New
Drug for Irritable Bowel Syndrome
The chronic,
recurring symptoms of irritable bowel syndrome (IBS) range from
mild to intense abdominal cramping and from diarrhea to constipation.
When a person experiences diarrhea or constipation 75% of the
time, the disorder is considered "diarrhea-predominant" or "constipation-predominant,"
respectively. When a person experiences bowel movements fluctuating
between diarrhea and constipation, his or her disorder is considered
"alternating IBS." The cause of IBS is unclear, and
right now there is no cure. Patients may be able to alleviate
their symptoms by taking certain dietary measures or prescription
drugs that treat individual symptoms.
In an effort to treat the diarrhea of IBS, a new drug does
the job, but sometimes a little too well. In a study of how
the drug alosetron affects patients suffering from diarrhea-predominant
IBS, results showed that alosetron significantly improved multiple
symptoms of the disorder, but these improvements were gained
in exchange for an increased rate of constipation.
Past studies have demonstrated that drugs that increase the
threshold for sensation and discomfort in the abdomen are beneficial
in treating IBS. Researchers compared the effects of alosetron,
a drug belonging to this class, to the effects of a placebo
on women suffering from diarrhea-predominant or alternating
IBS. They assessed whether the drug, taken twice a day, provided
relief from the pain associated with IBS, and improved bowel
functions. For the duration of the 12-week study, 41% of the
women taking alosetron reported adequate relief of symptoms,
compared with only 29% of the women taking the placebo drug.
Alosetron treated the pain associated with diarrhea-predominant
IBS but not alternating IBS. The drug did, however, improve
the three most bothersome symptoms (urgency, stool frequency,
and stool consistency) for both subtypes of IBS tested.
While alosetron was effective at relieving diarrhea, 30% of
the women taking the drug reported experiencing constipation
compared with only 3% of the women taking the placebo. The
researchers anticipated constipation as a possible consequence
of the treatment but did not believe it was necessarily a bad
thing. Despite the discomfort of constipation, most patients
remained in the study although laxatives were not permitted.
Alosetron has been approved by the FDA but exactly how best
to utilize it in the treatment of IBS will be better understood
over time. For example, researchers still need to complete
testing of alosetron in men, compare it to other drugs and
diet changes, and determine the cost effectiveness of the treatment.
Back
to Top
High
Blood Pressure Drugs and Diabetes Risk
Past studies
have suggested that two types of drugs used to treat high blood
pressure also promote the development of type 2 diabetes. These
results led doctors to think twice about prescribing thiazide
diuretics and beta blockers to their patients at high risk for
diabetes. But a new, extensive study shows thiazide diuretics
do not appear to increase the risk of diabetes, while beta blockers
may contribute. The data also suggest that perhaps the risk of
developing type 2 diabetes is associated with high blood pressure
itself, and not the medications used to treat it.
Thiazide diuretics and beta blockers are the first line of
treatment for most people with high blood pressure. Both therapies
reduce the risk for strokes and heart attacks and have been
shown to help people with high blood pressure live longer.
Thiazide diuretics such as hydrochlorothiazide and chlorthalidone
decrease blood pressure by reducing the volume of fluid in
the body. Beta blockers such as propanolol and atenolol decrease
blood pressure by blocking the nervous system’s response
to stress and thereby relaxing the heart muscle. Earlier studies
suggested that both drug classes might affect glucose tolerance
and lead to diabetes, but a more recent study suggests something
different..
To determine the relationship between the use of antihypertensive
medications and the risk of developing diabetes, researchers
in the U.S. followed 12,550 nondiabetic adults. They evaluated
3,804 hypertensive and 8,746 nonhypertensive patients for signs
of diabetes three and six years later. Results showed that
adults with high blood pressure (treated or untreated) were
2.5 times more likely to develop diabetes than were adults
without hypertension. The scientists also analyzed the
results by medication. The risk of developing diabetes was
28% greater for patients taking beta blockers than for patients
taking no medication, regardless of hypertension. Patients
taking other drugs to treat their hypertension were not at
an increased risk.
The researchers pointed out that their study was limited by
the lack of information regarding the dosage and duration of
treatment with antihypertensive drugs. In addition to this,
their results may have been affected by the perceived risk
of diabetes and its influence on what drugs doctors prescribe.
