes data from >50,000 routinely performed HIV drug resistance tests in the United Kingdom. The collaborative nature of the study group allowed them to examine resistance in almost 8000 individuals for periods of up to 8 years and to gain insight into the determinants of drug resistance in a “real world” setting.




Large longitudinal cohort studies such as this are an important complement to randomized clinical trials, particularly for monitoring drug resistance. As the authors point out, clinical trials of antiretrovirals tend to be relatively short and relatively small. They may also tend to include individuals who are more likely than average to be adherent to treatment. Most importantly, these randomized trials also typically monitor patients only until their initial treatment regimen fails, at which point they may drop out of the study, and no further analyses of resistance are performed.




Cohort studies such as this are one of the few ways to monitor the long‐term risk of developing HIV drug resistance. The authors find that the risk of developing a resistant genotype is <20% over 8 years for patients starting “modern” HIV treatment regimens. Given the number of antiretrovirals which are now available, this can only be considered to be good news for patients starting treatment. Other main conclusions of the study are that the risk of detecting mutations conferring resistance to the protease inhibitor class of therapy in those who started highly active antiretroviral therapy (HAART) regimens which included a modern ritonavir‐boosted protease inhibitor regimen was about one‐third of the risk of detecting nonnucleoside reverse‐transcriptase inhibitor resistance. Because there was no difference in the risk of nucleoside reverse‐transcriptase inhibitor resistance, the implication of the study is that those who started nonnucleoside reverse‐transcriptase inhibitor–based HAART were much more likely to have 2‐class HIV drug resistance than those who started therapy with boosted protease inhibitors. This conclusion is consistent with data from clinical trials and with studies by our own group in British Columbia and others.




There are a number of caveats which should be kept in mind when interpreting the data, many of which are addressed in detail in the Discussion section [1]. First, there have been temporal changes in the use of HIV drug resistance testing and in the nucleoside analogue pairs available over the long course of the study (see Table 1 [1]). The authors adjust their analysis for calendar year, but subtle confounding may remain. For example, it was simply impossible to obtain tenofovir‐emtracitabine during the first years of the study, but it appears to be one of the most common combinations later in the study. In addition, the observational nature of the study could result in potential contributions of sampling bias—some predictors of resistance may arise from being associated with being tested. The risk of developing resistance may not be simply disentangled from the calendar year of drug availability, the probability of undergoing resistance testing, or variable adherence to medications. It is also important to note that many patients changed their therapies over the course of the study as a normal part of routine clinical management. The main comparisons were made according to the type of regimen that individuals initially started regardless of subsequent drug switches of any part of their regimen.




Finally, many patients no longer initiate HAART with the nucleoside analogue pairs described in this study; thus, the estimates of drug resistance provided for those with the longest follow‐up may not accurately mirror those who start antiretroviral therapy in 2010. This statement is not a criticism of the study but merely reflects the fact that it is impossible to have both long term follow‐up and today’s most clinically relevant therapies in an area that changes as rapidly as HIV treatment. Overall, the study provides an important description of “where we are now.” The analysis provided is of the usual high quality of this group.



Acknowledgments




Financial support.CIHR/GSK Research Cair in Clinical Virology.




Potential conflicts of interest.P.R.H. has received grants from, served as an ad hoc advisor to, or spoken at various events of Pfizer, GlaxoSmithKline, Abbott, Merck, Virco, and Monogram.

Reference




    * 1.The UK Collaborative Group on HIV Drug Resistance and UK CHIC Study Group. Long‐term probability of detecting drug‐resistant HIV in treatment‐naive patients initiating combination antiretroviral therapy. Clin Infect Dis 2010;50(9):1275–1285 (in this issue).
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline georgep77

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Re: http://natap.org/
« Reply #102 on: April 16, 2010, 03:42:09 PM »
Thanks for the news Dragon   :)
Come on Sangamo,  Geovax,  Bionor immuno, ...Make us happy !!!
+ 2008

Offline red_Dragon888

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Re: http://natap.org/
« Reply #103 on: April 17, 2010, 01:32:21 PM »
"We have shown that the biochemical profile of G1 CHC patients is characterized by lower-than-normal serum 25(OH)D levels, and that a low 25(OH)D level is independently related to severe fibrosis and a low likelihood of SVR after standard-of-care antiviral therapy.....Our study shows that low 25(OH)D levels are independently associated with female sex and with severity of necroinflammatory activity....This study also offers the first evidence that low 25(OH)D serum levels, together with known risk factors for fibrosis severity, such as older age, low cholesterol levels, and high necroinflammatory activity,[26] are independently associated with the presence of severe fibrosis......It is conceivable that a reduced 25(OH)D level might by itself favor progression of fibrosis. Different experimental models showed that vitamin D, via interaction with vitamin D receptor, protects against oxidative stress production,[29] can influence the migration, proliferation, and gene expression of fibroblasts,[30][31] and reduces the inflammatory and fibrogenic activity of liver stellate cells.....However further prospective cohort studies will be needed to determine the causal association between vitamin D deficiency and fibrosis in patients with CHC....Another interesting finding of this study is the evidence that lower 25(OH)D serum levels were an independent negative risk factor for SVR....this observation will require further validation in different, large cohorts of patients, but is supported by experimental data that suggest a role of vitamin D in the modulation of the immune response,[32][33] and by recent clinical data[36] reporting higher early virological response rate in CHC treated with standard of care plus vitamin D, compared with those treated with standard of care only"



Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C



Hepatology April 2010


Salvatore Petta 1 2 *, Calogero Cammà 1 3, Concetta Scazzone 4, Claudio Tripodo 5, Vito Di Marco 1, Antonino Bono 4, Daniela Cabibi 5, Giusalba Licata 1, Rossana Porcasi 5, Giulio Marchesini 6, Antonio Craxí 1

1Cattedra ed Unità Operativa di Gastroenterologia, DiBiMIS, University of Palermo, Italy

2Dipartimento di Biopatologia e Metodologie Biomediche, University of Palermo, Italy

3IBIM Consiglio Nazionale delle Ricerche, Palermo, Italy

4Dipartimento di Biotecnologie Mediche e Medicina Legale Sezione Chimica e Biochimica Medica, University of Palermo, Italy

5Cattedra di Anatomia Patologica, University of Palermo, Italy

6Dipartimento di Medicina e Gastroenterologia, Alma Mater Studiorum, University of Bologna, Italy

email: Salvatore Petta (petsa@inwind.it)




*Correspondence to Salvatore Petta, Gastroenterologia & Epatologia, Piazza delle Cliniche, 2, 90127 Palermo, Italy







Abstract




25-Hydroxyvitamin D (25[OH]D) can potentially interfere with inflammatory response and fibrogenesis. Its role in disease progression in chronic hepatitis C (CHC) and its relation with histological and sustained virological response (SVR) to therapy are unknown. One hundred ninety-seven patients with biopsy-proven genotype 1 (G1) CHC and 49 healthy subjects matched by age and sex were consecutively evaluated. One hundred sixty-seven patients underwent antiviral therapy with pegylated interferon plus ribavirin. The 25(OH)D serum levels were measured by high-pressure liquid chromatography. Tissue expression of cytochrome (CY) P27A1 and CYP2R1, liver 25-hydroxylating enzymes, were assessed by immunochemistry in 34 patients with CHC, and in eight controls.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #104 on: April 17, 2010, 01:33:08 PM »
Drug shared by addicts seems to protect against HIV brain dementia
Could heroin hold the clues for a new protective agent?
Washington, DC – To their surprise, researchers at Georgetown University Medical Center (GUMC) have discovered that morphine (a derivate of the opium poppy that is similar to heroin) protects rat neurons against HIV toxicity - a finding they say might help in the design of new neuroprotective therapies for patients with the infection.


The discovery, being presented at the annual meeting of the Society of NeuroImmune Pharmacology, also helps explain why a subset of people who are heroin abusers and become infected with HIV through needle sharing don't develop HIV brain dementia. This brain disorder includes cognitive and motor abnormalities, anxiety and depression.


"We believe that morphine may be neuroprotective in a subset of people infected with HIV," says the study's lead investigator, Italo Mocchetti, PhD, Professor of neuroscience at GUMC.


"That is not to say that people should use heroin to protect themselves – that makes no medical sense at all – but our findings gives us ideas about designing drugs that could be of benefit.


"Needless to say we were very surprised at the findings," he added. "We started with the opposite hypothesis – that heroin was going to destroy neurons in the brain and lead to HIV dementia."


The researchers conducted the study because they knew that a number of HIV-positive people are also heroin abusers, and because of that, some are at high risk of developing neurological complications from the infection. Others, however, never develop these cognitive problems, Mocchetti says.


Because little is known about the molecular mechanisms linking opiates and HIV neurotoxicity, Mocchetti and his team conducted experiments in rats. They found that in the brain, morphine inhibited the toxic property of the HIV protein gp120 that mediates the infection of immune cells. With further investigation, they concluded that morphine induces production of the protein CCL5, which they discovered is released by astrocytes, a type of brain cell. CCL5 is known to activate factors that suppress HIV infection of human immune cells. "It is known to be important in blood, but we didn't know it is secreted in the brain," says Mocchetti. "Our hypothesis is that it is in the brain to prevent neurons from dying."


They say morphine blocked HIV from binding to CCR5 receptors it typically uses to enter and infect cells. The researchers believe CCL5 itself attached to those receptors, preventing the virus from using it. In this way, it prevented HIV-associated dementia. This effect, however, only worked in the M-trophic strain of HIV, the strain that most people are first infected with. It did not work with the second T-trophic strain that often infects patients later.


"Ideally we can use this information to develop a morphine-like compound that does not have the typical dependency and tolerance issues that morphine has," says Mocchetti.

http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #105 on: April 17, 2010, 01:34:29 PM »
FDA Updates Product Labeling for Sustiva (Efavirenz)

The Food and Drug Administration recently approved revisions to the package insert for Sustiva (efavirenz), a non-nucleoside reverse transcriptase inhibitor, for both capsules and tablets…


As of July 2009, the Antiretroviral Pregnancy Registry has received prospective reports of 661 pregnancies exposed to efavirenz-containing regimens, nearly all of which were first trimester exposures (606 pregnancies). Birth defects occurred in 14 of 501 live births (first trimester exposure) and 2 of 55 live births (second/third-trimester exposure). …


Monitoring of liver enzymes before and during treatment is recommended for patients with underlying hepatic disease, including hepatitis B or C infection; patients with marked transaminase elevations; and patients treated with other medications associated with liver toxicity. … Liver enzyme monitoring should also be considered for patients without pre-existing hepatic dysfunction or other risk factors. …


Posaconazole: Avoid concomitant use unless the benefit outweighs the risks[.]


Maraviroc: Refer to the full prescribing information for maraviroc for guidance on coadministration with efavirenz. …


Because of the extensive cytochrome P450-mediated metabolism of efavirenz and limited clinical experience in patients with hepatic impairment, caution should be exercised in administering Sustiva to these patients …


Some patients taking Sustiva have experienced serious liver problems including liver failure resulting in transplantation or death. Most of these serious side effects occurred in patients with a chronic liver disease such as hepatitis infection, but there have also been a few reports in patients without any existing liver disease.


The complete revised label is available at the FDA Web site.

More information is available:
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #106 on: April 17, 2010, 01:35:22 PM »
Pharmacokinetic-pharmacodynamic (PK-PD) analyses of TMC435 in treatment-naïve hepatitis C (HCV)-infected patients in the OPERA-1 study - see attached full poster report

 

Reported by Jules Levin, EASL Apr 14-18 2010 Vienna Austria

V. Sekar1, P. Vis2, O. Lenz2, P. Meyvisch2, M. Peeters2, G. De Smedt2 1Tibotec Inc, USA; 2Tibotec BVBA, Belgium

 

AUTHOR CONCLUSIONS

- In treatment-naive HCV-infected patients, following 28 days of treatment with TMC435 in combination with P/R, a dose-proportional increase in TMC435 exposure was observed from 25 to 75mg QD, with a more than dose-proportional increase in TMC435 exposure observed from 75 to 200mg QD.

- There was no clear PK-PD relationship between TMC435 exposure and antiviral activity with TMC435 doses of 75mg QD or higher.

- A trend towards mild increases in serum bilirubin and ALP was observed with higher TMC435 exposure, with increases mainly observed at the 200mg dose.

- However, no clear PK-PD relationship was observed for other liver parameters.

- The PK-PD findings reported here support the TMC435 75 and 150mg QD doses selected for further evaluation in treatment-naive patients as part of the ongoing Phase IIb trial, PILLAR.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #107 on: April 21, 2010, 03:33:26 PM »
Added Sugar Adds Up to Heart Risk



MedPage Today

Published: April 20, 2010



On average, Americans get nearly 16% of their total dietary calories from sugars added to processed foods during manufacturing, researchers found.




And a high intake of such sugars -- mainly sucrose from beets and cane and high fructose corn syrup -- is correlated with some key measures of dyslipidemia, according to Miriam Vos, MD, of Emory University in Atlanta, and colleagues.




Because dyslipidemia is a risk factor for cardiovascular disease, the findings support dietary guidelines aimed at reducing consumption of added sugars, Vos and colleagues said in the April 21 issue of the Journal of the American Medical Association.




The findings are not a surprise, according to Rachel Johnson, PhD, of the University of Vermont in Burlington. Johnson, a nutritionist, was the primary author of a statement on added sugars issued in August 2009 by the American Heart Association. (See Cut Back on Added Sugar, AHA Recommends)

Action Points 
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #108 on: April 21, 2010, 03:33:57 PM »
Gilead stops hepatitis drug test after ‘adverse events’
Tuesday, April 20, 2010


Citing “significant laboratory abnormalities and adverse events” in patients, Gilead Sciences stopped a clinical test of a hepatitis C drug.


The Foster City company (NASDAQ: GILD) will review data from this Phase II test of GS 9450, a caspase inhibitor. The company has been studying it for treatment of hepatitis C and also for nonalcoholic steatohepatitis.


Gilead licensed the drug from LG Life Sciences Inc. in 2007, paying $20 million upfront for the rights to the drug except in Korea, China and India. The company also agreed to pay for a collaborative research program and to pay milestones of up to $182 million if the drug did well in development.


“Patient safety is Gilead’s top priority,” the business said in a press release.


Gilead didn’t describe the problems in detail.
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #109 on: April 21, 2010, 03:35:22 PM »
Researchers discover a new way HIV infects women

http://www.labspaces.net/103040/Researchers_discover_a_new_way_HIV_infects_women

Friday, April 9, 2010

Women are susceptible to HIV, the virus that causes AIDS, but scientists have been puzzled as to how it finds its way into the female reproductive tract.

One theory has been that trauma, such as a little tear during intercourse, causes HIV to cross epithelial cells – the protective barrier that keeps out infection. There is also the suggestion an unknown mechanism is at work.

For the first time, researchers at McMaster University have discovered the culprit could be HIV itself and what the virus does when it binds to epithelial cells.

"What it does is that it makes the electrical barrier resistance of epithelial cells decrease. By doing that, the virus can cross the barrier," said lead researcher Charu Kaushic, associate professor in the Centre for Gene Therapeutics and the department of pathology and molecular medicine in the Michael G. DeGroote School of Medicine. She is also a researcher with the Michael G. DeGroote Institute of Infectious Disease Research.

"This is a significant step forward in defining where prevention strategies, such as microbicides and vaccine, need to focus. Instead of trying to stop HIV from infecting the target cells underneath the epithelium, we need to think about ways to stop the virus from attaching to epithelial cells themselves."

The study, which appears in the journal PLoS Pathogens, shows HIV can break down the mucosal barrier in the intestinal and female genital tract, allowing the virus to cross during intercourse.

The breakdown appears to be due to inflammatory factors produced by epithelial cells themselves, in response to HIV. This destroys the tight junctions between epithelial cells and gives HIV and other microbes access to inside the body, the researchers said.

Worldwide, half of the 40 million people infected with HIV are women. Among heterosexuals, women are the fastest growing group to be infected.

Scientists have been faced with the question of how HIV actually gets underneath epithelial cells to infect other cells that are susceptible to HIV. "It's not the cells on top," Kaushic said. "It is the immune cells underneath that have all the receptors that HIV likes to latch on to and that allow the virus to replicate and establish infection. But it has to cross the epithelial barrier first!"

The McMaster researchers grew purified primary epithelial cells in the laboratory from small pieces of tissues that were removed from women's uterus during hysterectomies, with their consent. Then, they began to study how HIV actually interacts with these cells. The electrical resistance in these cultures is used to monitor how well the epithelial cell cultures are growing and functioning.

Aisha Nazli, a researcher in Kaushic's laboratory, noticed every time she put HIV on epithelial cells their resistance went down significantly. Repeated tests confirmed this.

Kaushic said the surface protein of the virus causes the epithelial barrier to break. "The surface protein signals to the inside of the epithelial cells by binding to it", she said. "The epithelial cells start making inflammatory proteins which cause these cells to go on their self-destructive pathway."

Kaushic's lab conducted the research in collaboration with researchers in the department of molecular genetics at the University of Toronto and the department of medical biology at Laval University. She holds a New Investigator Award in HIV from the Canadian Institutes of Health Research (CIHR) and an Early Researcher's Award from the Ontario government.
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #110 on: April 22, 2010, 03:26:37 PM »
Health Department Highlights Health Risks of Unprotected Anal Sex among Heterosexual Women in New York City--New survey suggests that women are less likely than men to use protection during anal intercourse

'People engaging in anal sex should always use condoms'
"women are less likely than men who have sex with men to use condoms during anal sex. The figure is just 23%, according to the new report, compared to 61% among men who have sex with other men."Only 11% of the highest-risk women (versus 47% of those using condoms) said a provider had recommended testing in the past year – even though 94% of them had seen one"


April 21, 2010 – Unprotected anal sex poses well known health hazards for men, but new research suggests that the practice is a significant health issue for women as well. More than 100,000 New York City women engage in anal intercourse each year, according to a new report from the Health Department, and many are not taking the steps needed to prevent HIV and other sexually transmitted infections.


Anal membranes are easily damaged during sex, facilitating the spread of infection. Past studies suggest that anal exposure to HIV poses 30 times more risk than vaginal exposure. But the New York City findings suggest that women are less likely than men who have sex with men to use condoms during anal sex. The figure is just 23%, according to the new report, compared to 61% among men who have sex with other men. The full report is available at nyc.gov/health.


“Tens of thousands of New Yorkers are engaging in sexual behavior that is especially risky,” said Dr. Thomas Farley, New York City Health Commissioner. “Many people are aware of the risk of HIV when men have sex with other men, but this report shows that a large number of women also are putting themselves at high risk through unprotected anal sex. For both men and women, the overall message is clear: Never engage in unprotected anal sex. Use a condom every time.”


Just as condoms are especially important for people who engage in anal intercourse, so is HIV testing. Yet the new report finds that women who engage in unprotected anal sex have lower testing rates than women who always use condoms during anal sex – 35% versus 63%, respectively. By the same token, women who had unprotected anal sex were the least likely to report that a health care provider had offered HIV testing during the past year. Only 11% of the highest-risk women (versus 47% of those using condoms) said a provider had recommended testing in the past year – even though 94% of them had seen one.


The report does not estimate the HIV burden among women who engage in unprotected anal sex, but most HIV infections diagnosed in women result from heterosexual intercourse. Among women with known sources of exposure, heterosexual contact accounted for 90% of the infections diagnosed in New York City in 2008.
Unprotected anal sex is most common among younger women and those with multiple partners
Women 18 to 24 years old are nearly six times more likely than those aged 45 to 64 to report unprotected anal sex (11% versus 2%). And whereas 15% of women with three or more sex partners reported engaging in anal sex in the past year, the figure was just 4% among those with one partner. Reports of anal sex in the past year are similar across race and ethnicity, with Asian women reporting 8%, white women 7%, Hispanic women 6% and black women 4%.
Recommendations for reducing sexually transmitted infections
The new report highlights the importance of safer sex in a city where approximately 74,000 new sexually transmitted infections are reported each year, along with 3,800 new HIV diagnoses. Some recommendations:
Health care providers should offer STI and HIV testing to all patients, regardless of their stated sexual history.
People engaging in anal sex should always use condoms. Free NYC Condoms and other alternative male condoms, in addition to female condoms and lubricant, are available at locations throughout New York City. Call 311 or visit nyc.gov/condoms for more information.
Unless they’re in mutually monogamous relationships, people who have had unprotected sex should get tested for HIV and other STIs at least once a year. Free, confidential screening is available at Health Department clinics, no appointment required. Call 311 for clinic locations and hours of operation. Services are available to people 12 and older without parental notification and without regard to immigration or insurance status.
If you have exposed any partners to a sexually transmitted infection (including HIV), it is important to tell them so they can be tested and treated if necessary. People who want help notifying partners, or who want to do so anonymously, can find assistance by calling 311 or visiting inSPOT NYC (www.inspot.org/Newyorkcity).
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #111 on: April 23, 2010, 01:19:36 PM »
Zinc Linked to Prostate Cancer Survival. What are Good Zinc Food Sources?


Zinc Linked to Prostate Cancer Survival. What are Good Zinc Food Sources?



MedPage Today

April 22, 2010




Action Points 




    * In this study, men diagnosed with early stage prostate cancer had an increased chance of surviving the disease if they adhered to a diet rich in zinc.







    * Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.




WASHINGTON -- Men diagnosed with early stage prostate cancer have an increased chance of surviving the disease if they have eaten a diet rich in zinc, researchers said here at the annual meeting of the American Association for Cancer Research.




"Those men with high zinc intake were 74% less likely to die of prostate cancer than those with the lowest zinc intake," Mara S. Meyer, MS, a doctoral candidate at the Harvard School of Public Health, said during a poster presentation (95% CI 0.10 to 0.68, P=0.005).




Researchers also reported a trend indicating that men who consumed high levels of marine omega-3 docosahexaenoic acid were 30% less likely to die of prostate cancer than men who consumed the lowest levels of the fatty acids (95% CI 0.47 to 1.03, P=0.26).




Meyer found no apparent associations between prostate cancer-specific mortality and death from other causes involving dietary intake or saturated, monounsaturated, or omega-6 polyunsaturated fatty acids.




The researchers accessed data from the Örebro Swedish Cohort, including 525 confirmed prostate cancer cases among men living in Örebro County who were diagnosed from 1989 to 1991.




At the time of diagnosis, dietary data was collected by a food frequency questionnaire specific to the Swedish diet. Use of dietary supplements was negligible in this population, which was assembled before the introduction of PSA testing.




The researchers studied intake of zinc and fatty acids -- dividing intake into quartiles. They also noted time to death and whether death was caused by prostate cancer of some other illness.




Meyer noted that 218 men died from prostate cancer, and 257 men died from other causes. Fifty of the men in the cohort are still alive.




She said most of the men in this group ingested dietary zinc through consumption of grains.




"We did not see a relationship between zinc and mortality or disease specific mortality except among those patients who were diagnosed with an early stage prostate cancer," she said.




Twenty percent of the men diagnosed with Stage II cancer or a lower grade died of the disease, while 58% percent of these men died of some other cause.




