Israel Medical Association Journal

Background: Open neural tube defects are among the most common malformations of the fetus. Secondary prevention by early diagnosis during pregnancy and abortion of affected fetuses result in a marked reduction of NTD incidence at birth. The dramatic effect of folic acid for primary prevention of these defects led to recommendations for folic acid supplementation in women of reproductive age.

Objective: To describe the epidemiologic features of NTD in Israel in 1999±2000.

Methods: A national registry of NTD was begun in 1999. During the years 1999±2000, a non-syndromic NTD was diagnosed in at least 394 pregnancies (166 anencephaly, 166 spina bifida, 43 encephalo-cele, and 19 with other types of NTD). The religious-ethnic affiliation was known in 392 cases (209 Jews and 183 non-Jews).

Results: Despite a marked decline in the rate of NTD at birth in the last few decades, the total rates during pregnancy did not change significantly, demonstrating that the changes were secondary to termination of affected pregnancies. At birth, NTD were almost four times more frequent among non-Jews (3.6 per 10,000 live births for anencephaly and 5.9 for spina bifida) than among Jews (anencephaly 1/10,000 live births, spina bifida 1.4/10,000 live births). The complete data of the registry showed an approximately twofold difference in the overall rates during pregnancy between Jews (anencephaly 5.3, spina bifida 4.6, total 11/10,000 live births) and non-Jews (anencephaly 8.8, spina bifida 10.3, total 22.3/10,000 live births). The registry demon-strated that the significant differences in NTD incidence observed at birth between Jews and non-Jews are secondary to a combined effect of a higher frequency of the malformations among non-Jews and a lower proportion of termination of affected pregnancies among non-Jews.

Conclusions: The data presented here will serve as a basis for evaluating the impact of the Ministry of Health recommendations for folic acid supplementation on the incidence of NTD.
 

Recent events have drawn world attention to “mythological diseases” such as anthrax, plague and smallpox, which have been out of the spotlight for some decades. Much of our current knowledge of epidemic intervention and disease prevention was acquired over history through our experience with these very diseases, such that the sudden panic over the re-emergence of these historically well-known entities is perplexing. Over time, changes in the balance of the epidemiologic triangle have driven each of these disease systems towards a new equilibrium with which we are not familiar. While the pathogens may be similar, these are not the diseases of the past. These new disease systems are insufficiently described by the classic epidemiologic triangle, which lacks a dimension necessary for providing a valid model of the real-world effects of bioterror-related disease. Interactions within the classic epidemiologic triangle are now refracted through the prism of the global environment, where they are mediated, altered, and often amplified. Bioterror-associated diseases must be analyzed through the epidemiologic pyramid. The added dimension represents the global environment, which plays an integral part in the effects of the overall disease system. The classic triangle still exists, and continues to function at the base of the new model to describe actual agent transmission, but the overall disease picture should be viewed from the height of the fourth apex of the pyramid. The epidemiologic pyramid also serves as a practical model for guiding effective interventional measures.

Because of its high case-fatality rate, its very high transmission potential, and the worldwide shortage of effective vaccine, smallpox tops international lists of over a dozen possible bioterror and biologic warfare agents. In a scenario involving aerosol variola virus release, tens to hundreds of first-generation cases would ensue, as would hundreds to thousands of subsequent cases resulting from person-to-person transmission. A smallpox outbreak in Israel must not be regarded as a doomsday event: the methods of smallpox outbreak control are known and will be implemented. The rapidity with which organized outbreak control measures are competently executed will determine how many generations of cases occur before the outbreak is brought under control. Planning, vaccine stockpiling, laboratory expansion, professional training and public education, all carried out well in advance of an epidemic, will minimize the number of casualties. The reinstitution of routine smallpox vaccination in Israel, as in other countries, must be given serious consideration, since it has the potential for eliminating the threat of smallpox as a bioterror agent.

Background: Previous studies have demonstrated myocardial salvage by basic fibroblast growth factor administration following chronic myocardial ischemia or acute myocardial infarction.

Objectives: To study the effect of bFGF[1] on left ventricular morphometry following coronary occlusion and reperfusion episode in rats.

Methods: bFGF (0.5 mg) or placebo was continuously administered for a period of one week using an implanted osmotic pump. Animals were sacrificed 6 weeks after surgery and myocardial cross-sections were stained with Masson-trichrome and with anti-proliferating cell nuclear antigen antibody.

Results: LV[2] area, LV cavity diameter, LV cavity/wall thickness ratio, and injury size were unchanged compared with control animals. Proliferating endothelial cells were significantly more abundant in injured compared with normal myocardium, but with no differences between animals treated or not treated with bFGF.

Conclusions: One week of systemic bFGF administration following coronary occlusion and reperfusion had no additional effect on LV geometry or cellular proliferation in rats.

