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Wednesday, February 3, 2010

Strengthening the pelvic floor


Kegel exercises

The standard advice is to pretend as if you are passing gas. Women are sometimes advised to imagine that they are tightening the vagina around a tampon. In general, you should feel like you are pulling in the anal area.
It can be difficult to isolate the pelvic floor muscles. People contract their leg and abdominal muscles instead. It can help to put your hand on your belly so you can sense when you are contracting your abdominal muscles when you shouldn’t be.
The advice to practice pelvic muscle exercises during urination has been discarded. An article on urinary stress incontinence in women in the March 6, 2008, New England Journal of Medicine said this:
“Performance of pelvic floor exercises is not recommended during voiding, because frequent interruptions of voiding may cause voiding dysfunction, and the ability to stop the flow of urine intermittently does not confirm that the exercises are performed correctly.”
The second part of that statement seems especially important. An article on treatment of urinary incontinence in Uptodate, an online publisher of in-depth review articles on medical topics, has this to say:
“Instructions to interrupt urination on regular basis or do [Kegel] exercises ‘one hundred times per day’ are unphysiologic and doomed to failure.”

Biofeedback

Both men and women can sometimes learn to do Kegels more effectively with biofeedback. Monitors are placed inside the vagina or rectum (or both, if you are a woman). As you attempt to do Kegels, you watch a computer screen to see if you are activating the correct muscles. Just one session of biofeedback can help people learn to perform Kegels correctly. Others may need five or six biofeedback sessions.

Electrical stimulation

If you are unable to activate your pelvic floor muscles, electrical stimulation therapy can help. A small electrode is placed inside the vagina or rectum. That electrode is used to deliver an electric current that causes the pelvic muscles to contract. The current can be set at different strengths and time intervals. Electrical stimulation therapy can be done with at-home machines or in a doctor’s office.
Sacral nerve stimulation is another form of electrical stimulation therapy. A wire with a small electrode tip is implanted inside the body so the tip is near the sacral nerve in the lower spine. There’s a device at the end of the wire that generates small electrical impulses. Those impulses activate the sacral nerve, which controls bladder function.

Magnetic stimulation

Magnetic stimulation is similar, conceptually, to electric stimulation, but a pulsed magnetic field is used to activate pelvic floor muscles instead of an electric current. Treatment with a magnetic stimulation device called Neocontrol involves sitting in a chair that sends magnetic pulses into the body. Magnetic stimulation can also be delivered by magnets applied externally near the sacral nerve roots. Uptodate sounds a cautionary note:
“Trials of these devices have been uniformly small, included heterogeneous patient groups, and may have been incompletely blinded or had no control group.”

Vaginal cones

These small, plastic cones are placed in the vagina. They come in different shapes and weights, and women are usually instructed to begin with the lightest one first. The idea is to use the pelvic floor muscles to keep the cone in place. Vaginal cones are, in effect, a sort of low-tech biofeedback device.

Pessaries

Pessaries are inserted into the vagina and positioned so they support the urethra. They come in various shapes, but are basically circular with a knob that pushes gently against the urethra. Strictly speaking, the purpose of a pessary isn’t to strengthen the pelvic floor or activate its muscles. The notion is to provide additional physical support to the urethra.

Tuesday, February 2, 2010

Fatty Liver Disease Next Big Problem for Obese and Inactive People MU scientist says the problem can be overcome with exercise




It is known that low aerobic fitness is a strong predictor of early death. Now, a University of Missouri researcher has linked low aerobic capacity to a decreased ability to metabolize fat in the liver. Using rats bred over several generations for lower aerobic capacity and decreased ability to metabolize fat, the researchers showed that the rats’ livers are more susceptible to chronic disease, injury and dysfunction later in life. However, despite their genetic predisposition, the study found that exercise lowered the risk factors.


“Fatty liver disease will be the next big metabolic disorder associated with obesity and inactivity,” said John Thyfault, PhD, assistant professor in the MU School of Medicine’s Departments of Internal Medicine and Nutrition and Exercise Physiology. “It also is a significant contributor to type 2 diabetes.”