Men in the highest quartile of daily zinc consumption averaged about 15.7 mg or more of the trace metal; those in the lowest quartile consumed 12.8 mg or less, Meyer reported.




"The role of diet in cancer is always difficult to study," commented Charles Rabkin, MD, senior investigator in the Infections and Immunoepidemiology Branch in the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Md.




"It can be challenging to tease out what is real in these studies and what is not," he told MedPage Today. "But studies such as this one by Meyer and her colleagues definitely give us some clues to pursue."



Primary source: American Association for Cancer Research

Source reference:

Meyer M, et al "Diet, inflammation and prostate cancer survival in the Orebro Prostate Cancer Survivors Cohort" AACR 2010; Abstract 5747.

---------------------------


What are Good Zinc Food Sources?




An important mineral for the body for various functions



Zinc is one of the most important minerals used by the body for various functions and fortunately, there is a wide variety of zinc food sources available naturally for you to take advantage of. To give you an idea just how important it is, zinc helps in the production of about 100 enzymes in your body, builds you a healthy immune system, maintains your senses of smell and taste and is needed for DNA synthesis.



Foods Containing Zinc



Zinc is very much associated with protein foods. Thus, you may assume that most foods high in zinc are protein-rich as well. The best sources of zinc include beef, lamb, pork, crabmeat, turkey, chicken, lobster, clams and salmon.




If you are a vegetarian, you will most probably intake less zinc that those who have meat-based diets. Good zinc food sources aside from meats are dairy products such as milk and cheese, yeast, peanuts, beans, and wholegrain cereals, brown rice, whole wheat bread, potato and yogurt. Of all these vegetarian zinc foods, pumpkin seeds offer one of the most concentrated non-meat food sources of zinc.




Zinc Foods: Foods Rich in Zinc Content



Many foods contain some amounts of zinc, but to be considered a good zinc food source, the food must contain a substantial amount of the mineral relative to the calorie content. It should also contribute at least about 10% of the Recommended Dietary Allowance in one standard serving size.



Recommended Dietary Allowances for Zinc



For adults, the RDA for zinc should be about 11 milligrams per day for adult men and 8 milligrams for women. If you are lactating or pregnant, you need to put in about 3 mg more. For children, about 5 mg is needed for 4-8 year olds, and 8 mg for 9-13 year olds, while infants need only about 3 mg.



The Truth about Zinc Nutrition



The downside of taking these high zinc foods is that no matter how much of them you take in, only a mere 15%-40% of the zinc actually gets absorbed by your body overall. This is especially true for non-meat zinc food sources. Dietary fibers and phytic acid in brain prevents the absorption of zinc in your body. Phytic acid found in your brain forms a complex with the zinc that you take in, and this compound is insoluble so that it cannot be absorbed readily by your body. Whole grains are a better source of zinc than refined grains as they have the ability to produce enzymes that can destroy phytic acid. On the other hand, the zinc you get from eating meat is four times more bio-available than in grain foods.




It has been found that increasing intake of vitamins such as Vitamin C, E and B6 and minerals such as magnesium can increase zinc absorption in the body. So, it will be a good idea to add these to your daily vitamin and mineral intake.



Risks in Taking Too Much Zinc



If you are healthy and you eat a well-balance diet, you will rarely need supplements to complete your body's zinc needs. You should be careful in taking zinc supplements because too much of zinc can be potentially harmful to your body. It has been reported that intake of more than 50 milligrams of zinc (both from diet and from supplements) can lead to improper copper metabolism, altered iron function, reduction of HDL's (good cholesterol) and reduced immune function.




Zinc is very important to your body and you should make sure that you have enough zinc food source intake to complete your dietary needs. However, as always, taking too much can lead to harsh consequences, so make sure that you only take what is needed.



http://www.nutritional-supplements-health-guide.com
« Last Edit: April 23, 2010, 01:22:40 PM by red_Dragon888 »
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #112 on: April 26, 2010, 11:35:38 AM »

I think the national HIV prevalence is 0.5% making the HIV prevalence in NYC jails of 8.7% much higher

"HIV prevalence for all inmates in the serosurvey was 5.2%: 4.7% in men and 9.8% in women (Table 2). Adjusting our serosurvey prevalence to reflect all new admissions (those with and without remnant serum) based on proportion matching to HARS, the estimated true New York City inmate prevalence would be 8.7% overall (95% CI: 8.1% to 9.2%): 6.5% in males (95% CI: 6.0% to 7.1%) and 14% in females (95% CI: 12.7% to 15.3%)."


"More than a quarter of HIV-infected jail entrants appear to be undiagnosed at admission. This is substantially higher than the 5% estimated from a 2004 New York City household serosurvey9 and more aligned with the 12%-29% estimate calculated for New York City overall10 and CDC's nationwide 21% estimate.8 The vast majority (∼90%) of undiagnosed inmates did not self-report recognized HIV risk factors (ie, MSM or IDU activity). MacGowan et al18 reported similar results: only 15% of new diagnoses in Florida, Louisiana, upstate New York, and Wisconsin jails reported IDU or MSM activity. Likewise, among Los Angeles jail entrants, Harawa et al19 found that 68% of men and 55% of woman reported no HIV risk factors......Taken together, this information confirms that increasing acceptance of routine HIV testing (ie, offering all inmates testing regardless of risk) is likely the best approach to diagnosing more of the jail entrants with undiagnosed infection.....Two thirds of inmates did not consent to HIV testing.....It is likely that more inmates would consent to testing with a more streamlined opt out approach that does not include a separate written consent for each HIV test conducted. A separate written consent is still required by New York State despite CDC recommendations for their elimination,1 including in correctional settings



In conclusion, HIV prevalence appears to have substantially decreased among New York City jail entrants; however, over one quarter of HIV-infected jails entrants are undiagnosed, representing more than 100 persons in our sample alone. Despite a 4-fold increase in jail testing, most undiagnosed infections are not identified during voluntary jail testing, largely due to low testing acceptance rates. Most undiagnosed inmates did not report recognized HIV risk factors, reinforcing the need to improve inmate acceptance of the jails' current routine testing program rather than focus on increasing efforts among inmates reporting specific behaviors. To increase inmate's acceptance of routine testing, we are working to eliminate the required separate written consent for HIV testing to allow implementation of the CDC-recommended opt out testing model."



Undiagnosed HIV Infection Among New York City Jail Entrants, 2006: Results of a Blinded Serosurvey





JAIDS Journal of Acquired Immune Deficiency Syndromes:

1 May 2010 - Volume 54 - Issue 1 - pp 93-101



Begier, Elizabeth M MD, MPH; Bennani, Yussef MPH; Forgione, Lisa MA; Punsalang, Amado PhD; Hanna, David B MS; Herrera, Jeffrey BA; Torian, Lucia PhD; Gbur, Maria MD; Sepkowitz, Kent A MD; Parvez, Farah MD, MPH

From the New York City Department of Health and Mental Hygiene, New York, NY. Dr Farah Parvez was also associated with the National Center for HIV/AIDS, Viral Hepatitis, sexually transmitted disease, and TB Prevention, Centers for Disease Control and Prevention.



Abstract




http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #113 on: April 26, 2010, 11:36:39 AM »
Fish Oil Claims May be Snake Oil
MedPage Today
Published: April 23, 2010

Claims that fish oil supplements preserve cognition should not be swallowed hook, line, and sinker, researchers said.

In a randomized, placebo-controlled trial of nearly 900 septuagenarians, the omega-3 fatty acid supplements had no effect on cognition, according to Alan Dangour, PhD, of the London School of Hygiene and Tropical Medicine, and colleagues.

Over a two-year period, there was no difference in cognitive decline in either the fish oil or placebo arm of the study, the longest yet conducted, Dangour and colleagues said online in the American Journal of Clinical Nutrition.


Action Points 
--------------------------------------------------------------------------------

Explain to interested patients that fish oil supplements are proposed as a way to prevent cognitive decline with age.



Note that this large randomized trial found no such benefit.

"There is no evidence of an important benefit for memory or concentration," Dangour said in a statement.
Still, he cautioned that cognitive function can take years to decline, "and although this is the longest trial of its kind ever conducted, it may be that it was not long enough for any true beneficial effects to be detected among this healthy cohort of older people."


The findings come from the so-called OPAL study (for Older People And omega-3 Long-chain polyunsaturated fatty acids), which enrolled 876 healthy and cognitively sound people in Britain, ages 70 through 79.


They were randomized to get either an olive oil placebo or the combination of 200 milligrams of eicosapentaenoic acid and 500 milligrams of docosahexaenoic acid daily for two years.


Eicosapentaenoic and docosahexaenoic acid are omega-3 long-chain polyunsaturated fatty acids, commonly found in oily fish. They have been associated with cognitive benefits in observational studies, but there was no evidence of a positive effect in a recent six-month randomized trial, the researchers said.


"Current evidence of a benefit for cognitive health is not convincing," the researchers said.
In the current study, participants were tested on a range of cognitive tasks at the beginning of the trial and after 24 months, the researchers said.


The primary outcome was recall of a 16-word list from the California Verbal Learning Test, but the researchers also tested immediate and delayed recall, spatial memory, processing speed, reaction time, and executive function, among other things.


After 24 months, Dangour and colleagues found, participants getting the fish oils had more of them in their blood (at P<0.001 for both comparisons) than did those in the placebo arm.


At the same time, placebo participants had higher serum concentrations of two omega-6 fatty acids as well as two components of olive oil.


But there were no significant differences between the groups on the California Verbal Learning Test, they researchers said.


After adjustment for baseline cognitive function, age, sex, and age at leaving full-time education, the average difference between the fish oil and placebo arms in the total number of words recalled over three trials in the California Verbal Learning Test was minus 0.5 words.


The average difference in recall after a 20-minute delay was 0.1 words.


There was also no significant difference in any of the other cognitive function tests, the researchers said.
Adverse events were minor -- typically annoyances as flatulence, belching, abdominal discomfort, and loose stools -- and were not significantly different between the groups, the researchers found.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #114 on: April 30, 2010, 10:25:36 AM »
NATAP: Vitamin D Deficiency in HIV

I got mines, do you got yours...

NATAP http://natap.org/
_______________________________________________


High prevalence of severe vitamin D deficiency in combined antiretroviral therapy-naive and successfully treated Swiss HIV patients - (04/29/10)

AIDS:
15 May 2010

from Jules: we don't know the effect of vitamin D supplementation in HIV+ individuals; if vitamin D levels are getting eaten up in HIV+ individuals which appears to be the case, perhaps by HIV or HAART or poor absorption, then will even high-dose supplentation have a lasting affect on raising levels. We need to find out through study why vitamin D is gettibg eaten up in HIV.

"we suggest systematic screening for vitamin D deficiency in all HIV-positive patients..... With 42-52% in spring and 14-18% in fall, vitamin D deficiency was highly prevalent in our HIV-positive patients.....A comparison with deficiency rates in the general Swiss population is difficult, as recent data are missing. However, the rate of vitamin D deficiency in our HIV-positive cohort was clearly higher than the 6-15% rate found in the only assessment in the general Swiss population during winter [25]. Consistent with earlier reports [21], non-white ethnicities with darker skin pigmentation, in particular black patients, were most strongly affected by vitamin D deficiency.....The role of vitamin D supplementation in HIV-positive patients, and specific treatment goals in particular, must be defined by prospective studies with HIV-specific endpoints such as disease progression or change in CD4 cell counts. Also, the impact of NNRTIs on 25(OH)D and TDF on 1,25(OH)2D needs further consideration."
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #115 on: May 04, 2010, 11:18:30 AM »
MDs Contribute to the HIV Epidemic. Seriously.
huffingtonpost.com


At first I thought it was a fluke. But then I heard the same story told again. Different friend. Different doctor. Same problem.


I have been telling students, peers, and friends to get tested for HIV since I was fifteen years old. At the University of Pennsylvania, I volunteered at our anonymous HIV testing site. Aside from me, only two other individuals were tested at my site during my six month tenure. Clearly, the stigma surrounding HIV testing was a major obstacle.


But now, as my friends are older and not necessarily having monogamous relationships (not that they were back then, either), the people in my life are far more responsible about knowing their sexual health status. Though it still causes them great anxiety, they know that an HIV test is part of what it takes to be a sexually healthy person. I was ecstatic when my friend Jane (names have been changed to protect the responsible parties) told me that she was going to request an HIV test at her next check up.


And then last night, Jane called me. "So, I did it. Got the test, and it's negative. But I do need to tell you something." (I waited nervously.)


"Okay...I'm listening."


"So I asked the doctor for an HIV test. His response? 'Why? I don't think that you need to be tested. You're fine.' I said, But I am a single woman who is sexually active. I would like the test. Don't you test other patients? He replied, 'Yes, but only if they ask.'"


Holy crap. That doctor should have responded. "That's great, Jane. Very responsible. Sure, I'll test you.Is there anything that you would like me to know? Any other tests you feel like you want to have?"
But no. Instead Jane hears, "I don't think that you to be tested. You're fine."


WTF is going on???


The scary thing is that this is the second time I have heard this story this month. Haven't we learned (albeit the hard way) that you can't tell who has HIV just by looking at him/her? Haven't we learned that you cannot make assumptions about a patient based on what you perceive their lifestyle/orientation/gender to be?


Apparently not.


So this is my call to action: Patients speak up! Ask to be tested. And doctors - stop making it so damn difficult for people to be responsible. Give patients the test when they ask for it. Don't try to talk them out of it. And most importantly, offer the test when you are doing a general physical examination. Spend the extra thirty seconds that it takes to ask the question and send the nurse in to draw that blood. Otherwise, you are not part of the solution; you are part of the problem.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #116 on: May 04, 2010, 11:19:51 AM »
Vitamin D Deficit Common Among Southern Teens
MedPage Today
Published: May 03, 2010


Although they live in a relatively sunny climate, adolescents in southern states often have low blood levels of vitamin D, particularly if they are black, overweight, or inactive, a new study found.
Of adolescents tested, 56.4% had vitamin D insufficiency (<75 nmol/L) and 28.8% had deficiency (≤50 nmol/L), according to an online report in the May 3 Pediatrics.


Action Points
Explain to interested parents that even adolescents living in sunny regions appear to be at risk for low vitamin D levels.


Note that adolescents who were black, overweight or inactive were at higher risk for low vitamin D levels.
Compared to white youths, black youths had significantly lower blood plasma levels of 25-hydroxyvitamin D, regardless of the season:
Summer, 50.7 ± 4.0 vs 104.3 ± 4.0 nmol/L
Fall, 54.4 ± 4.0 vs 96.8 ± 2.7 nmol/L).
Winter, 35.9 ± 2.5 vs 77.4 ± 2.7 nmol/L
Spring, 46.4 ± 3.5 vs 101.3 ± 3.5 nmol/L
"Our data demonstrate that low vitamin D status is common among adolescents residing in the southeastern region and is related to various adiposity and lifestyle factors," Yanbin Dong, MD, PhD, of the Medical College of Georgia, and colleagues wrote.


"Taken together, these findings suggest that low vitamin D status is a growing national problem for adolescents in the United States, regardless of latitude."


Several studies have documented low vitamin D levels in children and adolescents living at northern latitudes, including communities in Pennsylvania, New Jersey, Ohio, Massachusetts and Maine.
Although exposure to sunlight helps the body produce vitamin D, data from the National Health and Nutrition Examination Survey has suggested that children living in southern states might also suffer from vitamin D deficiency.


To determine if that was the case, Dong and colleagues measured blood serum vitamin D levels in 559 adolescents from 14 to 18 years old, who were recruited from high schools in and around Augusta, Ga. (latitude 33.44°N) from January 2001 to June 2005. The researchers also measured the youths' fat tissue, physical activity and cardiovascular fitness.


Of the subjects, 45% were black and 49% were female.


After adjusting for age, gender, race, season, height and sexual maturation, the researchers found that all fat measurements, including BMI percentile (P=0.02), waist circumference (P<0.01), total fat mass (P<0.01), percentage of body fat (P<0.01), visceral adipose tissue (P=0.015) and subcutaneous abdominal adipose tissue (P=0.039), were associated with low vitamin D levels.


Participants who engaged in more vigorous physical activity (P<0.01) and had better cardiovascular fitness (P=0.025) were more likely to have higher levels of vitamin D.


"As an easy, inexpensive, adiposity measure, BMI percentiles could potentially be used alone for study of the relationship between adiposity and vitamin D levels in future studies," Dong and colleagues wrote. "Our data suggest that the relationship between 25-hydroxyvitamin D levels and adiposity in adolescents is independent of the site of fat content and fat distribution."


They noted that some scientists attribute low vitamin D levels observed among blacks to reduced skin synthesis caused by greater skin pigmentation, but Dong and colleagues proposed that the difference also could be related to relatively high rates of obesity in black populations.


The authors cautioned their analysis lacked information on the adolescents' sun exposure and dietary consumption of vitamin D and calcium.


They also noted that they did not measure individuals' plasma 25-hydroxyvitamin D levels in every season, which might have caused them to overlook seasonal variations of vitamin D levels.




"Prevalence of Low Vitamin D Status
Detailed prevalence rates of low vitamin D status, that is, insufficiency (</=75 nmol/L), deficiency (</=50 nmol/L), and severe deficiency (</=25 nmol/L), according to season, race, and gender
are shown in Table 2. The overall prevalence rates of vitamin D insufficiency and deficiency were 56.4% and 28.8%, respectively (Table 2). Vitamin D insufficiency rates were observed to
be 94.3% and 83.1% in black girls and boys, respectively, compared with 29.6% and 30.3% in white girls and boys. Vitamin D deficiency rates were found to be 73.8% and 46.9% in black girls and boys, respectively, compared with only 2.6% and 3.9% in white girls and boys. Severe vitamin D deficiency
was found only in black adolescents (5.2%). In summer, no white participants were found to have 25-
hydroxyvitamin D levels of </=50 mol/L, but 55% of black adolescents were shown to have levels indicative of vitamin D deficiency and 88.1% vitamin D insufficiency."
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #117 on: May 05, 2010, 05:32:43 PM »


Successful initiation of an anal cancer screening and treatment program at a New York City HIV clinic






AIDS:

24 April 2010

Correspondance



NYS Guidelines recommendations on anal pap smears
Click on "Clinical Guidelines" and you'll see current NYS DOH guidelines in ... multiple sexual partners, HPV infection, and receptive anal intercourse. ...
www.natap.org/2010/HIV/032510_01.htm


Tider, Diane S; Caprio, Gabriela Rodriguez; Gaisa, Michael; Klein, Robert S; Goldstone, Stephen E

Mount Sinai School of Medicine, New York, New York, USA.



We read with interest the correspondence by Shalev et al. [1]'s regarding new New York State AIDS Institute guidelines for anal cancer screening and treatment in HIV-positive persons. The authors assert that the guidelines would require almost 50% of their patients to undergo routine anal screening, which is a large figure considering the absence of Centers for Disease Control directives or national standards. They noted that such an endeavor takes time and resources, and questioned the justification of such expenditures, in advance of the creation of broader policy.




At Mount Sinai, we have spent the last year initiating an anal cancer screening and treatment program within our HIV clinic, in response to the New York State guidelines. On the basis of the proven reduction of morbidity and mortality with cervical Papanicolaou (Pap) testing, recommendations were extended in 2007 to include anal cancer screening with annual visual and digital anal exams for all HIV-positive adults, and annual anal Pap testing for men who have sex with men, women with prior abnormal cervicovaginal histology, and persons with prior anogenital condyloma. Those with abnormal findings require follow-up with high-resolution anoscopy (HRA), with biopsy and treatment when appropriate [2].




Human papillomavirus (HPV), an established carcinogen and causative factor in cervicovaginal [3–5] and anal cancers [6–14], is particularly virulent in HIV-positive persons [15]. Cervical cancer is an AIDS-defining malignancy [16], and HPV-related anal, gynecologic, penile, and oropharyngeal cancers have all been associated with HIV/AIDS [6]. Although rare in the general population [17], anal cancer is increasingly prevalent in HIV-positive persons on highly active antiretroviral therapy [18].




In 2008, we successfully applied for Ryan White Title III HIV Capacity Development funding for 1 year to initiate an anal screening and treatment program within our New York City HIV clinic. We identified an infectious diseases physician interested in HRA, and partnered with an expert in the field for training and oversight. We collaborated with our institution's colon and rectal surgery department to streamline the referral process for patients requiring surgery. Our overall goal was to diagnose and treat as many patients as possible in clinic, rather than in surgery, where anoscopy and ablation had been performed in the past.




We purchased equipment and supplies for anal Pap testing, HRA, and ablation, including swabs, cytobrushes, and Thin-Prep Pap Test collection kits, Baby Tischler biopsy punches, a universal power procedures examination table that converts to the knee–chest position, a state-of-the-art colposcope, and an infrared coagulator. A procedure room was identified and stocked in the clinic.




Primary care providers in the clinic were educated on the new guidelines and trained in performing anal Pap smears via literature and an instructional DVD from Johns Hopkins University. Anal Pap smears were added as annual visit quality indicators. We developed instruction sheets on the anal Pap smear technique and ordering, and adapted a referral algorithm to post in examination rooms. Finally, we developed a low health literacy brochure to help patients understand the purpose and significance of anal Pap smears, HRA, and the results obtained.




In a short period of time, providers integrated anal Pap testing into their practice. An initially high rate of inadequate specimens lead to discussions about technique and practice. After consulting with our pathologists, inconsistencies in cytology reporting were remedied, and providers were educated on the interpretation and implications of anal cytology results.




In just under a year, 212 patients (47% women) underwent anal Pap testing. Similar to the forecasted rates of Shalev et al. [1], 44% of adequate cytology specimens were abnormal and were scheduled for HRA. Patients with extensive disease on HRA are referred to colon and rectal surgery clinic. Patients with more limited disease are treated in-office with infrared coagulator ablation [19–21].




Although the initiation of our anal cancer screening program took substantial time, effort, and funding, over the last year, our team has built a successful and dynamic program to meet New York State AIDS Institute guidelines. We believe that the preliminary evidence justifying the need for this clinical service is convincing, even if it has not yet proven cost-effective in large multicenter clinical studies. Although further studies are warranted, epidemiologic data and anecdotal reports of substantial morbidity and mortality in young, HIV-infected persons from this treatable condition should not await definitive cost–benefit studies before action is taken. At Mount Sinai, we now provide a valuable clinical service to patients at high risk for anal dysplasia.

---------------


Targeted anal cancer screening in HIV-infected patients: prevalence of screening indicators



AIDS:

24 April 2010 6e9a1

Correspondance



Shalev, Noga; Olender, Susan A; Chiasson, Mary Ann

aDivision of Infectious Diseases, Columbia University Medical Center, USA




bPublic Health Solutions, New York, New York, USA.



We thank Tider et al. [1] for their response to our research letter. The incidence of anal cancer in HIV-infected individuals is far higher than the general population but the utility of screening has not been established [2]. As medical providers to HIV-infected patients, we share the respondents' concerns regarding the excessive morbidity and mortality associated with anal carcinoma. Tider et al. [1] provide a detailed description of anal cancer screening ‘scale up’ in an HIV clinic. However, the authors do not share information about key outcomes, such as the number of patients referred to high-resolution anoscopy, the proportion referred who underwent the procedure, or the correlation between cytological and anoscopic findings. In addition, neither the proportion of patients undergoing treatment, nor treatment response data are presented. These data are essential for guiding clinician practice.




