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NIH
funds $5.6 million center for PKD research
A five-year,
$5.6 million grant awarded by the National Institutes of Health
has established Yale as one of four centers of excellence for
the study of a kidney disorder that is the nation’s most
common life-threatening genetic disease. The new center brings
together investigators from several departments to focus on polycystic
kidney disease (PKD). Plans also are in the works to add a clinical
component to speed translation of research discoveries into treatment
advances.
Although not
all people with the disease are aware of the diagnosis, PKD is
believed to affect some 600,000 Americans. The inherited disorder
causes cysts to develop in the kidneys, interfering in their
normal functioning and frequently resulting in the need for dialysis
or transplantation. There is no treatment or cure for the disease,
which results in about 1,000 deaths each year due to kidney failure.
According to nephrologist Stefan Somlo, M.D., associate professor
of medicine and genetics and head of the center, “We’re
now able to bring in new investigators and new approaches to
study a disease for which there are currently no specific treatments.”
When it opens, the clinical center “will take advantage
of the basic-science expertise here and make it more accessible
for patients.”
Yale has long
been active in PKD research. In 1996 Somlo and colleagues discovered
PKD2, which is one of the two genes known to cause the disease.
The other is PKD1. In January, Somlo and colleagues published
findings in Nature Genetics about some of the previously
unknown normal functions of PKD2. “We know that loss of
function of either PKD1 or PKD2 causes the disease,” he
said. “We don’t know what the genes’ normal functions
are, but we’re getting much further along.” By understanding
those functions, new avenues for treatment, prevention and, perhaps,
a cure for PKD may emerge. |
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Mental
illness a barrier
to cardiac care
In a first-ever
study of the role mental illness plays in cardiovascular care,
a team of Yale psychiatric and public health experts found that
mentally ill patients receive significantly fewer cardiovascular
procedures following a heart attack than other patients. Previous
studies have shown that race and gender are important factors
in the treatment of cardiovascular patients, but this is the
first study to show that mental health also plays an important
role in cardiovascular care unrelated to the patient’s other
health and social issues.
The study’s
findings, which appeared in the January 26 issue of the Journal
of the American Medical Association, showed that a mental
disorder reduces a patient’s chances of receiving otherwise
standard cardiovascular procedures, including angioplasty, coronary-bypass
surgery, and cardiac catheterization, by up to 32 percent. According
to the director of the study, Benjamin G. Druss, M.D., M.P.H.
’95, assistant professor of psychiatry and of public health,
“It’s analogous to findings in the race and gender
literature about differences in practices. This difference in
care was not based on the severity of cardiac illness, or socioeconomic,
hospital or regional differences between groups.” The study
looked at a range of serious mental disorders, including schizophrenia,
anxiety, depression and substance abuse. “We saw a similar
pattern across the spectrum,” said Druss.
The causes for
the differences in care are not entirely clear. “It’s
complicated,” said Druss. “Our best guess is that it’s
something going on at the level of the patient-provider interaction.
There’s obviously something going on that merits a closer
look, and efforts should be made to raise patients’ and
physicians’ consciousness about the issue.”
Druss is now
leading follow-up studies looking into longer-term outcomes and
quality of care for patients with mental illness and ways of
overcoming barriers to their care. |
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Anti-cocaine
vaccine
passes first hurdle
Most of the
900,000 cocaine abusers who seek treatment for their addiction
each year in the United States eventually find their need for
the drug irresistible and begin to use it again. An experimental
vaccine designed to suppress the high that users get from taking
cocaine may one day prove a tool for reducing that relapse rate.
A Yale clinical study of the vaccine, TA-CD, found that it produced
cocaine antibodies that could potentially keep the drug from
reaching the brain and inhibit its effect.
Thomas R. Kosten,
M.D., HS ’81, professor of psychiatry and chief of psychiatry
of the VA Connecticut Healthcare System, and his team administered
the vaccine to 34 cocaine abusers who had three- to 10-year cocaine
habits and were living in a residential treatment facility. Supported
by the National Institute on Drug Abuse, the study showed that
TA-CD generated drug-specific antibodies, which bind to cocaine
and may prevent it from traveling through the bloodstream to
the brain, neutralizing its psychoactive effect. The vaccine’s
effectiveness in producing cocaine antibodies persisted throughout
the trial.
“The vaccine
is very safe, and we did not observe any major side effects,”
said Kosten. “TA-CD offers the potential for a completely
new and highly viable approach to a very serious problem for
which there are no alternative medication therapies available.
But we just don’t know yet about its benefits for preventing
cocaine relapse.” |
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Stress
worsens arrhythmias, increasing risk of sudden death
Stress is as
much a part of daily life as traffic jams and taxes. For those
susceptible to arrhythmia, an abnormal heart rhythm, psychological
stress can be especially dangerous because according to a Yale
study, it alters the characteristics of the arrhythmias, making
them potentially deadly.
The study sought
to explore how mental duress affects the hearts of patients with
implantable cardioverter-defibrillators. Using a programmed stimulation
system, the researchers triggered arrhythmias as part of routine
testing of the defibrillators. Then they induced mental stress
by asking the patients to discuss upsetting or frustrating situations
and by grilling them with rapid-fire arithmetic problems, again
triggering arrhythmias with programmed stimulation. The results,
published in the January 18 issue of Circulation, a journal
of the American Heart Association, showed that not only did programmed
stimulation during mental stress induce faster arrhythmias than
those induced during rest, but these arrhythmias were also more
difficult to terminate.
According to
cardiologist Rachel J. Lampert, M.D., assistant professor of
medicine and the study’s principal investigator, “This
shows that mental stress situations that raise adrenaline levels
alter the behavior of arrhythmic circuits, making them potentially
more deadly.” Lampert hopes to develop preventive therapies
and prognostic tools for at-risk patients. “For people with
arrhythmias,” she said, “interventions aimed at blocking
responses to stress may be helpful.” |
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Rate
of tick-borne disease
higher than suspected
Ehrlichiosis,
a disease carried by the same tick that transmits Lyme disease,
is occurring at much higher rates than previously suspected.
A three-year surveillance study of southeastern Connecticut residents
found annual rates of ehrlichiosis ranging from 24 to 51 cases
per 100,000 inhabitants. As happened with Lyme disease after
it was first described by Yale scientists in the mid-1970s, rates
of reporting of ehrlichiosis are expected to rise rapidly. The
annual rate of Lyme disease in the same survey area is 300 cases
per 100,000 persons, up from the 50 cases per 100,000 people
in the 1970s, according to associate research scientist Jacob
IJdo, M.D., who was the lead author of the study. |
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Conventional
Lyme treatment
found effective
Patients who
undergo conventional antimicrobial treatment for Lyme disease
report no greater level of health problems years later than comparable
groups who did not have the disease, according to the largest
study to date of long-term effects of the disease. “The
outcomes of the vast majority of patients with Lyme disease were
excellent and not much different from those who had not had the
condition,” said one of the study’s authors, Eugene
D. Shapiro, M.D., professor of pediatrics and of epidemiology.
As reported
in the February 2 issue of the Journal of the American Medical
Association, the study looked at 678 patients. “The
degree of anxiety about Lyme disease that many people have doesn’t
appear to be justified, given the positive, long-term outcomes
of treated patients that we have observed,” said Shapiro.
“The prognosis for the vast majority of Lyme disease patients
who receive conventional antibiotic treatment is excellent.”
Lyme disease
has been a lightning rod for controversy for years, with a vocal
group of patients and some physicians insisting that the disease
is underdiagnosed and undertreated. Many physicians, however,
counter that a short-term regimen of antibiotics is adequate
to treat the disease. |
