Dear friends,

Along the past years (since 1979), Rashad Internet University has been able to
organize many medical courses preparing to pass many Exams e.g. USMLE (United
States Medical Licensing Exam) And American Board In many specialty e.g.
(anesthesia, neonatology, internal medicine…etc) .
The Egyptian representatives Prima vision comes in continuation to the effort
that has been exerted over the past years.
Venue?
Cairo, Egypt September 18-27, 2006

Who should participate?
Medical students and young doctors who are interested in upgrading their medical
knowledge and who have been involved in medical licenses Exams are all invited.

Why attend?
The Course offers a unique opportunity to get the updated knowledge to get the
degree you seek

How to apply?
Visit our website where you will find a link titled “Registration form”. This
link will take you to the page where you can provide all the needed information
and where you can also select your course
Once you have submitted your registration you will receive an official
invitation letter that will enable you to start your preparations to travel.
This letter will also facilitate the process of obtaining the visa to Egypt from
the nearest Egyptian Embassy to where you live or study.
What are the courses available in Egypt?
USMLE Step 1
USMLE Step 2
USMLE Step 3
Anesthesia Written Board Review
Cases Anesthesia Oral Board Review
Pain Board Review
Internal Medicine Board Review
Neonatology Board Review
Pediatric Board Review
Emergency Medicine Board Review
Advanced Cardiac Life Support
Family Practice Board Review
Critical Care Board Review
Obstetrics and Gynecology Board Review
Physicians Assistant Board Review
What is New in the Practice of Anesthesia?
The Business Course for Anesthesiologists
The Business Course for Physicians
Visit our web site to find details about each courses www.Prima-vision.com
Courses Fee
Each course has its fees. Contact us for the course details
This fee covers your participation and the certificate of attendance.

Official Language
The official language is English.
As part of our strategy aiming at widespread of the Rashad University medical
courses In Egypt, I am kindly asking you to forward this "Announcement" e-mail
to all interested medical students and doctors in your countries and to medical
e-mail servers you might have subscription to.

Your help is crucial and will be highly appreciated.

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In a general population aged 85 and older, low systolic blood
pressure (SBP below 140 mmHg) is associated with increased
mortality, Finnish researchers report.

"The biological reasons for the association need to be examined in
further studies," Dr. Tuula Pirttil told Reuters Health. "It is
possible that low blood pressure was a sign of decreased vitality
and poor health in some subjects, but this is not the whole
explanation."

Dr. Pirttil, from Kuopio University Hospital in Finland, and
colleagues studied the association between BP and mortality in 521
residents of the city of Vantaa who were 85 years of age or older in
1991. During 9 years of follow up, 479 died.

After adjusting for age, sex, functional status, dementia, cancer,
and cardiovascular disease, there was a strong link between low SBP
and all-cause mortality, the team reports in the June Journal of the
American Geriatrics Society.

The hazard ratio for death was highest in individuals with SPB less
than 140 mmHg (HR = 1.35) and there was a non-statistically
significant trend toward lower mortality in individuals with SBP of
160 mmHg or greater (HR = 0.97).

These findings have two important messages for clinicians, Dr.
Pirttil told Reuters Health. First, "an individual aged 85 or older
with low blood pressure should be examined carefully since low blood
pressure may a sign of treatment-demanding conditions," said Dr.
Pirttil.

Second, the effects of treating hypertension, and thus lowering
blood pressure, need to be examined separately in the very old.
Antihypertensive treatment trials that have been performed
in "considerably younger subjects can not be generalized for this
group," Dr. Pirttil warned.

"Sufficiently high BP may be necessary to guarantee adequate cardiac
and cerebral perfusion," the investigators offer.

Ongoing clinical trials will hopefully point to the best way to
treat hypertension in the very old, Dr. Pirttil concluded.

J Am Geriatr Soc 2006;54:912-914

Patients found to have small aneurysms that are not amenable to
surgical treatment experience no major psychosocial consequences,
according to a report in the June issue of the Journal of Neurology,
Neurosurgery, and Psychiatry.

Patients who survive subarachnoid hemorrhage (SAH) may be at risk of
developing new aneurysms at other sites, the authors explain, but
very small aneurysms may be left untreated because the surgical risk
outweighs the potential benefit.

Dr. Irene C. van der Schaaf from University Medical Centre Utrecht,
Utrecht, the Netherlands and colleagues assessed the quality of life
and symptoms of anxiety and depression in 35 patients with a
previous episode of SAH who were found to have small, untreatable
aneurysms on follow-up screening.

Quality of life scores were consistently, but not significantly,
lower among the 35 patients than among 34 controls who were found to
be free of aneurysms on screening, the authors report.

Similarly, the mean anxiety subscore was 5.4 for the patients and
3.9 for the controls (a nonsignificant difference), the results
indicate, and the mean depression subscore was also not
significantly different at 5.9 for the patients and 5.7 for the
controls.

Anxiety and depression scores were each in the pathological range in
four patients, the researchers note, but none of the controls had
pathological anxiety or depression scores.

The two groups did not differ significantly in negative changes in
social circumstances, fear in daily activities, denial of insurance,
or regrets over participation in the screening program.

More patients than controls changed to a healthier lifestyle, the
report indicates.

"Finding an aneurysm in screening for new aneurysms years after SAH,
but not treating this aneurysm has no major or moderate impact on
quality of life, mood, and psychosocial functioning on group level,"
the investigators conclude. "However, minor effects on individual
level cannot be excluded by our study. Therefore, extra attention
should be paid to the psychosocial status of these patients."

"In spite of limited generalizability and the lack of statistical
significance, the merits of this study are that patient relevant
outcomes are being investigated in addition to neurosurgical risk
assessment," writes Dr. Michael Brainin from Donau-Universitat
Krems, Austria in a related editorial. "Future studies on outcome
will have to include patients' preferences when reporting such
cases."

J Neurol Neurosurg Psychiatry 2006;77:748-752,713

In general, people with diabetes have about the same risk of
cardiovascular disease (CVD) as that of people who are 15 years
older without diabetes, Canadian investigators report. However,
until about age 40, diabetics do not seem to be at high risk of CVD.

Clinicians often believe that all adults with diabetes have a higher
risk of CVD, regardless of age, Dr. Gillian L. Booth and associates
note in the July 1st issue of The Lancet. Some guidelines suggest
that all adults with diabetes be treated the same -- with lipid-
lowering therapy, aspirin, and angiotensin-converting-enzyme
inhibitors -- to reduce their CVD risk.

To clarify the relation between age and CVD risk in diabetics, Dr.
Booth, an endocrinologist at St. Michael's Hospital in Toronto, and
associates conducted a population-based cohort study using Ontario
resident databases covering all individuals age 20 years and older
in April of 1994.

On that date, 379,003 were identified as diabetics and 9,018,082
were nondiabetic. During follow-up until March 2000, acute MI,
stroke, revascularization, or death had occurred in 573,515
individuals, including 104,702 (18%) who had diabetes.

As noted, diabetics had about the same risk of CVD as non-diabetics
who were 15 years older. Age-adjusted rates of acute MI and all-
cause mortality were about two to four times higher in subjects with
diabetes than in those with no diabetes or recent acute MI.

The analysis suggests that the transition from moderate to high risk
of CVD takes place at about age 41 for men with diabetes and 48 for
women with the disease.

Dr. Booth's group suggests that for middle-aged and older people
with diabetes, "aggressive and risk-reduction strategies are
warranted." In contrast, they write, "our data support present
guidelines recommending that risk-reduction efforts be
individualized in patients with diabetes who are less than 40 years
of age."

Further study, they add, "to develop appropriate algorithms for CVD
risk in young adults with type 1 and type 2 diabetes is critically
important to guide therapeutic decision in these individuals."