Our concerns about anal cancer screening rest on the fear that screening will result in unnecessary diagnostic work-up and treatment without decreasing morbidity and mortality. As was recently illustrated by the US Preventive Service Task Force's revised recommendations on the use of mammograms [3], the benefit of screening is far more nuanced than our desire to prevent illness.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #118 on: May 05, 2010, 05:33:36 PM »
Pharmasset shows promising PhIIa hep C data
May 4, 2010


Pharmasset showed a promising batch of mid-stage data for its hepatitis C therapy and promised to swiftly pivot into a Phase IIb trial that could provide longer-term feedback on efficacy and safety.


After 28 days of therapy, 88 percent of patients taking 100 mg of PSI-7977 had undetectable levels of the virus. That figure rose to 94 percent at a 200 mg dose and 93 percent for 400 mg. That compares to only 21 percent of the patients in the placebo group whose virus levels dropped below the detection level.


Most adverse events reported were mild with a few moderate complaints. No serious side effects were recorded. Princeton, NJ-based Pharmasset's shares were down slightly this morning.


"Our platform technology continues to generate nucleoside/tide analogs with a high degree of efficacy, high barrier to resistance, and a safety profile that we believe differentiates them from other classes of direct acting antivirals," said Pharmasset CMO M. Michelle Berrey. "We plan to quickly progress PSI-7977 into Phase IIb studies starting in the fourth quarter 2010, to generate longer term efficacy and safety data."


- check out Pharmasset's press release
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Re: http://natap.org/
« Reply #119 on: May 05, 2010, 05:35:12 PM »
NATAP http://natap.org/
_______________________________________________

"In summary, this pilot study demonstrated that short-term niacin therapy could improve endothelial function in HIV-infected individuals on stable ART who have low HDL-c."


Short-term effects of extended-release niacin on endothelial function in HIV-infected patients on stable antiretroviral therapy



AIDS:

24 April 2010



Chow, Dominic C; Stein, James H; Seto, Todd B; Mitchell, Carol; Sriratanaviriyakul, Narin; Grandinetti, Andrew; Gerschenson, Mariana; Shiramizu, Bruce; Souza, Scott; Shikuma, Cecilia

aHawaii Center for AIDS, University of Hawaii John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA

bDivision of Cardiovascular Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA

cPublic Health Sciences, University of Hawaii, Honolulu, Hawaii, USA.



Abstract




Objective: To assess the short-term effects of extended-release niacin (ERN) on endothelial function in HIV-infected patients with low high-density lipoprotein-cholesterol (HDL-c) levels.




Methods: Randomized controlled study to determine the short-term effects of ERN on endothelial function, measured by flow-mediated vasodilation (FMD) of the brachial artery, in HIV-infected adults with low HDL-c. Participants on stable HAART with fasting HDL-c less than 40 mg/dl and low-density lipoprotein-cholesterol less than 130 mg/dl were randomized to ERN or control arms. ERN treatment started at 500 mg/night and titrated to 1500 mg/night for 12 weeks. Controls received the same follow-up but were not given ERN (no placebo). Participants were excluded if they had a history of cardiac disease, uncontrolled hypertension, diabetes mellitus, or were on lipid-lowering medications such as statins and fibrates. Change in FMD was compared between arms with respect to baseline HDL-c.




Results: Nineteen participants were enrolled: 89% men, median age 50 years, 53% white/non-Hispanic, median CD4 cell count 493 cells/μl, and 95% of them had HIV RNA below 50 copies/ml. Participants receiving ERN had a median HDL-c (interquartile range) increase of 3.0 mg/dl (0.75 to 5.0) compared with −1.0 mg/dl in controls (−6.0 to 2.5), a P value is equal to 0.04. The median change in FMD was 0.91% (−2.95 to 2.21) for ERN and −0.48% (−2.65 to 0.98) for controls (P = 0.67). However, end of study FMD for ERN was significantly different from controls after adjusting for baseline differences in FMD and HDL-c, 6.36% (95% confidence interval 4.85–7.87) and 2.73% (95% confidence interval 0.95–4.51) respectively, a P value is equal to 0.048.




Conclusion: This pilot study demonstrated that short-term niacin therapy could improve endothelial function in HIV-infected patients with low HDL-c.



Introduction




The incidence of myocardial infarction (MI) in HIV-infected individuals has been increasing. Although much of the coronary artery disease (CAD) risk in the HIV population has been attributed to elevated levels of low-density lipoprotein-cholesterol (LDL-c) and hypertriglyceridemia, low levels of high-density lipoprotein-cholesterol (HDL-c) also contribute to CAD risk. In the general population, low serum levels of HDL-c are associated with increased risk for MI, restenosis after angioplasty, sudden cardiac death, and stroke [1–3]. The primary mechanism by which HDL-c exerts its atheroprotective effect is believed to be reverse cholesterol transport; however, HDL-c also has antioxidant effects [4]. Additionally, HDL-c has direct arterial effects that help preserve endothelial function. Endothelial dysfunction is an early phenomenon in atherosclerosis that precedes structural changes of the arterial wall and clinical manifestations of CAD [5]. This protective effect of HDL-c on endothelium-dependent vasoreactivity may depend on the binding of HDL-c to scavenger receptor class B type I and subsequent stimulation of nitric oxide formation [6]. HDL-c activates both extracellular signal-regulated kinase 1/2 and Akt, resulting in enhanced stability of endothelial nitric oxide synthase [7].




In dyslipidemic HIV-infected patients on stable antiretroviral therapy (ART), low levels of HDL-c have been associated with endothelial dysfunction [8]. Moreover, use of statins in HIV-infected patients on ART improves endothelial function [9]. We hypothesized that increases in HDL-c associated with the use of niacin also would improve endothelial function in HIV-infected individuals. Therefore, we conducted a pilot study to assess the effects of niacin on endothelial function in HIV-infected patients with low HDL-c levels.



Discussion




In this pilot study, we demonstrated that HIV-infected patients on stable ART with low HDL-c had improved brachial artery FMD after 12 weeks of ERN. The improvement in FMD was more significant in patients with low baseline HDL-c. In individuals with HIV, low HDL-c levels increase risk of future CAD [12–14]. Changes in HDL-c with ART also seem to affect short-term CAD [15]. Our study is consistent with recent studies on individuals without HIV infection, showing that interventions targeted at raising HDL-c levels may have vascular benefits. Indeed, two studies [16,17] have shown that in individuals with low HDL-c, use of ERN can improve FMD. Similarly, ERN has been shown to significantly regress carotid intima–media thickness [18]. Our study is the first to determine the effect of niacin on endothelial function in HIV-infected individuals. This is a clinically relevant finding, as many patients with HIV and dyslipidemia have low HDL-c, and the effects of raising HDL-c on endothelial function in patients with HIV have not been investigated previously. Also, niacin's effects on lipids in patients with HIV seem to be less than observed in the general population [19].




Niacin can inhibit vascular inflammation by decreasing endothelial reactive oxygen species production and subsequent LDL-c oxidation and inflammatory cytokine production, key events involved in atherogenesis. Potential mechanisms of the vascular protective effects of HDL-c have been described [20]. HDL-c enhances reverse cholesterol transport, promoting the efflux of cholesterol from atherosclerotic plaque rupture, thus promoting stabilization [21]; HDL-c and its associated proteins attenuate the formation of the highly atherogenic oxidized LDL-c species previously shown to impair endothelial function [22]; HDL-c stabilizes prostacyclin, an important vasodilator and platelet inhibitor [23]; and HDL-c may augment the ability of the endothelium to produce nitric oxide [16]. In addition to the protective effects of HDL-c, niacin helps increase LDL-c particle size, which also may improve endothelial function. Our finding supports the paradigm that niacin-induced increases in HDL-c contribute to improvements in endothelial function in participants with low HDL-c. Of interest, in ACTG study A5152s, positive correlations were observed between ART-associated increases in HDL-c, large HDL-c particles, and FMD (personal communication).




There are several limitations to our study. First, this was an unblinded pilot study with a small sample size and its results require verification, as well as evaluation of the mechanism for these observations. Second, the increase in HDL-c was less than that would be predicted based on data in non-HIV-infected cohorts [16], although this study was of short duration (all treated participants were at the maximal daily dose of 1500 mg of ERN for only 4 weeks), and niacin's beneficial effects on HDL-c levels can continue to increase up to 36 weeks after maximum dose titration [24].




In summary, this pilot study demonstrated that short-term niacin therapy could improve endothelial function in HIV-infected individuals on stable ART who have low HDL-c.



Results



Baseline characteristics




The demographic and clinical characteristics of the 19 participants are presented in the Table 1. Participants consisted of 17 men and two women, with a median age of 50 years (range 28–65 years). Four were current and seven were former smokers. The median CD4 cell count was 493 cells/μl (range 280–1096). All participants had undetectable HIV viral loads except for one participant with a viral load of 1520 copies/ml. The majority of participants (47%) were on an efavirenz-based regimen, whereas 42% were on a protease inhibitor-based regimen. A nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen was used in 60% of the ERN group compared with 44% of controls; a protease inhibitor-based regimen was used in 30% of ERN and 56% of controls. One participant in the ERN group was on an NRTI-only regimen. At baseline, there were differences (P < 0.10) between the arms in FMD, nitroglycerin-mediated dilation (NTGMD), and HDL-c.




All participants achieved the titrated dose of ERN of 1500 mg daily. Only one participant receiving ERN developed serious flushing (grade 2), which was attributed to the participant accidentally taking twice the prescribed dose. This flushing resolved after the ERN dose was reduced. There were no grade 3 or higher adverse events during the study in either group.




After 12 weeks, participants receiving ERN had a median HDL-c (interquartile range) increase of 3.0 mg/dl (0.75 to 5.0) compared with −1.0 mg/dl in controls (−6.0 to 2.5), P value is equal to 0.04. There was no significant change in brachial diameters; the median change in participants receiving ERN was 0.00 mm (−0.01 to 0.03) compared with −0.01 mm in controls (−0.02 to 0.02), P value is equal to 0.56. The median change in FMD from baseline to week 12 was 0.91% (−2.95 to 2.21) for those on ERN vs. −0.48% (−2.65 to 0.98) for controls (P = 0.67). However, after adjusting for baseline differences in FMD and HDL-c, there was a statistically significant increase in FMD in participants receiving niacin (P = 0.048, see Fig. 1). Participants with low HDL-c had a more dramatic improvement in FMD with niacin. In participants with HDL-c 35 mg/dl or less, the adjusted end of study FMD was 8.4% with 95% confidence interval (CI) (6.7 to 10.1) for the niacin group and 4.4% with 95% CI (3.18 to 5.68) for the control group (P = 0.01). There were no differences in NTGMD between the two arms, even after adjusting for baseline NTGMD and HDL-c.



Methods




This was a randomized controlled study evaluating endothelial function, measured by flow-mediated vasodilation (FMD) of the brachial artery, in HIV-1-infected adults with low HDL-c before and after 12 weeks of treatment with extended-release niacin (ERN). Participants randomized to the treatment arm received ERN (Niaspan; Abbott Laboratories, Abbott Park, Illinois, USA) starting at 500 mg per night and titrated to a maximum tolerated dose (not exceeding 1500 mg per night) over 8 weeks. Participants in the control arm received the same follow-up as the treatment arm but were not be given ERN (no placebo) and were instructed to not take any supplemental niacin. CD4 cell count, HIV RNA viral load, FMD, lipid parameters, insulin sensitivity, and C-reactive protein were obtained at baseline and after 12 weeks for both control and treatment arms.




Participants were eligible for the study if they were HIV-infected and were at least 18 years of age. Participants must have been on stable HAART for at least 6 months prior to study entry and have a HDL-c below 40 mg/dl and LDL-c below 130 mg/dl. Participants were excluded if they had cardiac disease, uncontrolled hypertension, pregnancy, or diabetes mellitus. Participants were ineligible if they were on nitrates, metformin, or thiazolidinediones. Treatment with lipid-lowering drugs such as statins and fibrates were excluded. A pharmacist prepared a computer-generated single-block randomized treatment list to determine each patient's treatment assignment. The study pharmacist did not participate in the selection and assessment of patients or the collection of any trial data. This study was approved by the Institutional Review Board of University of Hawaii. All participants provided informed consent.




Endothelial function was assessed by ultrasound brachial artery reactivity testing. Testing was performed in the morning. Participants were required to fast for 12 h. Those who regularly used tobacco products refrained for at least 8 h. After 10-min rest in a temperature-controlled room (70–76°F), the diameter of the right brachial artery and baseline blood flow were measured with a high-resolution linear array vascular ultrasound transducer (Siemens Medical Solutions Inc., Mountain View, California, USA). Increased forearm blood flow was induced by inflating a pneumatic blood pressure tourniquet placed around the widest part of the forearm and inflated to 250 mmHg. This was followed by deflation after 5 min. Repeat brachial artery diameter and blood flow scans were obtained immediately thereafter. Twenty minutes were allowed for vessel recovery and repeat resting brachial artery diameter and blood flow scans were obtained. Sublingual nitroglycerin (400 μg) was administered, and final scans were performed after 3 min. Each study was recorded digitally and sent to the University of Wisconsin Atherosclerosis Imaging Research Program core ultrasound laboratory in Madison, Wisconsin, USA. Brachial artery diameters were measured in triplicate by a single blinded reader [8,10,11].




The primary objective was to assess the change in FMD with respect to 12 weeks of ERN vs. control. The Shapiro–Wilks normality test was used to assess the homogeneity of variances between and within the study arms. Categorical variables were compared using the χ2 test. Continuous variables were analyzed by Wilcoxon rank test. For between-group differences, a two-way analysis of covariance (ANCOVA) for both arms was conducted and controlled for within patient correlation. To control for the effects of baseline FMD and HDL-c, a multivariate ANCOVA was performed. A two-sided probability of P value is less than 0.05 was used to determine statistical significance. All statistical analyses were performed using the JMP statistical program (SAS Institute Inc., Cary, North Carolina, USA).

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Offline red_Dragon888

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« Reply #120 on: May 07, 2010, 10:10:19 AM »
Clue Found to HIV 'Elite Controllers'

MedPage Today

May 06, 2010

Action Points 

    * Explain to interested patients that some people with HIV progress slowly if at all to AIDS, so-called "elite controllers," and this study suggests a reason for that phenomenon.




Researchers believe they have found an important clue in the mystery of the elite controllers -- patients whose HIV infections progress only slowly, if at all, to full-blown AIDS.




A combination of computer modeling and human studies suggests that the elite controllers have killer T cells that are more sensitive to fast-mutating viruses such as HIV, according to Bruce Walker, MD, of Massachusetts General Hospital in Boston, and colleagues.




The result appears to be a more robust immune response in the early stages of HIV infection, Walker and colleagues wrote online in Nature.




Those T cells arise because -- perhaps paradoxically -- the immune system molecules that prime them do a relatively poor job, failing to present large numbers of self-proteins, the researchers said.




The finding derives from the observation that some immune system gene variants -- or HLA class I alleles -- are "markedly enriched" in elite controllers, the researchers said.




The strongest association is for an allele dubbed HLA-B57, so Walker and colleagues analyzed its role in preparing T cells in the thymus.




In general, the HLA molecules bind to and then present a range of self-proteins to the nascent T cell; a cell that reacts too strongly to a self-protein is prompted to self-destruct.




In computer algorithms, Walker and colleagues showed that a molecule associated with HLA-B57 -- dubbed HLA-B*5701 -- only presents about 70,000 of the roughly 10,000,000 possible self-protein sequences to a nascent T cell.




In contrast, a molecule that doesn't protect against HIV -- HLA-B*0701 -- presents about 180,000.




The result, the researchers argued, is that T cells in people with the HLA-B57 genes recognize more peptides once they leave the thymus and are more responsive to small mutations of sequences they recognize.




A series of computer experiments suggested that the argument is correct, they said, and "compelling experimental data" from another group showed the effect actually occurs in humans.




Indeed, they said, "we predict that HIV-infected individuals with HLA alleles that bind fewer self-peptides are more likely to control viral loads to low values."




To test the prediction, they examined two HLA-typed cohorts of people with HIV, including 1,110 controllers with less than 2,000 HIV particles per milliliter of serum without the use of antiretroviral therapy and 628 progressors with viral loads exceeding 104 per milliliter.




Three HLA molecules were significantly associated with nonprogression and two with progression, they found:




    * For HLA-B*0702, the odds ratio for progression was 1.90, which was significant at P=0.0001.

    * As well, HLA-B*3501 had an odds ratio for progression of 1.95, significant at P=0.0007.

    * On the other hand, HLA-B*5701 was protective, with an odds ratio of 0.28, significant at P=10-8.

    * The same was true of two other variants, HLA-B*5703 and HLA-B*2705, with odds ratios of 0.13 and 0.45, respectively. They were significant at P=2x10-7 and P=0.0001, respectively.




The nonprotective molecules were shown to bind to more self-peptides than the protective molecules "in support of our predictions," the researchers noted.




One implication is that people with the protective alleles should also do better when faced with other fast-mutating viruses. Walker and colleagues said that HLA-B57 is, in fact, protective against hepatitis C.




Another implication is that T cells primed by HLA-B57 molecules should be more prone to recognizing self-peptides, possibly leading to autoimmune reactions. And in fact, they noted, HLA-B57 has been associated with autoimmune psoriasis and hypersensitivity reactions.




The study is "remarkable" for its breadth, according to Nobel laureate David Baltimore, PhD, of the California Institute of Technology in Pasadena, Calif.




"It starts from a clinical observation, integrates it with experimental observations, generates a valuable model, and derives from the model a deep understanding of the behavior of the human immune system," Baltimore said in a statement.




"Rarely does one read a paper that stretches the mind so surprisingly far," he said.




Walker and colleagues noted that while such broadly reactive T cells are not common in people with other HLA types, they do exist and vaccine strategies should aim at activating them.
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #121 on: May 07, 2010, 10:11:17 AM »
Rate of Primary Liver Cancer Type Still Climbing
MedPage Today
Published: May 06, 2010
Rates of hepatocellular carcinoma in the U.S. continue to increase, according to the CDC.

From 2001 to 2006, the rate of the disease rose from 2.7 per 100,000 to 3.2 (P<0.01), CDC researchers reported in the May 7 issue of Morbidity and Mortality Weekly Report.

The largest annual percentage changes occurred in whites (3.8%), blacks (4.8%), and individuals in their 50s (9.1%).

Cases increased for both genders, although the annual percentage change was significantly higher in men (3.6% versus 2.3%, P&l t;0.05).

The findings indicate that long-term increases in cases of hepatocellular carcinoma -- of which more than three-quarters are caused by infection with hepatitis B or hepatitis C virus -- continue, according to the researchers.

"Development of viral hepatitis services, including screening with care referral for persons chronically infected with HBV or HCV, full implementation of vaccine-based strategies to eliminate hepatitis B, and improved public health surveillance are needed to help reverse the trend in hepatocellular carcinoma," they wrote.

The researchers analyzed data from the CDC's National Program of Cancer Registries and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) surveillance system.

Only microscopically con firmed cases of hepatocellular carcinoma were included, which, according to an accompanying comment from the MMWR editors, likely yielded more conservative estimates than previous analyses.

From 2001 to 2006, there were 48,596 cases identified, with a median age of 64 at diagnosis (62 for males and 69 for females).

The average annual rate of hepatocellular carcinoma was 3.0 per 100,000. It increased by 3.5% a year.

Individuals in their 70s were most affected, with a rate of 13.7 per 100,000, followed by those in their 80s (10.0), 60s (9.6), 50s (6.8), and 40s (2.1). Cases were infrequent in the younger age groups.

The incidence rate during the study period was about three times higher in males th an in females (5.0 versus 1.3 per 100,000), with a larger annual inc rease in men.

The racial/ethnic group most affected was Asians/Pacific Islanders (7.8 per 100,000), followed by blacks (4.2), American Indians/Alaska natives (3.2), and whites (2.6). Rates increased over the study period for white and black individuals only.

The rate rose for both Hispanic and non-Hispanic individuals, with annual percentage changes of 3.6% and 1.7%, respectively (P<0.05 for both).

The report also provided the first state-specific information on hepatocellular carcinoma trends.

Disease rates ranged from 1.4 per 100,000 in South Dakota to 5.5 in Hawaii. Eleven states had significant increases from 2001 to 2006, with the largest annual percentage changes in Okla homa (11.7%), Iowa (9.0%), and Georgia (7.4%).

The MMWR editors listed three limitations of the analysis, including possible misclassification of race and ethnicity, the lack of national data on specific Asian subgroups, and the fact that cancer registries do not routinely collect information on etiologic factors for hepatocellular carcinoma, including chronic viral hepatitis.


Primary source: Morbidity and Mortality Weekly Report
Source reference:
O'Connor S, et al "Hepatocellular carcinoma -- United States, 2001-2006" MMWR 2010; 59: 517-20.
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #122 on: May 07, 2010, 10:14:04 AM »
Merck and The ADAP Crisis Task Force Announce Key Initiatives to Help Provide Funding Relief to AIDS Drug Assistance Programs (ADAPs) across the U.S.
 
 
 
  Download the PDF here
 
Price Freeze of ISENTRESS® (raltegravir) tablets for ADAPs Through 2013 and Acceleration of Rebate Payments to States among Important Initiatives Highlighted
 
Press release by Merck & NASTAD
 
WHITEHOUSE STATION, N.J., May 5, 2010 -Today, Merck & Co., Inc., and the ADAP Crisis Task Force (ACTF) announced a series of key initiatives to help struggling state AIDS Drug Assistance Programs (ADAPs) continue to provide people living with HIV access to medicines.
 
The ACTF is pleased that, among these initiatives, Merck is:
 
- Extending the price freeze of ISENTRESS® that was first established with the ACTF in 2008 to eligible ADAPs through Dec. 31, 2013.
- Extending the price freeze on CRIXIVAN (indinavir sulfate) capsules that was first established with the ACTF in 2003 to eligible ADAPs through Dec. 31, 2013.
- Working with the ACTF to provide expanded financial relief to eligible ADAPs through increased discounts for ISENTRESS and CRIXIVAN.
- Expediting the processing of state rebate claims to speed up rebate payments to eligible ADAPs.
- Working with the National Alliance of State and Territorial Directors (NASTAD) to find solutions to provide technical assistance to ADAP programs.
 
