|
SciMed -
Healthcare
|
|
TS-Si News Service
|
|
Monday, 01 December 2008 09:00 |
 San Francisco, CA, USA. A quarter of drug trials submitted in support of new drug applications to the US Food and Drug Administration (FDA) remain unpublished five years after the fact, says new research published in the journal PLoS Medicine.
Among those trials published, unexplained discrepancies between the FDA submissions and their corresponding publications — the addition or deletion of outcomes, changes in the statistical significance of reported outcomes, and changes in overall trial conclusions — tended to lead to more favorable presentations of the drugs in the medical literature available to health care professionals.
|
|
Last Updated on Monday, 01 December 2008 08:29 |
|
SciMed -
Healthcare
|
|
TS-Si News Service
|
|
Thursday, 20 November 2008 15:00 |
Blomington, UN, USA. Researchers continue to accumulate evidence of a complex interplay between a female's  brain and her hormones. While a woman's brain and body may need female hormones for proper functioning, it is also known that varying levels of female hormones can have physiological and emotional effects.
Scientists have long known that women's preferences for masculine men change throughout their menstrual cycles, a time of fluctuating hormone levels. Understanding the effects of varying hormone levels is essential to proper maintenance of women's health. This has implications for natal women before and after menopause, as it does for other females on hormone dosages, such as MtF patients.
|
|
Last Updated on Friday, 21 November 2008 07:51 |
|
SciMed -
Healthcare
|
|
TS-Si News Service
|
|
Monday, 08 September 2008 16:30 |
 Amsterdam, The Netherlands. Individuals with a sexually transmitted disease (STD) and women with yeast and bacterial vaginal infections have increased risks HIV infection if exposed to the virus through sexual contact. There are several different proposed explanations, but reasons for this STD effect have not been clear.
A sexually transmitted disease (STD) is a type of illness with a significant probability of transmission by sexual contact between humans or animals. Examples include chlamydia, genital herpes, gonorrhea, and syphilis. The specific acts can include anal sex, oral sex, and vaginal intercourse.
The broader term, sexually transmitted infection (STI), refers to an infected person who may not show signs of disease but retains the potential for infecting others. Some STIs have been well known centuries for their transmission via childbirth or breastfeeding, and now by reusing an IV drug needle after its use by an infected person.
HIV-1 Budding. Scanning electron micrograph of HIV-1 budding from cultured lymphocyte.
The image is colored to highlight important features. The multiple round bumps on the cell surface represent sites of assembly and the budding of infectious virus particles (virions).
Human immunodeficiency virus (HIV) is a member of the retrovirus family (lentivirus) that can lead to acquired immunodeficiency syndrome (AIDS). In the latter condition, the immune system begins to fail and leads to life-threatening opportunistic infections. HIV infection can occur by the transfer of blood, pre-ejaculate, semen, vaginal fluid, or breast milk.
The major tranmission routes are unprotected contaminated IV needles, sexual intercourse, breast milk, and passage from an infected mother to her newborn baby. In the developed world, blood product screening has largely eliminated HIV transmission through transfusions or blood products. Even so, human HIV infection is a worldwide pandemic.
Considerable work is underway to prevent all modes of HIV transmission. Now, Teunis B.H. Geijtenbeek and colleagues, at the VU University Medical Center, The Netherlands, [N1] have described a way in which STDs can increase acquisition of HIV-1 infection they hope might be amenable to therapeutic modulation to prevent HIV transmission.
The research team used living human tissue that had been removed and cultured in an artificial medium the ex vivo human skin explant model). Although immature immune cells known as Langerhans cells (LCs) captured HIV, they did not efficiently transmit the virus to T cells, something that is essential for the initiation of full disease. [N2]
By contrast, the team was ablr to observe efficient virus transmission if LCs were activated by inflammatory stimuli. The infectious agents that cause the STDs thrush and gonorrhea triggered the same inflammatory stimuli in vaginal and skin explants. This suggests that in the presence of an STD-causing infectious agent, LCs might become activated, thereby increasing an individual's risk of becoming infected with HIV.
Further, these data suggest that antiinflammatory therapies might provide a way to prevent HIV transmission, a subject for further investigation.