Lancet 2006;368:29-36

As a rehabilitation technique for stroke, repetitive transcranial
magnetic stimulation (rTMS) can slow the hyperactivity seen in the
unaffected hemisphere, resulting in an improvement in motor function.

The findings, from a study reported in the June 30th rapid access
issue of Stroke, indicate that the magnitude and duration of motor
benefits can be safely increased through the use of more than one
rTMS session. With five consecutive sessions, sustained improvements
in motor function were noted over the 2-week study period.

After a stroke, the authors explain, the unaffected hemisphere
attempts to recover the function lost by the affected hemisphere,
but in so doing inhibitory signals are sent to the affected
hemisphere and this may impair functional recovery. Transcranial
magnetic stimulation is thought to work by reducing the frequency of
these inhibitory signals.

The study involved 15 patients with chronic stroke who were
randomized to undergo active or sham rTMS, applied to the unaffected
hemisphere. Motor function and corticospinal excitability were
assessed at baseline, during, and after treatment by a rater blinded
to the assigned treatment.

Active, but not sham, rTMS was associated with significant
improvements in motor function in the affected hand over the study
period. At the same time, corticospinal excitability decreased in
the unaffected hemisphere, while it increased in the affected
hemisphere.

"In the simple-reaction-time task, patients were, on average, 30%
faster than at baseline after five days of treatment, and this
effect lasted for 2 weeks," lead author Dr. Felipe Fregni, from
Harvard Medical School in Boston, said in a statement.

"Interestingly, the improvement was cumulative. Patients were, on
average, 10%, 20%, 27%, and 30% faster on days two, three, four, and
five, respectively. And this improvement in motor function was
significant when compared to sham stimulation," he added.

There was no evidence that five sessions of rTMS adversely affected
cognitive performance or promoted seizures, the report indicates.

The researchers call for larger studies to replicate their findings
and to explore other stimulation parameters that may enhance motor
function further.

Stroke 2006

Bedtime snacks are not a reliable method of relieving nocturnal
hypoglycemia in type 1 diabetics and terbutaline treatment has
shortcomings, researchers report in the June issue of the Journal of
Clinical Endocrinology and Metabolism.

"Iatrogenic hypoglycemia, particularly nocturnal hypoglycemia, is a
problem for many people with diabetes that has not been solved,"
senior researcher Dr. Philip E. Cryer told Reuters Health.

To investigate possible bedtime solutions to nocturnal hypoglycemia,
Dr. Cryer and colleagues at Washington University School of
Medicine, St. Louis, Missouri studied 21 patients over 5 nights.

They were randomized to receive no treatment, a snack, a snack and
the alpha- glucosidase inhibitor acarbose, an uncooked cornstarch
bar or 5 mg of oral terbutaline.

"We found that a conventional bedtime snack [with or without
acarbose], or bedtime ingestion of uncooked cornstarch, did not
consistently prevent nocturnal hypoglycemia in people with type 1
diabetes using contemporary methods of aggressive glycemic therapy,"
Dr. Cryer said.

For practical purposes, "bedtime administration of the epinephrine
simulating beta2-adrenergic agonist terbutaline prevented nocturnal
hypoglycemia, but it also caused hyperglycemia the following
morning."

In light of this, Dr. Cryer concluded, "we need to find out if a
lower dose of terbutaline would be effective in preventing nocturnal
hypoglycemia without causing morning hyperglycemia."

J Clin Endocrinol Metab 2006;91:2087-2092

Waiting the guideline-mandated 3 months (and 9 months required by
some third-party payors) between diagnosis of nonischemic dilated
cardiomyopathy (NIDCM) and placement of an implantable cardioverter-
defibrillator (ICD) may not be in the best interest of some
patients, according to an analysis of data from the DEFINITE trial.

"The primary theoretical reason (for waiting several months) is that
there are some people who develop myocarditis who will get better,
and because of that concern, people shouldn't get implanted
immediately after diagnosis," Dr. Alan Kadish told Reuters Health.

"However, I think this guideline should be reevaluated," the
researcher added, "because, based on the data from this trial and
other retrospective studies, there is evidence that some people
don't do well if they wait (before receiving an ICD)."

Dr. Kadish, from the Feinberg School of Medicine in Chicago, and his
associates analyzed data from the Defibrillators in Nonischemic
Cardiomyopathy Treatment Evaluation (DEFINITE) trial, which included
patients with NIDCM and left ejection fraction < 36%, and which
excluded individuals with potentially reversible NIDCM.

"We said in our instructions to clinicians that if a patient does
not appear to have a reversible problem, the patient could be
included," Dr. Kadish explained, "which gave us the opportunity to
look back to see if it made a difference in patients' outcome if
treating soon after their diagnosis made any difference."

In the original study, 458 patients were randomly assigned to
standard medical therapy with or without an ICD, regardless of time
since diagnosis. Dr. Kadish's group evaluated outcomes as related to
time between diagnosis and randomization to ICD treatment or not,
with 3 months and 9 months as cut-points.

Results published in the June 20th issue of the Journal of the
American College of Cardiology show that when a cut point of 3
months was used, 10.2% of patients with recently diagnosed NIDCM
died within the next 2.5 years, whereas among patients who were
treated 9 months after diagnosis, 11.2% died during the same period.

"The ICD insertion was associated with a reduced risk of death for
patients who had been diagnosed shortly before their enrollment in
the study," the researchers found.

Specifically, the all-cause mortality rate was 7.3% in those
diagnosed within 3 months of ICD treatment compared with 15.0% among
those who were treated more than 3 months after diagnosis, for a
hazard ratio (HR) of 0.37 (p < 0.05).

The difference around the 9-month cutpoint was similar: 9.2%
mortality before vs. 15.6% after (HR = 0.48, but p = 0.058).

"These figures show that some patients with NICDM don't do very well
if they wait for several months before an ICD is implanted, whereas
some live a long time," Dr. Kadish said. The trend for those with a
recent diagnosis indicated that prognosis was better with early
implantation.

"It may be that some people have a more dangerous form of NICDM, and
some have a less dangerous form," he added. "For those with the more
dangerous form, an ICD does improve survival."

"We can't be dogmatic about any of this," the cardiologist
continued. "It appears that some patients who were diagnosed months
or years before receiving an ICD may have derived less benefit. I'm
more concerned (about waiting for months) that we may be missing
patients who need an ICD soon after they're diagnosed."

In an accompanying editorial, Dr. Francis E. Marchlinski and Dr.
Mariell Jessup agree with Dr. Kadish's contention that a task force
of experts should develop a list of reversible myopathies for which
the need for an ICD would be ruled out, and thus identify patients
who should be treated soon after diagnosis.

Drs. Marchlinski and Jessup, cardiologists at the University of
Pennsylvania School of Medicine in Philadelphia, list a variety of
biomarkers of irreversibility, including increased expression of the
cell surface Fas and presence of cardiac fibrosis.

They also cite clinical parameters that indicate irreversible
disease, including pulmonary hypertension, LVEF < 20%, comorbid
right ventricular dysfunction, and elevated levels of B-type
natriuretic peptide and troponin. Another important factor, they
add, is intolerance to medications.

To test these markers of irreversibility, Dr. Kadish said, "will
require an observational study, where an ICD would be put in, then
seeing which factors predict shock from the ICD," a study that he
and his associates are currently designing.

"But it will be a few years before results will be available," he
added.

J Am Coll Cardiol 2006;47:2477-2482

Metformin administration during puberty delays menarche and leads to
greater adult height in certain low-birth-weight girls, in
particular those who are overweight around the age of 8 years,
European researchers report in the June issue of The Journal of
Clinical Endocrinology and Metabolism.

Dr. Lourdes Ibanez of the University of Barcelona and colleagues
note that such girls who enter puberty around the age of 8 or 9
years tend to have earlier menarche, earlier growth arrest and
shorter stature.