Expansion of Special Pricing Program for ISENTRESS and CRIXIVAN and extension of price freeze to eligible ADAPs through 2013
 
The ACTF, a group of state ADAP and AIDS directors that is convened by NASTAD, requested that drug companies consider implementation of cost control measures, such as a price freeze of HIV drugs to ADAPs to help mitigate the current financial crises. In response, Merck established an expanded Special Pricing Program for its HIV medicines for eligible ADAPs. The expanded Special Pricing Programs for ISENTRESS and CRIXIVAN will begin July 1, 2010 and extend through Dec. 31, 2013. The price freeze extension follows Merck's earlier agreement with the ACTF in 2008 to freeze the price of ISENTRESS to eligible ADAPs at its launch price. The extension of its price freeze on CRIXIVAN to eligible ADAPs will also last through Dec. 31, 2013. When it announced its voluntary price freeze in 2003, Merck was the first company to freeze the price of an anti-retroviral (ARV) drug to ADAPs. Merck will reassess these programs in 2014, after implementation of the U.S. government's newly expanded Medicaid program and subsidized private health insurance plans mandated by health care reform legislation (Patient Protection and Affordable Care Act).
 
Fast pay of rebates and technical assistance
 
In addition to the expanded Special Pricing Program for ISENTRESS and CRIXIVAN, Merck is committed to assisting eligible ADAPs with cash flow and to reducing the number of patients waiting to receive treatment. As such, the Company has changed its existing state invoice payment process to accelerate the payment of Merck rebates to eligible ADAPs.
 
Merck's patient assistance programs in the U.S.
 
Merck's commitment to patients' access to its products is evidenced through its HIV SUPPORT program, which helps patients who have been prescribed ISENTRESS or CRIXIVAN by providing personalized support and patient advocacy regarding individual reimbursement issues. The SUPPORT program also offers patient assistance, which may include providing ISENTRESS or CRIXIVAN free of charge to eligible patients. Information about the SUPPORT Program can be obtained by calling 1-800-850-3430 or at www.isentress.com..
 
Patients who are on ADAP waiting lists or who are awaiting ADAP approval may be eligible to receive ISENTRESS or CRIXIVAN for free through the SUPPORT program.
 
Merck's co-pay assistance program
 
In addition to the SUPPORT Program, Merck has a co-pay assistance program in the U.S. for eligible patients on ISENTRESS who are commercially insured and have co-pays or coinsurance above $30, up to $400 per prescription. With this program, eligible patients can receive savings off their out-of-pocket costs for 12 prescriptions prior to the programs expiration in July 2011. Information about the co-pay assistance program can be obtained by calling 866-350-9232 or at www.isentress.com.   
 
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #123 on: May 17, 2010, 10:10:48 AM »
Testosterone Improves Metabolic Syndrome

MedPage Today
Published: May 15, 2010


PRAGUE -- Depot testosterone injections in men with metabolic syndrome and hypogonadism led to improvements in several important components of their disease, including significant weight loss and reduced glucose dysregulation, a researcher said here.

Action Points

Explain to interested patients that the testosterone product used in the study is not available or FDA approved in the U.S.


Explain that testosterone levels tend to be depressed in men with diabetes and the metabolic syndrome, but it is not yet proven that testosterone supplements are an effective treatment for these conditions.


Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.
Interim results from a randomized, placebo-controlled trial showed that men receiving the hormone injections lost more than 4 kg (9 lb) in the first 30 weeks of a planned three-year study versus almost no change with placebo (P<0.001), reported Farid Saad, PhD, of Bayer Schering in Berlin.


Although fasting plasma glucose levels did not change, insulin levels dropped significantly among participants in the active treatment group, mainly among those with abnormally high levels at baseline, Saad told attendees here at the World Congress on Controversies to Consensus in Diabetes, Obesity, and Hypertension.


There were also trends toward normalized levels of certain blood lipids, serum leptin, and inflammation markers.


Many men with diabetes or metabolic syndrome show abnormally low testosterone levels, which has prompted several research groups and now the drug industry to investigate testosterone supplements as a therapy.


In March, for example, British researchers reported favorable results in diabetic and prediabetic men with a testosterone gel produced by a different company.


Bayer Schering has its own topical testosterone gel, with some results reported here as well, but the company is also interested in marketing its depot injectable version (Nebido) for this purpose. The product is currently approved outside the U.S. as a treatment for hypogonadism.


In the study Saad reported here, 184 men were randomized in a 3:2 ratio to the testosterone injection, at 1 g per dose, or placebo. Three injections were given, at weeks zero, six, and 18. Saad reported results of evaluations conducted at weeks 18 and 30.


Men receiving the hormone injections showed markedly greater decreases at week 30 in body mass index (BMI) and waist circumference as well as in body weight, according to Saad.


Mean BMI declined by 1.3 points from a baseline level of 36, compared with a 0.1-point decrease in the placebo group (P<0.001).


Similarly, waist circumference in the active treatment group shrank by 6 cm (2.5 inches) versus 1.5 cm (less than one inch) with placebo (P<0.001). Mean waist circumference at baseline was about 117 cm (46 inches).


Men in the placebo group lost about 0.3 kg compared with the 4-kg decline in the testosterone group (P<0.001).


Saad indicated that the weight loss was probably not a direct hormonal effect. Instead, he said, men on testosterone likely felt more energetic, exercising more and feeling motivated to eat a healthier diet.


Little to no change in fasting plasma glucose was noted during these first 30 weeks of treatment, Saad reported, but there was a significant decline in fasting insulin levels with the hormone treatment.


From a baseline value of about 26 mIU/L, insulin levels fell to 20. In the placebo group, mean levels increased slightly from 20.5 to 22 mIU/L (P=0.04 testosterone versus placebo).


Saad observed that the most substantial declines occurred in those patients with insulin levels above 26.4 mIU/L at baseline. The mean for those receiving the hormone dropped from 44 to 32 mIU/L (P=0.001), whereas there was almost no decline seen in patients with baseline insulin in the normal range.


The testosterone group showed nonsignificant trends toward reductions in LDL cholesterol (also seen with placebo) as well as increases in HDL levels. Mean serum leptin fell by nearly half (P<0.001) by week 30, with the 14.04-ng/mL level just above the normal range (upper limit, 13 ng/mL).


Saad also reported significant reductions in C-reactive protein and tumor necrosis factor-alpha levels in the treatment group, whereas increases or no change were seen in the control patients.


Session chair Robert Niecestro, PhD, managing director of the drug development firm Accelapharm in New York City, commented that the weight loss seen with the treatment was particularly impressive.
"I'll be interested to see if it persists for three years," he said.


Niecestro cautioned that these were early results from a planned three-year study. Consequently, some of the nonsignificant trends could become significant as the study progresses, or they could turn out to be temporary blips, he suggested.



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Offline red_Dragon888

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Re: http://natap.org/
« Reply #124 on: May 17, 2010, 10:11:20 AM »
Combo Treatment Effective in NASH

MedPage Today
Published: May 16, 2010

PRAGUE -- Adding the nutritional supplement alpha-lipoic acid to ursodeoxycholic acid (UDCA, ursodiol) reduced the major symptoms of non-alcoholic steatohepatitis (NASH) in a small controlled trial, it was reported here.

Action Points

Explain to interested patients that NASH is a serious complication of diabetes and obesity. FDA-approved treatments are available but many patients do not respond adequately.


Explain that it's important for patients to tell their doctors when they are taking so-called nutritional supplements, especially if they are also taking conventional prescription or over-the-counter medications.


Point out that this was a small study with a short follow-up period.


Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.
Measures of fibrosis, liver transaminase levels, and overall disease severity were all improved significantly relative to diet-based treatment in a six-month, 20-patient study, according to Vincenzo Gianturco, MD, of the University of Rome "La Sapienza" in Italy.


UDCA is already an FDA-approved treatment for NASH, one of the major complications of diabetes and obesity, but many patients fail to show substantial improvement on the treatment.


Gianturco, speaking here at the World Congress on Controversies to Consensus in Diabetes, Obesity, and Hypertension, said about 2% to 3% of the population in Western countries suffers from NASH, an advanced stage of non-alcoholic fatty liver disease.


Both conditions are most common in middle-age, obese women with diabetes. However, according to Gianturco, NASH may be seen in individuals of any age or gender.


Alpha-lipoic acid is an antioxidant compound found naturally in human cells and in many foods -- and, in capsule form, in health food stores. It is used in complementary medicine to treat various diabetic complications and some neurologic conditions, on the theory that it has cytoprotective effects.


UDCA also appears to have cytoprotective effects, by a different mechanism; hence the idea to combine the two agents as a one-two punch against NASH.


Gianturco and colleagues randomly assigned 10 patients to receive ALAURSO -- 400 mg of alpha-lipoic acid plus 300 mg UDCA -- daily for six months. Ten other patients were randomized to a placebo group that was treated only with a low-calorie diet plan.


Patients with hepatitis B or C virus infection, alcohol drinkers, and those with gallbladder stones were excluded. Patients underwent liver biopsy at baseline, confirming the diagnosis, and again at the end of treatment.


Essentially no change in mean liver enzyme levels were seen in the control group, whereas the ALAURSO group showed substantial and statistically significant reductions (P=0.001) relative to controls, even with the small number of patients involved:
Aspartate acetyltransferase: baseline 47.0 mg/dL (SD 6.0); 30.6 mg/dL (SD 4.0) after treatment
Alanine acetyltransferase: baseline 50.9 mg/dL (SD 5.7); 33.4 mg/dL (SD 3.1) after treatment
Gamma-glutamyl acetyltransferase: baseline 57.7 mg/dL (SD 7.0); 34.2 (SD 3.5) after treatment
In the control group, none of the liver enzymes changed by more than 1 mg/dL with treatment.


Fibrosis scores increased in the control group, from 1.4 at baseline to 1.52, whereas scores declined significantly in the ALAURSO group, from 1.2 at baseline to 1.01 (P=0.04), Gianturco said.
Both compliance and tolerability were good, he told attendees here.


However, he cautioned that detailed histological analyses had not been performed. The small number of patients and the relatively short follow-up were also limitations, Gianturco said.


Session moderator Robert Niecestro, PhD, of the drug development firm Accelapharm in New York City, commented that alpha-lipoic acid is a chiral molecule, with both R- and S- enantiomers contained in commercially sold versions.


He said the R- enantiomer is responsible for the compound's beneficial effects, whereas the S- version tends to offset them somewhat.


Niecestro suggested that using only the R- form might further boost the effectiveness of the ALAURSO combination.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #125 on: May 17, 2010, 10:11:56 AM »
Latest Hepatitis C Figures Show Year On Year Increase, UK

New figures released by the Health Protection Agency (HPA) show reported cases of Hepatitis C infection in England to have increased by 4.5% from 8,196 cases reported in 2008 to 8,563 cases in 2009.

This year's figures released in advance of World Hepatitis Day bring the cumulative reported total (from 1992 to 2009) to 78,428 diagnosed cases.

There has been a steady increase in the number of laboratory confirmed diagnoses of hepatitis C infection since 1995. These gradual yearly increases indicate an increase in public awareness with more people coming forward to get tested. Healthcare campaigns by the Department of Health, the NHS and the voluntary sectors are all likely to have contributed to this increase in awareness over recent years.

Hepatitis is a condition characterised by inflammation of the liver and can be caused by the viral infections hepatitis A, B, C and E. Hepatitis C, is a blood-borne virus which if left untreated can eventually result in chronic liver disease, liver failure or death. Many individuals are unaware that they have become infected with the virus because signs and symptoms are rare in the early years of infection.

Currently, the greatest risk of contracting hepatitis C in the UK is through sharing equipment for injecting drugs. Sharing injecting equipment, even on a one-off basis, or a long time ago, could place an individual at risk of hepatitis C. Also, hepatitis C is more prevalent in the South Asian communities who have often acquired their infections via other routes. Others may have acquired their infections via blood transfusion in the UK more than two decades earlier, before the introduction of routine screening of blood for the virus in 1991.

There is currently no vaccine to protect against hepatitis C but simple measures such as using sterile injecting equipment and not sharing personal items like toothbrushes and razors will minimise your chances of being exposed to it.

Dr Mary Ramsay, Hepatitis expert at the Centre for Infections, at the HPA: "We must not get complacent about this, it is critical that awareness campaigns are sustained and enhanced if more people at risk of this infection are to be tested and treated."

"Liver disease is largely preventable and yet it continues to rise. The majority of hepatitis C infections can be treated successfully or prevented from occurring in the first place, yet new infections are continuing to occur and many existing infections remain undiagnosed"

"If people think they may have been exposed to the virus, they should contact their GP and request a test. Tackling undiagnosed hepatitis C infections by increasing awareness and encouraging people to come forward for testing could have a major impact on the number of people suffering needlessly from liver disease in the future."

The work of the HPA includes monitoring trends in hepatitis C at a national level and working with other agencies through a network of local leads to improve services for the prevention, diagnosis and treatment of hepatitis.


Source
Health Protection Agency

http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #126 on: May 17, 2010, 10:12:59 AM »
1st International Workshop on HIV & Aging


4-5 October 2010, Baltimore, MD, USA
 
The  venue of the workshop is currently under deliberation.
If you would like to stay updated on the latest developments, please subscribe to our Newsletter: subscription form
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Dear Colleagues,


It is our great pleasure to announce the 1st International Workshop on HIV & Aging, to be held in Baltimore, MD, USA, on 4-5 October 2010.

With an aging HIV-infected population - and suggestions that HIV itself may cause conditions normally associated with aging - there is a pressing need for more scientific dialog on this topic. This workshop will present a unique and much needed platform for international scientific exchange on the increasingly recognized problems of HIV and aging.
Progress in research and a large and increasing number of antiretrovirals have led to improved survival and quality-of-life for people living with HIV but aging patients today still face many challenges. Although some research is being performed on the effects of aging on HIV (and vice versa), no platform currently exists for the presentation and discussion of these data by cross-disciplinary experts in a small, focused scientific setting. We are convening the 1st International Workshop on HIV & Aging to address this objective.

The workshop will gather a cross-disciplinary team of  experts and trainees involved in HIV and aging research, in order to present and discuss the latest developments and strategies for the future, in an interactive and science - focused setting.

The meeting will have a two day program consisting of invited lectures, abstract-driven scientific presentations and poster sessions. The latest developments will be reviewed and evaluated in order to identify important topics for future research, develop better approaches to treatment, and create a strategic agenda for future management problems associated with HIV and aging.
The program will include important focus areas, such as: 
Neurology
Pharmacology
Metabolic complications
Immunology
Virology
Effects of aging on organ systems (renal, hepatic, endocrine, musculoskeletal)
Impact of human genetics on susceptibility to aging-related complications of HIV
Research / clinical trials
We invite you to attend the 1st International Workshop on HIV & Aging and encourage you to submit abstracts on your research in this field.
We hope to see you in Baltimore!
On behalf of the Organizing Committee,
Charles Flexner MD, Johns Hopkins University, USA 
Scott Letendre MD, UCSD, USA
Chairs 2010
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #127 on: May 18, 2010, 06:14:04 PM »
Generic 3TC+d4T Fixed Dose Tablets FDA Approved

On May 17, 2010, the Food and Drug Administration (FDA) granted tentative approval for lamivudine and stavudine Fixed Dose Combination tablets, 150mg/30mg, indicated in combination with other antiretrovirals for the treatment of HIV-1 infection in adults. This new fixed dose combination is manufactured by Hetero Drugs Limited, of Hyberdad, India.

FDA's tentative approval means that although a product meets all of the safety, efficacy, and manufacturing quality standards required for marketing in the U.S., existing patents and/or proprietary issues currently prevent marketing of the product in the United States. Tentative approval, however, does qualify the product for consideration for purchase under the President's Emergency Plan for AIDS Relief, or PEPFAR program.

As with all generic applications, FDA conducts an on-site inspection of the manufacturing facilities and of the facilities performing the bioequivalence studies prior to granting approval or tentative approval to evaluate the ability of the manufacturer to produce a quality product and to assess the quality of the bioequivalence data supporting the application.

These products were reviewed for PEPFAR under the FDA guidance titled Fixed Dose Combinations, Co-Packaged Drug Products, and Single-Entity Versions of Previously approved Antiretrovirals for the Treatment of HIV developed to clarify what regulatory requirements apply to such applications, what issues might be of concern, and how these issues should be addressed. The guidance is intended to encourage sponsors to submit applications for combination and co-packaged products, and to facilitate submission of such applications to FDA.

A list of all FDA approvals and tentative approvals for PEPFAR can be found on the FDA web site.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #128 on: May 18, 2010, 06:15:10 PM »
Decreased Kidney Function Predicts Death Risk in General Population

from Jules: in the general population kidney function declines with age and in HIV it does appear as though patients are in general experiencing accelerated aging or premature comorbidities. HIV+ individuals often have more risk factors for kidney dysfunction including a history of substance abuse, being African-American, diabetes (perhaps insulin resistance causes decline in kidney function), recent studies at conferences have been reported HIV+ individuals more often have proteinuria, an association between certain ARTs and kidney function, and HIV appears to be reswrvoired in the kidney. All suggesting that as the HIV patient population ages kidney function is likely to decline perhaps more than in the general population. Aging appears to be perhaps the number 1 concern for patients. Aging research has begiun to gain traction, the 1st Intl Aging/HIV Workshop is scheduled for Oct 2010 in Baltimore. We must get an understanding of how we can hopefull prevent premature and early onset for these comorbidities including besides kidnet disease - cardiovascular, diabetes, cancers, bone, the brain/CNS.

MedPage Today
Published: May 17, 2010

Two measures of impaired renal function are independent predictors of increased mortality risk among the general population, a meta-analysis showed.

Action Points

Explain to interested patients that this meta-analysis suggested that both estimated glomerular filtration rate and urinary albumin-to-creatinine ratio (ACR) may be useful in defining and staging chronic kidney disease.


This meta-analysis suggests, but does not establish a cause and effect, for increased mortality risk among individuals with a higher urine ACR and a reduced glomerular filtration rate.
Estimated glomerular filtration rates (eGFRs) of 60 mL/min/1.73 m2 or lower and urine albumin-to-creatinine ratios (ACR) of 1.1 or higher were associated with a greater risk of death in a pooled analysis of 21 studies, according to Josef Coresh, MD, PhD, of Johns Hopkins Bloomberg School of Public Health in Baltimore, and colleagues from the International Chronic Kidney Disease Prognosis Consortium.


The findings are consistent with thresholds set by the Kidney Disease Outcomes Quality Initiative -- eGFR of 60 mL/min/1.73 m2 or less and albumin-to-creatinine ratio of 3.4 or higher -- for increased mortality, the researchers reported online in The Lancet.


In an accompanying editorial, Roberto Pontremoli, MD, PhD, of the University of Genoa in Italy, and colleagues, wrote, "Data from today's meta-analysis confirm beyond doubt that the current thresholds are indicative of increased all-cause and cardiovascular mortality risk."


The findings "will hopefully promote greater use of renal function tests in clinical practice aimed at global risk assessment," they said.


According to Coresh and his colleagues, there is continuing controversy around the use of eGFR and the presence of urinary albuminuria (protein in urine) to define chronic kidney disease and assign its stages.
They performed the meta-analysis to evaluate the associations of each measure -- both separately and combined -- with mortality in cohorts from the general population.


The analysis included 21 studies from Asia, Europe, North America, and Australia -- 14 with 105,872 total participants and urine albumin-to-creatinine ratio measurements and seven with 1,128,310 participants and urine protein dipstick measurements.


Through a median follow-up of 7.9 years, there were 45,584 deaths, including 9,637 from cardiovascular disease.


In the studies with ACR measurements, eGFRs between 75 and 105 mL/min/1.73 m2 were not significantly associated with mortality, but lower eGFRs were linked with a greater risk of death.


Compared with an eGFR of 95 mL/min/1.73 m2, the adjusted hazard ratios for all-cause mortality were 1.18 (95% CI 1.05 to 1.32) for 60 mL/min/1.73 m2, 1.57 (95% CI 1.39 to 1.78) for 45 mL/min/1.73 m2, and 3.14 (95% CI 2.39 to 4.13) for 15 mL/min/1.73 m2.


The hazard ratios tended to be higher in participants younger than 65 than in older patients, although tests for an interaction between eGFR and age did not reach statistical significance in most studies.


Urine albumin-to-creatinine ratio was associated with mortality in a linear fashion.


Compared with a ratio of 0.6 mg/mmol, the adjusted hazard ratios for all-cause mortality were 1.20 (95% CI 1.15 to 1.26) for 1.1 mg/mmol, 1.63 (95% CI 1.50 to 1.77) for 3.4 mg/mmol, and 2.22 (95% CI 1.97 to 2.51) for 33.9 mg/mmol.


All of the findings were similar in studies using dipstick measurements and when cardiovascular mortality was the outcome.


Both measures of reduced kidney function independently predicted mortality risk and, in most studies, did not have significant interactions with each other.


"In other words," the editorialists wrote, "knowing one's level of urine albumin excretion provides additional prognostic information for almost any given value of eGFR, and vice versa."


Coresh and his colleagues noted that the meta-analysis had several limitations:a lack of uniform study protocol and centralized analysis of laboratory results for all cohorts, and no standardized measurements for creatinine and albuminuria.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #129 on: May 19, 2010, 05:53:48 PM »
Bone Guidelines

Osteoporosis in Men
Apr 3, 2008 ... Guidelines The International Society for Clinical Densitometry recommends bone mineral density screening in men 70 years of age or older and ...
www.natap.org/2008/HIV/040708_01.htm
"These guidelines recommend bisphosphonates as first-line treatment for men in this age group whose bone mineral density is in the osteoporotic range, for men over the age of 50 years who have had fractures and have a T score below -1.5, and for men of any age who have osteopenia and have taken corticosteroids for 3 or more months or who have hypogonadism. Recent National Osteoporosis Foundation guidelines59 recommend pharmacologic therapy in men 50 years of age or older with hip or vertebral fractures; in men with a T score below -2.5; and in men with a T score between -1.0 and -2.5 with either a 10-year hip fracture probability of 3% or more or a total minimal trauma fracture probability of 20% or more."


Aging/HIV Clinical Care & Research - New IDSA Guidelines
New IDSA HIV Guidelines Push 'Adherence to Care' - (08/17/09) Bone Guidelines Excerpted From New IDSA Guidelines- pdf of full paper attached - (08/12/09) ...
www.natap.org/2009/HIV/082509_03.htm

"Baseline bone densitometry should be performed in postmenopausal women aged >65 years and in younger postmenopausal women with >1 additional risk factor(s) (other than being female and postmenopausal) for premature bone loss. Baseline bone densitometry should be considered in HIV-infected persons aged >50 years, especially if they have 1 risk factor(s) for premature bone loss. If the test demonstrates osteopenia or if the patient has a history of fragility or fracture, intervention with a bisphosphonate or other medical therapy should be considered"

CLINICIAN'S GUIDE TO PREVENTION AND TREATMENT OF OSTEOPOROSIS ...
NATIONAL OSTEOPOROSIS FOUNDATION http://www.nof.org. Since the NOF first published the guide in 1999, it has become increasingly clear that many patients ...
www.natap.org/2008/HIV/070708_01.htm

"In postmenopausal women and men age 50-70, recommend BMD testing when you have concern based on their risk factor profile......

