To report all of the new medical and scientific discoveries that are made -- almost daily -- in Yale's laboratories and research centers would take far more pages than the Yale Bulletin & Calendar can accommodate on a weekly basis. Gathered below are brief summaries of some of the noteworthy findings made by Yale medical researchers in past months.
High-risk behaviors such as smoking, physical fighting, alcohol use and sexual activity are associated with increased risk of suicide attempts among adolescents, Yale researchers and their collaborators found.
In a study of 1,285 randomly selected children and adolescents aged 9 though 17, the researchers looked at the relationships between suicidal thoughts or attempts and family environment, personal characteristics (including psychiatric diagnoses) and various risk behaviors. Of the study participants, 3.3% had attempted suicide and 5.2% had expressed suicidal thoughts.
The researchers found that compared with their non-suicidal peers, children and adolescents with a history of suicidal thoughts or attempts were more likely to have experienced stressful life events; to have become sexually active; to have smoked, gotten drunk or used drugs; or to have been involved in physical fighting, according to Dr. Robert King, professor of child psychiatry and psychiatry at the Yale Child Study Center and lead author of the study. The researchers also found that a lack of parental monitoring was associated with increased suicide risk. (Journal of the American Academy of Child and Adolescent Psychiatry, July.)
Rewarding drug users with vouchers that they can exchange for food and clothing -- or, as one did, a robe for singing in a church choir -- was effective in keeping patients drug-free and on a medication regimen, according to research at Yale.
In a study led by Kathleen Carroll, professor of psychiatry, researchers looked at ways to encourage patients addicted to opioids, such as codeine, morphine and heroin, to take the drug naltrexone regularly. Naltrexone is a non-addictive medication that blocks the effect of opioids in the brain.
Funded by the National Institute on Drug Abuse, the study included 127 patients, each of whom received naltrexone three times a week and attended a group therapy session once a week. A second group of patients also received vouchers redeemable for goods and services contingent on targeted behaviors. Yet another group was offered, in addition to vouchers and naltrexone, family therapy sessions with a non-substance abusing friend or relative. Patients who complied perfectly could earn up to $561 worth of items during the 12-week treatment.
The researchers found the use of the vouchers significantly improved treatment retention and naltrexone compliance. Family therapy did not improve retention in the program, but did improve family functioning. One session with a significant other, in addition to vouchers, had an effect on treatment retention, naltrexone compliance and opioid use.
"Research suggests that the usual level of compliance with any medication is around 50%," says Carroll. "It's possible these types of strategies also could be used with any other medications."
Yale researchers have shown for the first time that a component of the medicinal herb feverfew targets a protein called IkappaB Kinase and halts the protein's role in the inflammatory process.
Feverfew, which is commonly used as an alternative medicine for migraine headaches, and some other anti-inflammatory medicinal herbs, are rich in a group of compounds thought to mediate the anti-inflammatory nature of these plants. The component in feverfew is called parthenolide.
"The results pave the way for the development of novel anti-inflammatory drugs for a variety of illnesses and symptoms, such as headache, swelling, redness and inflammation," says Craig Crews, associate professor of molecular, cellular and developmental biology, and of chemistry and pharmacology.
Crews led the research team that set out to identify the molecular basis of parthenolide's anti-inflammatory activity. The team made a derivative of parthenolide, which they used to look for proteins that bind to the feverfew component. They found that IkappaB was one such binding protein, which is responsible for inflammation. (Chemistry and Biology, August.)
A method called prospective surveillance, which studies unexplained illness and death due to possibly infectious causes, allowed for earlier detection of emerging and reemerging infections in 73% of cases, Yale researchers concluded in a study.
The study compared ongoing hospital-bed surveillance (prospective surveillance) with retrospective surveillance, which reviewed hospital discharge data at seven New Haven County acute care hospitals in 1995 and 1996. The results revealed that 22 patients had either died or become seriously ill from what appeared to be an infectious disease.