Low aerobic fitness can partially be linked to genetics but is mainly an end product of physical inactivity. The links between low aerobic fitness and metabolic disease in studies like this highlight the importance of being physically active, which can sustain or improve aerobic fitness across our lifespan, said Thyfault, who also is a health scientist at Harry S. Truman Memorial Veterans Hospital.


In contrast, the same study examined rats that were bred over several generations for high aerobic fitness. Those rats were protected from liver problems. A healthy liver is much better protected from fibrosis, the precursor to non-alcoholic liver cirrhosis. A higher aerobic capacity also means a better functioning heart, lungs, muscles and a lower risk for chronic diseases and early mortality.


“Your personal aerobic fitness is not something you will see in the mirror, but it is an important predictor of your long-term health,” Thyfault said. “The most important part of physical activity is protecting yourself from diseases that can be fatal or play a significant role in increasing the risk factors for other metabolic diseases. Too much fat in the liver also can lead to hyperglycemia.”


Using sedentary rats genetically bred to be low capacity runners allowed researchers to biochemically study the connection between low aerobic capacity and increased fat in the liver. Their main finding was that low aerobic capacity was linked to reduced mitochondrial content and function in the liver, which made the liver more susceptible to fat storage. The researchers believe the rats used in the study mimic the pathology of human chronic metabolic disease better than animal models where single genes are altered.


The study will be published in the Physiological Society’s Journal of Physiology. Jamal Ibdah, MD, PhD, Raymond E. and Vaona H. Peck Chair in Cancer Research and senior associate dean for research in the MU School of Medicine, collaborated on the study.

Low Serotonin Eyed as Mechanism for SIDS



By Crystal Phend, Senior Staff Writer, MedPage Today
Published: February 02, 2010
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston


Low brainstem levels of serotonin and the enzyme that makes it could underlie sudden infant death syndrome (SIDS), researchers suggested.
In an autopsy study, SIDS cases showed 26% lower serotonin levels in two major components of the medulla's serotonin system -- the raphé obscurus (P=0.05) and paragigantocellularis lateralis (P=0.04) -- compared with age-adjusted controls who died from known causes.
These brainstem circuits control breathing, blood pressure, and heart rate during sleep, Hannah C. Kinney, MD, of Children's Hospital Boston, and colleagues reported in the Feb. 3 issue of the Journal of the American Medical Association.

A baby with an abnormality in control of these systems might not be able to respond to a life-threatening challenge like asphyxia by rousing from sleep or turning its head the researchers explained.

Action Points
Explain to interested patients that this study supports serotonin as part of the mechanism of SIDS, but how this can be exploited in prevention of SIDS remains to be seen.

SIDS occurs in the "critical first year of life, when homeostatic systems are still maturing," they noted.

Mary McClain, RN, MS, of Boston University Medical Center, who counsels families that have lost a baby to SIDS, commented that these findings help establish the biological basis for urging parents to place their babies on their backs to sleep.

The researchers obtained tissue samples from autopsies of 41 children who died from SIDS, seven who died acutely from known causes (including a car accident, drowning, pneumonia, and unsuspected congenital heart disease), and five who died in the hospital with chronic conditions causing hypoxia-ischemia.

SIDS cases had mean serotonin levels of 31.4 pmol/mg of protein in the paragigantocellularis lateralis, compared with 40.0 pmol/mg among the controls who died acutely (P=0.04).

Levels averaged 55.4 versus 75.5 pmol/mg of protein, respectively, in the raphé obscurus (P=0.05).

These abnormalities in the medulla did not appear to involve the catecholamine system. Catecholamine levels were similar between SIDS cases and controls.

Nor was there evidence for excessive degradation of dopamine or neurotransmitter turnover in SIDS cases, supporting the idea that the key abnormality is reduced synthesis of serotonin, the researchers said.

Another marker of serotonin function -- tryptophan hydroxylase (TPH2), the key enzyme involved in synthesis of serotonin -- also supported this conclusion, with 22% lower levels in the raphé obscurus in SIDS than in controls (P=0.03).