Clinical Assessment of Osteoporosis in Postmenopausal Women and Men Age 50 and Older
-- Obtain a detailed patient history pertaining to clinical risk factors for osteoporosis-related fracture
-- Modify diet/supplements and other clinical risk factors for fracture
-- Estimate patient's 10-year probability of hip and any major
osteoporosis-related fracture using the
US-adapted WHO algorithm
-- Decisions on whom to treat and how to treat should be based on clinical judgment using this guide and all available clinical information
-- Consider FDA-approved medical therapies based on the following:
- A vertebral or hip fracture
- A DXA hip (femoral neck or total site) or spine T score ≦ -2.5
- Low bone mass and a U.S.-adapted WHO 10-yr probability of a hip fracture ≥ 3% or probability of any major osteoporosis-related fracture ≥ 20%
- Patient preferences may indicate treatment for people with 10-yr fracture probabilities below
these levels
-- Consider non-medical therapeutic interventions
- Modify risk factors related to falling
- Consider physical and occupational therapy including walking aids and hip pad protectors
- Weight-bearing activities daily
-- Patients not requiring medical therapies at the time of initial evaluation should be clinically reevaluated
when medically appropriate
-- Patients taking FDA-approved medications should have laboratory and bone density re-evaluation after two years or when medically appropriate"

Low Bone Mineral Density, Renal Dysfunction, and Fracture Risk in ...
Dec 1, 2009 ... Although the National US Osteoporosis Foundation does not recommend BMD screening for all patients with HIV, it explicitly states that ...
www.natap.org/2009/HIV/113009_01.htm

Men and Osteoporosis from the National Osteoporosis Foundation Today, 2 million American men have osteoporosis, and another 12 million are at risk for this disease. Yet, despite the large number of men affected, osteoporosis in men remains underdiagnosed and underreported.


Bone growth
During youth, bones grow in length and density. During the teen years, maximum height is reached, but bones continue to grow more dense until about age 30 when peak bone mass is attained. After that point, bones slowly start to lose density or strength. Throughout life, bone density is affected by heredity, diet, sex hormones, physical activity, lifestyle choices and the use of certain medications. Men have larger, stronger bones than women which explains, in part, why osteoporosis affects fewer men than women.


Risk factors for osteoporosis
The following risk factors are associated with osteoporosis in men:
Prolonged exposure to certain medications, such as steroids used to treat asthma or arthritis, anticonvulsants, certain cancer treatments and aluminum-containing antacids
Chronic disease that affects the kidneys, lungs, stomach and intestines and alters hormone levels
Undiagnosed low levels of the sex hormone testosterone
Lifestyle habits:
1. Smoking
2. Excessive alcohol use
3. Low calcium intake
4. Inadequate physical exercise
Age: Bone loss increases with age
Heredity
Race: Of all men, white men appear to be at greatest risk for osteoporosis. However, men from all ethnic groups develop osteoporosis
How is osteoporosis diagnosed?
Unfortunately, the diagnosis of osteoporosis in men is often overlooked. Your physician may take a medical history to identify risk factors and conduct a complete physical exam, in bone mineral density test (BMD Test), a special type of x-ray that can diagnose osteoporosis.


If you notice a loss of height, change in posture or sudden back pain, it is important to inform your doctor.


How can osteoporosis in men be prevented and treated?
Experts agree that all persons should take the following steps to preserve bone health.
Recognize and treat any underlying medical conditions that affect bone health. Identify and evaluate the use of medications that are known to cause bone loss.
Change unhealthy habits, such as smoking, excessive alcohol intake, and inactivity.
Make sure to get enough calcium each day to keep bones healthy.  Men under age 50 need 1,000 mg of calcium daily, and men age 50 and over need 1,200 mg of calcium daily.
Make sure to get adequate vitamin D.  Men under age 50 need 400-800 IU of vitamin D daily, and men age 50 and over need 800-1,000 IU of vitamin D daily.
Engage in a regular regimen of weight-bearing exercises where bone and muscles work against gravity. This includes walking, jogging, racquet sports, stair climbing and team sports. Also, lifting weights or using resistance machines appears to help preserve bone density. Exercise also improves balance and muscle tone and imparts a sense of well-being. If you have already been diagnosed with osteoporosis, any exercise program should be evaluated for safety by your doctor before you begin. Twisting motions and impact activities may need to be curtailed depending on the severity of your condition.
What medications can slow or stop bone loss in men?
Medications to treat osteoporosis fall into two main categories:  antiresorptives and anabolics. Antiresorptives slow bone loss. The Food and Drug Administration (FDA) has approved three antiresorptive medications to treat osteoporosis in men.  These are alendronate (brand name Fosamax?), risedronate (brand name Actonel?) and zoledronic acid (brand name Reclast?). These medications are in a class of drugs called bisphosphonates.



Anabolics speed up bone formation. Only one anabolic medication has been approved to treat osteoporosis. This medication is teriparatide (brand name Forteo?), and it is approved for men. This medication is in a class of drugs called parathyroid hormone.



Testosterone helps protect the bones of men.  When osteoporosis is due to low testosterone levels, testosterone replacement therapy may be a treatment option.


New members of the NOF family receive our quarterly newsletter, Osteoporosis Report, and a copy of our newly revised, 100+ page handbook, Boning Up on Osteoporosis. Renewing members receive NOF's quarterly newsletter.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #130 on: May 20, 2010, 06:33:38 AM »
When it Comes to Sparking a Woman?s Sexual Desire, Most Men ? and Even Women ? May Not Know Where to Start
- Actress Lisa Rinna kicks off campaign highlighting connection between brain, body and sexual desire -


Washington, D.C., May 12, 2010 ?When it comes to sex, more than half of men and women don?t recognize the brain as an important female sexual organ, according to a new survey.*
?The root of a woman?s desire is complex, but it is thought to start with her brain.  The brain is the center for thoughts and emotions, but it is also home to a complex system of nerves, hormones and other chemicals that can affect sexual desire,? said Laura Berman, LCSW, Ph.D., and sex and relationship expert.



Interestingly, the survey revealed that women and men?s feelings about sex and sexual desire are more alike than people may think, as they both agree that sexual health is important for a woman?s overall health and well being.  Yet, while most women surveyed would be concerned if they experienced, and most men would be concerned if their partner experienced, a decrease in sexual desire, less than half of both women and men have ever discussed these issues with their partner.


Today, the Society for Women?s Health Research (SWHR), along with actress and TV personality Lisa Rinna, launched ?Sex Brain Body: Make the Connection,? a new educational campaign about female sexual health, particularly about the role the brain is thought to play in female sexual desire.



?As a woman, wife and mother, I know that women?s sexual desire can fluctuate.  For some women that?s normal, but for others it may be something more,? Rinna said.  ?Everyone is entitled to a healthy sex life.  That?s why I?m encouraging women to learn more about their sexual health and the brain?s potential role in desire, so they can talk more openly about it with a partner and health care provider.  By visiting www.SexBrainBody.com, I want to empower women to learn more about their sexual health and better understand sexual desire.?   



Experts believe that chemicals in the brain may play a role in sexual response, impacting a woman?s sexual desire.  Women and men surveyed believe that desire is important for a healthy sex life, and that a decline in a woman?s desire would be distressing to the woman.  Yet, few people realize that a lack of sexual desire accompanied by distress might be something more than stress from a demanding career or family commitments.  It may be a medical condition known as Hypoactive Sexual Desire Disorder, or HSDD.


By visiting www.SexBrainBody.com, women can learn more about HSDD, as well as find helpful tips for starting what may be an uncomfortable conversation with their partners or health care providers about their sexual health and any issues they may be experiencing.



?For 20 years, SWHR has provided resources and knowledge to empower women to take control of their health.  We are proud to be supporting this campaign to help women understand their sexual health and give them the confidence to discuss their needs,? said Phyllis E. Greenberger, M.S.W., President and CEO of SWHR in Washington, D.C.


Survey Findings
The ?Sex Brain Body: Make the Connection? survey included 1,300 women ages 30 to 55 years and 1,129 men ages 30 to 65 years.  The survey was designed to explore the attitudes and behaviors of women regarding their sexual health, as well as men?s perception of a woman?s sexual health.



Highlights of the survey include the following:


Nearly 75 percent of women report experiencing a lack of sexual desire at least occasionally, with 20 percent reporting a lack of desire frequently
Both women and men believe a woman?s lack of desire for sex would cause distress in a relationship (78 percent women, 63 percent men); more than half of women and men say that a lack of desire would have a negative impact on their relationship
Most women (roughly 60 percent) say they would discuss low sexual desire with their health care provider, yet only 14 percent have actually done so
More women would rather discuss other health topics such as allergies, skin care, hair loss and weight issues with their health care provider than talk about their sexual health
Women are seven times more familiar with erectile dysfunction (66 percent) than Hypoactive Sexual Desire Disorder (HSDD) (9 percent)


About ?Sex Brain Body: Make the Connection?
?Sex Brain Body: Make the Connection? is an educational campaign meant to help women recognize the potential links between the brain, the body and sexual desire, so they can better understand and address their own sexual health.  The campaign is sponsored by the Society for Women?s Health Research and content was developed with the support of a sponsorship from Boehringer Ingelheim Pharmaceuticals, Inc.  To learn more about the sex-brain-body connection, visit www.SexBrainBody.com.


Low sexual desire is the most commonly reported female sexual complaint.  Approximately one in 10 women reported low sexual desire with associated distress, which may be HSDD.  HSDD is a form of female sexual dysfunction (FSD) and has been recognized as a medical condition for more than 30 years.  As defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), HSDD is the persistent or recurrent lack (or absence) of sexual fantasies or desire for any form of sexual activity causing marked distress or interpersonal difficulty and not better accounted for by another disorder (except another sexual dysfunction), direct physiological effects of a substance (including medications), or a general medical or psychiatric condition.  Generalized, acquired HSDD is not limited to certain types of stimulation, situations or partners, and develops only after a period of normal functioning.  There has been an unmet need for women as there is no FDA-approved treatment for HSDD.  It can affect women of all ages and at any stage of life.


*About the Survey
A demographically representative national internet sample of 1,300 women between the ages of 30 and 55 and 1,129 men 30-65 were invited via email to participate in a 10-minute self-administered online survey.  Women meeting any of the following criteria were eliminated from participating: had a full hysterectomy, currently take hormone replacement therapy, are post-menopausal and have already gone through menopause.  The surveys were administered between February 8 and March 18, 2010.  Data for these studies are tested for statistical difference at a confidence level of 95 percent.  Data are weighted to reflect accurate representation of population.


About Society for Women?s Health Research
The Society for Women?s Health Research (SWHR), a national non-profit organization based in Washington, D.C., is widely recognized as the thought leader in research on sex differences and is dedicated to improving women?s health through advocacy, education, and research.  SWHR was founded in 1990 by a group of physicians, medical researchers and health advocates who wanted to bring attention to the myriad of diseases and conditions that affect women uniquely.  Women?s health, until then, had been defined primarily as reproductive health.  Women were not routinely included in most major medical research studies and scientists rarely considered biological sex as a variable in their research.


About GfK Healthcare
GfK Healthcare (www.gfkhc.com) is the largest provider of fully integrated custom health care marketing research in the United States. With the broadest range of custom, syndicated and proprietary research offerings, paired with expertise in managed markets and sales force effectiveness, GfK Healthcare is equipped to meet a product?s needs across its life cycle, through flexible marketing research resources, responsive to clients? evolving challenges. GfK Healthcare is part of the GfK Group.


About Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.


The Boehringer Ingelheim group is one of the world?s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.


In 2009, Boehringer Ingelheim posted net sales of US $17.7 billion (12.7 billion euro) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #131 on: May 20, 2010, 06:34:31 AM »
Boehringer Ingelheim Sexual Drive Drug For Women in Clinical Trials

http://www.femininereview.com

Girosa or Flibanserin?
Girosa is supposed proposed name given to the Flibanserin drug under clinical trials by Boehringer Ingelheim. There is a lot of secrecy shrouding the product line and not much information can be found and for good reason. It is estimated that the market for the sometime called female Viagra is valued at around $30 million dollars a year in sales. The product has been under development and trials for several years now and the name has typically been known as Flibanserin but there is knowledge that Girosa will be the official product name if it is approved for use in the United States.
What is it?
Girosa is actually a non-hormonal drug made up from dopamine or D4 receptors and serotonin receptors known as 5-HT. Ironically it was first researched to become an antidepressant but our guesses are that as soon as improvements in female libido were recognized the company saw that there would be more profit in this area than the over flooded mood enhancer arena. Basically, it is a drug that raises dopamine in the female body. Dopamine is partially responsible for sexual desire and arousal and therefore this drug may have the ability to help with pre-menopausal Hypo Sexual Desire Disorder or Female Sexual Dysfunction. At least, that's the target market and goal for the end product.
Ironically Boehringer Ingelheim is not completely sure how the positive impact on sexual health occurs from Flibanserin but they are seeing positive results during all of their 4 clinical trials that have included over 5,000 women located in over 220 clinics worldwide. Just like BioSante is aiming to get LibiGel approved by the FDA in the next 18 months Boehringer is hoping to have an FDA approval for US medical use in 2009. Aiming at the Viagra market but for women it is easy to see how a billion dollar industry for men can have a trickle effect into the women's market being that scientists and doctors currently estimate 40% of all women in the US suffer from some symptom of FSD or HSDD.
Can I buy Girosa?
Currently the race is on to make a product available for women suffering from lower libido or any of the ailments associated with decreased sexual activity. However, there currently is not a legal option for women in the United States. This drug looks very promising as the clinical trials have been under development for quite some time. We will commit to keeping our readers up to date with the most recent information on Flibanserin.
Tell me about these clinical trials
The German bio pharmaceutical firm Boehringer Ingelheim has been sponsoring clinical studies to research the ability for Girosa (Flibanserin) to aid in women suffering from HSDD or FSD. The studies are taking place in over 350 locations around the world including the US, Europe, and Canada and more than 5,000 women have partaken in the study or trials.
During the clinical trials, it has been noted that the number one coprimary endpoint of mean desire in a month stabilised at about 9 months at an approximate 4.5 decrease from the randomized baseline of 34.2. By just under 9 months. This was a significant improvement over the group administered a placebo which stabilised much later around 11 months and showed a lesser decrease of approximately 8.5 percent decrease.
The second study which basically measured the amount of satisfying sexual events per month has shown some pretty clear results in a positive side for Girosa compared to the measured placebo group and at a much quicker rate as well.
Are there any known side effects yet?
As with any medication there are bound to be side effects found and established. The body simply does not agree with every type of therapy and every person reacts differently. While this is not an FDA approved product yet and all information is preliminary there have been some Girosa side effects mentioned including:
Fatigue or Tiredness
Headaches
Some Dizziness
Nausea or General Sickness
Rare cases of Urinary Infections
Sinusitis
Some cases of Diarrhea
These don't appear to be extremely adverse effects related to the drug and the results that it could promise may be well worth the risks.
What about now?
Well, as we always mention you should probably talk to your doctor about all available therapies and treatments that can help with symptoms you may be experiencing. There are plenty of natural resources available on the market and you can browse through our review section to see what women have been saying about some of the products like Lyriana and Provestra which both are getting pretty decent reviews that appear to be backing up the product manufacturers claims. We will be sure to let everybody know the latest info on Girosa though.
----------------------




Boehringer Ingelheim announces new data on flibanserin in pre-menopausal women with HSDD
New analyses from pivotal Phase III flibanserin trials presented today
http://www.eurekalert.org



Ridgefield, CT, May 18, 2010 ? Data from pivotal Phase III clinical trials demonstrate that a higher proportion of pre-menopausal women with Hypoactive Sexual Desire Disorder (HSDD) receiving flibanserin 100mg reported both an improvement in their condition and a meaningful benefit from their treatment, compared to placebo. Flibanserin is an investigational compound being developed by Boehringer Ingelheim Pharmaceuticals, Inc. for the treatment of HSDD in pre-menopausal women. HSDD is a persistent or recurrent decrease or lack of sexual desire that causes distress for the patient, may put a strain on relationships with partners, and is not due to the effects of a substance, including medications, or another medical condition.


The findings, presented at the 58th Annual Clinical Meeting of the American College of Obstetricians and Gynecologists in San Francisco, include data from a pre-specified pooled analysis of two pivotal North American trials (DAISY? and VIOLET?) assessing flibanserin 100mg in pre-menopausal women suffering from HSDD.


"These new data offer a unique perspective on the effects of flibanserin 100 mg from the patient's point of view. Not only did pre-menopausal women with HSDD report feeling an improvement in their symptoms of low desire and associated distress when taking flibanserin, but they also reported that this change had a meaningful benefit to them," said John Thorp, MD, study investigator, Professor of Obstetrics and Gynecology, University of North Carolina Medical School.


These findings add to data from the primary and secondary endpoint analysis of flibanserin pivotal trials. According to the pre-specified pooled analysis of women who completed 24 weeks of treatment, flibanserin 100mg showed statistically significant improved measures of sexual desire, overall sexual functioning, distress associated with low sexual desire, and the number of satisfying sexual events (SSE), compared with placebo.


"HSDD is an under-recognized and often misunderstood condition that can take a toll on women," said Peter Piliero, MD, executive director, Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "We are committed to advancing flibanserin's development to help understand and find a treatment for women affected by this distressing medical condition."


North American Phase III Trial Results


Patient Perspective Analysis
The pooled analysis included 1,378 pre-menopausal women with HSDD treated with either flibanserin 100 mg or placebo for 24 weeks. The women evaluated their overall improvement in "bothersome decreased sexual desire" using the Patient's Global Impression of Improvement (PGI-I), which is a 7-point scale from 1 (very much improved) through 4 (no change) to 7 (very much worse). By 24 weeks, 48.3 percent of women receiving flibanserin and 30.3 percent of women receiving placebo reported feeling very much improved, much improved or minimally improved (p<0.0001).


In addition, more women in the flibanserin group versus placebo reported experiencing a meaningful benefit from the study medication (40.5 percent versus 25.2 percent, respectively; p < 0.0001), using a single-question Patient Benefit Evaluation (Overall, do you believe that you have experienced a meaningful benefit from the study medication?).


Analysis of Completers
The pooled analysis included 971 (flibanserin 100 mg qhs: 450; placebo: 521) pre-menopausal women who completed the 24-week trials. In that analysis, flibanserin 100mg significantly increased the frequency of SSE versus placebo (increase of 2.1 events vs. 0.9 events, respectively; p < 0.0001) over the 24-week study period. The analysis also found that, compared with placebo, flibanserin 100 mg showed statically significant improved measures of sexual desire using an electronic daily diary or eDiary (primary endpoint) and on the Female Sexual Function Index (FSFI) desire domain (secondary endpoint). Compared with placebo, flibanserin also showed statistically significant improved sexual functioning (as measured by the FSFI total score), and distress related to low sexual desire (based on the Female Sexual Distress Scale-Revised, FSDS-R, total score), which were secondary endpoints.


The FSFI and FSDS-R desire scores are independently developed and validated tools that provide additional measurement of changes in desire over a four-week recall period. The FSFI is a 19-item self-administered questionnaire composed of six domains (desire, arousal, lubrication, orgasm, satisfaction, and pain). The FSDS-R is a 13-item self-administered questionnaire. The total score ranges from zero to 52, with the higher scores indicating more sexual distress.


Pivotal Trials Safety Data
The most commonly reported adverse events (AEs) with flibanserin 100mg in the pivotal North American trials were mild to moderate and emerged during the first 14 days of treatment. These AEs reported by more women on flibanserin than on placebo included somnolence (daytime sleepiness), dizziness, fatigue, anxiety, dry mouth, nausea and insomnia. The majority of these AEs resolved with continued treatment. About 15 percent of women on flibanserin 100mg and seven percent of women on placebo discontinued treatment due to AEs.


###


About Flibanserin
Flibanserin is an investigational compound being developed by Boehringer Ingelheim for the treatment of HSDD in pre-menopausal women. Pooled data from pivotal phase III trials demonstrated that flibanserin 100mg increased the number of satisfying sexual events (SSE) and sexual desire while decreasing the distress associated with HSDD. The most commonly reported adverse events (AEs) with flibanserin 100mg were mild to moderate and emerged during the first 14 days of treatment. These AEs reported by more women on flibanserin than on placebo included somnolence (daytime sleepiness), dizziness, fatigue, anxiety, dry mouth, nausea and insomnia. The majority of these AEs resolved with continued treatment. About 15 percent of women on flibanserin 100mg and seven percent of women on placebo discontinued treatment due to AEs.


About Hypoactive Sexual Desire Disorder
Low sexual desire is the most commonly reported female sexual complaint. Approximately one in 10 women report low sexual desire with associated distress, which may be HSDD. HSDD is a form of female sexual dysfunction (FSD) and has been recognized as a medical condition for more than 30 years. As defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), HSDD is the persistent or recurrent lack (or absence) of sexual fantasies or desire for any form of sexual activity causing marked distress or interpersonal difficulty and not better accounted for by another disorder (except another sexual dysfunction), direct physiological effects of a substance (including medications), or a general medical or psychiatric condition. Generalized, acquired HSDD is not limited to certain types of stimulation, situations or partners, and develops only after a period of normal functioning. There is an unmet need for women as there is no FDA-approved treatment for HSDD. It can affect women of all ages and at any stage of life.


Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.


The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.


In 2009, Boehringer Ingelheim posted net sales of US $17.7 billion (12.7 billion euro) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.


For more information, please visit http://us.boehringer-ingelheim.com
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #132 on: May 20, 2010, 06:35:23 AM »
Boehringer?s sexual desire drug for women hits the spot

19 May 2010
pharmatimes.com

Boehringer Ingelheim has posted interesting late-stage data for its female sexual dysfunctional drug flibanserin which suggests that the treatment increases satisfaction.

Data from two Phase III trials run in North America were presented at the American College of Obstetricians and Gynaecologists annual meeting in San Francisco. They demonstrate that a higher proportion of pre-menopausal women with hypoactive sexual desire disorder receiving flibanserin 100mg ?reported both an improvement in their condition and a meaningful benefit from their treatment, compared to placebo?.

The analysis included 1,378 pre-menopausal women with HSDD who were evaluated about "bothersome decreased sexual desire" using a seven-point scale from 1 (very much improved) through 4 (no change) to 7 (very much worse). After 24 weeks, 48.3% of women receiving flibanserin and 30.3% on placebo reported feeling very much improved, much improved or minimally improved . In addition, more women on the Boehringer drug reported experiencing a meaningful benefit from the study medication (40.5% versus 25.2%).

Study investigator John Thorp of the University of North Carolina Medical School said the data ?offer a unique perspective on the effects of flibanserin from the patient's point of view?. Not only did the women feel an improvement ?in their symptoms of low desire and associated distress when taking flibanserin, but they also reported that this change had a meaningful benefit to them?.

These latest findings add to data from other pivotal trials which have shown that flibanserin demonstrated statistically significant improved measures of sexual desire, overall sexual functioning, distress associated with the condition and the number of satisfying sexual events, compared with placebo.

Flibanserin, an oral treatment that was originally developed as an antidepressant, affects levels of serotonin and other chemicals in the brain but how it affects sex drive remains unclear. In mid-June, an advisory panel of the US Food and Drug Administration will vote on whether to recommend approval.