But the study was an improvement on past studies that were
smaller and influenced by confounding factors.
In light of the results, doctors can now easily identify a
group of patients at high risk for developing diabetes — tjpse
wjp tale beta blockers — and perhaps help them develop
a prevention program. In addition, physicians should be reassured
about prescribing thiazide diuretics. The study investigators
noted that despite the apparent increase in risk for diabetes
associated with beta blockers, these drugs do have proven benefits
for people with heart disease, and that a careful weighing
of the potential risks against known benefits is important.
Back
to Top
Reducing
Atrial Fibrillation Episodes
Atrial fibrillation occurs when the upper chambers of the heart,
the atria, quiver and beat irregularly. The intermittent, or
sometimes persistent, palpitations can be disabling and render
the heartbeat less efficient. During fibrillation blood pools
in the atria because the heart is not pumping effectively.
Clots may form in stagnant blood and may break loose into the
circulation. A clot can clog a blood vessel, blocking the blood
flow to parts of the body. If the clot blocks an artery in
the brain, the result is an ischemic stroke. Atrial fibrillation
quintuples the risk of stroke.
To improve symptoms and reduce stroke risk, doctors may try
to restore the normal rhythm of the heart. This can be done
through electrical cardioversion or through the use of certain
medications (although many of these drugs have serious side
effects, including causing new heart rhythm problems). Despite
treatment, atrial fibrillation recurs within six months in
at least half of the patients. Studies suggest that a low-dose
of the drug amiodarone may be more effective than the other
antiarrhythmic drugs in restoring rhythm and preventing episodes
of atrial fibrillation. Amiodarone is currently used primarily
in patients who do not respond to other drugs.
A recent large, randomized study tested the long-term efficacy
of amiodarone in comparison to two other drugs, sotalol and
propafenone. Researchers selected 403 patients who had experienced
an episode of atrial fibrillation lasting at least 10 minutes
within the preceding six months. Half of the patients received
amiodarone, while the other half received either sotalol or
propafenone. By the start of the follow-up period, 21 days
after drug treatment began, a normal heart rhythm had returned
in 93% of the patients taking amiodarone and in 81% of those
taking sotalol or propafenone. Researchers assessed the patients
for a minimum of 12 months and measured the length of time
to a first recurrence of atrial fibrillation. Over a mean of
15 months of follow-up, only 35% of the patients taking amiodarone
had experienced a recurrence of atrial fibrillation compared
with 63% of the patients taking sotalol or propafenone. By
the end of the study period, more than half of the patients
taking amiodarone remained free of a recurrence of atrial fibrillation.
These results indicate that amiodarone is more effective than
sotalol and propafenone at maintaining heart rhythm. But researchers
still need to demonstrate the long-term safety of amiodarone.
Eighteen percent of the patients taking amiodarone discontinued
the medication because of adverse side effects, whereas only
11% of those taking sotalol or propafenone discontinued for
the same reason. Four patients taking amiodarone developed
lung problems, and thyroid disfunction occurred in three patients
taking this drug. A longer study may resolve some of the questions
that remain concerning the balance between the benefit and
toxicity of low doses of amiodarone.
Back
to Top
High-Dose
Chemotherapy and Stem Cell Transplantation for Breast Cancer
Most women with metastatic breast cancer respond to conventional
doses of chemotherapy. 10 years after their disease is detected,
fewer than 5% of these women are still alive. This sobering
statistic was the impetus for research into more effective
treatments. In the late 1980s, initial studies on patients
with metastatic breast cancer treated with high-doses of chemotherapy
and stem cell transplantation yielded some promising results.
Stem cells are the immature cells that form all blood cells.
The therapy involved harvesting and preserving stem cells from
the breast cancer patient prior to treatment with high doses
of chemotherapy (which destroys bone marrow as well as the
cancer cells). Following chemotherapy the stem cells were transplanted
back into the patient. The treatment became popular for women
with metastatic or high-risk breast cancer (which has spread
to the lymph nodes but not other organs), despite the lack
of solid evidence from randomized clinical trials.