CitationTLR agonists increase susceptibility to HIV-1 transmission by human Langerhans cells ex vivo. Marein A.W.P. de Jong, Lot de Witte, Menno J. Oudhoff, Sonja I. Gringhuis, Philippe Gallay and Teunis B.H. Geijtenbeek. Journal of Clinical Investigation doi: 10.1172 / JCI34721.
Abstract
Genital coinfections increase an individual’s risk of becoming infected with HIV-1 by sexual contact. Several mechanisms have been proposed to explain this, such as the presence of ulceration and bleeding caused by the coinfecting pathogen. Here we demonstrate that Langerhans cells (LCs) are involved in the increased susceptibility to HIV-1 in the presence of genital coinfections. Although LCs are a target for HIV-1 infection in genital tissues, we found that immature LCs did not efficiently mediate HIV-1 transmission in an ex vivo human skin explant model. However, the inflammatory stimuli TNF-α and Pam3CysSerLys4 (Pam3CSK4), the ligand for the TLR1/TLR2 heterodimer, strongly increased HIV-1 transmission by LCs through distinct mechanisms. TNF-α enhanced transmission by increasing HIV-1 replication in LCs, whereas Pam3CSK4 acted by increasing LC capture of HIV-1 and subsequent trans-infection of T cells. Genital infections such as Candida albicans and Neisseria gonorrhea not only triggered TLRs but also induced TNF-α production in vaginal and skin explants. Thus, during coinfection, LCs could be directly activated by pathogenic structures and indirectly activated by inflammatory factors, thereby increasing the risk of acquiring HIV-1. Our data demonstrate a decisive role for LCs in HIV-1 transmission during genital coinfections and suggest antiinflammatory therapies as potential strategies to prevent HIV-1 transmission.
|
|
Last Updated on Tuesday, 26 May 2009 09:12 |
|
SciMed -
Healthcare
|
|
TS-Si News Service
|
|
Saturday, 30 August 2008 16:30 |
Los Angeles, CA, USA. Many theories have sought to explain what causes the baggy lower eyelids that come with aging, but UCLA researchers have now found that fat expansion in the eye socket is the primary culprit. As a result, researchers say, fat excision should be a component of treatment for patients seeking to address this common complaint.
The study, published in the September issue of the peer-reviewed Journal of Plastic and Reconstructive Surgery, is the first to examine the anatomy of multiple subjects to determine what happens to the lower eyelid with age. It is also the first to measure what happens to the face with age using high-resolution magnetic resonance imaging ( MRI).
Lower baggy eyelids are caused by fat expansion in the eye socket. (Placeholder title) Sean Darcy, Timothy Miller, Robert A. Goldberg, Pablo Villablanca, Joseph L. Demer and George H. Rudkin. Journal of Plastic and Reconstructive Surgery 122(3). Forthcoming. ISSN: 0032-1052; Online ISSN: 1529-4242.
"A common treatment performed in the past and present is surgical excision of fat to treat a 'herniation of fat' — meaning that the amount of fat in the eye socket does not change but the cover that holds the fat in place, the orbital septum, is weakened or broken and fat slips out," said lead author Dr. Sean Darcy, a research associate in the division of plastic and reconstructive surgery at the David Geffen School of Medicine at UCLA and a plastic surgery resident at the University of California, Irvine. "This orbital septum weakening or herniation-of-fat theory is what most plastic surgeons have been taught.
"However, our study showed there is actually an increase in fat with age, and it is more likely that the fat increase causes the baggy eyelids rather than a weakened ligament," Darcy said. "There have been no studies to show that the orbital septum weakens."
The study looked at MRIs of 40 subjects (17 males and 23 females) between the ages of 12 and 80. The findings showed that the lower eyelid tissue increased with age and that the largest contributor to this size increase was fat increase.
Currently, many plastic surgeons performing procedures to treat baggy eyelids do not remove any fat at all. They reposition the fat or conduct more invasive tightening of the muscle that surrounds the eye, or they tighten the actual ligament that holds the eyeball in place. These procedures are performed despite there being no data indicating that these structures change with age.