Given the nature of HSDD, it is unsurprising that flibanserin is being referred to in some media circles as ?female Viagra?. However, Paula Hall, a sexual and relationship psychotherapist from the UK, said that although HSDD affects thousands of women, ?it is often misunderstood or overlooked?. She added that in both of these study analyses, ?we?re seeing very positive outcomes with flibanserin, which is really quite exciting and could hold hope for those suffering with this distressing condition.?
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #133 on: May 20, 2010, 06:37:53 AM »
press announcement

Boehringer Ingelheim Announces New Data on Flibanserin in Pre-Menopausal Women with Hypoactive Sexual Desire Disorder
- New analyses from pivotal Phase III flibanserin trials presented today -


Ridgefield, CT, May 18, 2010 ?Data from pivotal Phase III clinical trials demonstrate that a higher proportion of pre-menopausal women with Hypoactive Sexual Desire Disorder (HSDD) receiving flibanserin 100mg reported both an improvement in their condition and a meaningful benefit from their treatment, compared to placebo.  Flibanserin is an investigational compound being developed by Boehringer Ingelheim Pharmaceuticals, Inc. for the treatment of HSDD in pre-menopausal women.  HSDD is a persistent or recurrent decrease or lack of sexual desire that causes distress for the patient, may put a strain on relationships with partners, and is not due to the effects of a substance, including medications, or another medical condition.


The findings, presented at the 58th Annual Clinical Meeting of the American College of Obstetricians and Gynecologists in San Francisco, include data from a pre-specified pooled analysis of two pivotal North American trials (DAISY? and VIOLET?) assessing flibanserin 100mg in pre-menopausal women suffering from HSDD.



?These new data offer a unique perspective on the effects of flibanserin 100 mg from the patient?s point of view.  Not only did pre-menopausal women with HSDD report feeling an improvement in their symptoms of low desire and associated distress when taking flibanserin, but they also reported that this change had a meaningful benefit to them,? said John Thorp, MD, study investigator, Professor of Obstetrics and Gynecology, University of North Carolina Medical School.


These findings add to data from the primary and secondary endpoint analysis of flibanserin pivotal trials.  According to the pre-specified pooled analysis of women who completed 24 weeks of treatment, flibanserin 100mg showed statistically significant improved measures of sexual desire, overall sexual functioning, distress associated with low sexual desire, and the number of satisfying sexual events (SSE), compared with placebo.


?HSDD is an under-recognized and often misunderstood condition that can take a toll on women,? said Peter Piliero, MD, executive director, Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc.  ?We are committed to advancing flibanserin?s development to help understand and find a treatment for women affected by this distressing medical condition.?


North American Phase III Trial Results


Patient Perspective Analysis

The pooled analysis included 1,378 pre-menopausal women with HSDD treated with either flibanserin 100 mg or placebo for 24 weeks.  The women evaluated their overall improvement in ?bothersome decreased sexual desire? using the Patient?s Global Impression of Improvement (PGI-I), which is a 7-point scale from 1 (very much improved) through 4 (no change) to 7 (very much worse).  By 24 weeks, 48.3 percent of women receiving flibanserin and 30.3 percent of women receiving placebo reported feeling very much improved, much improved or minimally improved (p<0.0001).



In addition, more women in the flibanserin group versus placebo reported experiencing a meaningful benefit from the study medication (40.5 percent versus 25.2 percent, respectively; p<0.0001), using a single-question Patient Benefit Evaluation (Overall, do you believe that you have experienced a meaningful benefit from the study medication?).


Analysis of Completers

The pooled analysis included 971 (flibanserin 100 mg qhs: 450; placebo: 521) pre-menopausal women who completed the 24-week trials.  In that analysis, flibanserin 100mg significantly increased the frequency of SSE versus placebo (increase of 2.1 events vs. 0.9 events, respectively; p<0.0001) over the 24-week study period.  The analysis also found that, compared with placebo, flibanserin 100 mg showed statically significant improved measures of sexual desire using an electronic daily diary or eDiary (primary endpoint) and on the Female Sexual Function Index (FSFI) desire domain (secondary endpoint).  Compared with placebo, flibanserin also showed statistically significant improved sexual functioning (as measured by the FSFI total score), and distress related to low sexual desire (based on the Female Sexual Distress Scale-Revised, FSDS-R, total score), which were secondary endpoints.


The FSFI and FSDS-R desire scores are independently developed and validated tools that provide additional measurement of changes in desire over a four-week recall period.  The FSFI is a 19-item self-administered questionnaire composed of six domains (desire, arousal, lubrication, orgasm, satisfaction, and pain).  The FSDS-R is a 13-item self-administered questionnaire.  The total score ranges from zero to 52, with the higher scores indicating more sexual distress.



Pivotal Trials Safety Data

The most commonly reported adverse events (AEs) with flibanserin 100mg in the pivotal North American trials were mild to moderate and emerged during the first 14 days of treatment.  These AEs reported by more women on flibanserin than on placebo included somnolence (daytime sleepiness), dizziness, fatigue, anxiety, dry mouth, nausea and insomnia.  The majority of these AEs resolved with continued treatment.  About 15 percent of women on flibanserin 100mg and seven percent of women on placebo discontinued treatment due to AEs. 



About Flibanserin
Flibanserin is an investigational compound being developed by Boehringer Ingelheim for the treatment of HSDD in pre-menopausal women.  Pooled data from pivotal phase III trials demonstrated that flibanserin 100mg increased the number of satisfying sexual events (SSE) and sexual desire while decreasing the distress associated with HSDD.  The most commonly reported adverse events (AEs) with flibanserin 100mg were mild to moderate and emerged during the first 14 days of treatment.  These AEs reported by more women on flibanserin than on placebo included somnolence (daytime sleepiness), dizziness, fatigue, anxiety, dry mouth, nausea and insomnia.  The majority of these AEs resolved with continued treatment.  About 15 percent of women on flibanserin 100mg and seven percent of women on placebo discontinued treatment due to AEs.   



About Hypoactive Sexual Desire Disorder
Low sexual desire is the most commonly reported female sexual complaint.  Approximately one in 10 women report low sexual desire with associated distress, which may be HSDD.  HSDD is a form of female sexual dysfunction (FSD) and has been recognized as a medical condition for more than 30 years.  As defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), HSDD is the persistent or recurrent lack (or absence) of sexual fantasies or desire for any form of sexual activity causing marked distress or interpersonal difficulty and not better accounted for by another disorder (except another sexual dysfunction), direct physiological effects of a substance (including medications), or a general medical or psychiatric condition.  Generalized, acquired HSDD is not limited to certain types of stimulation, situations or partners, and develops only after a period of normal functioning.  There is an unmet need for women as there is no FDA-approved treatment for HSDD.  It can affect women of all ages and at any stage of life.


About Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.


The Boehringer Ingelheim group is one of the world?s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2009, Boehringer Ingelheim posted net sales of US $17.7 billion (12.7 billion euro) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.


http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #134 on: May 23, 2010, 11:28:04 AM »
New Aging/HIV Study: Study pinpoints how a normally defensive immune response can help HIV



May 19, 2010

http://news.ucsf.edu






Researchers have identified how a normal response to infection, one that usually serves to limit the amount of inflammation, actually contributes to disease progression and viral persistence in HIV-infected patients.




The findings, published in the May 19 issue of the journal Science Translational Medicine, offer important opportunities for further research, both for treatment of long-term persistence of HIV in those who are infected and for prevention of infection in those who are not, according to the study team.




The study, led by UCSF researchers, focused on the body?s production of an enzyme called indoleamine 2,3-dioxygenase 1 (IDO1). To prevent the harm associated with chronic inflammation, the body typically turns on IDO1, which then serves to suppress inflammation and immune responses. In the setting of HIV infection, the authors found that IDO1 instead acts to alter the balance between two types of T-cells that have opposing functions.




One type of immune cell, called TH17, releases interleukin-17, a cytokine that has a central role in maintaining the integrity of the mucosal barrier in the gut. The other type, named Treg, prevents inflammation in a non-specific manner and can also turn off immune responses against viruses such as HIV.




The authors found that induction of IDO1 by HIV results in loss of TH17 cells and a relative increase in Tregs. This change in the balance of TH17 cells and Tregs allows bacteria to cross the mucosal barrier of the gut, initiating new inflammatory reactions in the process. At the same time, the increased number of Tregs may prevent the immune system from attacking HIV in areas of the body where strong HIV-specific immune responses are most needed. The altered TH17/Treg balance, in sum, leads to an endless cycle of inflammation induced by the invading microbes, more induction of IDO1, and continued loss of TH17 cells.




?In most instances, reducing inflammation following immune system activation to fight infection is beneficial.  But, in HIV disease, this can establish a reinforcing cycle that is strongly linked to disease progression and that may help HIV to persist in patients, said study lead co-author, Jeff Mold, PhD, from the UCSF Division of Experimental Medicine.  ?Mucosal defenses are breached, microbes cross over, and inflammation results. This leads to increasing IDO1 activity, continued changes in the balance of TH17 and Treg cells, further weakening of the mucosal defenses, and even more inflammation.?




The findings represent the next step in a series of research studies reported previously by the same group of investigators, showing that SIV infection of monkeys leading to AIDS is associated with a similar change in TH17 and Treg balances.  The change in T cell balance was not observed in another primate, African green monkeys, where infection with SIV is harmless and does not cause disease.




In the current study, the investigators looked at IDO1 activity in HIV-infected human subjects at various stages of disease and in healthy non-infected subjects.




?We confirmed that IDO1 activity is associated with HIV disease progression.  But we went further and also looked at the TH17 and Treg balance, and found that the change in the ratio leading to decreasing TH17 cells is also associated with HIV disease progression,? said study lead co-author, David Favre, PhD, formerly at UCSF, now with the National Immune Monitoring Laboratory, Montreal.




With pharmacological inhibitors of IDO1 in development and currently in clinical trials for cancer immunotherapy, the finding may lead to new therapeutic approaches for assisting in the control of HIV disease, noted the study team.




?Most of an infected person?s own immune responses that are known to affect HIV disease outcomes cannot be manipulated or altered clinically and, hence, have not really had much of an impact for patients. This work, however, is very different, as it has uncovered several possible pathways that might be addressed clinically with developing or available therapeutics,? said study co-author, Steven Deeks, MD, professor of medicine at the UCSF Division of HIV/AIDS at San Francisco General Hospital.




IDO1 may play a role in the ability of HIV to persist in HIV-infected patients for their lifetimes, notwithstanding effective treatment with antiretroviral therapies.




?Steve Deeks and I are continuing to examine the role of IDO1 through a study recently announced by amfAR, the Foundation for AIDS Research, into whether the disruption of IDO1 will reduce the level of immune activation, which could then lead to a decrease in viral persistence,? said senior study author Joseph M. McCune, MD, PhD, chief of the UCSF Division of Experimental Medicine.




In addition to Favre, Mold, Deeks, and McCune, other study co-authors include Peter Hunt, Bittoo Kanwar, Lillian Seu, Jason Barbour, Margaret Lowe, Anura Jayawardene, Francesca Aweeka, Yong Huang, Jeffrey Martin, and Frederick Hecht from UCSF; Daniel Douek and Jason Brenchley from the National Institute of Allergy and Infectious Diseases, NIH, and P?ng Loke from NYU.




The research was funded by grants from the Elizabeth Glaser Pediatric AIDS Foundation, the National Institute of Allergy and Infectious Diseases, the National Institutes for Health, the Harvey V. Berneking Living Trust, the UCSF-GIVI Center for AIDS Research, and the UCSF Clinical and Translational Institute Clinical Research Center.




The UCSF Division of Experimental Medicine and the UCSF Division of HIV/AIDS at SFGH are affiliated with the AIDS Research Institute (ARI) at UCSF.  UCSF ARI houses hundreds of scientists and dozens of programs throughout UCSF and affiliated labs and institutions, making ARI one of the largest AIDS research entities in the world.




UCSF is a leading university dedicated to defining health worldwide through advanced biomedical research, graduate level education in the life sciences and health professions, and excellence in patient care.

------------------


 Sci Transl Med  19 May 2010:

Vol. 2, Issue 32, p. 32ps23



    COMMENTARY




Insights into Therapy: Tryptophan Oxidation and HIV Infection




   Michael F. Murray

 Department of Medicine, Brigham and Women?s Hospital, Boston, MA 02115, USA.

E-mail: mmurray@partners.org




Abstract




New data from Favre and colleagues strengthen the link between activation of the tryptophan oxidation (TOx) pathway?via the indoleamine 2,3-dioxygenase enzymes IDO1 and IDO2?and chronic inflammation in progressive HIV disease. It can now be appreciated that a pathogenic TOx activation cycle exists in HIV. TOx regulation is a therapeutic target for other diseases, such as cancer and autoimmune disorders. Here TOx control is examined with an eye to eventual therapeutic intervention in HIV disease.






HIV AND BEYOND




Microbial products, including lipopolysaccharide (LPS), the immunostimulatory endotoxin from the outer membrane of Gram-negative bacteria, are known to induce the tryptophan oxidation (TOx) pathway, which is the key degradation route for the essential amino acid l-tryptophan (l-Trp). The first (and rate-limiting) step in the pathway?the conversion of l-Trp to N-formyl-kynurenine?is catalyzed by the indoleamine 2,3-dioxygenases IDO1 and IDO2, two enzymes that are synthesized in both immune cells and other tissues and are the gatekeepers of the immune response via the TOx pathway. In this issue of Science Translational Medicine, Favre and colleagues add to a growing body of knowledge linking LPS-induced endotoxemia (the presence of bacterial endotoxins in the blood), activation of the TOx pathway, and the chronic inflammatory state of progressive HIV disease (1). Researchers currently are developing targeted therapies to alter TOx activation in a number of disease contexts, and a richer understanding of pathway regulatory mechanisms will help to guide these drug discovery and development efforts. Here various aspects of TOx regulation are examined from the perspective of potential therapeutic intervention.




TOX PATHWAY PERMUTATIONS




As an essential amino acid, Trp cannot be synthesized in humans and must be obtained through the diet. Dietary Trp feeds into three major metabolic pathways: (i) protein synthesis; (ii) synthesis of the neurotransmitter serotonin; and (iii) TOx, to form either energy [adenosine triphosphate (ATP)], nicotinamide and related compounds [nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP)], or other side products (such as xanthurenic acid). In humans, oxidative catabolism of Trp can be initiated by one of three different enzymes: tryptophan-2,3-dioxygenase (TDO2) in the liver, as well as IDO1 and IDO2, which have incompletely overlapping nonhepatic tissue distributions. These three enzymes open the indole ring, causing the irreversible loss of Trp (2). The TOx pathway is interconnected with other metabolic networks (3) and is variously regulated in a number of tissues.




The liver is thought to be the only organ with substantial TDO2 activity, and this enzyme is not believed to drive the immunoregulatory effects of TOx. Instead, TDO2 is induced by dietary protein and corticosteroids, but not by cytokines such as interferon-γ (IFN-γ) (4). Recent work by Schmidt et al. demonstrated an in vitro immunoregulatory effect associated with TDO2 activity, which may implicate the activity of pathway metabolites more than a clinically significant in vivo effect, although a contribution to immunomodulation within the liver has not been excluded (5). The hepatic end products generated via activation of this pathway are ATP, CO2, and water.




The metabolic pathway initiated by the extrahepatic enzymes IDO1 and IDO2 is shown in Fig. 1. IDO1 and IDO2 are inducible and less substrate-specific for Trp than TDO2. While there are many cytokine inducers of IDO-mediated TOx, the most effective pathway inducer appears to be IFN-γ (4). That said, there are important tissue-specific differences in cytokine induction, leading to different tissue responses to the same systemic signals. For example, in the brain it appears that interleukin-6, and not IFN-γ, drives IDO induction (6). Elucidation of the differences in IDO1- versus IDO2-induced cytokine responses will require further study. Many different microbial infections?bacterial, viral, and parasitic?have been implicated in IDO-induced TOx (7), and a number of microbial products can directly induce the pathway. Bacterial LPS and the HIV-Nef and HIV-Tat proteins are among the best-studied but are not likely to be unique in this capability.



The second enzyme in the TOx pathway is arylformamidase (AFMID), which is responsible for converting the dioxygenase product (N-formyl-kynurenine) to l-kynurenine (l-KYN). l-KYN is subsequently converted to 3-hydroxy-l-kynurenine (3-HKA) by kynurenine 3-monooxygenase (KMO), and 3-HKA is metabolized to 3-hydroxy-anthranilic acid (3-HAA) by kynureninase (KYNU). Favre et al. noted that the 3-HKA and 3-HAA metabolites have effects on the T helper 17 cell (TH17)?to?regulatory T cell (Treg) ratio in vitro (1). It appears that 3-HAA is removed from the tissue microenvironment only by the action of another dioxygenase, 3-hydroxyanthranilate 3,4-dioxygenase (HAAO). This means that, in order to prevent the in vivo accumulation of 3-HAA and its potential effects on T cell ratios, the organism is dependent on the relative activity of this specific enzyme. Outside of the central nervous system (CNS), TOx pathway activation does not lead to the accumulation of quinolinic acid (QA), suggesting that the relative activities of the aminocarboxymuconate semialdehyde decarboxylase (ACMSD) and quinolinate phosphoribosyltransferase (QPRT) enzymes are sufficient to divert QA to other products. In a multistep process initiated by QPRT, the downstream metabolism of QA results in the formation of NAD, NADP, and nicotinamide. In general, it is presumed that the QPRT-driven pathway to nicotinamide and nicotinamide nucleotides occurs preferentially in the extrahepatic TOx pathway, and the ACMSD-driven subpathway to ATP appears to occur preferentially by hepatic TOx, although further detailed studies may alter this understanding (4). In the CNS, QA is produced locally in response to either local or systemic inflammatory signals and stimulates the N-methyl-d-aspartate (NMDA) receptor, a key component in learning and memory (8). Overstimulation of NMDA receptors can cause neurotoxic effects that have been implicated in neurological diseases.




In HIV-infected patients, the amounts of QA measured in the brain and cerebrospinal fluid (CSF) are greatly increased compared to those in controls. In one study (8), a 100-fold variation in the amounts of QA in the CSF and brain tissue was detected among HIV patients, and these elevations did not correlate with serum QA concentrations (8). These data suggest that the degradation of Trp via the TOx pathway is stalled in the CNS. This tissue-specific accumulation of QA may result from a relatively low amount of QPRT activity compared to that of HAAO and other upstream enzymes (Fig. 1). Recent work by Connor and colleagues revealed that systemic stimuli such as LPS induce IDO and KMO activities in the mammalian brain but do not alter kynurenine aminotransferase (KAT) activity (6). A critical question is whether QPRT is also inducible and under what circumstances, because this effect would have the potential to draw down the local QA concentrations and interrupt the neurotoxic effects associated with high concentrations of this metabolite.




OVERACTIVE TOX




The new work by Favre et al. builds on the relationship between LPS and TOx first reported in 1978 by Yoshida and Hayaishi (9) and the findings of Brenchley and others (in 2006) that HIV infection is marked by chronically elevated circulating amounts of LPS (10). Favre et al. place the observations of Terness and others regarding TOx metabolites into a new disease-specific context (11, 12) and provide evidence that the intermediate TOx metabolites 3-HKA and 3-HAA are regulators of a specific T lymphocyte subset ratio; namely, the TH17:Treg ratio (1). The loss of a normal TH17:Treg ratio in the gut is associated with increased LPS endotoxemia and persistent induction of TOx overstimulation in the setting of HIV (13). These data add to an impression that chronic TOx induction during HIV infection is a central pathogenic process that results in the disruption of normal T lymphocyte function and is driven by a combination of endogenous cytokines (particularly IFN-γ), viral products (the HIV-Tat and HIV-Nef proteins), and bacterial products (including LPS) (Fig. 2).



The detrimental effects of TOx induction in progressive HIV disease contrast with the demonstrable benefit of TOx activation in the normal placenta and the presumed value of TOx in limiting microbial access to Trp in some nonviral infections (14). In HIV infection, the mediators of TOx pathogenicity appear to be the altered concentrations of the pathway products, in particular Trp, 3-HKA, 3-HAA, and QA.




The growing interest in targeted therapies to alter TOx activation in cancer management (15) needs to be extended to HIV infection, as well as reproduction, organ transplantation, neurodegenerative diseases, and autoimmune syndromes, in which TOx pathway activation has also been implicated in aspects of disease pathogenesis (16?20).




TOX THERAPEUTIC TACTICS




There is accumulating evidence that small molecules that participate in the TOx pathway are capable of acting as immune regulators outside of their direct role in amino acid catabolism. Further study of the tissue-specific bioavailability of 3-HKA and 3-HAA is needed to confirm their in vivo significance in pathogenic immunoregulatory signaling; however, what emerges through the work to date is a model for chronic activation of IDO-associated TOx, leading to T lymphocyte dysregulation in HIV infection (Fig. 2). Given the number of diseases in which TOx activation appears to be linked to pathogenesis, it is likely that multiple clinical trials will emerge to test agents that might therapeutically manipulate this pathway. Oral Trp loading is one approach to avoid in going forward, except perhaps in a carefully controlled research setting, because it has been associated with both an increase in circulating TOx pathway intermediates (21) and the still poorly understood phenomenon of eosinophilia-myalgia syndrome (22).




As with any metabolic pathway, the pharmacological regulation of extrahepatic TOx can be approached in several ways. The approach that is currently being tried is inhibition of the first and rate-limiting step in the TOx pathway, namely IDO activity (both IDO1 and IDO2). This is being pursued with the competitive inhibitor 1-methyl-D-tryptophan (D-1MT), and there are currently at least four D-1MT trials (phase 1 and 2) in the clinical oncology domain (23). D-1MT was also used in a study of SIV?infected macaques, an animal model of HIV, with some benefit (24). A number of other IDO inhibitory molecules have been studied, but they have not yet progressed to clinical trials (25). There also is interest in the use of Trp catabolite mimetics, such as 3,4-DAA [N-(3,4-dimethyoxycinnamoyl) anthranilic acid], which is orally active and may represent a lead compound for inhibiting autoreactive TH1 cells in autoimmune diseases (20). Furthermore, it may be desirable in some therapeutic settings to differentially regulate IDO1 and IDO2 (26). Because a functional IDO2 gene product is not expressed in as many as 25 to 30% of certain human populations (27), the consequences of this natural experiment need to be better understood, so that they may guide our evolving understanding of how to successfully use pharmacological agents to inhibit this pathway.




Other conceptual therapeutic approaches that target TOx include (i) diverting the pathway from toxic intermediates or end products by inducing benign metabolic side-product formation, (ii) inducing downstream pathway activity to drive end-product formation and avoid the accumulation of toxic intermediates, and (iii) feedback inhibition of the pathway via increased end-product concentrations. On the basis of data that suggested that HIV-infected patients display a metabolic drive toward increased available nicotinamide (28), we initiated a very small clinical trial of oral nicotinamide in part to provide potential feedback inhibition of the TOx pathway (29). We found that oral nico‐tinamide administration resulted in increased circulating Trp in HIV-infected patients, but followup is needed to determine the clinical implications of this result (4, 29). Nicotinamide and other endogenous TOx-related compounds may ultimately prove to be useful adjuncts to therapy or lead compounds for the development of new pharmacological agents to treat HIV and other diseases associated with TOx-induced pathogenesis.