Serotonin receptor binding was 29% to 55% lower in three medullary nuclei that receive serotonin projections, notable for a decrease in binding with older age in SIDS cases, but not controls, the researchers noted.

Given similar findings in three previous investigations, this "may reflect a progressive decrease with age in those infants with the 'SIDS abnormality,'" they wrote. Or it's possible that those with a "stronger abnormality take longer to outgrow the risk period for SIDS and continue to die at older ages," Kinney's group wrote.

Likewise, serotonin receptor binding in infants who died from SIDS was significantly lower in those without known risk factors for SIDS, such as sleeping face down, "suggesting that additional risk factors are necessary to precipitate death when the medullary serotonin system is less compromised," they added.

Although repetitive apnea and agonal impaired gasping before death have been reported in some SIDS cases, chronic impaired oxygenation in the hospitalized children in the study produced a very different serotonin pattern than that seen in SIDS.

Children who died with chronic hypoxia conditions had 55% higher serotonin levels in the raphé obscurus (P=0.02) and 126% higher levels in the paragigantocellularis lateralis (P=0.002) than the SIDS cases.

They also had 640% higher dopamine levels in the raphé obscurus than the SIDS cases (P=0.006).

This suggested "that the primary mechanisms underlying serotonin abnormalities in SIDS are not mediated by chronic hypoxia-ischemia," Kinney's group wrote.

The researchers cautioned that their neurotransmitter measurements may have been off somewhat due to prolonged postmortem intervals.

They also warned that the study was limited by inability to perform these measurements at the synapse in postmortem tissues and by the small sample of controls.


The study was supported by the First Candle/SIDS Alliance, CJ Martin Overseas Fellowship (National Health and Medical Research Council of Australia), CJ Murphy Foundation for Solving the Puzzle of SIDS, CJ Foundation for SIDS, National Institute of Child Health and Development, and the Developmental Disabilities Research Center at Children's Hospital Boston.
The researchers reported no conflicts of interest.
McClain provided no information on conflicts of interest.

Primary source: Journal of the American Medical Association
Source reference:
Duncan JR, et al "Brainstem serotonergic deficiency in sudden infant death syndrome" JAMA 2010; 303: 430-37.

Monday, February 1, 2010

Educational game in development will focus on the science of drug addiction (University of Missouri School of Medicine)

While video games sometimes get a bad rap for enticing children and teens to spend hours in front of a glowing screen, one University of Missouri School of Medicine researcher has the chance to prove games can be beneficial in the classroom.

Joel Epstein, PhD, MU associate professor of psychiatry and researcher at the Missouri Institute of Mental Health in St. Louis, recently received a four-year $1 million grant from the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health, to develop a video game focused on what happens in the brain and the body when a person uses drugs.

Epstein, the recipient of two previous NIDA grants for developing multimedia programs that educate children on the dangers of substance abuse, views this project as a progression of his 17 years of work with the MIMH. First there were videos, then interactive CD-ROMs that were distributed to 19,000 schools across the country, and now, a video game.

“We’ve always done something a bit different than kids are used to and they’ve responded really well to it,” Epstein said. “I think the more you can engage them in the learning process, the more likely it is that the information you’re trying to convey to them will be retained.”

As someone who worked as a freelance computer programmer while earning his doctorate in clinical psychology, Epstein is especially qualified to lead a creative team at MIMH in developing the video game software.

During the development phase, Epstein will work with St. Louis teachers to ensure that the game fits seamlessly into state curriculum standards and meets educational objectives. Focus groups with some important stakeholders – the fourth- and fifth-grade students who make up the target audience – will help developers determine how the game should look and function. The final result will be a single curriculum with two different versions of software, one competitive and one socially collaborative, to test how boys and girls respond to these different types of presentations.

Pretesting children to determine their knowledge about the science of addiction, their attitudes toward drug use and their attitudes toward science in general will help gauge the game’s success. Once the children have played the game, researchers will conduct several follow-up tests to see if playing time has had any impact on these variables.