Although the underlying mechanisms are unclear, the researchers
hypothesized that hyperinsulinemic insulin resistance may play a
part in early puberty onset.

With this in mind, the team conducted an open-label, prospective
study of 22 low-birth-weight girls with early-normal puberty. They
were randomized to receive metformin 850 mg per day for 36 months or
to no treatment. Both groups then continued for a further 6 months
without treatment.

Evaluation at 42 months showed that metformin treatment led to an
increase in the time from stage 2 breast development to menarche;
median time to menarche was 2 years in the untreated group, compared
to 3 years in the metformin group.

In addition, treated girls had a height gain of 19.5 cm during this
period compared to 16.0 cm in the untreated group.

At 36 months, treated girls had a lower body mass index (21.6 versus
22.7), as well as lower insulin resistance, lower leptin and IGF-1
levels, and a more favorable lipid profile.

Summing up, Dr. Ibanez told Reuters Health that "given the results
of metformin therapy, it would appear that insulin plays an
important role in the pubertal tempo and pubertal height gain in
girls."

J Clin Endocrinol Metab 2006;91:2068-2073

Among patients with suspected acute coronary syndrome, the
predictors of myocardial infarction before hospital admission differ
between men and women, according to results of a study published in
the May issue of the International Journal of Cardiology.

Dr. Johan Herlitz, of Sahlgrenska University Hospital, Goteborg,
Sweden, and colleagues conducted a prospective observational study
involving 433 patients (45% women) who were transported to the
hospital by ambulance with a suspected acute coronary syndrome
without ST-elevation.

The ambulance crew assessed the patients, obtained a short history,
and conducted a basic examination that included measurements of
blood pressure and heart rate. The ambulances were equipped to
record an ECG that could be transmitted to the hospital. The
paramedics also measured myoglobin, CK-MB and troponin-I "using the
second generation of tests."

Women tended to be older than men and had a lower prevalence of a
previous acute MI. Ultimately, it turned out that 17% of women and
26% of men developed acute MI (p = 0.054).

Among patients with initial ST-depression, 22% of women and 54% of
men developed acute MI (p = 0.001). The investigators observed a
significant interaction between gender and the influence of ST-
depression on the risk for development of MI.

Overall, among women a previous history of acute MI and advanced age
were independent predictors for the development of acute MI, Dr.
Herlitz and colleagues report. "Among men the following were
independent predictors: Presence of ST-depression and Q-waves and
elevation of any biochemical marker prior to hospital admission."

The team concludes that "the risk indicators for myocardial damage
might not be entirely the same among men and women in this
population."

Int J Cardiol 2006;109:241-247

Morbidly obese patients who do not undergo weight-loss surgery face
a substantially greater mortality risk than patients who undergo
bariatric surgery, according to a presentation this week at the 23rd
annual meeting of the American Society for Bariatric Surgery in San
Francisco.

"There has been a lot of controversy regarding morbidity and
mortality due to bariatric surgery, and if it worked, but we were
drawn to see what happens to these patients if they decide to not
undergo bariatric surgery," Dr. Randolph B. Reinhold told Reuters
Health.

Dr. Reinhold, chairman of the Department of Surgery at the Hospital
of Saint Raphael in New Haven, Connecticut, and his colleagues
reviewed the records of patients who were morbidly obese and had
been seen in their clinic between 1997 and 2004. According to their
meeting abstract, 1438 patients were evaluated, and 207 never
returned for surgery.

During follow-up the investigators were able to contact 101 patients
or their family members to document outcomes of those who went
untreated, and they also examined registries for information on
patients who had died.

"The survival rate at 1 year was 99% in the surgery group and 97% in
the no-surgery group," Dr. Reinhold said. "After that, the mortality
due to morbid obesity increased significantly compared to those who
underwent surgery because the consequences of obesity continue to
accrue."

"By year 3, the survival rate was 98% in the surgery group versus
88% among those who remained untreated," the surgeon continued. And
at 5 years, the corresponding survival rates were 97% and 78%.

"Morbid obesity is so dangerous that if it is left untreated,
patients face a mortality rate more than 10 times the expected
rate," Dr. Reinhold added. In his group's study, the average age at
death among nontreated patients was 54. For those in the general
population at that age, the expected mortality rate is < 1%.

He pointed out that "occasionally some patients in this population
can lose weight by dieting alone, but for the vast majority the
weight is regained."

Endoluminal stenting of a stenotic aortic arch vessel with cerebral
protection "may be a viable alternative to traditional open bypass,"
researchers at Northwestern University report in the June issue of
the Archives of Surgery.

The Chicago, Illinois-based investigators retrospectively reviewed
results of stenting in 20 brachiocephalic-origin vessels in 18
patients, mean age 68 years.

Mean stenosis was 85%, and target lesions were in the innominate,
the common carotid or the subclavian arteries.

Principal investigator Dr. Mark K. Eskandari told Reuters Health
that the only difference between coronary artery stenting and aortic
arch stenting is size. "It's a little easier to place (the aortic
stent)," he said. "We used stents between 6 and 7 mm in diameter
compared with an average of 2.0 to 2.5 mm diameter in coronary
artery stenting. "

Stenosis of the aortic arch vessels is "not nearly as common as
coronary artery disease...but the (nature of the) disease is exactly
the same," he added.

Balloon-expandable stents were placed via the femoral or brachial
artery, or a cut-down on the common carotid artery. In most cases,
cerebral protection was achieved with a distal embolic filter or
with surgical closure of the distal common carotid artery.

"The restenosis rate is pretty low," Dr. Eskandari said. "There has
been only one restenosis since we published the article."

"The only contraindication for stenting of the aortic vessels is if
they're completely blocked," Dr. Eskandari noted. "In those cases,
we can't snake a wire or a balloon through the stenosis, that would
really increase risk of stroke."

Follow-up care is the same as in a patient with coronary artery
disease, he added, with lipid-lowering agents and other medications
and measures to reduce risk.

The investigators are continuing to follow the patients in the study.

Arch Surg 2006;141:560-564

Pulse pressure (PP) appears to be associated with cardiovascular
mortality risk independently of left ventricular hypertrophy (LVH)
and systolic dysfunction, researchers report in the June issue of
the American Journal of Hypertension.

Dr. Mary J. Roman of Weill Medical College of Cornell University,
New York and colleagues note that systolic blood pressure, which is
a major component of PP, is associated with LVH and cardiovascular
events. However, whether PP is related to cardiovascular events
independently of LVH and ejection fraction is unknown.

To investigate, the researchers examined data from a population-
based study involving almost 3,000 American Indians without overt
signs of cardiovascular disease.

During a mean follow-up of about 7 years, there were 577 deaths of
which 166 were definitely due to cardiovascular causes.

The frequency of cardiovascular death was highest in those with the
highest levels of PP (more than 64 mm Hg). This was also true of all-
cause mortality. Compared to those with the lowest PP levels (42 mm
Hg or less), the frequency of cardiovascular death was about 3 times
higher in those with the highest levels.

Across the spectrum of PP values, this risk was about twice as high
in subjects with LVH compared to those without.

Overall, the team found that higher PP was associated with
cardiovascular mortality independently of traditional risk factors,
LVH and reduced ejection fraction. They conclude that "PP is an
efficient marker of cardiovascular risk."

Commenting on the implications of the findings, Dr. Roman told
Reuters Health that "the link between an increase in pulse pressure
and an increase in cardiovascular death appears to have
intermediaries other than left ventricular hypertrophy and impaired
left ventricular pump function, and further analyses in longitudinal
studies should seek to better elucidate these intermediaries."

Consequently, she added, "the study suggests that therapies to
reduce left ventricular hypertrophy and improve left ventricular
pump function may not be optimally beneficial if there is not a
concomitant reduction in pulse pressure."

