Jewish World Review June 20, 2003 / 20 Sivan, 5763
By Robert A. Wascher, M.D., F.A.C.S.
http://www.NewsAndOpinion.com |
Alzheimer's Disease (AD) and other causes of dementia in later life are
growing problems in our aging population. Over the past half century, many
of the most common causes of premature death have been, if not eliminated,
then at least markedly reduced. Infections, lung disease, cardiovascular
disease and many cancers are now far less frequent causes of death, and the
average lifespan of people living in the industrialized world continues to
increase.
Unfortunately, we have been less successful in preventing or
effectively treating diseases of the aging brain. (Improvements in the
control of hypertension and cardiovascular disease have somewhat reduced the
risk of developing so-called vascular dementia, which develops following a
series of mini-strokes that cumulatively result in progressive cognitive
decline and dementia.) Since the much publicized revelation of the Reagan
family that our 40th President was suffering from AD, funding for AD
research has increased dramatically. However, despite extensive ongoing
research into the causes of AD, we are still only beginning to understand
the biological underpinnings of this devastating disease. At the present
time, there are no good therapies for AD. Even estrogen/progestin hormone
replacement therapy, which was once thought to reduce the risk of AD, now
appears more likely to increase the risk of dementia with long-term use.
Several previous studies have suggested that the aging brain responds well
to continued stimulation, and that "exercising" your squash in your later
years may at least mildly reduce your risk of developing dementia. However,
as is frequently the case, other similar studies have not been able to
reproduce this finding. A new study in this week's New England Journal of
Medicine looked at 469 volunteers who were all older than 79 years of age.
All study volunteers lived in their own homes, none of the study
participants had any clinical evidence of dementia at the onset of the
study. Over the course of this 5-year study, 146 study participants
developed dementia (AD in 61 subjects, vascular dementia in another 30
volunteers, and other types of dementia in 8 other subjects). When the
study's authors looked at the leisure activities of the study volunteers,
they found that reading, playing board games, playing musical instruments,
and dancing were all associated with a significant reduction in the risk of
developing dementia. However, the overall level of physical activity did
not appear to affect the risk of developing dementia. Thus, this study
appears to confirm previous animal and human studies that show a reduction
in dementia associated with frequent involvement in cognitively challenging
leisure activities later in life (who would've thought that dancing would be
identified as a cognitively challenging leisure activity...?). These
results are also in line with animal research, dating back to the 1960s,
that revealed an increase in the complexity of neuronal circuitry in the
brain, and overall brain size, in animals that were placed in environments
that provided cognitively stimulating recreational activities. More
recently, this phenomenon has also been confirmed to occur in the brains of
older animals as well.
The old maxim, "use it or lose it," appears to apply to the brain as much as
it does to any other organ of the body. Perhaps board game manufacturers
will take a page from the food industry's recent habit of placing pro-health
statements on containers of oatmeal and orange juice, among other food
products:
"Playing this game may reduce your risks of developing Alzheimer's Disease
or other causes of dementia."
NEW MRI DETECTS TINY PROSTATE CANCER LYMPH NODE METASTASES
The current generation of CT and MRI scanners are able to detect clusters of
tumor cells measuring about 5 to 10 millimeters in diameter, or about
two-tenths to four-tenths of an inch. By the time a 10 millimeter (1
centimeter) tumor has formed, however, approximately 1 billion cells are
already present. Thus, even the most sensitive scanners are still
relatively crude instruments for detecting tumors cells at the earliest
stages of cancer. In my own area of research, we are working with powerful
diagnostic tests that amplify, hundreds of thousands of times, the genetic
material of occult tumor cells floating unseen in the blood, bone marrow and
lymph nodes of patients with cancer. Using this RT-PCR technique, we can
identify the presence of a single tumor cell floating in a sea of more than
a million normal surrounding cells. However, RT-PCR is expensive,
time-consuming, and requires a huge investment in equipment and highly
trained personnel.