“My hope is that we can create a unique, memorable and effective learning experience,” Epstein said. “The students will be so engaged in the storyline of the game that they’ll also be engaged in the content we’re trying to get across.”

Click here to view and download Epstein’s previous multimedia programs that teach students about the science of addiction.

Other current projects at the Missouri Institute of Mental Health include:
MIMH is evaluating the Youth Suicide Prevention and Early Intervention program for the Missouri Department of Mental Health. Activities will include outcome evaluation and assessment of suicide prevention trainings conducted by approximately 14 regional centers. Funding for the prevention and intervention program is provided by the Substance Abuse and Mental Health Services Administration (SAMHSA).
Faculty with the MIMH Child and Family Division will evaluate the Safe Schools Healthy Students program for the Hazelwood School District in St. Louis. Safe Schools Healthy Students is a national initiative designed to reduce violence and substance use and improve mental health for students attending elementary and secondary schools. Funding is provided by the U.S. Department of Education, the Substance Abuse and Mental Health Services Administration and the Department of Justice.
MIMH faculty, along with researchers at Saint Louis University and Southern Illinois University Edwardsville are conducting a study examining substance abuse and mental health issues in the metropolitan St. Louis Bosnian community. The study is funded by a one-year grant from the Missouri Foundation for Health (MFH) and is part of a multi-year effort supporting both broad-based and targeted projects addressing mental health and substance abuse issues.
MIMH, in conjunction with the Missouri Department of Mental Health, has received a more than $13 million grant from SAMHSA to create an early intervention program in medical settings for people with risky behaviors. These behaviors include excessive use of alcohol or tobacco, use of illegal drugs, or abuse of prescription medications.

Sunday, January 31, 2010

Patient-Centered Medical Homes in Ontario (From the New England Journal of Medicine)


Walter W. Rosser, M.D., Jack M. Colwill, M.D., Jan Kasperski, R.N., M.H.Sc., and Lynn Wilson, M.D.

