Jewish World Review March 31, 2004 / 9 Nissan, 5764
By Robert A. Wascher, M.D., F.A.C.S.
http://www.NewsAndOpinion.com |
A great deal of research is underway using the class of drugs known as COX-2
(cyclooxygenase-2) inhibitors. These drugs belong to a larger group of
anti-inflammatory drugs known as COX inhibitors, which includes aspirin,
ibuprofen, naproxen, and piroxicam, among others. The COX-2 inhibitors block
the pro-inflammatory effects of one form of the COX enzyme (COX-2), and are
thought to have fewer side-effects than nonspecific COX inhibitors. Celebrex
and Vioxx are the two most frequently prescribed COX-2 inhibitors in the US.
Previous research has shown that the COX-2 enzyme plays an important role in
the development of several cancers, as well as in cardiovascular disease;
and so it is not surprising that COX-2 inhibitors are being evaluated in
clinical trials as potential preventive agents for these diseases. A new
study in the current volume of the journal Circulation looked at the effects
of COX-2 inhibitors in mice with heart failure. The mice were treated with
doxorubicin (a common chemotherapy drug with known cardiac toxicity side
effects) for 6 weeks, and the presence of significant congestive heart
failure (CHF) was subsequently confirmed in all of the animals using
ultrasound. After 6 weeks of doxorubicin treatment, left ventricular
function was assessed in 100 mice (the left ventricle pumps blood throughout
the body, and becomes weakened and less effective after the onset of CHF).
Half of the mice were then placed on a diet that included a COX-2 inhibitor,
and the remaining 50 mice were fed standard mice chow without a COX-2
inhibitor.
Repeat cardiac ultrasound examinations were performed on the mice
every 2 weeks. At 70 days into the study, the left ventricular pumping
efficiency (left ventricular ejection fraction) in the mice fed only
standard mice chow had declined by 29%, while the mice fed chow containing a
COX-2 inhibitor experienced only a 9% decline in ventricular function.
Moreover, while 38% of the mice consuming standard mice chow died during the
course of this study, only 18% of the mice treated with a COX-2 inhibitor
died.
This is a fascinating study with potentially significant implications. An
estimated 4 to 5 million Americans live with failing hearts, and the
incidence of CHF appears to be rising in proportion to our increasing
lifespans. Indeed, the two greatest risk factors for CHF are preexisting
coronary artery disease and advanced age. More than 90% of patients with CHF
have a history of coronary artery disease or/and chronic high blood
pressure. Diabetes is also associated with a higher incidence of CHF, as
well as elevated rates of coronary artery disease and high blood pressure.
In view of the enormous impact of CHF on the health of our aging population,
the findings of this study may prove to be very important indeed. The
results of this study suggest that the development of CHF after an acute
injury to the heart may be markedly attenuated by COX-2 inhibitors. As a
corollary to this finding, the ability of a COX-2 inhibitor to markedly
reduce the incidence of CHF 6 weeks after the initiation of cardiotoxic
treatment with doxorubicin suggests that there is a substantial interval
between the initial cardiac injury and the onset of clinically significant
CHF. I also find the reduction in CHF risk following doxorubicin therapy to
be interesting as a cancer physician, as this drug is commonly used to treat
cancers of the breast, as well as other types of cancers. While the
judicious dosing of doxorubicin rarely results in significant cardiac injury
in patients with healthy hearts, the use of this chemotherapeutic agent is
generally contraindicated in cancer patients with preexisting heart disease.
Thus, this study suggests that the concomitant use of a COX-2 inhibitor with
doxorubicin and related chemotherapy drugs might enable patients with
preexisting heart disease to receive standard chemotherapy regimens. Of
course, this study was performed in mice, and its findings will have to be
confirmed in humans before the routine use of COX-2 inhibitors for CHF
prevention can be recommended. Still, this is a very exciting study, and the
implications of its findings may be very profound, indeed.
IRAQI PHYSICIAN COMPLICITY IN HUMAN RIGHTS ABUSES
Sadly, 71% of the physician respondents reported physician involvement in
torture was a very common occurrence in Saddam Hussein's Iraq. According to
the physicians' surveys, 50% of their physician peers directly participated
in physician-assisted or physician-conducted "nontherapeutic" amputations of
ears, 49% falsified medical records to conceal acts of torture, and 32%
falsified the death certificates of people who died following torture. Not
surprisingly, only a handful of the study's volunteers reported
participation in such activities At the same time, 52% of the surveyed
doctors indicated that physicians taking part in torture-related activities
did so involuntarily, and 93% of the respondents stated that the Iraqi
paramilitary force Fedayeen Saddam was primarily responsible for compelling
physician participation in such activities. Complicit physicians explained
their coerced participation in torture-related activities in terms of fear
for their families' safety, as well as fear of harm to themselves.