A new method of performing MRI scans may now significantly increase the
ability of physicians to detect very small clumps of tumor cells in the
lymph nodes of patients with prostate cancer, and perhaps with other cancers
as well. Unlike CT (Computed Tomography) scans, which use x-rays, MRI
(Magnetic Resonance Imaging) relies upon a powerful magnetic field to
slightly and reversibly alter the atoms of our bodies, resulting in
exquisitely detailed anatomic images. Currently, the element Gadolinium is
injected into patients undergoing MRI cancer imaging, resulting in improved
image quality and resolution. However, as I've already mentioned,
conventional Gadolinium-enhanced MRI scans have a maximum resolution of only
5 to 10 millimeters. A high-resolution MRI scanner has recently been
developed to take advantage of a newly developed image enhancer known as
lymphotropic superparamagnetic nanoparticles. (Drop that mouthful at your
next cocktail party!) These iron-based nanoparticles are extremely fine,
and are injected into the bloodstream. Unlike other MRI enhancing agents
that are too large to filter into and through the body's lymph nodes, the
nanoparticles are able to freely permeate lymph nodes and, in the process,
dramatically improve the MRI scanner's ability to detect tiny deposits of
tumor cells within the nodes.
A new study that employed nanoparticle-enhanced MRI to evaluate 80 patients
with prostate cancer is being reported in the current issue of the New
England Journal of Medicine. All patients underwent enhanced MRI scans,
both with and without nanoparticles, prior to undergoing surgery for their
cancers. The results of the preoperative MRI scans were then compared to
the pathologists' findings after surgery. A total of 334 lymph nodes were
recovered from the 80 patients during their operations, and 63 of these
lymph nodes, from 33 patients (41%), were positive under the microscope for
involvement with tumor cells. Using conventional MRI scanning techniques,
45 (71%) of these 63 histopathologically-positive lymph nodes were abnormal
on the preoperative MRI scans . However, the nanoparticle-enhanced
preoperative MRI confirmed the presence of metastatic tumor in the lymph
nodes of all 33 patients who were subsequently confirmed, postoperatively,
to have tumor spread to their lymph nodes. When the study's authors
analyzed all 334 lymph nodes recovered from the 80 patients during surgery,
they found that the nanoparticle-enhanced MRI scans picked-up a rather
amazing 90.5% of all tumor-involved lymph nodes, whereas the conventional
MRI scans picked up only 35.4% of involved nodes. These are very impressive
results, and may allow physicians to more accurately stage their patients'
cancers before the patients go to the operating room. This knowledge, in
many cases, might alter patient care plans by identifying those patients who
might benefit from chemotherapy, radiation, or other so-called adjuvant
treatments prior to undergoing surgery. Additional study of this new MRI
technology should also be directed at other types of tumors that have a
propensity to spread through the lymph nodes, including cancers of the lung,
breast, colon, stomach, pancreas; and melanomas and lymphomas, to name a
few.
SOY INTAKE & BREAST CANCER RISK IN JAPAN
The role of isoflavones, soy-derived compounds, in cancer prevention is
unclear at this time. There are good research data that support both a
positive and a negative impact of isoflavones on the risk of developing
breast cancer. Some of the more recent research, including studies
performed recently in the laboratory of the "other Dr. Wascher" (my lovely
wife), suggest a dose-dependant effect of isoflavones on breast cancer risk.
Very high doses of soy-derived isoflavones in the laboratory appear to
stimulate normal breast cells to divide excessively, which increases the
risk for cancer development. On the other hand, lower doses of isoflavones
in the lab appear to have a potentially protective effect on breast cell
proliferation. Unfortunately, the jury is still out on the clinically
relevant effects of dietary soy products on breast cancer risk in human
beings (often, what happens to a culture of a single type of cells in the
laboratory does not accurately reflect the more complex biology of a living
human being).