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Offline red_Dragon888

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Re: http://natap.org/
« Reply #135 on: May 24, 2010, 01:38:35 PM »
Prolonged Control of Viremia After Transfer of Autologous CD4 T ...
17th CROI Conference on Retroviruses and Opportunistic Infections ... Expressing Long Antisense to HIV env (VRX496). Reported by Jules Levin CROI 2010 ...
www.natap.org/2010/CROI/croi_182.htm


VIRxSYS Presents Results from Multiple Studies at the 13th ASGCT Annual Meeting
 
GAITHERSBURG, MD ? May XX, 2010 ?VIRxSYS Corporation, a privately held company developing vaccines and RNA therapies for serious diseases such as AIDS and cardiovascular disease, will present eight abstracts at the 13th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) taking place in Washington, DC, from May 17-22, 2010. The abstracts represent results of the company?s clinical trials for Lexgenleucel-T (VRX496?), an autologous cell and gene therapy product for the treatment of HIV/AIDS; preclinical trials of the company?s prophylactic HIV vaccine, VRX1273; and work utilizing the company?s spliceosome mediated RNA trans-splicing (SMaRT?) platform technology.
 
?We are honored to present so much of our research at the 13th ASGCT Annual Meeting,? said Dr. Riku Rautsola, PhD, President and CEO of VIRxSYS. ?Our clinical trials continue to demonstrate promising results as we work toward new treatments for HIV.  We are also pleased to see our SMaRTTM platform technology performing well in critical pre-clinical studies.?
 
Highlights of the presentations include data from VIRxSYS?s Phase 2 study of Lexgenleucel-T, which continue to show no evidence of long-term safety issues after the cumulative infusion of over 4 x 1012 vector copies in a total of 2 x 1012 modified CD4 T cells. To date, data from the Lexgenleucel-T clinical trial program comprises of the largest safety database of subjects enrolled in a clinical trial using a lentiviral vector. In accordance with FDA guidelines, all subjects will continue to be monitored for safety for up to 15 years. Additional data from the Lexgenleucel-T Phase 2 study demonstrate that the therapeutic efficacy of Lexgenleucel-T treatment is not affected by the development of anti-vector antibodies, nor is the development of these antibodies associated with clinically detectable adverse events, a common concern in gene therapy trials.
 
Other highlights include:
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #136 on: May 24, 2010, 01:39:29 PM »

 

Do n-3 fatty acids prevent osteoporosis?
Ovariectomized mice fed a diet high in fish oil had significantly less bone loss at the femur and lumbar vertebrae than did ovariectomized mice fed a diet ...
www.natap.org/2007/HIV/032607_02.htm
Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Diseases
J Am Coll Cardiol, 2009
Wang C, Harris WS, Chung M, et al. n-3 fatty acid from fish or fish-oil supplements .... Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular ...
www.natap.org/2009/HIV/080509_04.htm

Convincing evidence from extensive research over the past 3 decades points out the potential beneficial effects of -3 PUFA in primary prevention, CHD and post-MI, SCD, HF, atherosclerosis, and AF. Based on the growing evidence for the benefits of fish oils, we agree that this story represents a "fish tale withgrowing credibility."


A detailed discussion of all of the potential mechanisms of -3 PUFA and CV diseases (summarized in Table 2) is beyond the scope of this review. It appears that -3 PUFA confer CV benefits largely through DHA and EPA enrichment of membrane phospholipids (65). In addition to mechanisms discussed above, -3 PUFA produces vasodilation, reduces blood pressure (31,66), improves arterial and endothelial function (67), and reduces platelet aggregation (68). The antiplatelet, anti-inflammatory, and triglyceride-lowering effects of -3 PUFA (Fig. 5) (69) require relatively higher doses of DHA and EPA (e.g., 3 to 4 g/day), whereas some of the antiarrhythmic effects, reduction of SCD, and improvement in HF can be achieved at lower doses (500 to 1,000 mg/day). Nevertheless, higher doses may be even more effective in HF, as discussed previously. Although the effects of -3 PUFA on C-reactive protein levels have been inconsistent (70), these agents have been shown to suppress production of pro-inflammatory cytokines such as interleukin-1B, interleukin-6, and tumor necrosis factor-alpha (71). When administered to obese patients, 1.8 g of EPA increased the levels of adiponectin, which can reduce inflammation and improve insulin sensitivity (72), in addition to the potential beneficial HF effects discussed earlier. Although benefits on the autonomic nervous system are well established and are reviewed earlier, studies in patients undergoing heart transplantation suggest that -3 PUFA can reduce heart rate independently of vagal activation (73), in addition to reducing mean arterial pressure and systemic vascular resistance by 25% and reducing LV hypertrophy and improving diastolic function in heart transplantation patients with cyclosporine-induced hypertension (66).


Fish Reduces Risk of Dementia by 47% in Framingham Heart Study
Nov 11, 2006 ... from the diet or can be obtained directly by consuming foods rich in DHA such as fish or fish oil or supplements containing DHA. ...
www.natap.org/2006/HIV/121806_06.htm


Heart Association Recommends Daily Intake of Omega-6 Fatty Acids
Jan 26, 2009 ... omega-3 fatty acid a-linolenic acid,57,59,60 and simultaneous recommendations to increase fish and cod liver oil use.58 Nevertheless, ...
www.natap.org/2009/HIV/012809_02.htm


Nut-Enriched Mediterranean Diet Helps Reverse Metabolic Syndrome
"The traditional MedDiet is characterized by a high intake of cereals, vegetables, fruits, and olive oil; a moderate intake of fish and alcohol, ...
www.natap.org/2008/HIV/120908_01.htm


Fish Intake, Contaminants, and Human Health
Oct 18, 2006 ... Fish oil capsules contain 20% to 80% of EPA and DHA by weight (200-800 mg/g185-
186), little to no mercury,187 and variable levels of PCBs ...
www.natap.org/2006/HIV/102606_11.htm


http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #137 on: May 25, 2010, 06:24:41 AM »
NATAP http://natap.org/
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Upcoming FDA Advisory Committee Meeting on Egrifta (tesamorelin acetate) to reduce excess visceral abdominal fat in HIV-related lipodystrophy


Food and Drug Administration - March 22, 2010
Richard Klein & Kimberly Struble

--------------------------------------------------------------------------------
The Food and Drug Administration (FDA) will hold a public meeting of its Endocrinologic and Metabolic Drugs Advisory Committee to discuss the safety and efficacy of new drug application (NDA) 22-505, EGRIFTA (tesamorelin acetate), sterile lyophilized powder for injection, by Theratechnologies, Inc. EGRIFTA is an analogue (a chemical compound that resembles another compound in structure) of growth hormone releasing hormone (GHRH). The proposed indication (use) for EGRIFTA in this application is to induce and maintain a reduction of excess visceral abdominal fat in human immunodeficiency virus (HIV)-infected patients with lipodystrophy (a condition in which abnormal deposits of fat are seen partly as a result of using certain drugs to treat HIV disease).


The meeting will take place on May 27, 2010, from 8 a.m. to 5 p.m, at The Inn and Conference Center, University of Maryland University College (UMUC), 3501 University Blvd. East, Adelphi, MD. You can contact the hotel directly at 301-985- 7300 for directions or to arrange accomodations.
The meeting will be open to the public, and no registration is required.


Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee.


Written submissions may be made to Paul Tran, Center for Drug Evaluation and Research (HFD- 21), Food and Drug Administration, 5600 Fishers Lane (for express delivery, 5630 Fishers Lane, rm. 1093) Rockville, MD 20857, 301-827-7001, FAX: 301- 827-6776, e-mail: paul.tran@fda.hhs.gov on or before May 13, 2010.


Oral presentations from the public (the open public hearing) will be scheduled between approximately 1 p.m. and 2 p.m. Those desiring to make formal oral presentations should notify Paul Tran, and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation on or before May 5, 2010.


Time allotted for each presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably accommodated during the scheduled open public hearing session, FDA may conduct a lottery to determine the speakers for the scheduled open public hearing session.
Those requesting time to present will be notified regarding their request to speak by May 6, 2010.


FDA intends to make background material available to the public no later than 2 business days before the meeting. If FDA is unable to post the background material on its Web site prior to the meeting, the background material will be made publicly available at the location of the advisory committee meeting, and the background material will be posted on FDA's Web site after the meeting. Background material can be found at http://www.fda.gov/AdvisoryCommittees/Calendar/default.htm. Scroll down to the appropriate advisory committee link.


Please call the FDA Advisory Committee Information Line for up-to-date information about this meeting, at 1-800-741-8138 (301-443-0572 in the Washington, DC area), and use code 3014512536. A notice in the Federal Register about last minute modifications that impact a previously announced advisory committee meeting cannot always be published quickly enough to provide timely notice. Therefore, you should always check the agency's Web site and call the appropriate advisory committee hot line/phone line to learn about possible modifications before coming to the meeting.


Persons attending FDA's advisory committee meetings are advised that the agency is not responsible for providing access to electrical outlets.


FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with physical disabilities or special needs. If you require special accommodations due to a disability, please contact Paul Tran at least 7 days in advance of the meeting.
FDA is committed to the orderly conduct of its advisory committee meetings. Please visit our Web site at http://www.fda.gov/ AdvisoryCommittees/AboutAdvisoryCommittees/ucm111462.htm for procedures on public conduct during advisory committee meetings.


Richard Klein
Office of Special Health Issues
Food and Drug Administration


Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
100322
FD100302
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Offline red_Dragon888

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Re: http://natap.org/
« Reply #138 on: May 26, 2010, 04:32:56 PM »
FDA:Theratechnologies Drug Cuts Abdominal Fat In HIV Patient


By Jennifer Corbett Dooren
Of DOW JONES NEWSWIRES
 WASHINGTON (Dow Jones)--A proposed Theratechnologies Inc. (THTCF) drug cut abdominal fat in HIV patients, but might increase the risk of
diabetes, a U.S. Food and Drug Administration staff review said Tuesday.


Theratechnologies, based in Montreal, is seeking FDA approval for a proposed drug tesamorelin to treat HIV-associated lipodystrophy, an accumulation of a specific type of fat in the abdominal region that puts patients at risk of developing cardiovascular disease.


Tesamorelin, which the company has proposed selling under the brand name Egrifta, faces a review on Thursday by the FDA's Endocrinologic and Metabolic Drugs Advisory Committee.


The committee, which is made up of non-FDA medical experts, is being asked to vote on whether it thinks the product should be approved. The product, an insulin-like shot that would be self-injected daily, is designed to help the body produce a growth hormone.


In briefing documents posted to the FDA's website Tuesday, agency staff reviewers said patients treated with tesamorelin had their levels of excess abdominal fat reduced by an average of 17.5%. However, the FDA said the fat mostly returned after treatment was stopped, suggesting patients would have to be treated with tesamorelin on an on-going basis.


Two studies were conducted that involved a total of 816 patients. During the studies 543 patients received tesamoralin while the rest received a placebo, or fake treatment for six months. At the end of the study, patients in the placebo group were then treated with tesamorelin for six months while patients previously treated with the drug were re-randomized to stay on the drug or receive a placebo shot. FDA's review said more patients developed diabetes during the study compared to patients receiving a placebo, while some patients in the study shifted from what's considered pre-diabetes to diabetes during treatment.


In Toronto Tuesday, shares of Theratechnologies have dropped 54% to C$2.02.


Canaccord Genuity analyst Neil Maruoka said the diabetes risk came as a surprise, but said questions about whether the product could reduce the risk of cardiovascular disease were expected.


Lipodystrophy was thought to be solely associated with anti-retroviral drugs that are used to treat HIV but there's evidence that having HIV itself plays a role.


Daniel Berger, an HIV specialist and founder of Northstar Healthcare in Chicago, said about 25% of HIV patients have lipodystrophy, which is marked by an accumulation of visceral fat or fat inside the body cavity. It differs from subcutaneous fat, or that type of fat that accumulates underneath the skin, and is thought to be more dangerous. Berger was one of the leaders of tesamorelin's clinical studies.


Theratechnogolies noted, in a document also posted to FDA's website, that there's no approved treatment for lipodystrophy and said tesamorelin has a "positive impact" on reducing visceral fat. The company also said some patients stop their anti-retroviral therapy which puts them at risk of HIV progression and other complications.


-By Jennifer Corbett Dooren, Dow Jones Newswires; 202-862-9294; jennifer.corbett@dowjones.com
-Andy Georgiades contributed to this report.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #139 on: May 29, 2010, 10:43:47 AM »
_______________________________________________

Clean Teeth Again Linked to Healthy Heart
"Low-grade inflammation appeared to be playing a role.....the risk of a fatal or nonfatal event was 40% greater for those who brushed once rather than twice a day and 2.3-fold higher for those who brushed less than once a day....They also had increased concentrations of both C reactive protein [inflammation marker] (β 0.04, 0.01 to 0.08) and fibrinogen (0.08, ?0.01 to 0.18).....The literature clearly shows that raised pro-inflammatory cytokines are present in both cardiovascular disease and periodontal disease"

MedPage Today
Published: May 28, 2010

Regular toothbrushing could help stave off cardiovascular disease, according to a nationally-representative study in Scotland.

Action Points 
--------------------------------------------------------------------------------
Explain to interested patients that poor dental hygiene -- brushing less than twice daily -- is thought to be a major cause of periodontal disease and may also impair cardiovascular health.


Individuals who rarely or never brushed were 70% more likely to have a heart attack or other cardiovascular disease event (P<0.001) even after controlling for many other factors, found researchers led by Richard Watt, MSc, PhD, of University College London.


Even brushing once a day rather than twice a day was associated with a significant 30% increase in the risk of these fatal or nonfatal events.


Low-grade inflammation appeared to be playing a role, although whether it is a causal role remains uncertain, Watt's group reported online in BMJ.


These increases in risk could have a "profound public health impact," they wrote in the study.
Nearly 40% of the population has some degree of periodontal disease, a complex chronic inflammatory condition largely caused by poor oral hygiene, the investigators noted.


Its link to cardiovascular disease has been extensively studied with results affirmed and strengthened by the new population-level data.


The researchers used self-reported frequency of toothbrushing as a proxy for periodontal disease, which wouldn't have been feasible for a large-scale population study, they said.


The analysis included 11,869 men and women ages 35 and older (mean 50) who retained their natural teeth and were without preexisting cardiovascular disease in the 1995, 1998, and 2003 iterations of the Scottish Health Survey of the general population.


Overall, their oral health was good. Regular visits to a dentist at least every six months were reported by 62% of respondents and 71% reported brushing twice a day.


More frequent toothbrushing appeared to be dose-dependently protective against cardiovascular disease events -- fatal or nonfatal, including cardiovascular disease-related hospitalization, acute MI, coronary artery bypass surgery, percutaneous coronary angioplasty, stroke, and heart failure.
In the analysis adjusted only for age and sex, the risk of a fatal or nonfatal event was 40% greater for those who brushed once rather than twice a day and 2.3-fold higher for those who brushed less than once a day (P=0.001 for trend).


Further adjustment for socioeconomic status, smoking, physical activity, and visits to the dentist attenuated the link. Additional controls for body mass index, family history of cardiovascular disease, hypertension, and physician-diagnosed diabetes also reduced the relationship but not to the point where significance was lost.


For cardiovascular disease-related death alone, similar trends were seen with a 10% elevated risk with once-a-day brushing and 50% elevated risk with less than once-a-day brushing compared with twice daily. However, this relationship lost significance with multivariate adjustment.


The other independent predictors of fatal and nonfatal cardiovascular disease events combined included:
Smoking (hazard ratio 2.4, 95% confidence interval 1.9 to 2.9)
Hypertension (HR 1.7, 95% CI 1.4 to 2.0)
Diabetes (HR 1.9, 95% CI 1.4 to 2.7)
A subgroup of 4,830 study participants gave blood samples from which markers of inflammation (C reactive protein) and coagulation (fibrinogen) were measured.


Among them, less frequent toothbrushing appeared to have an effect that remained significant after multiple adjustments (P=0.46 for trend in C reactive protein levels and P=0.015 for trend in fibrinogen levels).


Inclusion of inflammatory markers partly attenuated the point estimates for the link between toothbrushing and cardiovascular disease "thus suggesting a possible mediating role," Watt's group wrote in BMJ.


They cautioned that residual confounding may have played a role as well.


Even though the study could not prove that inflammation from poor dental hygiene was causing the increase in cardiovascular events, Watt and colleagues concluded that "educating patients in improving personal oral hygiene is beneficial to their oral health regardless of the relation with systemic disease."




BMJ, 27 May 2010


"Toothbrushing, inflammation, and risk of cardiovascular disease: results from Scottish Health Survey"


Discussion
Abstract
Introduction
Methods
Results
Discussion
References


Toothbrushing is associated with cardiovascular disease, even after adjustment for age, sex, socioeconomic group, smoking, visits to dentist, BMI, family history of cardiovascular disease, hypertension, and diagnosis of diabetes. Our results largely confirm those of previous studies.20 21 We examined the association between toothbrushing behaviour and cardiovascular disease and whether markers of low grade inflammation/coagulation were associated with low frequency of toothbrushing. Our results also suggest that toothbrushing is associated with concentrations of C reactive protein and fibrinogen. To the best of our knowledge, this is the first study to show an association between a single item self reported measure of toothbrushing and incident cardiovascular disease in a large representative sample of adults without overt cardiovascular disease. As self reported measures of oral hygiene have been associated with clinically confirmed periodontal disease,13 a simple self report measure of toothbrushing could therefore be associated with future risk for cardiovascular disease.


Oral health and cardiovascular disease
The role of oral health in the aetiology of cardiovascular disease has received considerable attention. Periodontal disease is a complex chronic inflammatory disease, resulting in a loss of connective tissue and bone support of the teeth.22 It is a major cause of tooth loss in adults aged over 40, and, according to the World Health Organization, affects people worldwide at prevalence rates of up to 10-20% for the most severe forms.23 Periodontal disease is highly prevalent, especially in late middle age when coronary artery disease is also most common,24 and it is caused mostly by poor oral hygiene.


In our study, participants who brushed their teeth less often had a 70% increased risk of a cardiovascular disease event in fully adjusted models. These results confirm findings from several observational epidemiological studies that showed that poor periodontal health status is associated with an increased risk of cardiovascular disease.1 In a study of 15 year follow-up data from the First National Health and Nutritional Examination Survey (NHANES I) Epidemiologic Follow-up Study, DeStefano et al found that people with periodontal disease had a 25% increased risk for coronary heart disease relative to those with minimal periodontal disease, after adjustment for age, sex, race, education, poverty index, marital status, systolic blood pressure, total cholesterol concentration, diabetes, BMI, and alcohol consumption.25 In a longitudinal study, Beck et al found that the odds ratios were 1.5 for total coronary heart disease and 1.9 for fatal coronary heart disease among people with periodontal bone loss compared with those without bone loss, after adjustment for several risk factors for cardiovascular disease.26


One meta-analysis concluded that periodontal disease and poor oral health overall indeed contribute to the pathogenesis of cardiovascular disease.27 Another meta-analysis, by Bahekar et al, confirmed that having periodontal disease might enhance the risk for cardiovascular disease but concluded that this risk was not robust.20


Periodontal disease seems to be associated with a 19% increase in the risk of future cardiovascular disease. This increase in relative risk is more prominent (44%) in people aged under 65. The increment of risk between people with or without periodontal disease in the general population is modest, at around 20%, because nearly 40% of the population have periodontal disease. This modest increase might, however, have a profound public health impact.28
In our study, less frequent toothbrushing was associated with increased concentrations of both C reactive protein and fibrinogen, and these associations remained significant after multiple adjustments including acute infections such as influenza. The work on serum markers of inflammation in both cardiovascular and periodontal research is extensive. The literature clearly shows that raised pro-inflammatory cytokines are present in both cardiovascular disease and periodontal disease. As a result, accumulating evidence has associated severe periodontal disease with increased odds of future cardiovascular disease events.3 Our study suggests a possible role of poor oral hygiene in the risk of cardiovascular disease via systemic inflammation. Raised inflammatory and homoeostatic responses as well as lipid metabolism disturbance caused by periodontal infection might be possible pathways underlying the observed association between periodontal disease and the increased risk for cardiovascular disease.29 Few studies, however, have examined these potential pathways. If these biological mechanisms are responsible for a slight increase in the risk of cardiovascular disease, better controlled and larger studies will be needed to identify them. Such efforts would be important because of the relatively high prevalence of periodontal disease.


Strengths and limitations
The Scottish Health Survey is nationally representative, with a rigorous design and data linked to a patient based database of hospital admissions and deaths with follow-up. The Scottish population is relatively homogeneous, with a high incidence of cardiovascular disease and poor indicators of oral health, thus our findings have high relevance to this population.


Though clinical data regarding the periodontal disease status of the participants might have strengthened our findings, previous research has also shown a good correlation between self report and clinical evaluation of periodontal disease.13 We had no follow-up data on toothbrushing behaviour. There is, however, evidence showing stability of oral health related behaviour such as toothbrushing and dental flossing,30 thus small changes in oral health behaviour are unlikely to affect the present findings. Both residual confounding and potential influence of effect modifiers could be responsible for a substantial attenuation of the relative risk in fully adjusted models. In addition, misclassification of both the exposure and the outcome could have played a role.


Conclusions
Our results confirmed and further strengthened the suggested association between oral hygiene and the risk of cardiovascular disease. Furthermore, inflammatory markers were significantly associated with poor oral health behaviour. Future experimental studies will be needed to confirm whether the observed association between oral health behaviour and cardiovascular disease is in fact causal or merely a risk marker. Nevertheless, use of a simple one item measure of self reported toothbrushing could be a useful and cost effective marker of future health risk in large scale population studies.


Given the high prevalence of oral infections in the population, doctors should be alert to the possible oral source of an increased inflammatory burden. In addition, educating patients in improving personal oral hygiene is beneficial to their oral health regardless of the relation with systemic disease.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #140 on: May 29, 2010, 10:45:43 AM »
http://oudaily.com/news/2010/may/28/ou-researchers-discover-vaccine-potential-treat-hi/

OU researchers discover vaccine with potential to treat HIV, cancer
Daily Staff Report/The Daily
Friday, May 28, 2010


 
Microbiology professor William Hildebrand. Photo provided.
 
For the first time, OU researchers have discovered a way to create a new vaccine using a protein that activates a distinct part of the immune system.

The OU Health Sciences Center research has potential treatment and prevention applications for cancer, tuberculosis, HIV and several other viral diseases, according to a press release from the HSC.

Until now, vaccines have focused on generating antibodies, or B-cells, to keep from getting sick. But this T-cell vaccine uses a protein to activate a distinct part of the immune system, according to the release.

?No one has ever done this with a T-cell vaccine, so we?re learning; but now we are starting to get some traction. We are finding that a T-cell vaccine can work,? said William Hildebrand, the lead researcher on the project.

Hildebrand and his research team have been working with the body's alarm system to learn how cells alert the immune system that something is wrong. The goal is to create viable targets for vaccines that activate T-cells in the immune system, said Hildebrand, microbiology and immunology professor.

