(Complimentary Newsletter from Target Health Inc.)
[Home] [Target e*CRO] [Target e*CRF] [Publications] [Press Release] [Advisors] [FDA Process] [Advertising]
15 May 2006
I.
WHAT'S NEW?
Annual
DIA Meeting
II. QUIZ
(Fill In The Blanks)
Mother's
Day Quiz - When Only Mothers’ Milk Will Do
III.
HISTORY OF MEDICINE
Julius
Cohnheim (1839-1884)
IV. CARDIOLOGY
Genetic Basis For Coronary Heart Disease
V. NEUROLOGY
C-Reactive Protein Levels and Stroke Outcome
VI. WOMEN'S HEALTH
Can an Eye Exam Predict Risk of Stroke and Cerebral Infarction?
VII. PUBLIC HEALTH
How Do Brains of Drug Abusers Work?
VIII. FDA
FDA Approves New Treatment For Smoking
IX. Target Health Inc.
Annual DIA
Meeting
Target Health is pleased
to announce that Dr. Mitchel will be presenting a talk on Data Standards at the
annual DIA meeting in Philadelphia,. The talk will take place on Tuesday, June
20, 2006 at 10:30 am, and we will share our extensive experience based on over
80 electronic data capture (EDC) studies with multiple clients. Please also
visit our booth (1956) and let us know if you will be coming. We will be presenting demos of our new
EDC software as well as Target Encoder. For more information, please contact Dr.
Jules T. Mitchel.
Mother's Day Quiz - When Only
Mothers’ Milk Will Do
Before a wallaby
migrates to its mother’s pouch, it is barely the size of a human 1) ___. It
lacks a developed 2) ___ system, relying on compounds in its mother's milk to
protect it against 3) ___. Now a unique antimicrobial has been discovered in
wallaby milk that could be used in hospitals to fight deadly
antibiotic-resistant 4) ___. Wallabies are 5) ___, born with a heart, but no 6)
__. Tammar wallabies (Macropus eugenii) crawl into their mother's pouch,
where they latch onto milk-bearing teats. A great deal of development takes
place in the pouch. During that time, wallabies rely only on 7) __. It has been
discovered that the mother's milk contains a 8) ___ that is 100 times more
effective than the most potent form of 9) ___, against Gram-negative bacteria
such as E. coli. The molecule, called AGG01, also kills four types of
Gram-positive bacteria and one type of 10) __. The work was presented at the US
Biotechnology Industry Organization 2006 meeting in Chicago in April 2006.
AGG01 was probably lost from placental mammals, whose young have their own
immune systems, when they split from marsupials.
Answers: 1) fetus; 2)
immune; 3) pathogens; 4) bacteria; 5) marsupials; 6) lungs; 7) milk; 8)
molecule; 9) penicillin; 10) fungus
Julius Cohnheim
(1839-1884)
Julius Cohnheim, a pupil of
Virchow, was born at Demmin in Pomerania (now northwest Poland and northeast
Germany), and trained in Wurzburg and Berlin. Cohnheim’s major contributions
were in experimental pathology, and in particular in demonstrating that
inflammation was an active dynamic process. He described the diapedesis of
leucocytes (movement or passage of blood cells through intact capillary walls
into surrounding body tissue) as follows: In the veins "..the originally
plasmatic zone becomes filled with innumerable colouless corpuscles. A pointed
projection is seen in the external contour of the vessel wall...this grows
longer and thicker, throws out fresh points, and gradually withdraws itself
from the vessel wall, with which it is at last connected only by a long thin
pedicle. Finally ...there lies outside the vessel ..a colourless blood
corpuscle."
Genetic Basis For Coronary
Heart Disease
Coronary heart
disease is a major public health problem, with approximately 1.2 million
Americans estimated to experience a coronary heart disease (CHD) event this
year. According to an article published in Human Molecular Genetics
(2006;15:1640-1649), it has been observed that a common genetic variation
(polymorphism) makes some people more susceptible to CHD. Caucasians who carry
this gene variation, named K55R, are approximately 1.5 times more likely to
have a CHD event, such as a heart attack, than those who do not have the gene
variation, independent of other risk factors, like cigarette smoking, diabetes,
and hypertension. About 15% of all Caucasians have this particular
polymorphism. Preliminary findings showing that people who smoked and carried
K55R gene variation were at the highest risk for CHD. This same association was
not observed in African Americans who had the same K55R polymorphism.
Caucasians with the K55R polymorphism had an accelerated break down of
beneficial fatty acids called epoxyeicosatrienoic acids or EETs, which are
known to play a protective role in the cardiovascular system. These fatty acids
help to lower blood pressure, prevent blood clotting and fight inflammation.