The proposed breast-protective effects of dietary soy were originally based
upon the purely anecdotal observation that Japanese women living in their
native country experienced a much lower incidence of breast cancer than
American women. The dietary soy intake among Japanese living in Japan is
indeed considerably higher than is found in the typical American diet. When
you look at the breast cancer incidence among Japanese women who emigrate to
the United States, the protective effect of being a Japanese woman in Japan
is gradually lost after relocation to the US, and continues to decline over
time. Moreover, the American-born daughters of Japanese immigrants have
breast cancer rates that approximate those of other American-born women
without a Japanese heritage. However, no solid research evidence has yet
been presented that elevates this conjectural linkage between dietary soy in
Japan and breast cancer risk to the level scientific fact. A new study in
the current issue of the Journal of the National Cancer Institute attempts
to clarify this soy/breast cancer debate.
In this Japan Public Health Center prospective study, 21,852 Japanese women
(aged 40 to 59 years) completed a questionnaire that included detailed
questions about dietary soy intake. During the 9-year course of the study,
179 of the study participants were diagnosed with breast cancer. The
study's authors then analyzed the self-reported dietary intake of miso soup
(a soy-derived food that contains high levels of isoflavones) and other
soy-rich foods, comparing the soy, isoflavone and miso soup intakes of
patients who developed breast cancer with those of volunteers who did not
develop breast cancer. The study found that women who reported the highest
frequency of miso soup in their diets, and the highest intake of isoflavones
in general, experienced a reduction in the risk of breast cancer by as much
as 54% (relative risk). Interestingly, high levels of foods containing
soybeans did not appear to decrease the risk of developing breast cancer.
Thus, this large-scale prospective study does appear to give some validity
to the proposed breast cancer reduction properties of dietary isoflavones,
including those found in miso soup. Now, if someone could make tofu
actually taste good, that would be a true miracle...
PROZAC & PREMATURE EJACULATION
Unfortunately, the tender sexual psyche of most of us men can
render this problem a source of major anxiety and concern. In addition to
the traditional desensitizing methods first popularized by Masters &
Johnson, the antidepressant drug Prozac has recently been advocated to
treat PE. (Prozac, it seems, can improve almost any medical disease or
condition....)
In the current issue of the Journal of Urology, the standard 20 mg per day
dose of Prozac was compared to a single weekly 90 mg dose for patients
suffering from PE. All patients were first evaluated to exclude physical
causes of PE, such as diabetes and cardiovascular disease. Eighty
volunteers with an average age of 36 years were randomized into two groups:
20 mg of Prozac each day versus 90 mg per week. The average time to
ejaculation was assessed for all patients at the beginning of the study, and
again, 3 months later, at the conclusion of the study. The average time to
ejaculation prior to beginning Prozac therapy was about 30 seconds for the
80 study participants. After 3 months of either daily or weekly Prozac
therapy, the average time to ejaculation increased to 3.37 and 3.57 minutes,
respectively. Partner satisfaction and time-to-ejaculation tended to be
superior with the 90 mg per week dose, although this trend was not
statistically significant. Nausea, insomnia and headache were the most
commonly reported side effects, but did not vary between the two treatment
groups.
Thus, this study shows that a single weekly dose of 90 mg of Prozac was as
effective in treating PE as a 20 mg daily dose, and without any observed
difference in side effects profiles as well. I find this to be an
interesting application of Prozac, the granddaddy of the selective seretonin
uptake inhibitor (SSRI) class of antidepressants. Ironically, one of the
most common reasons that patients discontinue SSRI drugs is because of
reduced libido and difficulty in obtaining erections. However, the
anxiety-reducing effects of Prozac appear to provide therapeutic benefit to
patients with PE that compensates for any potentially detrimental effects on
sexual function that are known to be associated with this medication.
JWR contributor Dr. Robert A. Wascher is a senior research fellow in molecular & surgical oncology at
the John Wayne Cancer Institute in Santa Monica, CA.
Comment by clicking here.
Leisure activities & the risk of dementia
Quite apart from the amusing depictions of premature ejaculation (PE) in
teen-themed movies, PE is a condition that causes considerable distress to
many men and their partners, and is the most commonly diagnosed male sexual
dysfunction (poor libido is the most common dysfunction diagnosed in women).
The incidence of premature ejaculation among men aged 18 to 59 years has
been estimated to be approximately 20% (Journal of the American Medical
Association, 1992), although the definition of PE is subjective and somewhat
arbitrary.
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