As the United States debates health care reform, the concept of “patient-centered medical homes” is receiving increasing attention.1 Many experts believe that medical homes with multidisciplinary teams and financial incentives for providing comprehensive care will lead to improvements in health, increase efficiency, andreduce costs of care while making practice more attractive for primary care physicians. Lessons regarding the implementation of medical homes and their ability to accomplish these goals can be gleaned from Ontario’s experience with Family Health Teams (FHTs).
Back in 1969, Canada adopted a universal health insurance program. The federal government provided partial funding, and each province developed its own health care system under national guidelines. At first, the system was well funded, and most Ontarians were satisfied. Family physicians practiced solo or in small groups and were paid on a fee-for-service basis. But by the mid-1980s, family doctors struggled to keep up with practice demands. Rising costs and either static or falling incomes pressured physicians to increase the number of patient visits, which, many observers believe, negatively affected both the quality of care and physicians’ personal lives. Interest in family medicine declined, and the proportion of Ontario medical graduates entering the field fell to 24% in 1998, though the health care system was based on the expectation that 50% of physicians would be in family practice, Canada’s only primary care specialty.
In the early 1990s, the chairs of Ontario’s five university departments of family medicine became increasingly concerned that the payment system rewarded high-volume practices rather than broad, patient-centered care.2,3 In response, a government-appointed committee identified a “basket” of services that family practicesshould provide. After physicians and politicians had been persuaded of its merits, the FHT was introduced in 2004. The FHT model is designed to expand the capacity of primary care through development of interdisciplinary teams and to improve the breadth and quality of care through incentives provided by a blended payment model. Today, about 720 physicians in 150 FHTs serve more than 1 million patients.
The model is flexible, and no two FHTs are the same. A typical practice includes at least seven family physicians and a multidisciplinary team that provides a broad range of services and 7-day-a-week access to care. Physicians sign a contract with the Ministry of Health to provide the basket of services and agree to theremuneration package. Patients wishing to receive care from an FHT must register with the Ministry and select a physician at a given practice. There is no certification process for FHTs, but electronic data, such as results of screening for colon cancer, document the services and provide information for reimbursement by the Ministry.
Primary care services focus on patient advocacy and coordination of care. Specifically included are episodic and acute care; mental health care; chronic disease care; evidence-based prevention; education for self-care; care in the hospital, at home, and in the community; support for the terminally ill; and arrangements for around-the-clock response for urgent problems. In essence, the FHT serves as the focus for all patient care, providing the majority of care and coordinating that provided by specialists and by other community resources. Not every physician delivers every service, but each group must be organized to do so. The patient’s physician sees to it that appropriate services are provided.
Physicians have responsibility for a defined panel of patients and are assisted by other health professionals, such as nurses, nurse practitioners, psychologists, pharmacists, social workers, and health educators. A typical physician panel includes about 1400 patients, smaller than a typical U.S. practice. Inclusion of a nurse practitioner adds 800 patients to the expected practice size. The Ministry provides salaries for the other health professionals and funding for an electronic record system meeting Ministry requirements.
Physician payment is based on age- and sex-based capitation that is calculated from Ontario’s fee-for-service experience. Additional fees are provided for services deemed to require added emphasis — visits for infants, for instance, or patients over 75 years of age. Physicians receive fees for procedures and for visits to hospitals, homes, and nursing homes. Graded bonuses are provided for achieving prevention goals for one’spatient panel. Family doctors receive a bonus of $100 to $300 for every new patient, depending on the complexity of that patient’s needs. The physician forfeits 1 month’s capitation fee when a patient seeks care elsewhere. About 60% of physicians’ incomes come from capitation and 40% from other fees and bonuses. Each FHT has a governing board with community representatives and is responsible for ensuring that standards are met, but standards of care are established by physicians.
Primary care reform in Ontario took more than a decade from conceptualization to implementation. Although many physicians were initially skeptical about its potential for success, as-yet-unpublished studies document high levels of patient and physician satisfaction. When the Ministry recently sought to delay expansion to 200FHTs, protests by patient groups and physicians led to cancellation of the delay.
The use of interdisciplinary teams expands the range of services provided and reduces overload for individual physicians. Since income is not based primarily on physician visits, practices can explore broader roles for team members and may use telephone, e-mail, and group visits to enhance efficiency. The total number of visits per patient has not declined, but more visits appear to be occurring with team members other than the primary physician. One study has shown that control of hypertension is better among patients in FHTs than among those in fee-for-service practices.4 The use of integrative electronic record systems appears toimprove efficiency and communication, and we believe that quality incentives have made participating physicians more proactive in providing preventive services and providing care management for chronically ill patients. A full evaluation of this model’s effects on health outcomes, quality measures, and costs will be completed in 3 to 5 years. One effect that is already obvious is an increase of approximately 40% in physicians’ incomes: the average net income for a family physician has increased from $180,000 (Canadian) in 2004 to $250,000 within FHTs, but it has not risen substantially in the fee-for-service sector.
Most Ontario teaching practices are FHTs and emphasize the values of patient-centered care in both family medicine residency programs and undergraduate medical education. The percentage of Ontario medical school graduates entering family medicine has increased from 25% in 2004 to 39% in 2009 (as compared with an increase from 24% to 29% in other Canadian provinces). Anecdotal information suggests that the first choice of Ontario’s family medicine residents is now to practice in FHTs. Family physicians who were initially skeptical are now seeking to participate.
Per capita, Canada has one third fewer active physicians than the United States, 15% more primary care physicians, and half as many specialists. Consequently, the heavy responsibilities of Canadian specialists promote shared care with family physicians, and specialists rarely see patients without referral. In the United States, only 30% of visits to specialists occur through referrals,5 and patients are likely to see multiple specialists. Canada’s physician mix has helped to contain costs, but the government recognizes that it faces shortages of both primary care and specialist physicians. Its goal is for every person to have a family physician. Ontario’s large investment in FHTs signifies its commitment to enhancing the capacity and qualityof primary care.
Could medical homes be implemented in the United States? For many in primary care, Ontario’s model represents the type of practice they always hoped to have. Already, many managed care organizations and some integrated delivery systems are headed in that direction. But multiple insurers in a region, rather than a single payer, would have to invest in the medical home for it to be viable for most primary care practices.
U.S. health care reform legislation anticipates a strong foundation of primary care — but that foundation is crumbling. Having faced similar problems, Ontario continues to convert fee-for-service practices to patient-centered medical homes, so far with positive results, including more graduates entering family medicine. Its experience can provide useful lessons for the United States as it addresses its primary care crisis.
Financial and other disclosures provided by the authors are available with the full text of this article at NEJM.org.
Source Information
From the Department of Family Medicine, Queen’s University, Kingston, ON, Canada (W.W.R.); the Department of Family and Community Medicine, University of Missouri School of Medicine, Columbia (J.M.C.); the Ontario College of Family Physicians, Toronto (J.K.); and the Department of Family and Community Medicine, University of Toronto, Toronto (L.W.).
This article (10.1056/NEJMp0911519) was published on January 6, 2010, at NEJM.org.
References
  1. The patient centered medical home: history, seven core features, evidence and transformational change. Washington, DC: Robert Graham Center, November 2007. (Accessed January 5, 2010, at http://www.graham-center.org/online/etc/medialib/graham/documents/publications/mongraphs-books/2007/rgcmo-medical-home.Par.0001.File.tmp/rgcmo-medical-home.pdf.)
  2. Forster J, Rosser W, Hennen B, McAuley R, Wilson R, Grogan M. New approach to primary medical care: nine-point plan for a family practice service. Can Fam Physician 1994;40:1523-1530. [Web of Science][Medline]
  3. Rosser WW, Kasperski J. Organizing primary care for an integrated system. Healthc Pap 1999;1:5-21. [Medline]
  4. Tu K, Cauch-Dudek K, Chen Z. Comparison of primary care physician payment models in the management of hypertension. Can Fam Physician 2009;55:719-727. [Free Full Text]
  5. Valderas JM, Starfield B, Forrest CB, Sibbald B, Roland M. Ambulatory care provided by office-based specialists in the United States. Ann Fam Med 2009;7:104-110. [Free Full Text]