Am J Hypertens 2006;19:601-607

Aortic calcification scores can be calculated from computed
tomography (CT) of the colon, and the scores correlate with
cardiovascular mortality, Mayo Clinic radiologists report in the
July issue of Radiology.

They note that while CT colonography -- popularly known as virtual
colonoscopy -- aims at assessment of the colorectum, evaluation of
other soft tissues in the abdomen and pelvis can also be performed.
In fact, clinically important abnormalities outside of the colon
have often been seen on CT colonography.

Dr. Jesse A. Davila and colleagues retrospectively calculated aortic
calcification scores obtained during CT colonography performed on
467 patients. The subjects had a median age of 65 and 59% were men.
Other cardiovascular risk factors were assessed from the patients'
medical records.

The Rochester, Minnesota, team found that nine patients had
cardiovascular events subsequent to CT colonography.

The investigators saw a "significant association between myocardial
infarction or cardiac event-related death and calcium scores of the
aortic bifurcation that exceeded 895, the value for the 75th
percentile for this calcium variable."

Dr. Davila and colleagues also determined that there was an
association between other cardiac risk factors and aortic calcium
scores.

The Mayo Clinic team notes that this information on cardiovascular
risk "can be obtained without additional scanning or risk to the
patient." Patients with aortic calcium scores indicative of
cardiovascular risk may be candidates for lipid-lowering therapy.

Radiology 2006;240:110-115

A major shake-up in the way doctors are being advised to treat high
blood pressure was announced by Britain's drugs watchdog on
Wednesday.

GPs will no longer offer drugs called beta blockers as a first
treatment for the condition.

Instead black people suffering from high blood pressure and all
those over 55 will be given a type of medication known as a calcium
channel blocker, or a diuretic drug.

Those under 55 will first be treated with a class of medicine known
as an ACE inhibitor.

Patients can also be offered a combination of the three drugs.

The advice comes after research showed the newer drugs carry less
risk of a heart attack or stroke.

The National Institute for Health and Clinical Evidence (NICE)
issued the new advice in conjunction with the British Hypertension
Society following a review of the treatments available.

"What we have found is that although beta blockers remain effective
at reducing stroke and heart disease, they are slightly less
effective than alternative forms of treatment," said Professor Bryan
Williams of University Hospitals NHS Trust in Leicester.

He told the BBC the watchdog's recommendations would lead to
a "significant reduction" in stroke and heart disease over the next
five years, at the same time saving the NHS around 250 million
pounds in treatment costs.

High blood pressure, or hypertension, affects around 40 percent of
adults in England and Wales and the National Health Service spends
15 percent of its drugs budget on treatments for the condition.

Multidetector-row CT (MDCT) measurements of proximal coronary artery
diameters correlate well with those obtained by angiography and
intravascular ultrasound (IVUS), according to a report in the June
issue of the International Journal of Cardiology.

MDCT has already been shown to identify angiographically proven
stenosis of proximal segments of coronary arteries, the authors
explain, but little information is available about how MDCT
determination of coronary artery dimensions compares with
measurements obtained by more invasive techniques.

Dr. Anil-Martin Sinha and colleagues from University Hospital,
Aachen, Germany evaluated the accuracy of 4-row MDCT for measurement
of coronary artery lumen diameters in comparison to quantitative
coronary angiography and IVUS in 18 patients with known or suspected
coronary artery disease.

Measurements obtained with different techniques did not differ
significantly near the origin of the artery, the results indicate,
but significant differences were observed more distally.

Specifically, the correlation between MDCT and angiography
measurements was greater than 90% at the origin and at 10 mm distal
to the origin, but decreased to 84.1% at 30 mm and 78.0% at 50 mm
distal to the origin.

Similarly, the researchers note, the correlation between MDCT and
IVUS was 93.4% at the origin, but fell to 86.7% at 10 mm, 88.0% at
30 mm, and 72.7% at 50 mm from the origin.

The differences in lumen diameters as measured by the three
techniques ranged from 0.01 to 0.88 mm, the report indicates, with
larger differences observed in patients with intracoronary stents in
the target vessels (30 and 50 mm distal to the origins of the
vessels).

"Multidetector-row computed tomography seems to be a reliable
noninvasive technique for the evaluation of proximal segments of
coronary arteries," the investigators conclude. "An advantage of
noninvasive visualization of coronary arteries is the lower risk of
procedure-related complications and the shorter investigation time
as compared to invasive techniques."

They add, "We expect better results and good correlation for more
distal segments using 16-row computed tomography."

Int J Cardiol 2006;110:40-45

Exenatide therapy results in weight loss and a substantial decrease
in insulin doses in some of the most difficult-to-manage patients
with type 2 diabetes, a new study reveals.

Coinvestigator Ajay Chaudhuri, MD, presented results of a
retrospective study here at ENDO 2006, the 88th annual meeting of
The Endocrine Society. Dr. Chaudhuri is an assistant professor of
medicine at the State University of New York at Buffalo and a
physician at Kaleida Health.

"Treatment of obese patients with type 2 diabetes who are on insulin
therapy and continue to have poor glycemic control and weight gain
is a clinical and therapeutic challenge," Dr. Chaudhuri said during
his presentation. "We wanted to see if the appetite-suppressing,
glucose-lowering, and weight-loss properties of exenatide might be
useful in this population."

Dr. Chaudhuri and colleagues conducted a retrospective analysis of
28 women and 17 men who had type 2 diabetes for a mean duration of
10 years (± 4 years). All were receiving insulin therapy and insulin
sensitizers. They were all also receiving statins and angiotensin-
converting enzyme inhibitors, or angiotensin receptor blockers.
During the course of the study, no changes were made to any
medications except insulin.

At baseline, participants had a mean blood pressure of 124/77 mm Hg,
a mean low-density lipoprotein cholesterol level of 69 mg/dL, and a
mean high-density cholesterol level of 35 mg/dL. In spite of insulin
treatment, all subjects had glycated hemoglobin (A1C) levels of more
than 7%.

Participants self-administered 5 µg of exenatide subcutaneously
twice daily. Three patients experienced severe nausea early in the
study and did not continue therapy.

Mean duration of follow-up was 26 weeks. Patients lost an average of
2 pounds per month, with a mean weight of 115.06 kg at baseline
decreasing to 110.49 kg at follow-up (P < .001). "The weight loss
that we saw was much greater than what is shown in published studies
of exenatide, which is approximately 1 pound per month," Dr.
Chaudhuri told Medscape. "The effect on suppression of appetite and
the effect on decrease in blood glucose was seen very rapidly,
within 2 to 3 days of beginning treatment," he said.

A1C decreased an average of 0.6%, from 7.79% to 7.18% (P = .003).

"There were 9 patients that did not lose weight," Dr. Chaudhuri
said, "but they did not gain weight either, and they also had a
lowering of A1C."

Triglyceride levels decreased from 154.68 mg/dL to 115.33 mg/dL (P =
0.02). C-reactive protein (CRP) levels decreased 33% from 9.88 mg/L
to 5.53 mg/L (P = .002), with the decrease independent of weight
loss and reduction in A1C.

"The reduction in CRP was exciting," Dr. Chaudhuri said, "because
this was a group of patients who were already on all the medications
that are known to have an effect on CRP." The reduction in CRP may
be due to glucose lowering, a decrease in macronutrient intake, or a
novel anti-inflammatory effect of exenatide, Dr. Chaudhuri said
during his presentation. "It may have implications in terms of
antiatherogenic effects and cardiovascular disease," he told
Medscape.

Participants receiving short-acting insulin who were treated with
exenatide decreased their doses by 30% on average, from a mean of
62.1 U/day to 40.54 U/day (P < .001). Long-acting insulin doses also
decreased by 10%, from a mean of 56.17 U/day to 48.89 U/day (P
= .001).