Now, results from a clinical trial show that this grueling
therapy does not improve survival in women with metastatic
breast cancer. The study, which began in 1990 in Philadelphia,
compared the effect of high-dose chemotherapy and stem cell
transplantation with conventional doses of chemotherapy. Researchers
initially treated 553 metastatic breast-cancer patients with
standard doses of chemotherapy. The 199 women who responded
to this treatment were then randomly assigned to receive either
the experimental treatment or conventional doses of chemotherapy.
Researchers analyzed each therapy by length of survival, time
to disease progression, and toxic effects.
Women receiving the experimental therapy had a three-year survival
rate of 32%, while women receiving conventional chemotherapy
had a slightly higher three-year survival of 38%. The median
time to disease progression was similar among both groups;
9.6 months for the experimental group and 9.0 months for the
conventional treatment group. These results suggest that high-dose
chemotherapy combined with stem cell transplantation offers
no advantage over conventional therapy in terms of survival
rate and time to progression. Furthermore, the incidence of
serious adverse effects was greater among women treated with
the experimental therapy.
These data contradict a previous study that reported that high-dose
chemotherapy combined with stem cell transplantation significantly
improved the survival of women with high-risk breast cancer.
This was the only randomized study that reported positive results
with the therapy.The study has been discredited due to scientific
misconduct. Researchers also believe that selection bias toward
healthier and younger women may have played a role in the positive
results seen in the initial studies from the 1980s.
Results of further studies on women with metastatic or high-risk
breast cancer may clarify approaches to the most effective
treatment for this disease. For the time being, however, high-dose
chemotherapy with stem-cell transplantation is not recommended
for women with metastatic breast cancer outside of clinical
trials.
Back
to Top
Aspirin
for Preventing Stroke and Other Vascular Problems
An aspirin
a day keeps a stroke away in patients with a history of heart
disease, but a recent review in Archives of Neurology reveals
the drug’s stroke-preventing properties may not extend to
healthy people.
Researchers from the University of Texas Health Science Center
and three other institutions have concluded aspirin does not
reduce the risk of stroke in people without heart disease.
Indeed, their results suggest regular aspirin use might even
slightly increase the risk in people at low risk for vascular
problems. These conclusions were reached after the investigators
performed a meta-analysis on five existing studies examining
the preventive effects of aspirin. (A meta-analysis is a mathematical
method used to compare the results of similar studies.) The
researchers also reviewed four large observational studies
that looked at regular aspirin use and stroke risk in low-risk
individuals.
The five trials used in the meta-analysis involved a total
of 52,251 participants with a mean age of 57 years. Three of
the studies excluded women, though women accounted for roughly
20% of the total number of patients. Three studies used people
at high risk for vascular disease, such as those with high
blood pressure or diabetes, while the other two used healthy
males at low risk. Dosage varied from 75 mg to 650 mg per day.
The mean rate of stroke was 0.3% per year during an average
study period of five years.
The meta-analysis found no significant risk reduction for patients
taking aspirin compared with those taking a placebo. In contrast,
the participants still enjoyed a 26% decrease in heart attack
risk.
The researchers' review of four observational studies found
aspirin modestly increases the risk of bleeding into the brain
in low-risk patients
— such bleeding can cause hemorrhagic stroke. However,
hemorrhagic stroke accounts for only 10—15% of all strokes.
Most strokes are ischemic, meaning they are caused by a temporary
interruption in the blood flow to brain. When the four studies
were pooled, no significant increase in risk of ischemic stroke
was apparent.
The researchers stress that more information is needed before
guidelines regarding stroke risk and aspirin use can be generalized.
Certainly, people with a history of heart disease or whose
risk of a heart attack eclipses their risk of stroke can benefit
from aspirin. However, the majority of the subjects in the
reviewed studies were middle-aged males. Men in this age group
are more likely to suffer heart attacks, not strokes. Women
and the healthy elderly were underrepresented, yet they are
more prone to strokes rather than heart attacks. As a result,
it’s still unclear whether anyone with a low risk of heart
problems should be regularly taking aspirin.
Back
to Top
Less
Painful Newborn Circumcision
Each year, millions of newborn males undergo circumcision.