T-cells are responsible for killing virus-infected cells in the body. T-cells also kill cells that become cancerous. Some vaccines such as the smallpox vaccine activate T-cells, but this occurs inadvertently. Until now, vaccines have focused on generating antibodies to keep people from getting sick, according to the release.

While many of these antibody vaccines work well, the dependence on antibodies has prompted some viruses to skirt antibody immunity, making vaccines less effective or not effective at all for some viruses. With a T-cell vaccine, researchers would be able to activate another arm of the immune system to target a specific virus in the body and kill it.

To develop the vaccine, Hildebrand began by determining how the immune system distinguishes between a virus-infected or cancerous cell and a healthy cell.

Researchers started with West Nile virus since it doesn't change like the flu or develop resistance like cancer or HIV. After developing the target, researchers at the HSC worked with colleagues at Washington University in St. Louis to create a vaccine, the release stated.

The process is now being repeated for targets and vaccines in other areas, such as cancer, where activating T-cells can be difficult.

"Now that we have demonstrated the feasibility of developing a T-cell-specific vaccine, we intend to use the same process to discover other reliable targets, validate them and develop additional vaccines,? Hildebrand said.

The research appears in the latest issue of The Journal of Immunology and is funded by grants and contracts totaling $15 million from the National Institutes of Health, according to the release.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #141 on: June 01, 2010, 10:52:25 AM »
Vaginal Gel That Kills Herpes, HIV May Be Available by 2012 (Just in time for the end of the World)

May 31, 2010


June 1 (Bloomberg) -- The world?s first herpes-killing vaginal gel may be available within two years, said its developer Starpharma Holdings Ltd., which plans to start patient studies on its effectiveness.


Starpharma is in discussions with ?a number of groups? about trials of its VivaGel product in women at risk of contracting genital herpes, Chief Executive Officer Jackie Fairley said in an interview in Singapore, declining to identify the partners. The Melbourne-based company licensed its VivaGel- coated condoms in 2008 to SSL International Plc, maker of the world?s best-selling Durex brand.


No cure exists for genital herpes, a condition that infects about one in six Americans and produces painful sores and increases HIV transmission, U.S. Centers for Disease Control and Prevention data show. While other gels are being developed to prevent HIV infections, VivaGel is the only microbicide designed to stop herpes infections, Fairley said.


?Commercially it?s actually the herpes market which we think is a more important market? than that for HIV, she said May 27. ?Because herpes is such a massive problem, particularly in the U.S., we think that the herpes opportunity alone is more than attractive enough.?


The company expects to complete the discussions on funding this year, before setting a date for trials to start, Fairley said. Starpharma is also seeking public funding for separate studies of VivaGel aimed at preventing HIV infection, she said.


Deadliest Disease


Trials of microbicides have so far failed to prevent the spread of HIV, the world?s deadliest infectious disease, which kills about 2 million people each year, according to World Health Organization figures.


PRO 2000, a gel made by Endo Pharmaceuticals Holdings Inc. failed in a late-stage trial in December after an earlier study suggested it worked.


Carraguard, a gel produced from seaweed that was developed by New York-based nonprofit group Population Council, flopped in 2008. A year earlier, tests of a product called Ushercell, from Toronto-based Polydex Pharmaceuticals Ltd., were halted after more of the women who used it became infected with HIV than those who received a placebo.


A trial of VivaGel in 61 healthy, sexually active women showed the product was safe, Starpharma said in March. The company plans to study the product?s effectiveness against bacterial vaginosis, the most common vaginal infection in women of childbearing age, later this year, it said at the time.


Condoms are more effective at preventing HIV than genital herpes because the herpes virus is spread through sores on the skin.


Starpharma, which said in September 2008 that VivaGel is designed to halt both viruses, expects to start receiving royalties from condom maker SSL, in 2011, Fairley said.


Starpharma shares have slumped 28 percent since reaching a five-year high of 75 Australian cents in February. The company had A$23.7 million in cash as of Dec. 31 and doesn?t plan to use that money to fund its trials, Fairley said.


--Editors: Lena Lee, Carey Sargent.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #142 on: June 01, 2010, 11:18:36 AM »
Hopes for breast cancer vaccine - pdf attached full article
 
A radiologist studies mammograms 
news.bbc



American scientists say they have developed a vaccine which has prevented breast cancer from developing in mice.


The researchers - whose findings are published in the journal, Nature Medicine - are now planning to conduct trials of the drug in humans.


But they warn that it could be some years before the vaccine is widely available.


The immunologist who led the research says the vaccine targets a protein found in most breast tumours.


Vincent Tuohy, from the Cleveland Clinic Learner Research Institute, said: "We believe that this vaccine will someday be used to prevent breast cancer in adult women in the same way that vaccines have prevented many childhood diseases.


Unique challenge
"If it works in humans the way it works in mice, this will be monumental. We could eliminate breast cancer."


In the study, genetically cancer-prone mice were vaccinated - half with a vaccine containing ?-lactalbumin and half with a vaccine that did not contain the antigen.


None of the mice vaccinated with ?-lactalbumin developed breast cancer, while all of the other mice did.


The US has approved two cancer-prevention vaccines, one against cervical cancer and one against liver cancer.


However, these vaccines target viruses - the human papillomavirus (HPV) and the Hepatitis B virus (HBV) - not cancer formation itself.


 

 We look forward to seeing the results of large-scale clinical trials to find out if this vaccine would be safe



Caitlin Palframan, Breakthrough Breast Cancer

 
In terms of developing a preventive vaccine, cancer presents problems not posed by viruses - while viruses are recognised as foreign invaders by the immune system, cancer is not.


Cancer is an over-development of the body's own cells. Trying to vaccinate against this cell over-growth would effectively be vaccinating against the recipient's own body, destroying healthy tissue.


Caitlin Palframan, of charity Breakthrough Breast Cancer, said: "This research could have important implications for how we might prevent breast cancer in the future.


"However, this is an early stage study, and we look forward to seeing the results of large-scale clinical trials to find out if this vaccine would be safe and effective in humans."


She added there were already steps women could take to reduce the risk of breast cancer, including reducing alcohol consumption, maintaining a healthy weight and taking regular exercise.
Cancer Research UK's professor of oncology, Robert Hawkins, said: "This very early study describes an interesting approach to the prevention of breast cancer.


"It will be several years before this vaccine can be tested fully to assess its safety and effectiveness as a way to stop the disease developing in women."


Breast cancer is the most common cancer in the UK, affecting more than 45,500 women every year.


The study authors gave vaccinations to mice that were genetically engineered to be susceptible to cancer. The mice that were vaccinated with an anti-cancer antigen didn't develop tumors, but all the others did.


Researchers say the vaccine would be targeted at women over the age of 40, because it disrupts breast-feeding and older women are less likely to become pregnant. Older women are also more likely to develop breast cancer.
----------------


Nature Medicine | Letter
Published online
30 May 2010
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #143 on: June 02, 2010, 07:34:45 AM »
NATAP http://natap.org/
_______________________________________________

Microbicides Conference
May 22-25, 2010
Pittsburgh, Pennsylvania

New ARTs Research Takes The Lead: HIV Microbicides Conference Report - (05/28/10)

Researchers upbeat on ART/HIV drugs as Microbocides: We hope that by 2012, we would have found evidence to the fact that ARVs do work in preventing HIV transmission

By Paidamoyo Chipunza recently in PENNSYLVANIA, US

HIV and Aids researchers from across the world are hopeful there will be breakthroughs in two years that will bring a glimmer of hope to people infected with the virus.

Speaking at the International Microbicide Conference that ended in Pittsburgh last week, Pro-Vice Chancellor of the University of KwaZulu Natal in South Africa Dr Salim Abdool Karim was optimistic that by 2012, technological developments would enable researchers to tell if participants of current research were adhering to trial drugs.

Prof Karim said: "Currently, there is no way we can tell that these participants are adhering to their drugs except to take participant?s word of mouth and this really affects the results.

"We hope technological developments will speed up the whole process of conducting clinical trials and gathering information from participants."

Leading Zimbabwean researcher Professor Mike Chirenje, who is working with the University of Zimbabwe in collaboration with the University of San Francisco in California, was confident that the next two years would prove or disprove the safety of microbicides use in pregnant women.

"We do not know if microbicide use is safe in pregnant women. Several studies are currently underway to determine if the use of these chemicals is safe for development of the foetus. Results of these studies are expected before 2012," Prof Chirenje said.

Chief executive officer of the International Partnership for Microbicides Dr Zeda Rosenberg said the future of HIV prevention lay in antiretroviral drugs.

"There is future in antiretroviral drugs. We hope that by 2012, we would have found evidence to the fact that ARVs do work in preventing HIV transmission," Dr Rosenberg said.

The microbicide conference is held biannually to evaluate progress in global HIV research.

This year?s meeting ? unlike previous conferences ? covered other HIV prevention strategies such as male circumcision and ARVs among other issues.

The conference?s theme was "Building bridges in HIV prevention".

The next high-level meeting has been scheduled for Australia in 2012.

http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #144 on: June 02, 2010, 07:36:13 AM »
Control Serum Glucose to Reduce HF Risk in Diabetics

MedPage Today
Published: June 01, 2010

BERLIN -- For patients with diabetes, moderate chronic kidney disease, and anemia, glycated hemoglobin (HbA1c) and estimated glomerular filtration rate (GFR) are independent risk factors for developing heart failure, researchers reported here.

Those findings emerged from a post hoc analysis of data from the Trial to Reduce Cardiovascular Events with Aranesp (TREAT) study, which revealed that the hazard ratio for developing heart failure was 1.11 for every 1% increase in HbA1c from baseline (P=0.002, 95% CI 1.04 to 1.19), said Eldrin F. Lewis, MD, of Harvard Medical School and Brigham and Women's Hospital in Boston.

For estimated GFR, heart failure risk decreased with every 1 unit increase from baseline (HR 0.99, 95% CI 0.98 to 1.00, P=0.047), Lewis reported in a late-breaking clinical poster presented here at the Heart Failure Congress.

Action Points 
--------------------------------------------------------------------------------

This analysis suggests that tight management of modifiable risk factors such a HbA1c and estimated GRF may reduce the risk for developing heart failure in anemic patients with diabetes or chronic renal disease.


Point out that these conclusions come from a post-hoc analysis and therefore can be considered hypothesis generating only.


Note that this study was published as a poster and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.


In an interview with MedPage Today, Lewis said the strongest independent predictor of heart failure among patients in the TREAT study was a history of heart failure (HR, 2.47 95% CI 1.98 to 3.07, P<0.001), followed by baseline loop diuretic use (HR 1.64, 95% CI 1.28 to 2.09, P<0.001), and history of myocardial infarction (HR 1.48, 95% CI 1.19 to 1.85 P<0.001).


But, he said the analysis indicated it is "the modifiable risk factors such as diabetes and estimated GFR that should be the focus of prevention efforts."


The TREAT study enrolled 4,038 patients with diabetes, chronic kidney disease (defined as estimated GFR of 20 to 60 mL/min/1.732) and anemia, defined as hemoglobin ≤11 g/dL. The patients were randomized to darbepoetin (Aranesp) or placebo and followed for a median of 29 months.


The median age of the patients was 68 and 57% were women. The median estimated GFR was 34 mL/min/ 1.732. Roughly 18% of the study population had a history of myocardial infarction and 10.7% had a confirmed history of heart failure.


Overall, 10.7% of the TREAT patients developed heart failure during follow-up. In this group, age, a history of heart failure, higher HbA1c, lower estimated GFR, a history of myocardial infarction, male gender, and baseline use of loop diuretics were independently associated with increased risk of acute heart failure or cardiovascular death.


Included in the 434 patients who developed heart failure, there was a subset of 173 patients who developed incident heart failure during follow-up.


Lewis said that when he and his colleagues analyzed data from this subset, they discovered similar patterns of risk factors as independent predictors.


The TREAT trial investigated the potential role for darbepoetin alfa (Aranesp) for treatment of patients with diabetes or chronic renal disease and anemia. The trial found no benefit for darbepoetin alfa but did reveal a doubling of the risk for stroke. In this analysis, there was no significant association between randomization to darbepoetin alfa and incident heart failure.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #145 on: June 02, 2010, 07:38:22 AM »
--------------------------------------------------------------------------------

NATAP http://natap.org/
_______________________________________________

Microbicides Conference
May 22-25, 2010
Pittsburgh, Pennsylvania

New ARTs Research Takes The Lead: HIV Microbicides Conference Report - (05/28/10)

Researchers upbeat on ART/HIV drugs as Microbocides: We hope that by 2012, we would have found evidence to the fact that ARVs do work in preventing HIV transmission

By Paidamoyo Chipunza recently in PENNSYLVANIA, US

HIV and Aids researchers from across the world are hopeful there will be breakthroughs in two years that will bring a glimmer of hope to people infected with the virus.

Speaking at the International Microbicide Conference that ended in Pittsburgh last week, Pro-Vice Chancellor of the University of KwaZulu Natal in South Africa Dr Salim Abdool Karim was optimistic that by 2012, technological developments would enable researchers to tell if participants of current research were adhering to trial drugs.

Prof Karim said: "Currently, there is no way we can tell that these participants are adhering to their drugs except to take participant?s word of mouth and this really affects the results.

"We hope technological developments will speed up the whole process of conducting clinical trials and gathering information from participants."

Leading Zimbabwean researcher Professor Mike Chirenje, who is working with the University of Zimbabwe in collaboration with the University of San Francisco in California, was confident that the next two years would prove or disprove the safety of microbicides use in pregnant women.

"We do not know if microbicide use is safe in pregnant women. Several studies are currently underway to determine if the use of these chemicals is safe for development of the foetus. Results of these studies are expected before 2012," Prof Chirenje said.

Chief executive officer of the International Partnership for Microbicides Dr Zeda Rosenberg said the future of HIV prevention lay in antiretroviral drugs.

"There is future in antiretroviral drugs. We hope that by 2012, we would have found evidence to the fact that ARVs do work in preventing HIV transmission," Dr Rosenberg said.

The microbicide conference is held biannually to evaluate progress in global HIV research.

This year?s meeting ? unlike previous conferences ? covered other HIV prevention strategies such as male circumcision and ARVs among other issues.

The conference?s theme was "Building bridges in HIV prevention".

The next high-level meeting has been scheduled for Australia in 2012.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline WhySoUnfair

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Re: http://natap.org/
« Reply #146 on: June 02, 2010, 12:00:18 PM »
1.5 more years, fingers & toes crossed...

Offline red_Dragon888

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Re: http://natap.org/
« Reply #147 on: June 02, 2010, 03:43:40 PM »
HIV-associated neurocognitive disorders: is there a hidden epidemic? - Editorial Comment



"the population of HIV-infected individuals is aging and further study is needed to assess the concatenation of age-related and HIV-related cognitive deterioration. We cannot ignore the very unique characteristics of the brain as a potential sanctuary for persistent infection and ongoing inflammatory damage.......the data suggest that we cannot be complacent and assume that systemic virological and immunological control will uniformly control CNS disease.....we must develop and promulgate screening techniques to detect and track HAND and screening should be included in routine care. Furthermore, integration of these data into treatment guidelines is important and the assuming that systemic treatment ?will take care of the brain? is dangerous....association of previous advanced immunosuppression with prevalent and sustained impairment suggests that there may be a non-reversible component of neurological injury that tracks with systemic disease progression [24]. Furthermore, 21% developed HAND despite effective HAART (although the precise number who were aviremic is unclear) [24]. Similarly, in a cohort of individuals with AIDS, 21% of aviremic individuals (who also had undetectable CSF HIV RNA) progressed to HAD [25]. A third prospective study also identified HAND in 8?34% (depending on the time point of the assessment) of aviremic patients without comorbidities and with a nadir CD4 cell count less than 200 cells/μl [26]......Identified risk factors for HAND include a high HIV viral set point, lower CD4 cell counts [27], anemia, low body mass index, increasing age, systemic symptoms [27,28], injection drug use [29], and female sex"



AIDS:

1 June 2010 - Volume 24 - Issue 9 - p 1367?1370




McArthur, Justin C; Brew, Bruce J

aDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

bDepartment of Neurology, St Vincent's Hospital, Darlinghurst, New South Wales, Australia.



The neurocognitive disorders associated with HIV (HAND) remain among the most common clinical disorders encountered in people infected with HIV, even in an era in which potent antiretroviral therapy is widely deployed. HAND is currently considered to encompass a hierarchy of progressively more severe patterns of central nervous system (CNS) involvement ranging from asymptomatic neurocognitive impairment (ANI), to minor neurocognitive disorder (MND), to the more severe HIV-associated dementia (HAD) [1]. With the improved survival of individuals treated with antiretrovirals, comorbid conditions have become increasingly salient, including particularly coinfection with hepatitis C and the effects of aging. Treatment guidelines for preferred initial antiretroviral regimens and for second or salvage regimens are essentially silent on the approach to HAND. For example, HIV-nephropathy is one indication for initiation of HAART, yet inexplicably HAND is not, unless it is severe enough to manifest as dementia. Brain penetration is crucial to achieve the goal of maximal suppression of HIV replication. Cerebrospinal fluid (CSF) antiretroviral concentrations are generally much lower than plasma concentrations, particularly for the protease inhibitors, and active efflux pumps, such as the P-glycoprotein may eliminate this class of drug [2]. An index of the CNS penetration of antiretrovirals can differentiate HAART regimens by their theoretical CNS penetration [3] and specific combinations have better brain penetration or greater efficacy in reversing HAND's deficits or suppressing CSF HIV RNA [4?7]. It remains uncertain whether individuals who have had prolonged aviremia can develop HAND. The study by Simioni et al. [8] sheds new light on this question by studying individuals with long-duration aviremia. It also raises concerns about the adequacy of current screening techniques for HAND. In their study, HAND was diagnosed in a high proportion of 200 long-duration (several years) aviremic individuals. The overall prevalence of cognitive complaints was 27%. The prevalence of HAND was 84% among patients with cognitive complaints and 64% in those without. ANI was found in 24%, MND in 52%, and HAD in 8%. HAND was more common in women, those with lower premorbid IQ (as measured by NART scores), or with neuropsychiatric symptoms.
http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #148 on: June 02, 2010, 03:44:17 PM »
The role of cytology (Pap tests) and human papillomavirus testing in anal cancer screening



AIDS:

1 June 2010 - Volume 24 - Issue 9 - p 1307?1313



Salit, Irving E; Lytwyn, Alice; Raboud, Janet; Sano, Marie; Chong, Sylvia; Diong, Christina; Chapman, William; Mahony, James B; Tinmouth, Jill

aHealth Network, Toronto General Hospital, Canada

bUniversity of Toronto, Toronto, Canada

cHenderson Hospital, Canada

dMcMaster University, Hamilton, Canada

eSt. Joseph's Hospital, Toronto, Canada

fSt. Joseph's Healthcare, Hamilton, Canada

gSunnybrook Medical Centre, Toronto, Ontario, Canada.



Abstract




Objective: To assess anal oncogenic human papillomavirus (HPV) and anal cytology as screening tests for detecting high-grade anal intraepithelial neoplasia (AIN 2+), as this is an immediate anal cancer precursor.




Design: Cross-sectional study of 401 HIV-positive men who have sex with men (MSM). The endpoint was histologically confirmed AIN 2+ obtained by high-resolution anoscopy. Cytology and biopsy specimens were assigned random numbers and independently assessed by two pathologists.




Methods: We did concomitant anal cytology, anal HPV testing and HRA with directed biopsies without knowing the results of each intervention. The main outcome measures were the sensitivity, specificity, negative predictive value and positive predictive value of anal cytology and oncogenic HPV for the detection of AIN 2+.




Results: Cytology was abnormal in 67% of patients: high-grade squamous intraepithelial lesion, 12%; low-grade squamous intraepithelial lesion, 43% and atypical squamous cells of undetermined significance, 12%. Biopsies were abnormal in 68% of patients: AIN 2+, 25% and AIN 1, 43%. HPV was detected in 93% with multiple HPV types in 92% and oncogenic HPV types in 88%. Test performance characteristics for the detection of AIN 2+ using any abnormality on anal cytology were: sensitivity 84%, specificity 39%, negative predictive value 88% and positive predictive value 31%; using oncogenic HPV: sensitivity 100%, specificity 16%, negative predictive value 100% and positive predictive value 28%.




Conclusion: Anal cytology and HPV detection have high sensitivity but low specificity for detecting AIN 2+. HIV-positive men who have sex with men have a high prevalence of AIN 2+ and require high-resolution anoscopy for optimal detection of high-grade anal dysplasia.

http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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Offline red_Dragon888

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Re: http://natap.org/
« Reply #149 on: June 02, 2010, 03:45:00 PM »
Rosiglitazone improves lipoatrophy in patients receiving thymidine-sparing regimens



AIDS:

1 June 2010 - Volume 24 - Issue 9 - p 1291?1298



Tungsiripat, Marisa; Bejjani, Dalia El; Rizk, Nesrine; O'Riordan, Mary Ann; Ross, Allison C; Hileman, Corrilynn; Storer, Norma; Harrill, Danielle; McComsey, Grace A

aCleveland Clinic, USA

bMetrohealth Medical Center, USA

cCase Western Reserve University, and University Hospitals Case Medical Center, Cleveland, Ohio, USA.



Abstract




Objective: Thymidine reverse transcriptase inhibitors (tNRTI) are strong inhibitors of PPAR-γ and clearly implicated as a cause of lipoatrophy. Thiazolidenediaones (TZD), potent PPAR-γ agonists, would be expected to be beneficial in HIV lipoatrophy, but prior studies have been conflicting. None specifically excluded the use of tNRTIs. We report the first study in individuals treated with tNRTI-sparing regimens using a TZD for treatment of HIV lipoatrophy.




Design: This double-blind, placebo-controlled study evaluated limb fat in HIV-infected individuals with lipoatrophy who discontinued tNRTI at least 24 weeks prior to enrollment.




Methods: Individuals were randomized to rosiglitazone vs. placebo for 48 weeks. Dual energy X-ray absorptiometry (DEXA)-scans and fasting metabolic assessments were serially performed.




Results: We enrolled 71 individuals, 17% were female and 51% white. Baseline characteristics were similar between groups except for higher total cholesterol in the placebo group (P = 0.04). At 48 weeks, limb fat (grams) increased significantly (P = 0.02) more in the rosiglitazone than in the placebo group: median (IQR) 448 (138, 1670) vs. 153 (−100, 682), respectively. Of lipids parameters, only total cholesterol increased significantly more in the rosiglitazone group (P = 0.008). Prevalence of metabolic syndrome and total bone mineral density did not change between or within groups.




Conclusion: In the absence of tNRTI, rosiglitazone significantly improves lipoatrophy without deleterious effect on bone mineral density. Total cholesterol, but not triglycerides, significantly increased in the rosiglitazone arm. The glitazones may be a promising addition for accelerating fat recovery in individuals who had switched off tNRTI and remain with significant lipoatrophy.

http://www.youtube.com/watch?feature=player_embedded&v=I3ba3lnFHik

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