The K55R polymorphism is a naturally-occurring, inherited variation of EPHX2,
the epoxide hydrolase gene. EPHX2 generates an enzyme that rids the body of
beneficial EET fatty acids, as part of normal human metabolism. In people with
the K55R polymorphism, this normal process is accelerated and even more of the
protective EETs are lost. According to the authors, the study builds on a body
of evidence suggesting the importance of this gene and its fatty acid products
in the cardiovascular system. It also suggests that this metabolic pathway may
serve as a useful target for the prevention or treatment of cardiovascular
disease. For the study, 2,065 participants were genotyped for ten known
polymorphisms in the EPHX2 gene. Participants of this study were part of a
larger study, the Atherosclerosis Risk in Communities (ARIC) Study, a long-term
study consisting of nearly 16,000 men and women age 45-64 from four diverse
communities in the US. The study, which started in 1987, seeks to investigate
and identify cardiovascular disease risk factors in men and women.
C-Reactive Protein Levels
and Stroke Outcome
It is well known
that after acute stroke, increased levels of C-reactive protein (CRP), measured
at discharge, predict unfavorable clinical outcomes. As part of a followup
investigation, published in Stroke (2006;37:1205-1210), a study was performed
to investigate whether CRP measured before tissue plasminogen activator (tPA)
treatments may add prognostic information to guide stroke treatment. Study
participants included 151 consecutive patients with an ischemic stroke
involving the middle cerebral artery territory who received tPA within 3 hours
of symptom onset. High-sensitivity CRP was measured before tPA administration,
and CRP gene polymorphisms were determined (G1059C and C1444T). Functional
outcome was evaluated by 3-month modified Rankin Scale (mRS). A total of 143
tPA-treated patients were valid for analyses after exclusion of those with
inflammatory diseases and those probably infected (CRP >6 mg/dL). Patients
with history of previous stroke, hypertension, or atrial fibrillation had the
highest levels of CRP (P<0.05). CRP was higher in patients who died after
thrombolysis (n=19) than in survivors (0.85 versus 0.53 mg/dL; P=0.002). Among
the 94 patients with proximal middle cerebral artery occlusions, CRP level was
0.53 for 81 survivors versus 0.81 mg/dL for 13 who died (P=0.001). CRP-survival
association was found even among patients who recanalized by the end of tPA
infusion (P=0.007). A correlation between CRP and mRS was also found (r=0.36,
P=0.02), although CRP polymorphisms were not related to neurological outcome.
In a logistic regression model, CRP and age were the only baseline mortality
predictors. According to the authors, CRP levels at the time of hospital
admission predict mortality among tPA-treated stroke patients, and that very
early recanalization does not ameliorate the negative prognostic impact of
elevated CRP.
Can an Eye Exam Predict
Risk of Stroke and Cerebral Infarction?
Because they share many
features with cerebral vessels, retinal vessels may provide information on
cerebral vascular pathology. While it has been reported that a smaller ratio of
the retinal arteriolar-to-venular diameters predicts the risk of stroke, it is
unclear if this is due to arteriolar narrowing or venular dilation. As a
result, a study published in the journal Neurology (2006;66:1339-1343), was
performed to investigate whether smaller arteriolar or larger venular diameters
are related to the risk of stroke and cerebral infarction. The study was based
on the prospective population-based Rotterdam Study and included 5,540
participants of 55 years or over, who had gradable fundus transparencies and
were free of stroke at baseline (1990 to 1993). For each participant, retinal
arteriolar and venular diameters were measured on digitized images of one eye.
After a mean follow-up of 8.5 years, 411 participants had a stroke, of whom 259
had cerebral infarction. Results showed that larger venular diameters were
associated with an increased risk of stroke and cerebral infarction. Smaller
arteriolar diameters were neither related to the risk of stroke nor to the risk
of cerebral infarction. After additional adjustment for other cardiovascular
risk factors, the results did not change. According to the authors, larger
retinal venular diameters are associated with an increased risk of stroke and
cerebral infarction, and that the role of venules in cerebrovascular disease
warrants further exploration.
How Do Brains of Drug
Abusers Work?