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[1] bFGF = basic fibroblast growth factor

[2] LV = left ventricular

Background: The large number of cases of West Nile fever diagnosed in Israel in 2000 once again brought into focus the confusion that frequently accompanies the use of the term “epidemic”.

Objective: To examine the different definitions of the term “epidemic” and to propose ways in which it can be used to both improve communication among professionals and provide the public with a better sense of the associated risks.

Methods: The literature wes reviewed for the various definitions of the terms “epidemic” and “outbreak”. Sources included popular and medical dictionaries, ancient documents, epidemiology texts, legal texts, and the medical literature.

Result: The term epidemic is variously defined. The broad definition given by epidemiologists - namely, more disease the is anticipated by previous experience - is less meaningful to the general public. In some ways it conflicts with the definitions found in the popular literature, which generally imply danger to the public and a very large number of victims.

Conclusions: The interpretation of the term epidemic may vary according to the context in which it is used. For risk communication, we suggest that every effort be made to add descriptive terms that characterize the epidemic.

Background: The evaluation of hospitalized patients with chest pain and non-diagnostic electrocardiogram is problematic and the optimal cost-effective strategy for their management controversial.

Objectives: To determine the utility of myocardial perfusion imaging with thallium-201 for predicting outcome of hospitalized patients with chest pain and a normal or non-diagnostic ECG.

Methods: On pain cessation, 109 hospitalized patients, age 61+14 years (mean+SD), with chest pain and non-diagnostic ECG underwent stress myocardial perfusion SPECT imaging with thallium-201. Costs related to their management were calculated. The occurrence of non-fatal myocardial infarction or cardiac death was recorded at 12+5 months follow-up.

Results: A normal SPECT was found in 84 patients (77%). During one year follow-up, only 1 (1.2%) compared to 7 (28%) cardiac events (6 myocardial infarctions, 1 cardiac death) occurred in patients with normal versus abnormal scans respectively (P < 0.0001). Negative predictive value and accuracy of the method were 99% and 83% respectively. Multivariate regression analysis identified an abnormal SPECT as the only independent predictor of adverse cardiac event (P = 0.0016). Total cost from admission until discharge was 11,193 vs. 31,079 shekels (P < 0.0001) for normal and abnormal scan. Considering its high negative predictive value, shortening the hospital stay from admission until scan performance to 2 days would result in considerably reduced management costs (from NIS 11,193 to 7,243) per patient.

Conclusion: Stress SPECT applied to hospitalized patients with chest pain and a normal or non-diagnostic ECG is safe, highly accurate and potentially cost effective in distinguishing between Iow and high risk patients.
 

Background: Rectal administration of iodoacetamide induces colitis by blocking sulphhydryl groups and generating inflammatory mediators. Thalidomide, a non-barbiturate hyp­notic, also has an anti-inflammatory effect, presumably by suppressing the production of tumor necrosis factor alpha. In patients with Crohn’s disease, neutralization or suppression of TNFá reduces inflammation.

Objectives: To evaluate the effects of thalidomide in a model of experimental colitis.

Methods: Colitis was induced in rats by intracolonic administration of 3% iodoacetamide. In the treatment group, thalidomide 50 mg/kg was given daily by gavage and continued for 7 days until the rats were sacrificed. Their colons were then processed for wet weight, lesion area, weight of mucosal scraping, myeloperoxidase activity and histology. Serum levels of TNF were determined.

Results: Colonic wet weight, lesion area, myeloperoxidase activity and serum levels of TNFá were significantly lower (P<0.05) in the treatment group (iodoacetamide + thalido­mide) than the control group (iodoacetamide only). Histologi­cally, colonic inflammation in the treated group was markedly decreased.

Conclusions: Thalidomide effectively decreases colitis induced by iodoacetamide. The mechanism is probably associated with inhibition of TNFá, and should be further studied.
 

The novel neuropeptides hypocretin/orexin have recently been located on the lateral hypothalamus cells. This system has been linked to the regulation of both feeding and sleep, and recent studies have found an association between a defect in these neuropeptides and narcolepsy. We conducted a MED­LINE review of all the articles published since the discovery of hypocretin/orexin peptides, narrowing the field to the relation­ship between these neuropeptides and sleep. The finding of a deletion in the transcription of the hypocretin receptor 2 gene in narcoleptic Doberman pinschers and the development of a knockout of the hypocretin gene in mice pointed to the relevance of this system in the sleep-wake cycle. We provide further evidence of the role of the hypocretin/orexin system in narcolepsy and in sleep regulation and present an integrative model of the pathophysiology of narcolepsy. The discovery of the link between these peptides and narcolepsy opens new avenues to both the understanding of sleep mechanisms and therapeutic implications for sleep disorders.