Although neither technique identified all cases of unexplained illness and death, prospective surveillance -- a network capable of identifying trends in symptoms of infectious disease -- was 32% more sensitive than retrospective evaluation, says Dr. Andre N. Sofair, assistant professor of medicine and coauthor of the study.
"Before a new disease is identified and named, it can make countless people ill and even lead to death," says Sofair. "Our approach provides clues to isolating an unknown disease, thereby allowing public health professionals to mobilize prevention efforts."(American Journal of Public Health, August.)
To help improve treatment for premenstrual syndrome (PMS) and the more serious premenstrual dysphoric disorder (PMDD), researchers at Yale are examining the body's emotional and physiological responses across the menstrual cycle.
"We are trying to determine whether menstrual cycle phase has an impact on the body's startle reflex and whether the menstrual cycle effect is different in women with PMDD compared to a healthy control group," says principal investigator C. Neill Epperson, assistant professor of psychiatry and obstetrics and gynecology.
Epperson and her team are testing changes in physiological responses (startle, heart rate and skin conductance) while study participants are viewing pleasant, neutral and unpleasant pictures. The researchers test the responses of healthy females and women with PMDD at different times in the menstrual cycle. Men will also be included in the study as a comparison group.
About 80% of women of reproductive age experience PMS, which is characterized by varying degrees of body aches, water retention, migraine headaches, fatigue, irritability and impatience. Only about 3% to 7% of women meet the criteria for PMDD. Epperson says her study may lead to more effective prevention and treatment programs for PMS and PMDD.
Yale researchers report that a protein called Akt2 or Protein Kinase B plays an important role in maintaining glucose balance, a finding that could lead to a drug target for preventing Type-2 diabetes.
"When we inactivated the Akt2 protein in study mice, we found that these mice had defects in insulin's action in liver and skeletal muscle, suggesting that Akt2 plays an important role in insulin signaling and action," says Jason Kim, an author on the study and research scientist in the Department of Internal Medicine.
Future studies will examine whether a mutation in the Akt2 protein is seen in people with diabetes, says Kim, who is also an associate at the Howard Hughes Medical Institute and a co-director of the NIH-Yale Mouse Metabolic Phenotyping Center.
Type-2 diabetes is the most common metabolic disease in the world, affecting 120 million people. Insulin resistance plays a primary role in the development of the disease. Kim says diabetes research is now focused on understanding how insulin acts in the body, especially in the area of the insulin signaling pathway. (Science, June.)
Yale researchers have developed a topical estrogen that alleviates vaginal dyspareunia or dryness, a painful symptom of menopause that causes sexual dysfunction, without the side effects of conventional estrogen.
"The topical estrogen we've created confines itself to a specific region of the body and helps eliminate the side effects associated with estrogen found in hormone replacement therapies (HRT)," says Dr. Richard B. Hochberg, professor of obstetrics and gynecology and the lead investigator of the study.
Although 40% of women experience vaginal dryness or other symptoms associated with menopause, fear of side effects such as breast and endometrial cancer and stroke cause many women to steer clear of HRT. The new cream developed by Yale researchers contains a powerful but local estrogen that is metabolized quickly in the tissues and blood, Hochberg says.
The new topical estrogen also includes anti-aging properties and may alleviate some of the symptoms of aging skin, he adds. (Journal of Medicinal Chemistry, June.)
When stable methadone patients, who were formerly addicted to heroin and other narcotics, switch from a narcotic treatment program to a physician's office for continuing methadone maintenance treatment, they become more accepting of the treatment and continue to do well, Yale researchers have found.
Dr. David A. Fiellin, assistant professor of medicine and lead author of the study, said the results highlight a possible solution to the problem of providing treatment for the estimated 800,000 patients that need it. "Opioid dependence and heroin addiction is at a crisis level in America," he says. "We need to provide treatment for over 800,000 patients, and because of space limitations, only 170,000 are enrolled in formal treatment programs."