"Our findings may change the way some plastic surgeons treat baggy eyes," said study co-author Dr. Timothy Miller, professor and chief of plastic surgery at the Geffen School. "Our study showed that a component of a patient's blepharoplasty procedure should almost routinely involve fat excision rather than these procedures."
Blepharoplasty refers to surgical rejuvenation of the upper or lower eyelids, or both, depending on the extent of aging or disease. The procedure is usually performed on the lower eyelid because the most common complaint patients have is that their eyes appear tired, puffy or baggy. The surgeon makes external incisions along the natural skin lines of the eyelid to remove the excess fat and improve the contour of the lower eyelid.
"Although baggy lower eyelids are a significant result of aging and fat expansion, there are other factors that can contribute too," Miller said. "We recommend that surgeons evaluate each component and address them accordingly in an individualized approach to blepharoplasty."
The next phase of research will be to perform MRIs of people with baggy eyelids.
[N1] The study was supported in part by a UCLA research-enabling grant and a grant from the U.S. Public Health Service (PHS).
[N2] Study authors included lead author Dr. Sean Darcy, Dr. Timothy Miller, Dr. Robert A. Goldberg, Dr. J. Pablo Villablanca, Dr. Joseph L. Demer and senior author Dr. George H. Rudkin, all of UCLA.
Lower baggy eyelids are caused by fat expansion in the eye socket. (Placeholder title) Sean Darcy, Timothy Miller, Robert A. Goldberg, Pablo Villablanca, Joseph L. Demer and George H. Rudkin. Journal of Plastic and Reconstructive Surgery 122(3). Forthcoming. ISSN: 0032-1052; Online ISSN: 1529-4242.
|
|
Last Updated on Saturday, 30 August 2008 14:07 |
|
SciMed -
Healthcare
|
|
TS-Si News Service
|
|
Friday, 29 August 2008 16:30 |
|
Ann Arbor, MI, USA. Women with depression may be much more likely than men to get relief from a commonly used, inexpensive antidepressant drug, a new national study finds.
But many members of both sexes may find that it helps ease their depression symptoms.
The persistence of a gender difference in response to the drug — even after the researchers accounted for many complicating factors — suggests that there's a real biological difference in the way the medication affects women compared with men. The reasons for that difference are still unclear, but further studies are now examining hormonal variations that may play a role.
Sex differences in response to citalopram: A STAR*D report. Elizabeth A. Young, Susan G. Kornstein, Sheila M. Marcus, Anne T. Harvey, Diane Warden, Stephen R. Wisniewski, G.K. Balasubramani, Maurizio Fava, Madhukar H. Trivedi, A. John Rush. Journal of Psychiatric Research 42(In press). doi: 10.1016 / j.jpsychires.2008.07.002
The study involved citalopram hydrobromide, a commonly used antidepressant that is available both as a generic drug and under the brand name Celexa®.
Researchers from the University of Michigan Depression Center and their colleagues from around the country tested the drug's ability to help depression patients achieve remission, or total relief from their symptoms, in a multi-year study called STAR*D.
The gender differences emerged from a detailed analysis of data from 2,876 men and women who had a clear diagnosis of major depression, and took citalopram over a number of weeks, with the doses increasing over time.
In the end, women were 33 percent more likely to achieve a full remission of their depression, despite the fact that women in the study were more severely depressed than the men when the study began.
The study showed no differences between men and women in side effects, the amount of time that patients stuck to taking the drug, or the amount of time it took for them to achieve remission of their symptoms.
The new findings, which represent the largest and most rigorous analysis ever of gender differences in response to an antidepressant, are published online in the Journal of Psychiatric Research.
Elizabeth Young, M.D., a professor and associate chair of psychiatry at the U-M Medical School and member of the Depression Center, is the study's lead author. "Other studies have suggested that there are differences between men and women in response to different antidepressants, but the evidence has been conflicting," she says. "This study is large enough, and we were able to control for enough complicating factors, that we feel confident there is a true difference. These results have clear implications for the clinical treatment of depression."
