16 December 2007
I. WHAT'S NEW?
Holiday Time at Target Health - We Are Closed December 25-January 1, 2007
II. QUIZ - (Fill In The Blanks)
Unraveling Where Chimp And Human Brains Diverge
III. HISTORY OF MEDICINE
Early Human May Have Carried Tuberculosis
IV. WOMEN'S HEALTH
Gender Differences in Acute Coronary Syndrome (ACS)
V. PUBLIC HEALTH
Smoking and Risk of Type 2 Diabetes
VI. OBSTETRICS
Mothers Who Smoke Negatively Affect Themselves and Their Offspring
VII.
REGULATORY AFFAIRS
FDA Completes Safety Review of Nexium and Prilosec
VIII. TARGET HEALTH
II. QUIZ
(Fill
In The Blanks)
Unraveling Where Chimp And Human Brains Diverge
Six million years ago, chimpanzees and humans diverged from a common ancestor and evolved into unique 1) ___. UCLA scientists have identified a new way to pinpoint the 2) ___ that separate us from our closest living relative -- and make us uniquely human. We share more than 95% of our genetic blueprint with chimps. What sets us apart from chimps are our 3) ___: homo sapiens means 'the knowing man. During evolution, changes in some genes alter how the human brain functions. Research has identified an entirely new way to identify these genes in the small portion of our DNA that differs from the chimpanzee's. By evaluating the correlated activity of thousands of genes, a UCLA team identified not just individual genes, but entire networks of 4) ___ genes whose expression patterns, within the brains of humans, varied from those in the chimpanzee. Genes don't operate in 5) ___ -- each functions within a system of related genes. If we examine each gene individually, it would be similar to reading every fifth word in a paragraph -- you don't get to see how each word relates to the other. So instead we use a systems biology approach to study each gene within its context. The scientists identified networks of genes that correspond to specific brain regions. When they compared these 6) ___ between humans and chimps, they found that the gene networks differed the most widely in the cerebral cortex -- the brain's most highly evolved region, which is three times larger in humans than chimps. They also discovered that many of the genes that play a central role in cerebral cortex networks in humans, but not in the chimpanzee, also show significant changes at the 7) ___ level. When we see alterations in a gene network that correspond to functional changes in the genome, it implies that these differences are very meaningful. This finding supports the theory that variations in the DNA sequence contributed to human evolution. Relying on a new analytical approach the UCLA team used data from DNA microarrays -- vast collections of tiny DNA spots -- to map the activity of virtually every gene in the 8) ___ simultaneously. By comparing gene activity in different areas of the brain, the team identified gene networks that correlated to specific brain regions. Then they compared the strength of these correlations between humans and chimps. Many of the human-specific gene networks identified by the scientists related to 9) ___, brain cell activity and energy metabolism. If you view the brain as the body's engine, findings suggest that the human brain fires like a 12-cylinder engine, while the chimp brain works more like a 6-cylinder engine. It's possible that our genes adapted to allow our brains to increase in size, operate at different speeds, metabolize energy faster and enhance 10) ___ between brain cells across different brain regions. Adapted from materials provided by University of California - Los AngelesIV. WOMEN'S HEALTH
Gender Differences in Acute Coronary Syndrome (ACS)
Coronary heart disease is the leading cause of death among U.S. women, and affects one in 10 women over the age of 18. Optimal diagnosis and timely treatment of patients with an acute coronary syndrome (ACS) depends on distinguishing differences between popular "myths" about ischemic symptoms in women and men. Chest pain or discomfort is regarded as the hallmark symptom of ACS, and its absence is regarded as "atypical" presentation. While chest pain is still the most common sign of a heart attack for most women, studies have shown that women are more likely than men to have symptoms other than chest pain or discomfort when experiencing a heart attack or other form of ACS. As a result, in order to assess whether women should have a symptom message that is separate or different from that for men, a study published in the Archives of Internal Medicine (2007;167: 2405 - 2413) was performed to evaluate the presenting symptoms of ACS in women compared with men. The study reviewed MEDLINE (1970-2005), bibliographies of articles, and pertinent abstracts focusing on studies of ACS presentation, especially those reporting differences in symptoms by gender. As a result, 69 of 361 possible studies were included in the analysis. Results showed that, depending on the size of the study (which ranged from large trials to single centers and interviews), between 30% and 37% of women did not have chest discomfort during a heart attack. In contrast, 17% to 27% of men did not experience chest discomfort. Overall, the majority of women and men had chest discomfort with a heart attack (two-thirds to three-quarters, depending on the study size). The authors also found that older people are more likely to have a heart attack without chest discomfort, and that women are more likely than men to experience other forms of cardiac chest pain syndromes, such as unstable angina, and they appear to report a wider range of symptoms associated with ACS. For example, women are more likely to report pain in the middle or upper back, neck, or jaw; shortness of breath; nausea or vomiting; indigestion; loss of appetite; weakness or fatigue; cough; dizziness; and palpitations. Absence of chest discomfort is a strong predictor for missed diagnosis and treatment delays. Noting that many studies excluded patients who did not report chest pain, the authors called for additional research from well-designed studies to further investigate gender differences in heart attack symptoms. The authors concluded that while women are significantly less likely to report chest pain or discomfort compared with men, these differences, however, are not likely large enough to warrant gender-specific public health messages regarding the symptoms of ACS at the present time, and that public health messages should continue to emphasize chest pain or discomfort, shortness of breath, and other common signs of heart attack.V. PUBLIC HEALTH
Smoking and Risk of Type 2 Diabetes