According to an article
published in the journal Science (2006;312:754-758), in what is the first brain
imaging study of the feeling of dread in substance abusers, it has been shown
that drug users who experience substantial dread about an adverse experience
can be biologically distinguished from those who can better tolerate the
experience. These results may offer unique insight into the biological
mechanisms involved in decision-making, which is invaluable in developing
tailored treatment strategies for addiction and drug abuse. The reason is that
there is substantial evidence that drug abusers place more value on short-term,
rather than long-term outcomes. For the study, functional magnetic resonance
imaging (fMRI) was used to create images of brain activity in 32
nondrug-abusing participants awaiting brief electrical shocks to their feet. By
charting which regions experience increased blood flow over time, fMRI allowed
for the understanding of the relationship between particular types of mental
activity and specific areas of the brain. Results showed activity patterns
associated with the dread of waiting involved areas of the brain that govern
human pain perception. Specifically, the responses were seen in brain areas
that appear to be ruled by attention, more than regions associated with fear.
For the study, each participant's maximal pain threshold was initially
determined. The participant was then presented with a series of choices from 36
possibilities. For example, each person could elect to receive a shock that was
30% of their threshold in 27 seconds or one that was 60% in 9 seconds. It was
noted that normal, healthy subjects could be divided into two groups: 1)
extreme dreaders, who could not tolerate a delay and preferred an immediate
(and stronger) painful stimulus; and 2) mild dreaders, who could tolerate a
delay for a milder shock. Interestingly, extreme dreaders could be
distinguished from the mild dreaders by virtue of the information captured on
the brain scans. The findings suggest that dread derives, in part, from the
attention devoted to the expected physical response and is not simply a fear or
anxiety reaction. According to the authors, continuing to use drugs despite the
expectation of the practice's negative effects is a hallmark of addiction, and
that the results of the study form the foundation for future research to
determine whether drug abusers exhibit disruption in the brain systems that
process the anticipation of unpleasant consequences.
TARGET HEALTH excels in
Regulatory Affairs and works closely with many of its clients performing all
FDA submissions. TARGET HEALTH receives daily updates of new developments at
FDA. Each week, highlights of what is going on at FDA are shared to assure that
new information is expeditiously made available.
FDA Approves New Pfizer
Drug For Smoking Cessation
According to the Centers for
Disease Control and Prevention (CDC), an estimated 44.5 million adults in the
United States smoke cigarettes and more than 8.6 million of them have at least
one serious illness caused by smoking. The FDA has just approved Chantix
(varenicline tartrate) tablets to assist in smoking cessation. The active
ingredient in Chantix, varenicline tartrate, is a new molecular entity that
received a priority FDA review because of its significant potential benefit to
public health. Chantix acts at sites in the brain affected by nicotine and may
help those who wish to give up smoking in two ways: by providing some nicotine
effects to ease the withdrawal symptoms and by blocking the effects of nicotine
from cigarettes if they resume smoking. The effectiveness of Chantix in smoking
cessation was demonstrated in six clinical trials, which included a total of
3,659 chronic cigarette smokers who were treated with varenicline. Five of the
six studies were randomized, controlled clinical trials in which Chantix was
shown to be superior to placebo in helping people quit smoking. These smokers
had previously averaged 21 cigarettes a day for approximately 25 years. In two
of the five placebo-controlled studies, Chantix-treated patients were also more
successful in giving up smoking than patients treated with Zyban (bupropion).
The approved course of Chantix treatment is 12 weeks. Patients who successfully
quit smoking during Chantix treatment may continue with an additional 12 weeks
of Chantix treatment to further increase the likelihood of long-term smoking
cessation. In clinical trials, the most common adverse effects of Chantix were
nausea, headache, vomiting, flatulence (gas), insomnia, abnormal dreams, and
dysgeusia (change in taste perception). Chantix is manufactured and distributed
by Pfizer, Inc.
For more information
about our expertise in Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.
TARGET HEALTH INC. (www.targethealth.com) is a full service
e*CRO with fulltime staff dedicated to all aspects of drug and device
development. Areas of expertise include Regulatory Affairs, comprising, but not
limited to, IND, IDE, NDA, PMA and 510(k) submissions, execution of Clinical
Trials, Project Management, Biostatistics and Data Management, Web Trials,
utilizing Target e*CRF™, our proprietary Internet-based Clinical Trial System,
and Medical Writing. TARGET HEALTH's Pharmaceutical Advisory Dream Team (PADT)
assists companies in strategic planning from Discovery to Market Launch. Let us
help you on your next project.
TARGET HEALTH INC.
261 Madison Avenue
24th Floor
New York, NY 10016
Phone: (212) 681-2100; Fax (212) 681-2105
Target Health
Ad
www.targethealth.com
Dr. Jules T. Mitchel,
President
Ms Joyce Hays, CEO
©2006 Target Health Inc. All rights reserved