Their facial expressions and crying indicate that circumcision
causes immense pain, yet many physicians do not administer
anesthesia or pain medication for this procedure. In part,
this is because many doctors are unfamiliar with the use of
such medications in infants and are concerned about possible
side effects.
A number of interventions
can help reduce the pain of circumcision. Dorsal penile nerve
block (DPNB), lidocaine-prilocaine cream (a mixture of local
anesthetics), sucrose, and acetaminophen are each individually
safe and effective but do not completely eliminate pain in
all infants. Another approach is to use the Mogen clamp, which
is associated with less pain than the Gomco clamp.
In an effort to minimize
the pain of circumcision, researchers conducted a study on
86 infant males to assess the efficacy and safety of a combination
of interventions. Fifty-seven infants were circumcised using
the Mogen clamp and a combination of analgesics that included
acetaminophen, lidocaine-prilocaine cream placed on the penis,
gauze embedded with sugar and dipped in grape juice placed
in the mouth, and an injection of DPNB. Researchers videotaped
the infants during the procedure and assessed pain by analyzing
facial activity and the percentage of time spent crying. The
researchers compared the results with data from a previous
study in which 29 infants were circumcised using the Gomco
clamp and lidocaine-prilocaine cream.
Results from this
study suggest that circumcision with the Mogen clamp took less
time than circumcision with the Gomco clamp did (mean time
of 55 seconds compared to 9 minutes, 37 seconds). Infants in
the combination group had less facial activity indicating pain
and cried for a smaller percentage of time than the infants
in the single intervention group did. Furthermore, 46% of the
infants in the combination group did not cry at all during
the procedure and 12% cried less than 10% of the time. Infants
in the combination group did not experience any adverse effects.
Facial activity and crying was not eliminated in all infants
treated with the combination of interventions, yet researchers
do not know if these responses were due to the pain of the
procedure or the discomfort of restraint. This study demonstrates
that circumcision with the Mogen clamp and combined analgesia
is safe, takes less time, and substantially minimizes pain.
Parents of male infants and the physicians performing circumcisions
should consider this approach.
Back
to Top
Carbonated
Beverages and the Risk of Bone Fractures
in Teenaged Girls
Osteoporosis,
or the loss of bone density,
is usually thought of as a geriatric
condition. But the disease may
have its roots in adolescence
as bone mass reaches its peak
level. Factors that affect the
accumulation of bone mass during
this time can increase the risk
of bone fractures and osteoporosis.
In this context, teenaged girls
may be jeopardizing their current
and future health by drinking
too many carbonated beverages.
Past results indicate that
consumption of carbonated beverages
is associated with bone fractures
among teenaged girls. A recent
cross-sectional study involving
460 9th- and 10th-grade girls
confirmed these findings. The
teenagers completed a questionnaire
describing their physical activities
and personal and behavioral
habits. Researchers analyzed
the results to determine an
association between consumption
of carbonated beverages and
bone fractures.
Of the girls surveyed, 80%
drank carbonated beverages,
and nearly two-thirds of the
girls drank cola. One-fifth
of the girls reported having
had bone fractures. Analysis
showed that the risk of bone
fracture in girls who drink
carbonated beverages is three
times that of girls who do
not. The risk is highest, seven
times greater, among
physically active girls who
drink both cola and noncola.
The results suggest a strong
association between consumption
of carbonated beverages and
bone fractures in teenaged
girls, but the researchers
caution that a cause and effect
relationship cannot be assumed.
Despite that, they have a few
theories that may explain the
association. Laboratory research
has shown that the high phosphorous
concentration in cola can cause
bone loss that may lead to
a greater risk of bone fractures.
Another plausible theory is
that the consumption of carbonated
beverages takes the place of
consumption of milk, an important
source of calcium. Low calcium
intake can increase the risk
of osteoporosis. Between 1970
and 1997, the consumption of
carbonated beverages increased
by 118% per capita in the United
States, while milk consumption
declined 23%.