Observational studies have suggested an association between active smoking and the incidence of type 2 diabetes. As a result, a study published in the Journal of the American Medical Association (2007;298:2654-2664) conducted a systematic review with meta-analysis of studies assessing the association between active smoking and incidence of type 2 diabetes. For the study, data collection included search of MEDLINE (1966 to May 2007) and EMBASE (1980 to May 2007) databases, supplemented by manual searches of bibliographies of key retrieved articles, reviews of abstracts from scientific meetings, and contact with experts. Studies were included if they reported risk of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes in relationship to smoking status at baseline; had a cohort design; and excluded persons with diabetes at baseline. The literature search yielded 25 prospective cohort studies (N = 1.2 million participants) that reported 45,844 incident cases of diabetes during a study follow-up period ranging from 5 to 30 years. Of the 25 studies, 24 reported adjusted relative risks (RRs) greater than 1 (range for all studies, 0.82-3.74). The pooled adjusted RR was 1.44. Results were consistent and statistically significant in all subgroups. The risk of diabetes was greater for heavy smokers ( 20 cigarettes/day; RR, 1.61) than for lighter smokers (RR,1.29) and lower for former smokers (RR, 1.23). The authors concluded that active smoking is associated with an increased risk of type 2 diabetes and that future research should attempt to clarify its mechanisms and to establish whether the association is causal.VI. OBSTETRICS
Mothers Who Smoke Negatively Affect Themselves and Their Offspring
Parathyroid hormone (PTH) is the most important endocrine regulator of calcium and phosphorus concentration in extracellular fluid. This hormone is secreted from cells of the parathyroid glands and finds its major target cells in bone and kidney. A study published in the Journal of Pediatrics (2007;151:618-623) was performed to evaluate the effect of smoking on the vitamin D-PTH system during the perinatal period. For the study, 61 healthy women with singleton pregnancies and their newborns participated in a cohort study. Serum PTH and BsmI polymorphism of the vitamin D receptor gene, 25 hydroxyvitamin D (25(OH)D), 1,25 dihydroxyvitamin D, calcium, phosphorus, and bone alkaline phosphatase (bALP) were compared in a smoking group (n = 32) versus a non-smoking group (n = 29), controlling for lifestyle confounders. The mothers were examined at 30 to 32 weeks and 38 to 40 weeks of pregnancy, and the infants were examined at 2 to 3 days of postnatal life. Results showed that mothers who smoked and their newborns showed decreased serum PTH in pg/mL: (30-32 weeks, 26.9 vs. 37.1; 38-40 weeks, 32.2 vs. 46.2; newborns, 43.4 versus 64.1) and increased phosphorus. These differences reached statistical significance. Newborns of mothers who smoked also had significantly lower anthropometric measurements and serum 25(OH)D (14.2ng/mL versus 22.3, P = .009). In addition, pregnant women who smoked had lower bALP (30-32 weeks, 31U/L versus 44; 38-40 weeks, 55 vs. 97, P = .005). According to the authors, smoking during pregnancy negatively influences calcium-regulating hormones, leading to relative hypoparathyroidism in both the mother and their newborns.VII. REGULATORY AFFAIRS
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 Completes Safety Review of Nexium and Prilosec
Prilosec and Nexium are members of a class of drugs known as proton pump inhibitors (PPIs). Nexium (esomeprazole) is the newer formulation of the original Prilosec (omeprazole) product. As prescription products, they are used to treat the symptoms of gastroesophageal reflux disease (GERD) and other conditions caused by excess stomach acid. On May 29, 2007 AstraZeneca, the maker of Prilosec and Nexium, sent FDA data from two long-term studies in patients with severe gastroesophageal reflux disease (GERD) that were being treated with either Prilosec or Nexium. The studies were designed to assess the effectiveness of treatment with Prilosec, or Nexium, or surgery for severe GERD. Participants were randomly assigned to receive treatment with either a drug (Prilosec in one study and Nexium in the other) or surgery. During the studies, cardiovascular events raised a question about whether long-term use of these drugs increases the risk of heart attacks, heart failure, and heart-related sudden death in patients taking either one of the prescribed drugs compared to patients who received surgical treatment. On Aug. 9, 2007 FDA released an "Early Communication of an Ongoing Safety Review" of these drugs. The agency’s initial review determined that there was no increased risk of heart problems associated with long-term use of these drugs. At FDA’s request, AstraZeneca submitted a large amount of additional information about these and other studies and FDA undertook a comprehensive review of all available data regarding this potential safety concern. FDA has completed a comprehensive, scientific review of known safety data for the drugs Prilosec and Nexium. While both of the long-term studies reported to FDA on May 29, 2007 collected safety data, the study protocols did not specify how heart problems, such as heart attacks, were defined or verified. As a result, evaluating the information that was gathered about the safety of both drugs in these studies was challenging. FDA’s assessment of the information from the data gathered was further supported by an additional analysis of 14 comparative studies of Prilosec, four of which were placebo-controlled. Although these studies were not specifically conducted to assess the risk of heart problems, and patient follow-up was incomplete, they do not suggest an increased risk of heart problems with the use of Prilosec or Nexium. Based on everything now known at the agency, the reported difference in the frequency of heart attacks and other heart-related problems seen in the earlier analyses of the two small long-term studies does not indicate the presence of a true effect. Therefore, FDA continues to conclude that long-term use of these drugs is not likely to be associated with an increased risk of heart problems.VIII. TARGET HEALTH
TARGET HEALTH INC. (www.targethealth.com) is a full service eCRO with full-time 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 assists companies in strategic planning from Discovery to Market Launch. Let us help you on your next project.TARGET
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