Friday, January 29, 2010

MU Researcher Developing New Preventive Agent for Stopping Spread of HIV

Tests show EFdA is much more effective than other microbicides

Nearly 30 years after the discovery of the virus that causes AIDS, contracting the disease is no longer a quick death sentence. While high-tech therapies help patients live longer, healthier lives, one University of Missouri researcher is fighting HIV on another level — with a microbicide that stops the virus in its tracks.

Stefan Sarafianos, PhD, assistant professor of microbiology and immunology in the MU School of Medicine, and his collaborators Michael Parniak, PhD, at the University of Pittsburgh and Hiroaki Mitsuya, MD, PHD, at the National Institutes of Health have shown that the molecule EFdA can be used as a highly effective microbicide to prevent HIV transmission. They are in the process of patenting the chemical compound, which is up to 60,000 times more powerful than any other drug currently used for the treatment of HIV infection.

EFdA is a nucleoside reverse transcriptase inhibitor, meaning it targets the main HIV enzyme responsible for viral replication. In laboratory tests, human cells treated with EFdA can still become infected with HIV, but the compound stops the virus from replicating and spreading. Then, the immune system rids cells of the invader.

“The immune system has the capability to kill a little of the virus in the background, so it becomes manageable,” Sarafianos said. “Infection is the result of an overwhelming attack of the virus, but if you manage to keep the viral load low, the body has mechanisms to defend itself and clean up the virus on its own.”

With HIV vaccine efforts at an impasse, increased emphasis is placed on the discovery of alternate strategies to prevent HIV infection. Internationally, researchers are focused on developing microbicides that contain the same or related antiretroviral drugs used as treatments for people infected with HIV. Scientists hope the drugs can double as preventive agents in the form of vaginal gels and creams, empowering women to protect themselves when their partners refuse to use condoms.

One of the most popular drugs, tenofovir, is being tested as a microbicide in gel form. When EFdA is tested head-to-head with tenofovir in lab trials, there’s no competition, Sarafianos said.