The study looked at 46 men and women who were randomly assigned either to remain at their narcotic treatment program or to receive treatment in a physician's office. Fiellin and his team showed that 82% of patients assigned to a physician's office remained clinically stable during the six months. In addition, they found that 73% of the patients were more satisfied with treatment in the physicians' offices, and the physicians felt confident caring for these patients.
The study was funded by the Center for Substance Abuse Treatment and the State of Connecticut Department of Mental Health and Addiction Services. (Journal of the American Medical Association, Oct. 10.)
Homeless people with mental illness manage better if they live in cities and towns with high levels of social capital or community activism, Yale researchers report.
"This is the first study to show that the level of awareness and activism, often called social capital, in a community directly affects the delivery of mental health services to homeless people," says lead investigator Dr. Robert Rosenheck, professor in the Departments of Psychiatry and of Epidemiology and Public Health.
For one year, Rosenheck and his colleagues tracked the progress of over 2,500 mentally ill homeless people from 18 towns and cities in the United States. They analyzed community voting records, participation in volunteer work or community projects, and the cohesiveness of the various agencies that help homeless people in these communities. At the end of the study period, 40% of the participants were living in stable housing. Results showed that these ex-homeless people were more likely to be from areas with high levels of social capital.
"The more community residents vote, participate in volunteer activities and attend meetings in their communities, the more they experience trusting relationships that allow people from different agencies to work together," notes Rosenheck, who is also director of the Northeast Program Evaluation Center at the VA Connecticut Healthcare System. (Health Services Research, August.)
About 76% of elderly people stay in bed for at least half a day or cut down on activities because of an illness or injury, yet many do not seek medical attention, according to Yale researchers.
The study also showed that women had higher rates of restricted activity than men and identified more problems as causes of their restricted activity.
The study's lead investigator, Dr. Thomas M. Gill, associate professor of medicine, and his coauthors used monthly telephone calls for an average of 15 months to follow a group of 754 people aged 70 or older living in the Greater New Haven area. Results showed that 76.6% of participants reported restricted activity during at least one month and 39.3% reported restricted activity during two consecutive months. Fatigue, pain, joint stiffness and dizziness were among the different causes for restricted activity.
About one-third of participants' doctor visits during months with restricted activity were for routine follow-up, rather than for the causes of their restricted activity, Gill reported.
"Restricted activity should not be acceptable as a normal part of aging by patients, families or physicians," Gill says. "When restricted activity persists, older people should see their physicians for an evaluation, and physicians should be attentive to the multiple potential causes for restricted activity among their older patients." He adds that the study also demonstrates "the compelling need for preventive and therapeutic interventions to improve the health and functional status of older women." (Annals of Internal Medicine, Sept. 4.)
A study of HIV-infected prisoners shows that they are more likely to accept antiretroviral therapy (ART) if they have trust in the treatment, in their physicians and in medical institutions -- highlighting the role that trust plays in HIV therapy, Yale researchers report.
The researchers also found that lack of social support, complexity of medication regimen and adverse side effects all reduce adherence to ART. The study was led by Dr. Frederick L. Altice, associate professor of medicine (AIDS Program).
Altice and his team surveyed 205 HIV-infected prisoners in four ambulatory prison HIV clinics. Sixty-four percent of the study participants had only been offered ART within a prison setting and only 3% had prescriptions for ART at the time of the incarceration. The team found that 80% of study participants adhered to their HIV therapy and that participants who had trust in their medical institutions were about 20% more likely to adhere to ART than their more mistrustful counterparts.
"These results underscore the idea that caregivers need to have the patient buy into the treatment process if marginalized members of the HIV population are going to reap the benefits of the latest treatment options for AIDS," Altice says. (Journal of Acquired Immune Deficiency Syndromes, September.)
The frequently prescribed antihistamine and sedative medication diphenhydramine is associated with a 70% increased risk of changes in mental status and evidence of delirium symptoms in older, hospitalized patients, according to Yale researchers.