Three patients experienced mild hypoglycemia. To help prevent
hypoglycemia in this study's subjects, Dr. Chaudhuri cautioned that
careful titration of insulin was important.

Dr. Chaudhuri concluded that the study's findings show exenatide may
be a safe and effective option in difficult-to-control obese
subjects with type 2 diabetes. "This is a group that is a
therapeutic nightmare. When they get to this stage, you don't know
what else to do with them. You start thinking about putting them on
an insulin pump or continuous insulin infusion."

"It's interesting that this shows exenatide can be effective in
patients on insulin, since it's currently only approved for use in
patients on oral medications only," Jean Chan, MD, the session
moderator, commented in an interview with Medscape. "The average
weight loss was significant and was accompanied by improvements in
insulin requirements." Dr. Chan is from the endocrinology department
at Beth Israel Deaconess Medical Center in Boston, Massachusetts,
and was not associated with the study.

"One drawback to exenatide is that patients must self-administer an
extra 2 injections a day." Dr. Chan said.

Dr. Chaudhuri commented that the extra injections were a real
concern. "We initially thought these patients would have trouble
adding another 2 injections, when the majority were on 4 injections
[of insulin] already. But what was really surprising was this did
not turn out to be a problem — because they saw that they were
losing weight."

No outside funding was received for this study. The authors report
no relevant financial relationships.

ENDO 2006: Oral Abstracts Session 10-1. Presented June 24, 2006

A new observational study examining data from the Framingham Heart
Study found no link between subclinically high or low thyroid
stimulating hormone (TSH) levels and an increased risk of
cardiovascular disease or mortality. Elizabeth Pearce, MD, assistant
professor of medicine at Boston University in Massachusetts,
presented these findings here at ENDO 2006, the 88th annual meeting
of The Endocrine Society.

"The results of our study add a little bit more to the debate about
whether there are important cardiovascular effects of subclinical
thyroid dysfunction," Dr. Pearce told Medscape. "It's very
controversial whether patients with subclinical thyroid dysfunction
should be treated, or whether we should be screening for this."

Dr. Pearce told attendees that 8 previous large observational
studies examining subclinical and overt thyroid dysfunction on the
risk of cardiovascular disease and increased mortality have yielded
conflicting results. "Of the 8 studies, 5 showed no effect on
mortality. Some studies showed adverse cardiovascular risk with high
TSH, some with low TSH, and some showed no effect," she said.

Dr. Pearce and colleagues thought that examining the Framingham
Heart Study data set could shed some light on the issue. "The
Framingham Heart Study is a general community sample, and the
outcomes data for cardiovascular disease of all kinds is superb, and
there is excellent follow-up data," she told Medscape.

The study involved data on 1992 men and 2339 women selected from the
Framingham Heart Study. The researchers included subjects who had
serum TSH values determined at baseline. They excluded subjects who
had cardiovascular disease or were receiving thyroid hormone
medications at baseline. Subjects were a mean age of 54 years at the
beginning of the study.

The researchers divided the subjects into 3 groups according to
baseline TSH levels. Of the 4331 subjects, about 7% (n = 287) had
low TSH levels (<0.5 mU/L), almost 87% (n = 3763) had normal TSH
levels (0.5 - 5.0 mU/L), and about 6% (n = 281) had high TSH levels
(>5.0 mU/L).

At follow-up (mean, 16.7 years), more than 24% (n = 1069, 55% men)
had developed cardiovascular disease, defined as any of the
following: angina, transient ischemic attack, intermittent
claudication, myocardial infarction, coronary insufficiency,
congestive heart failure, and stroke. The researchers identified a
subset with more severe or "hard" cardiovascular disease (n = 969,
54% men), defined as myocardial infarction, coronary insufficiency,
congestive heart failure, and/or stroke. Approximately 37.4% (n =
1620, 53% men) died.

"Cardiovascular risk did not differ based on TSH categories," Dr.
Pearce said during her presentation. The hazard ratio (HR) for the
low TSH group vs the euthyroid group was 1.04 with a 95% confidence
interval (CI) of 0.83 - 1.13. For the high TSH group vs the
euthyroid group, the HR was 1.07 with a 95% CI of 0.85 - 1.35.

The risk for developing "hard" cardiovascular disease also did not
vary among the TSH categories. The HR for the low TSH group was 0.96
(95% CI, 0.76 - 1.23) and 1.07 (95% CI, 0.84 - 1.37) for the high
TSH group.

Similarly, no increased risk for mortality was seen for the low TSH
group (HR, 1.03; 95% CI, 0.86 - 1.23) or the high TSH group (HR,
0.97; 95% CI, 0.79 - 1.20).

"In this adequately powered investigation of a large community-based
sample, baseline serum TSH was not associated with risk for
cardiovascular disease or mortality," Dr. Pearce concluded.

The study had some limitations. TSH levels were only measured at
baseline, and thyroid antibody or peripheral thyroid hormone levels
were not available. In addition, the Framingham cohort was
predominantly white.

Jayne Franklyn, MD, a member of The Endocrine Society's Research
Affairs Committee and professor of medicine at the University of
Birmingham in the United Kingdom, commented to Medscape on the
conflicting results of studies examining subclinical thyroid
dysfunction. In regard to subclinical hyperthyroidism, she
said, "There is pretty good evidence now that translates into
clinically significant effects, particularly an increased risk of
atrial fibrillation and possibly increased risk of mortality from
vascular disease."

The situation is much less clear for subclinical hypothyroidism, Dr.
Franklyn said. "Some evidence exists that shows subclinical
hypothyroidism may be associated with increased risk of ischemic
heart disease and congestive heart failure, but not all studies show
that. In fact, the largest ones fail to show that. The jury is still
out in terms of whether subclinical hypothyroidism has a significant
effect on the cardiovascular system."

The study was funded by grants from the National Institutes of
Health and the National Institutes of Health/National Heart, Lung,
and Blood Institute contract. The authors report no relevant
financial relationships.

ENDO 2006: Abstract OR42-1. Presented June 27, 2006

Subcutaneous adipose tissue appears to be an appropriate site for
monitoring glucose concentrations in patients after major cardiac
surgery, and could be used for maintaining tight glycemic control in
this situation, Austrian researchers report.

As lead investigator Dr. Martin Ellmerer told Reuters Health, there
is substantial evidence that hypoglycemia, "as frequently seen in
diabetic, but also non-diabetic critically ill patients is
associated with a substantial risk for mortality and morbidity."

Moreover, "for the treatment of high glucose concentrations in
critically ill patients ... measurements of glucose are required on
at least a 1 to 4 hourly basis."

For diabetes care, he added, there is ongoing research into the
development of continuous glucose monitoring systems using
subcutaneous adipose tissue as a sampling site.

However, Dr. Ellmerer of Medical University Graz and colleagues note
in the June issue of Diabetes Care that such an approach has not
been tested in critically ill patients. In order to do so, the
researchers studied 40 such patients in the ICU after undergoing
cardiac surgery.

For sampling interstitial fluid, a microdialysis catheter was
inserted into subcutaneous adipose tissue in the umbilical region,
and dialysate was collected in hourly batches for analysis for up to
48 hours. For blood monitoring, samples from an arterial line were
collected at hourly intervals over the same period.

After appropriate calibration, there was a good correlation between
blood glucose and adipose tissue-derived glucose levels. In clinical
evaluation, the researchers established that 96.1% of the adipose
tissue readings would allow acceptable treatment and glycemic
control.

"In principle," Dr. Ellmerer concluded, "our finding opens a new
application field for the use and development of continuous glucose
monitoring systems in critically ill patients."

Diabetes Care 2006;29:1275-1281

Statin therapy before carotid angioplasty with stent placement
protects against stroke, myocardial infarction, and death in the
early post-procedural period, a retrospective study shows.