“EFdA provides a much longer-term barrier to HIV infection, up to days whereas other microbicides last hours,” Sarafianos said. “EFdA also has a low toxicity against normal cells, and it is active against a broad spectrum of HIV subtypes.”

Sarafianos co-investigator Michael Parniak, a professor of microbiology and molecular genetics, has spent more than 15 years studying and developing antiviral drugs for HIV/AIDS. His work in this area has resulted in eight patents issued or pending. Along with EFdA, he is developing the antiviral drug UC781, which is currently in clinical trials as a microbicide to prevent HIV transmission.

Parniak calls EFdA the most potent HIV inhibitor discovered so far.

“To me, this is the molecule that should and will move forward as a microbicide,” Parniak said. “A combination of EFdA and UC781 would be a powerhouse, a one-two punch pretty much guaranteeing significant blockage of HIV transmission.”

Just as an EFdA and UC781 combination could someday knockout HIV, Sarafianos and Parniak posses a dynamic and complementary working relationship. Parniak, who specializes in virology, is the principal investigator for the microbicidal use of EFdA, while Sarafianos is the biochemical expert and principal investigator for work to understand EFdA’s mechanism of action — he understands precisely how EFdA works against the virus.
Sarafianos, Parniak and Hiroaki Mitsuya, head of the experimental retrovirology section at the NIH and inventor of several approved HIV drugs, recently submitted a patent disclosure. The scientists now have one year to apply for a patent to use EFdA, originally synthesized by the Japanese company Yamasa, to minimize the sexual transmission of HIV. Once patented, the microbicide could be integrated into a product already commonly used for protection during sexual intercourse, such as a spermicide or other form of birth control.

“If we can reduce the transmission of HIV, we can finally get a handle on overall infection spread,” Parniak said. “If we could reduce HIV transmission by only 30 percent or 40 percent, that would make a huge difference.”

According to estimates by the World Health Organization and UNAIDS, 33 million people were living with HIV at the end of 2007. That same year, some 2.7 million people became newly infected, and 2 million died of AIDS, including 270 000 children.

In the distant future, EFdA could also evolve into a treatment for patients already infected with HIV. In a study conducted by Parniak at the University of Pittsburgh, EFdA effectively treated rhesus monkeys infected with simian immunodeficiency virus (SIV) who showed end-stage simian AIDS symptoms. Monkeys with end-stage SAIDS typically die within a few weeks; the EFdA-treated animals lived for more than six months, a positive predictor that EFdA could have a similar effect in humans.

Parniak attributes much of EFdA’s potential to the novel mechanism of action discovered by Sarafianos’ lab at MU.

“He’s so excited about research, that he recharges me every time,” Parniak said of their weekly conversations to share data. “He’s one of our brightest young investigators and a real gem for Mizzou.”

The investigators’ EFdA research is funded by seven grants. Funding sources include multiple NIH grants, a grant from the American Foundation for AIDS Research and indirect federal funding of Sarafianos’ lab in MU’s Christopher S. Bond Life Sciences Center.

Thursday, January 28, 2010

More on the Stroke Belt study (From the Harvard Health Letter)


Maria Glymour and her colleagues at the Harvard School of Public Health conducted their study of the Stroke Belt by using data from the 1980, 1990, and 2000 censuses and mortality data from the National Center for Health Statistics for those same years. One of the strengths of their study was the use of “hard” mortality data, which is based on official death certificates.
They defined the Stroke Belt as being the states of North Carolina, South Carolina, Georgia, Alabama, Mississippi, Tennessee, and Arkansas. These are the seven states included in the federal government’sStroke Belt elimination project.
Using the census and mortality data, the researchers created four “exposure” categories, with the exposure being either birth in the Stroke Belt or residence in a Stroke Belt state as an adult. The exposure groups stack up like this:

  • Born in the Stroke Belt, adulthood in the Stroke Belt (double exposure)

  • Born in the Stroke Belt, adulthood out of the Stroke Belt (out-migrants)

  • Not born in the Stroke Belt, adulthood in the Stroke Belt (in-migrants)