Physicians who refused to participate in human rights abuses reported the
subsequent loss of their jobs, imprisonment, or torture, while other
noncompliant physicians simply "disappeared." When asked what could be done
to reduce the potential for future physician involvement in human rights
abuses, 99% of the respondents recommended increased human rights and ethics
training for Iraqi physicians, 97% recommended a tightening of laws
regulating physician behavior, 96% advised that punitive sanctions against
physicians participating in such abuses should be enhanced, and 95% of the
respondents suggested that a mechanism be devised to ensure independence of
physician from state authorities.
While the veracity of these disturbing allegations cannot be independently
verified, they nonetheless suggest at least some significant level of
physician involvement in state-sanctioned torture and other human rights
abuses in Saddam Hussein's Iraq. Previous instances of physician complicity
in human rights abuses are hardly unknown, including large-scale human
experimentation and mass-murder by Nazi and Japanese physicians during World
War II, and the more recent tortures and genocidal actions committed by
Taliban physicians in Afghanistan, and by the Bosnian-Serbian psychiatrist
Radovan Karadzic, all of whom remain at large still. Of course,
physician-murderers are not always involved in state-sanctioned thuggery. In
2000, British physician Harold Shipman was sentenced to 15 concurrent life
sentences after being convicted of murdering an estimated 260 patients over
a period of at least 20 years, making him the most prolific mass-murderer in
British history. (He later committed suicide in his cell in January of this
year.)
Primum non nocerum, or, first do no harm, is a fundamental precept for the
vast majority of physicians throughout the world. However, in the setting of
totalitarian states bent on terrorizing its citizens, history has shown that
some physicians will violate this precept, either willingly or unwillingly,
and sometimes in egregious ways. As a physician, I cannot think of a more
tragic and reprehensible abuse of medical knowledge and training than to use
them to intentionally inflict harm on another human being.
BRIEFLY...
British Medical Journal: A year-long randomized prospective study of 401
chronic and/or migraine headache sufferers in the UK was undertaken to
assess the efficacy of acupuncture as an alternative to standard medical
therapy. The patients who received acupuncture reported fewer and
less-severe headaches than did the patients who received standard medical
therapy. Moreover, the acupuncture-treated patients experienced 22 fewer
days of headaches per year and used 15% less headache medications. Although
not statistically significant, there was also a trend towards fewer visits
to primary care doctors and fewer days of sick-leave taken by the group
receiving acupuncture.
JWR contributor Dr. Robert Wascher is an oncologic surgeon, professor of surgery, oncology research scientist, and author. He lives in Honolulu with his wife and two daughters.
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Anti-inflammatory drugs may help failing hearts; physician complicity in human rights abuses; more
On a somewhat darker note, a report in the current Volume of the Journal of
the American Medical Association (JAMA) assesses the extent of physician
involvement in human rights abuses in Iraq during the regime of Saddam
Hussein. In June and July of 2003, the study's authors surveyed 98 Iraqi
physicians at 3 major hospitals in southern Iraq. These Iraqi doctors
independently completed research surveys, while another group of hospital
directors and physicians underwent more structured interviews. It should be
noted that 88% of the participating physicians were male, and 97% were Shi'a
Muslims (approximately 60% of the Iraqi populace are thought to be Shi'a
Muslims, and this segment of the population was brutally repressed by the
Saddam Hussein regime).
Lancet: A prospective study (1993 to 2000) of 2,298 men presenting to
sexually transmitted disease (STD) clinics in India with non-HIV venereal
diseases evaluated the impact of circumcision on the risk of developing
HIV/AIDS. All of these men were tested for HIV/AIDS, as well as other
non-HIV STDs, on a quarterly basis, and all were free of HIV/AIDS infection
when they entered the study. The men in both groups were closely matched in
terms of sexual behaviors and related risk factors, irrespective of their
circumcision or religious history. Over the duration of the study, the 191
circumcised men were 85% less likely to develop positive blood tests for HIV
when compared to the 2,107 uncircumcised men. However, circumcision appeared
to offer no protection against syphilis, gonorrhea, or genital herpes.