"Although these results definitely need to be confirmed in a larger,
prospective trial, we would recommend that all patients who are
going to have a carotid angioplasty and stent procedure should be on
statins," Dr. Andreas Kastrup of University of Goettingen, Germany
told Reuters Health.

Based on several recent studies, which have shown that statin
pretreatment reduces the incidence of myocardial infarction after
coronary interventions, Dr. Kastrup and colleagues hypothesized that
statin therapy may also reduce procedure-related stroke, MI or death
among patients undergoing carotid angioplasty and stent placement.

"In support of this, we demonstrate that, (regardless) of
cholesterol level, preprocedural statin therapy does indeed reduce
the incidence of stroke, myocardial infarction and death," Dr.
Kastrup said.

The study involved 180 consecutive patients who underwent carotid
angioplasty and stent placement -- 127 were not on statin therapy
before the procedure and 53 were taking a statin before treatment.

Thirty days after surgery, the overall outcome was two (1%) MIs, 16
(9%) minor strokes, and one (0.5%) a major stroke; two patients (1%)
died, the team reports in the July issue of Radiology.

The incidence of cardiovascular events -- a composite of stroke, MI,
and death within 30 days of the procedure -- was significantly lower
in patients on statin therapy before carotid angioplasty and stent
placement (4%) compared with those not on preprocedural statin
therapy (15%).

These differences held up in analyses adjusting for age, sex and
other baseline characteristics including the degree of carotid
stenosis, use of cerebral protection devices, and the year in which
the procedure was performed.

"Because serum concentrations of lipid parameters were similar in
patients with and in those without preprocedural statin treatment,
these beneficial effects seem to be mediated by various non-lipid-
lowering effects of statins," the authors note.

Radiology 2006;240:145-151

In a study of hospitalized injection drug users, QT interval
prolongation was seen in a considerable number of patients treated
with methadone but not among those not treated with methadone.

Findings from laboratory studies have shown that methadone can
increase the QT interval in a dose-dependent fashion. The extent to
which this is seen in an inpatient, clinical setting, however, was
unclear.

To investigate, Dr. Georg B. Ehret, from Geneva University Hospital,
and colleagues analyzed data from 247 injection drug users who were
treated at a tertiary care hospital over a 5-year period. The
subjects included 167 who received methadone and 80 who did not.

The researchers' findings appear in the Archives of Internal
Medicine for June 26.

The rate of QTc prolongation to 0.5 seconds or longer was
significantly higher among methadone-treated patients than among
controls: 16.2% vs. 0%. Moreover, 3.6% of patients receiving
methadone had torsades de pointes.

A weak but significant association between QTc length and the daily
methadone dose was also noted, the investigators report. In addition
to the methadone dose, other factors tied to QT prolongation
included hypokalemia, lower prothrombin level, and the use of drugs
that inhibited cytochrome P-450 3A4.

"The recognition of cardiovascular adverse effects of methadone is
particularly important because young patients rarely undergo cardiac
monitoring and are susceptible to the use of drugs that interfere
with cardiac electrical activation," Dr. Ehret and colleagues state.

As they point out, "Effective and safe treatment of methadone-
induced long QT syndrome exists with the use of opioid rotation."

Arch Intern Med 2006;166:1280-1287

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Maternal smoking during pregnancy appears to be a strong risk factor
for increased symptoms severity in subjects with Tourette's
syndrome, and for comorbid obsessive-compulsive disorder (OCD).

Tourette's syndrome is believed be to associated with multiple
genetic and environmental factors, Dr. Carol A. Mathews and her
associates note. While few studies have examined the role of
environmental factors, there are suggestions that perinatal
incidents and the mother's prenatal habits may affect the occurrence
of the disorder, its severity, or the risk of comorbidity.

Dr. Mathews, from the University of California in San Francisco, and
her team hypothesized that transient fetal hypoxia could increase
the predisposition to developing Tourette's syndrome in those with a
genetic vulnerability.

To test this theory, psychiatrists in the research team evaluated
members of three cohorts of persons with the syndrome, which
included 53 individuals from Costa Rica, 99 individuals of Ashkenazi
Jewish descent, and 28 individuals involved in an affected sibling
pair study. The ages of the 180 subjects ranged from 3 to 59 years,
but 60% were below age 14 when they were interviewed.

The investigators report in the American Journal of Psychiatry for
June that the mean tic severity score was 38.6 out of a possible 50,
and the mean global severity score was 61 out of a possible 100.

The presence of OCD and comorbid self-injurious behavior was
strongly associated with tic severity. Comorbid attention
deficit/hyperactivity disorder (ADHD) was also associated with tics,
but the association was not as strong as the other two disorders.

More than half of the subjects reported at least one adverse
perinatal event, but these were generally similar to that in the
general population. Parental factors and perinatal events did not
seem to affect risk.

However, after adjusting for subject group, gender, and family
history, maternal smoking was significantly associated with total
tick and phonic tic severity. In fact, statistical modeling showed
that maternal smoking accounted for 42% of the variance in tic
severity.

Maternal smoking was also associated with an 8-fold increased risk
of comorbid OCD.

The researchers suggest that the association between smoking and tic
severity and OCD was evidence that chronic fetal hypoxia increased
the risk. However, they cannot rule out the possibility that
maternal smoking is an indicator for an associated variable that has
yet to be uncovered, such as socioeconomic status or parental ADHD.

Am J Psychiatry 2006;163:1066-1073.

Insulin resistance is independently associated with severe steatosis
both before and after bariatric surgery in very obese patients,
according to French researchers.

In the May issue of Gastroenterology, Dr. Philippe Mathurin of
Hopital Huriez, Lille and colleagues prospectively investigated
factors involved in the development of severe steatosis in 185
severely obese patients who were referred for bariatric surgery.

At preoperative biopsy, 27% of the patients showed steatosis of at
least 60%. Alanine aminotransferase and insulin resistance indices
were independent predictors of such steatosis.

One year after surgery, there was a significant 9.5 drop in BMI.
There also were significant reductions in steatosis score and
insulin resistance index. However, preoperative insulin resistance
index and preoperative steatosis were independent predictors of the
persistence of severe steatosis.

Weight loss was also significantly less in patients with a
refractory insulin resistance profile.

Altogether 10 patients continued to have severe steatosis. Moderate
or severe steatosis was seen more often in patients who continued to
have a high insulin resistance index after surgery than in those who
showed a reduction (44% versus 20.2%).

Given these findings, the researchers conclude that a refractory
insulin resistance profile "may help to identify patients who are
poor responders to the beneficial effects of bariatric surgery for
obesity-induced liver injury."

Gastroenterology 2006;130:1617-1624

Among women of normal weight, blacks appear to be at increased risk
for insulin resistance compared with other ethnic groups, according
to study findings presented Monday at ENDO 2006, the annual meeting
of the Endocrine Society, in Boston.

"The rates of insulin resistance are very similar among obese women
of different ethnic groups," Dr. Jorge Calles-Escandon, from Wake
Forest University in Winston-Salem, North Carolina, told Reuters
Health. "Among women of normal weight, however, insulin resistance
varies widely by ethnicity: African Americans have much higher rates
than the other groups."

In the study, 47% of black women of normal weight had insulin
resistance compared with less than 20% of Hispanic or white women. A
similar finding was noted among men, but the association did not
reach statistical significance.

The findings stem from an analysis of data for 1625 subjects who
were enrolled in the Insulin Resistance Atherosclerosis Study. The
subjects were generally healthy and none of them had diabetes or
impaired glucose tolerance. Insulin resistance was assessed using
the minimal model, a standard technique.