Dr. Joseph V. Agostini, a postdoctoral fellow in the Robert Wood Johnson Clinical Scholars Program at the School of Medicine and lead author of the study, says the findings suggest that using the medication as a routine sleeping aid and for other reasons should be discouraged. Diphenhydramine, commonly given for allergic conditions and as a sleeping aid, is available over-the-counter under several brand names, including Benadryl and Sominex. It is also a component in a variety of cold remedies and allergy and insomnia medications.
Agostini and his team followed 426 patients age 70 or older during their hospitalization in an academic medical center, and used detailed daily interviews and measurements to assess their mental status. They found that over one-quarter of the patients were given diphenhydramine during their hospital stays, 68% of the time to help the patient sleep and 21% of the time to decrease the risk of an allergic reaction when a patient was to receive a blood transfusion.
Diphenhydramine was also associated with longer hospital stays and an increased risk of having a bladder catheter inserted, increasing the risk of a urinary tract infection, the study found. "[Diphenhydramine's] role is very limited in the care of most older patients, who may experience more harm than benefit when given the medication," Agostini says. (Archives of Internal Medicine, Sept. 24.)
Giving blood transfusions to anemic heart attack patients significantly improves the survival rate for that group, Yale and other researchers report.
The study looked at 78,974 patients in the United States age 65 or older who were hospitalized with acute myocardial infarction (heart attack) between January 1994 and February 1995. The authors found that mortality rates were more than doubled in the most severely anemic patients compared with patients who were not anemic. Despite this higher mortality risk, less than one-quarter of the patients with clinically significant anemia received blood transfusions, says principal investigator Dr. Harlan M. Krumholz, associate professor of medicine in the Departments of Medicine and Epidemiology and Public Health.
"Surprisingly, we found that 43.4% of elderly patients hospitalized with a heart attack are anemic, or have a blood count below 39% at the time of admission," adds Saif Rathore, a lecturer in the Department of Medicine and a coauthor of the study.
"These data underscore the importance of investigating the unique challenges of heart disease in elderly patients, particularly given the demographic changes in our nation's population," Krumholz says. "Conditions such as anemia and appropriate treatments for these conditions, such as blood transfusion, require specific evaluation in elderly patients because of the many factors that guide treatment in this population." (New England Journal of Medicine, Oct. 25.)
Male gamblers are more likely than female gamblers to report addictive behavior related to strategic or "face-to-face" forms of gambling such as blackjack or poker, Yale researchers have found.
Their study also showed that female gamblers are more likely to report problems with nonstrategic, less interpersonal forms of gambling, such as slot machines or bingo. The difference observed in the study could lead to more targeted treatments for gambling addiction based on gender, says Dr. Marc N. Potenza, assistant professor of psychiatry and director of the Problem Gambling Clinic at Yale, who is the study's lead investigator.
The researchers examined the characteristics of male and female gamblers who called the Connecticut Council on Gambling's helpline in 1998 and 1999. Of the 562 calls used in the analyses, about 62% were from male callers and 38% were from female callers. Gender-related differences were observed in reporting patterns of gambling, gambling-related problems such as borrowing and indebtedness, legal situations, suicidal thoughts and acts, and mental health difficulties. In addition, the study found that female gamblers were more likely to report receiving nongambling-related mental health treatment, and male gamblers were more likely to report a drug problem or an arrest related to gambling. High rates of debt and psychiatric symptoms related to gambling, including anxiety and depression, were observed in both groups.
These gender-related differences in gamblers, says Potenza, demonstrate "that new strategies may be necessary to maximize treatment efficacy for men and women with gambling problems." (The American Journal of Psychiatry, September.)
Yale is one of 11 universities across the country participating in the first national study to determine the most effective current treatments for alcoholism by evaluating various combinations of counseling and medications.