Young and her colleagues, including Susan Kornstein, M.D., of Virginia Commonwealth University (VCU), and John Rush, M.D., formerly of the University of Texas Southwestern Medical Center at Dallas, conducted the analysis of data from men and women between the ages of 18 and 75, many of whom were being treated by primary care physicians and not psychiatrists. All of the patients had been experiencing depression for years, with the average length of experience around 12 years.
Unlike many previous industry-sponsored studies of antidepressants, it included a "real world" sample of people with major depression, and did not exclude people who had a history of suicidal thinking. The study did not include people with bipolar disorder. Participants in the study could continue with psychotherapy that they had been undergoing before the start of the study, but could take no other antidepressants.
Citalopram is one of a class of medicines known as SSRIs, or selective serotonin reuptake inhibitors. In earlier decades, gender differences had been seen in studies of patients taking an older generation of drugs called tricyclics, with men tending to respond better to such medications. But for more than 15 years, SSRIs have been the first choice for treating depression.
Although the current study didn't look at hormonal variations between men and women that might account for the difference in response to citalopram, Young and her colleagues note that animal studies have shown that estrogen modifies the brain systems involved in the activity of serotonin, a key brain chemical.
Kornstein is leading further analysis of the STAR*D results to look for possible differences among women according to their menopausal status and their use of hormone replacement therapy. Meanwhile, Young's research as a member of the U-M Molecular & Behavioral Neuroscience Institute focuses on the interactions of sex hormones and stress response in depression and other mood disorders.
Overall, women are more affected by depression than men, with about 12 percent of women suffering from some form of depression in a given year compared with 6 percent of men. Depression and other mood disorders are the leading cause of disability among women under the age of 45.
But the study's authors are quick to caution that their findings don't mean that citalopram should only be used in women. Raw data from the study show that 24 percent of men achieved remission with the drug, compared with 29 percent of women. The difference in remission rates grew larger once the researchers adjusted for other factors, but the fact remains that many men were helped.
Rather, they note that STAR*D and other studies have shown that many people with depression need to try several treatments to find the one that's right for them and will produce lasting results.
That's why a new study called CO-MED has begun. Young and colleagues from U-M and around the country are now enrolling people with depression for this study that will assess the impact of combinations of medications. One of the medications in that study is escitalopram, a cousin of citalopram, but it also includes other common SSRI antidepressants.
Sex differences in response to citalopram: A STAR*D report. Elizabeth A. Young, Susan G. Kornstein, Sheila M. Marcus, Anne T. Harvey, Diane Warden, Stephen R. Wisniewski, G.K. Balasubramani, Maurizio Fava, Madhukar H. Trivedi, A. John Rush. Journal of Psychiatric Research 42(In press). doi: 10.1016 / j.jpsychires.2008.07.002
Abstract
Objective. Controversy exists as to whether women with depression respond better to selective serotonin reuptake inhibitors (SSRIs) than men. The purpose of this report was to determine whether men and women differ in their responses to treatment with the SSRI citalopram using a large sample of real world patients from primary and psychiatric specialty care settings.
Method. As part of the sequenced treatment alternatives to relieve depression (STAR*D) study, 2876 participants were treated with citalopram for up to 12–14 weeks. Baseline demographic and clinical characteristics and outcomes were gathered and compared between men and women.
Results. At baseline, women were younger, had more severe depressive symptoms and were more likely to have: early onset; previous suicide attempt(s); a family history of depression, alcohol abuse or drug abuse; atypical symptom features; and one or more of several concurrent psychiatric disorders. Despite greater baseline severity and more Axis I comorbidities, women were more likely to reach remission and response with citalopram than men.
Conclusions. Women have a better response to the SSRI citalopram than men, which may be due to sex-specific biological differences particularly in serotonergic systems.
|
|
Last Updated on Friday, 29 August 2008 14:31 |
|
|
London, UK. Researchers have called for more studies into the practice of forcing psychiatric patients to take medication after a review showed that there have been very few rigorous investigations of the procedure. 
The TS-Si News Service
and the TS-Si Research Service are collaborations of TS-Si officials, staff, contributors, and corresponding institutions. The contents do not necessarily convey official positions of TS-Si or its owners, participants, partners, or affiliates.