The reason for the link between black ethnicity and insulin
resistance is unclear. Dr. Calles-Escandon said that one possibility
is that black women may have more intra-abdominal fat, which could
contribute to insulin resistance, than women of other ethnic
groups. "If this is the case, however, it still doesn't answer the
question why. Is there some underlying genetic difference?"

In terms of clinical implications, Dr. Calles-Escandon said that, at
present, there really is no simple way to measure insulin resistance
in the clinical setting. Still, physicians caring for black women
should be mindful of the strong link to insulin resistance and
strive to improve other cardiovascular risk factors that are easily
measured, such as blood pressure and cholesterol levels.

The European Commission has approved 20-mg tablets of rimonabant for
use as an adjunct to diet and exercise in the treatment of obese or
overweight patients with associated cardiometabolic risk factors
such as type 2 diabetes or dyslipidemia, and Health Canada has
approved albumin-bound paclitaxel particles for injectable
suspension for the treatment of metastatic breast cancer, including
first-line use.


Rimonabant (Accomplia) to Reduce Obesity-Related Risk Factors in EU

On June 21, the European Commission approved a 20-mg tablet
formulation of rimonabant (Accomplia, made by Sanofi-Aventis) for
use as an adjunct to diet and exercise in the treatment of obese
(body mass index [BMI] >/= 30 kg/m2) or overweight (BMI >27 kg/m2)
patients with associated cardiometabolic risk factors such as type 2
diabetes or dyslipidemia.

According to a company news release, patients presenting with
abdominal obesity who also have diabetes and/or dyslipidemia are
most likely to benefit from rimonabant therapy. Almost 50% of adults
with a large waist circumference (102 cm/40 inches in men, 88 cm/35
inches in women) also have at least 3 additional cardiometabolic
risk factors.

Rimonabant is the first in a new class of drugs called cannabinoid
subtype 1 (CB1) blockers, which work by selectively blocking
receptors in the brain and peripheral organs that play a key role in
glucose and lipid metabolism (eg, adipose tissue, the liver,
gastrointestinal tract, and muscle).

CB1 receptor blockade serves to decrease hyperactivity of the
endocannabinoid system, which has been recently characterized as
playing an important role in regulating body weight, controlling
energy balance, and glucose and lipid metabolism.

The approval was based on a review of data from the Rimonabant In
Obesity/Overweight (RIO) clinical trial in more than 6600 patients
worldwide, of which 4500 were followed for up to 2 years.

Results showed that administration of 20 mg of rimonabant daily
significantly decreased weight and waist circumference, HbA1c, and
triglycerides while increasing high-density lipoprotein (HDL)
cholesterol. Approximately 50% of the improvements in HbA1c,
triglyceride, and HDL cholesterol levels were beyond that expected
from weight loss alone.

In placebo-controlled studies, the most common adverse events
leading to discontinuation of therapy included nausea, mood
alteration with depressive disorders, anxiety, and dizziness.

Rimonabant should not be used in patients with hepatic or renal
impairment, or in patients with uncontrolled serious psychiatric
illnesses such as major depression.

According to the news release, rimonabant 20-mg once-daily tablets
will be introduced first in the United Kingdom in July 2006,
followed by launches in Denmark, Ireland, Germany, Finland, and
Norway during the second half of the year. The formulation is
currently under review for approval by the US Food and Drug
Administration.


Solvent-Free Albumin-Bound Paclitaxel (Abraxane) for Metastatic
Breast Cancer in Canada

On June 7, Health Canada approved albumin-bound paclitaxel particles
for injectable suspension (Abraxane, made by Abraxis Bioscience, Inc
[formerly American Pharmaceutical Partners, Inc]) for the treatment
of metastatic breast cancer, including first-line use.

The suspension consists only of albumin-bound paclitaxel
nanoparticles, eliminating the need for standard steroid or
antihistamine premedication to prevent solvent-based
hypersensitivity reactions. As a result of lowered toxicity, higher
doses of paclitaxel may be administered.

The approval was based on data from a pivotal phase 3, multicenter
clinical study of 460 women who were randomized to receive albumin-
bound paclitaxel particles (260 mg/m2) infused over 30 minutes, or
175 mg/m2 of paclitaxel (Taxol, made by Bristol-Myers Squibb) plus
standard steroid and antihistamine premedication infused over 3
hours.

Of the patient population, 41% received the study drug as first-line
therapy and 59% received it as second-line or greater therapy; 77%
had been previously exposed to anthracyclines.

Results for all patients showed that treatment with the higher-dose
albumin-bound paclitaxel yielded significant improvements in overall
target lesion response rate and time to tumor progression compared
with paclitaxel (33.2% vs 18.7% and 23.0 vs 16.6 weeks [5.3 vs 3.8
months], respectively).

These benefits translated into significant improvements in median
progression-free survival and overall survival in patients receiving
albumin-bound paclitaxel (22.7 vs 16.6 weeks [5.2 vs 3.8 months] and
65.0 vs 55.3 weeks [14.9 vs 12.7 months, respectively).

Although their link to therapy is unclear, most patients receiving
albumin-bound paclitaxel experienced adverse events. The most
commonly reported adverse events in the study were neutropenia (all
cases, 80%; severe, 9%), anemia (any, 33%; severe, 1%), infections
(24%), sensory neuropathy (any symptoms, 71%; severe, 10%), nausea
(any, 30%; severe, 3%), vomiting (any, 18%; severe, 4%), diarrhea
(any, 26%; severe, <1%), myalgia/arthralgia (any, 44%; severe, 8%),
and mucositis (any, 7%; severe, <1%).

Other adverse reactions included asthenia (any, 47%; severe, 8%),
ocular/visual disturbances (any, 13%; severe, 1%), fluid retention
(any, 10%; severe, 0%), alopecia (90%), hepatic dysfunction
(elevations in bilirubin, 7%; alkaline phosphatase, 36%; AST (SGOT),
39%), and renal dysfunction (any, 11%; severe, 1%). Thrombocytopenia
(any, 2%; severe, <1%), hypersensitivity reactions (any, 4%; severe,
0%), cardiovascular reactions (severe, 3%), and injection site
reactions (1%) were uncommon.

Safety labeling for the product warns that albumin-bound paclitaxel
should not be administered to patients who have baseline neutrophil
counts of less than 1500 cells/mm3. To monitor the occurrence of
bone marrow suppression, primarily neutropenia, which may be severe
and result in infection, it is recommended that frequent peripheral
blood cell counts be performed during treatment.

Because the albumin form of paclitaxel may substantially affect a
drug's functional properties compared with those of a drug in
solution, it should not be substituted for other paclitaxel
formulations.

Albumin-bound paclitaxel was approved by the US Food and Drug
Administration in January 2005 for the treatment of metastatic
breast cancer after failure of combination chemotherapy or relapse
within 6 months of adjuvant chemotherapy. Unless clinically
contraindicated, prior therapy should have included an anthracycline.

The drug is currently in various stages of development for various
oncologic indications, including first-line non-small cell lung
cancer, malignant melanoma, ovarian cancer, prostate cancer,
pancreatic cancer, gastric cancer, head/neck cancers, and as
adjuvant and neoadjuvant treatment for breast cancer.

The use of sirolimus-eluting stents (SES) in diabetic patients leads
to a significant reduction in in-stent neointimal hyperplasia,
compared with that seen when bare metal stents are used. However, a
higher rate of incomplete apposition in SES is a concern, Spanish
and US researchers report in the June 6th issue of the Journal of
the American College of Cardiology.

"The most important finding is the high incidence of late acquired
incomplete stent apposition observed by intravascular ultrasound at
9-month follow-up in the SES group," Dr. Manel Sabate of Hospital
Clinico San Carlos, Madrid told Reuters Health.

Dr. Sabate and colleagues evaluated 75 lesions in diabetic patients
who underwent SES implantation and another 65 lesions in patients
who received bare metal stents. In all, 117 patients were involved.