The Combining Medications and Behavioral Interventions (COMBINE) study was launched in January by the National Institute on Alcohol Abuse and Alcoholism, which is part of the National Institutes of Health. It is the first national study to evaluate the effectiveness of behavioral treatments alone and in combination with medications.
"COMBINE will explore whether treatment effectiveness is improved by pairing a medication that reduces
the risk of any drinking with one that reduces the risk of heavy drinking," explains Stephanie O'Malley, professor
of psychiatry and principal investigator at the Yale COMBINE site. "We are optimistic because the study begins at a time when advances in genetics, neuroscience and treatment research are paving the way for new alcoholism treatment."
Study participants will receive either counseling or a combination of counseling and one or more medications or a placebo. The behavioral therapies and medications being tested in COMBINE are expected to complement and possibly enhance one another.
A study by Yale researchers shows that gamma-delta
T cells, a special kind of white blood cell found in the skin, are critical in the defense against skin cancer development.
The Yale team, including colleagues at Guy's King's St. Thomas Medical College in London, also found that when T cells of the alpha-beta type are selectively reduced, tumor growth is also reduced, paving the way for new drug targets for skin cancer treatment.
The study's primary author, Dr. Michael Girardi, assistant professor of dermatology, said the researchers used genetically engineered or "knockout" mice that can't produce gamma-delta T cells, in order to demonstrate the role of these T cells in three different models of skin cancer. In all three models, Girardi and the team found that the absence of gamma-delta T cells resulted in a higher level of skin cancer formation. Paradoxically, they also found that in one model, the presence of alpha-beta T cells actually contributed to skin cancer development and progression. "There appears to be a yin-yang contribution by alpha-beta T cells to skin cancer in that they can act both in the defense against and in the promotion of carcinoma," Girardi says.
The researchers showed that gamma-delta T cells carry out their anti-cancer function by expressing a protein called NKG2d, which can focus in on a molecule called Rae-1, which is expressed by tumor cells. "Gamma-delta T cells play a major role in local immunity and are likely crucial to an early defense against skin cells that have recently transformed to a pre-malignant or malignant state," Girardi explains. (Science, Sept. 21.)
Leptin, a hormone known for its hunger-blocking effect on the brain, operates in a more complex way than previously thought, researchers from Yale and The Vollum Institute report.
The researchers say the findings further an understanding of how the area of the brain known as the hypothalamus regulates food intake and body weight.
Leptin, which exists in the body's fatty tissues, regulates body weight, promotes satiety, decreases appetite, decreases the degree to which the body synthesizes fat and increases the body's ability to burn fat. It may also play a role in diabetic eye disease.
The study explored what mechanism leptin uses to regulate brain circuitry, which in turn regulates food intake and energy expenditure. The researchers used genetically altered mice to select, record and label the particular neurotransmitter systems in the hypothalamus that are responsible for food intake and body weight regulation.
"For the first time, we've shown that leptin does not work like a traditional hormone and affects the brain in more complex ways than a simple hormone does," says Tamas Horvath, associate professor of obstetrics and gynecology and neurobiology, who is an author on the study. (Nature, May 24.)
T H I S
Bulletin Home
High-risk behaviors are
associated with teen suicide
Vouchers help drug addicts
to stick with treatment
Herb effectively treats
headache, inflammation
Method helps identify
infectious illnesses
Study aims to improve treatment
for menstrual disorders
Protein may have role
in development of diabetes
Topical estrogen relives painful
symptom of menopause
Primary physicians can effectively
administer methadone treatment
Homeless fare better
in certain kinds of towns
Many elderly do not seek medical
care for illness/injury
Trust plays a role in HIV therapy
Frequently prescribed medication increases mental instability
Blood transfusions help anemic
heart attack patients
Males more likely to be addicted
to 'face-to-face' gambling
National study to investigate
alcoholism treatments
Type of T cells help defend
against skin cancer
Hormone leptin has complex
effects on the brain
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Campus Notes
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