The study, however, did not
include questions concerning
the amounts of milk and carbonated
beverages consumed. Long-term
studies that include these
factors may help to assess
the effect of milk and carbonated
beverage consumption. Also,
the use of bone density measurements
may demonstrate a cause and
effect relationship between
carbonated beverage consumption
and bone fractures. Research
is necessary to determine how
carbonated beverages may lead
to bone fractures among physically
active girls. Despite the need
for further studies, the current
body of evidence suggests that
education on the health impact
of carbonated
beverage consumption may be
a possible way to promote optimal
bone development in teenaged
girls and prevent osteoporosis.
Back
to Top
Caution
Always Key in Using Herbal Medicines
A
recent study published in the New
England Journal of Medicine offers
another important reminder on
careful use of herbal remedies.
This caution is rooted in the
absence of strict pharmaceutical
controls in the manufacture of
such products and how the lack
of these requirements can leave
room for tragic errors.
In the mid-1990s, doctors at
a clinic in Belgium treated
43 patients with end-stage
kidney failure, requiring dialysis
or transplant. Not surprisingly,
these individuals had something
in common in their medical
histories. Between 1990 and
1992, each had used a Chinese
herbal remedy in combination
with two other drugs for weight
loss. The herbal preparation
supposedly contained Stephania
tetrandra and Magnolia
officinalis. But the sudden
appearance of kidney failure
in these patients, caused their
doctors to suspect that the
herb Aristolochia fangchi,
which is poisonous to the kidneys,
had unintentionally been substituted
for S. tetrandra. The
Chinese names for A. fangchi and S.
tetrandra sound similar
and the two are often confused.
Analysis showed that the herbal
remedy did, in fact, contain
aristolochic acids, which are
derived from A. fangchi. Aristolochic
acids cause cancer in rats
and mutations in bacteria and
mammals.
Reports of patients who had
developed urothelial carcinoma
(cancer of the tissues lining
the bladder, ureter, and part
of the kidney), as well as
kidney failure related to the
Chinese herbs, drew concern
among the Belgian doctors.
When one of their patients
also developed this cancer,
the doctors decided that all
patients with end-stage kidney
failure related to the use
of Chinese herbs should be
checked for cancer of these
organs. By removing these organs,
the doctors hoped to prevent
cancer from developing in their
patients. Thirty-nine of the
43 patients agreed to undergo
the preventive surgery. Of
these patients, 46% of them
already had cancerous growths
in the removed tissues. In
addition, 19 of the remaining
21 patients had abnormal growths
in the urinary system. The
investigators also analyzed
DNA samples taken from the
kidneys and ureters of each
patient. The DNA samples for
every patient showed changes
typically found after exposure
to aristolochic acid. The researchers
compared these results to analysis
of DNA samples taken from eight
patients with end-stage kidney
failure unrelated to Chinese
herbs. None of these control
samples showed DNA changes
formed by aristolochic acid.
The doctors calculated the
cumulative dose of the implicated
herb and other treatments for
each patient. They found that
the risk of cancer was related
to the cumulative dose of A.
fangchi. Because many of
the patients had also taken
appetite suppressants as well
as a diuretic, the doctors
noted that these drugs might
enhance the toxicity of aristolochic
acid.
This case study provides strong
evidence suggesting a relationship
between the Chinese herb A.
fangchi and urothelial carcinoma.
While a manufacturing mistake
led to the introduction of
this herb into an herbal preparation
for weight loss, this study
highlights the risks involved
in taking herbal remedies.
There is little control over
the quality of herbal medicines.
This means that the label on
an herbal medicine may not
accurately represent what is
actually in the container,
as was the case with S.
tetrandra. Several countries
have banned the use of herbs
that contain aristolochic acid,
yet Aristolochia is readily
available in the United States
in capsule form.
In the United States, the FDA
does not have the authority
to assess the safety and efficacy
of a dietary supplement before
it reaches the shelves of stores.
The agency is allowed to restrict
a supplement only after it
proves the substance is harmful
as commonly consumed, but there
is no adequate system for reporting
serious side effects associated
with these products. Furthermore,
the FDA does not have any way
of knowing which herbal remedies
contain harmful substances
such as aristolochic acid.
The case of the Chinese herbal
diet pill and its association
with urothelial cancer is just
one of a number of cases that
demonstrate the need for greater
oversight of dietary supplements
and caution in the use of supplements
on the part of consumers.
Back
to Top