  • Not born in the Stroke Belt, adulthood out of the Stroke Belt (no exposure)

Crude rates

Once the exposure groups were set, the researchers then calculated the number of stroke deaths per 100,000 people — the crude stroke mortality rate — for each of them. Here are the results:
1980
1990
2000
Stroke Belt birth, Stroke Belt adulthood (doubly exposed)
122
83
74
Stroke Belt birth, non-Stroke Belt adulthood (out-migrants)
115
89
88
Non-Stroke Belt birth, Stroke Belt adulthood (in-migrants)
63
43
39
Non-Stroke Belt birth, non-Stroke Belt adulthood (nonexposed)
78
52
47
Here is the same information just for whites:
1980
1990
2000
Stroke Belt birth, Stroke Belt adulthood (doubly exposed)
97
68
66
Stroke Belt birth, non-Stroke Belt adulthood (out-migrants)
86
65
66
Non-Stroke Belt birth, Stroke Belt adulthood (in-migrants)
60
41
40
Non-Stroke Belt birth, non-Stroke Belt adulthood (nonexposed)
75
51
46
And for blacks:
1980
1990
2000
Stroke Belt birth, Stroke Belt adulthood (doubly exposed)
211
128
96
Stroke Belt birth, non-Stroke Belt adulthood (out-migrants)
146
115
116
Non-Stroke Belt birth, Stroke Belt adulthood (in-migrants)
112
66
37
Non-Stroke Belt birth, non-Stroke Belt adulthood (nonexposed)
112
68
58
Note that in almost every category, the stroke mortality rate is higher for blacks. The lone exceptions are the so-called in-migrants — people who moved to the Stroke Belt after living elsewhere.
Glymour and her colleagues pointed out that excess stroke mortality from Stroke Belt exposure, either at birth or as an adult, declined from 1980 to 2000 in every category. The biggest decline was among blacks who were “doubly exposed” (from a rate of 211 stroke deaths per 100,000 people in 1980 to a rate of 96 stroke deaths per 100,000 in 2000).

More refined numbers

But these are crude mortality rates that don’t take into account sex and age. The researchers made those adjustments. They also expressed the stroke risk as an odds ratio relative to the nonexposed group. In simplified terms, that means calculating how much greater the stroke risk was for people who had spent time in the Stroke Belt (birth, adulthood, or both) compared with the stroke risk for those who were neither born nor lived there as adults — the nonexposed in the charts above.
So, for example, in the chart below, 45% means a 45% greater chance of having a stroke than the nonexposed group. Here are those results for whites:
1980
1990
2000
Stroke Belt birth, Stroke Belt adulthood (doubly exposed)
45%
29%
34%
Stroke Belt birth, non-Stroke Belt adulthood out (out-migrants)
31%
20%
20%
Non-Stroke Belt birth, Stroke Belt adulthood (in-migrants)
8%
7%
11%
For blacks:
1980
1990
2000
Stroke Belt birth, Stroke Belt adulthood (doubly exposed)
55%
47%
34%
Stroke Belt birth, non-Stroke Belt adulthood out (out-migrants)
20%
11%
9%
Non-Stroke Belt birth, Stroke Belt adulthood (in-migrants)
13%
49%
1%
The highest group for whites and blacks are the doubly exposed, although by 2000, there is no racial difference: the stroke death rate is 34% higher for both whites and blacks. It’s also interesting that the stroke risk for out-migrant blacks is lower than it is for out-migrant whites in all three years.
Glymour and her colleagues acknowledge that their study cannot answer perhaps the most interesting question: Why is there a Stroke Belt in the first place? Genetic explanations don’t seem to work, because the Stroke Belt effect is true for both blacks and whites, although it’s usually less pronounced in whites. Behaviors or perhaps environmental toxins of some sort are more likely explanations, but nobody knows for sure.
This study does raise new questions about timing and whether there might be something about being born and spending your early childhood (place of birth and place of early childhood are not the same but census information shows that they are closely related) in the American Southeast that leads to a greater chance of having a fatal stroke later in life.