At follow-up, the neointimal hyperplasia mean area in the SES group
was significantly reduced compared to that in the bare metal group.
The median area was 0.01 square millimeters versus 2.00 square
millimeters. This was also true of volume (0.11 cubic millimeters
versus 35.3 cubic millimeters).

In addition, say the investigators, stent edges in the SES group
showed a significant increase in lumen dimensions mainly due to a
significant increase in vessel volume. In those in the bare metal
group, there was vessel shrinkage leading to significant lumen
reduction.

However, late acquired incomplete stent apposition was seen in 11
lesions in SES group (14.7%) and in none of the patients in the bare
metal stent group.

This may be related to late events, such as stent thrombosis, Dr.
Sabate said. "Careful clinical follow-up is thus recommended in
patients in whom this phenomenon has been detected," he concluded.

J Am Coll Cardiol 2006;47:2172-2179

Regular consumption of low-fat milk, cheese, and yogurt is inversely
associated with prevalent hypertension, results of a cross-sectional
study suggest. According to a report in the August issue of
Hypertension, low-fat dairy consumption lowers systolic blood
pressure, but not diastolic blood pressure.

Previous studies looking at the effect of dairy products on blood
pressure have yielded inconsistent results, Dr. Luc Djousse and
colleagues note.

Dr. Djousse, from Harvard Medical School in Boston, and colleagues
looked at the effects of dietary dairy products, saturated fat, and
alpha-linolenic acid on blood pressure, using data from the National
Heart, Lung, and Blood Institute Family Heart Study.

A total of 4797 individuals, mean age 52 years, completed food
frequency questionnaires, at which time their blood pressure was
measured.

Results showed an inverse association between dairy consumption and
prevalence of high systolic blood pressure, but not high diastolic
blood pressure.

The team used a multivariate model to adjust for age, gender,
education, calorie intake, BMI, linolenic acid, fat consumption,
potassium, magnesium, caffeine, fiber, fruits and vegetables,
smoking, alcohol consumption, and history of coronary heart disease.

Even after all these variables were included, subjects in the
highest quartile of dairy consumption had a 36% lower prevalence
odds of hypertension compared with those in the lowest quartile (p
for linear trend = 0.001).

"This association was independent of calcium intake and was mainly
observed among subjects consuming fewer calories from saturated
fat," the team reports.

Linolenic acid -- a component of oil from fish, seeds and nuts --
was also inversely associated with hypertension. However, the
researchers observed no evidence of an interaction effect among
saturated fat, total linolenic acid, and dairy consumption in
relationship to high blood pressure.

"These findings lend support to the recommendation of low-fat dairy
consumption as a means to lower blood pressure," Dr. Djousse and
associates maintain. They also believe that randomized trials will
be needed to replicate their findings, and to identify which
components of dairy products reduce the risk of high blood pressure.

Hypertension 2006;48

Implementation of the American College of Cardiology's AMI
Guidelines Applied in Practice (GAP) program has increased adherence
to evidence-based therapies for patients with acute myocardial
infarction (AMI). However, women are still less likely to benefit
than men, researchers report in the June 12th issue of the Archives
of Internal Medicine.

"The GAP program and its associated discharge document were
important in increasing the rates of evidence-based care use in men
and women with AMI who were older than 65 years," senior
investigator Dr. Kim A. Eagle told Reuters Health.

The study results indicate that "the GAP discharge tool was
independently associated with a substantial reduction in mortality
after discharge at 1 year in women. Nevertheless, compared with men,
women were significantly less likely to have the discharge document
used as a component of their AMI care. Greater use of the GAP
discharge tool in women might narrow the post-MI gender mortality
gap."

Dr. Eagle of the University of Michigan, Ann Arbor and colleagues
investigated the management of about 1400 men and a like number of
women who had been treated before or after the adoption of GAP.

Among specific findings were that 27.9% of women received a
discharge document compared with 33.96% of men, a significant
difference (p < .01).

Dr. Philip Greenland, editor of the journal and co-author of an
accompanying editorial, told Reuters Health that "this study showed
that in the post-GAP period, women were still less likely than men
to receive a beta-blocker within 24 hours, and less likely to be
discharged with aspirin, an angiotensin-converting enzyme inhibitor,
or a lipid-lowering agent."

Dr. Greenland of Northwestern University, Chicago added that "women
were also less likely to undergo cardiac revascularization compared
with their male counterparts during this period. The reasons for
this persistent treatment inequality in women when there were
standardized orders in place are not clear and require further
examination. "

Arch Intern Med 2006;166:1162-1170

Although implantable cardioverter-defibrillators (ICDs) can save
lives, the estimated costs per year of life gained are high,
researchers report in the June 6th issue of the Journal of American
College of Cardiology.

"Given the large size of the eligible population, the high costs of
the intervention and the substantial uncertainties in all current
cost-effectiveness estimates, it is important that further studies
be conducted to provide better guidance to policy makers," lead
investigator Dr. Jack Zwanziger told Reuters Health.

Dr. Zwanziger, currently at the University of Illinois at Chicago,
and colleagues came to this conclusion after evaluating data from
1095 patients who were randomized to receive an ICD or conventional
medical care. All of the patients had a history of myocardial
infarction and low left ventricular ejection fraction.

The team used a variety of data to calculate hospital and other
costs, and calculated the incremental cost-effectiveness ratio
(iCER) based on costs and life expectancy within 3.5 years.

Over this study period, the average survival gain in ICD patients
was 2 months at an additional cost of $39,200. The iCER was $235,000
per year of life saved. However, in alternative projections for 12
years, the iCER ranged from $78,600 to $114,000.

The researchers note that they did not present iCERs based on
quality-adjusted life years, which may have led to a higher cost-
effectiveness.

They conclude that although estimated costs per year of life saved
over a period of 3.5 years were relatively high, the figure "is
projected to be substantially lower over the course of longer time
horizons."

J Am Coll Cardiol 2006;47:2310-2318

Somatic mutations in the gene for the gap-junction protein connexin
40 (GJA5), a cardiac protein that coordinates atrial electrical
activity, may account for some cases of atrial fibrillation that are
considered idiopathic, new research suggests. The authors believe
connexin 40 could serve as a target for novel antiarrhythmic agents.

"A fair proportion of individuals do not have an obvious cause for
their atrial fibrillation," lead author Dr. Michael H. Gollob, from
the University of Ottawa Heart Institute in Ontario, Canada, told
Reuters Health. The study results suggest that up to one third of
these cases may actually be due to mutations in GJA5, he added.

The findings, which appear in The New England Journal of Medicine
for June 22, are based on an analysis of GJA5 in cardiac tissue and
lymphocytes obtained from 15 patients with idiopathic atrial
fibrillation.

Four of the patients had heterozygous missense mutations in GJA5. In
three of the patients, the mutations were noted in cardiac tissue,
but not in lymphocytes, indicating a somatic origin for the defects.
In the fourth patient, the mutation was in both cell types,
suggesting a germ-line basis for the defect.

Functional testing of the GJA5 mutations revealed impairments in
intracellular transport or electrical coupling, the report indicates.

"Our findings suggest that connexin 40 should be considered a target
for the development of novel drugs in the treatment of atrial
fibrillation," Dr. Gollob said. "Current antiarrhythmic agents
target many nonspecific proteins that may or may not be involved in
the etiology of atrial fibrillation."

But the new findings may have implications beyond the etiology or
treatment of atrial fibrillation, Dr. Gollob said.

"Our study provides data for a very novel paradigm: common so-called
idiopathic diseases may, in fact, have a genetic basis with the
defect being confined to the diseased tissue," he explained. "It is
a common concept in cancer genetics, but not in everyday diseases
like atrial fibrillation."

N Engl J Med 2006;354:2677-2688