Israel Medical Association Journal

The appearance of “new” infectious diseases, the reemergence of “old” infectious diseases, and the deliberate introduction of infectious diseases through bioterrorism has highlighted the need for improved and innovative infectious disease surveillance systems. A review of publications reveals that traditional current surveillance systems are generally based on the recognition of a clear increase in diagnosed cases before an outbreak can be identified. For early detection of bioterrorist-initiated outbreaks, the sensitivity and timeliness of the systems need to be improved. Systems based on syndromic surveillance are being developed using technologies such as electronic reporting and the internet. The reporting sources include community physicians, public health laboratories, emergency rooms, intensive care units, district health offices, and hospital admission and discharge systems. The acid test of any system will be the ability to provide analyses and interpretations of the data that will serve the goals of the system. Such analytical methods are still in the early stages of development.

Background: Superantigens produced by Staphylococcus aureus and Streptococcus pyogenes are among the most lethal of toxins. Toxins in this family trigger an excessive cellular immune response leading to toxic shock.

Objectives: To design an antagonist that is effective in vivo against a broad spectrum of superantigen toxins.

Methods: Short peptide antagonists were selected for their ability to inhibit superantigen-induced expression of human genes for cytokines that mediate shock. The ability of these peptides to protect mice against lethal toxin challenge was examined.

Results: Antagonist peptide protected mice against lethal challenge with staphylococcal enterotoxin B and toxic shock syndrome toxin-1, superantigens that share only 6% overall amino acid homology. Moreover, it rescued mice undergoing toxic shock. Antagonist peptides show homology to a β-strand/hinge/a-helix domain that is structurally conserved among superantigens, yet remote from known binding sites for the major histocompatibility class II molecule and T cell receptor that function in toxic T cell hyperactivation.

Conclusions: The lethal effect of superantigens can be blocked with a peptide antagonist that inhibits their action at the top of the toxicity cascade, before activation of T cells occurs. Superantigenic toxin antagonists may serve not only as countermeasures to biologic warfare but may be useful in the treatment of staphylococcal and streptococcal toxic shock, as well as in some cases of septic shock.
 

Atropine is the drug of choice for treatment of organophosphate (OP) nerve agent and insecticide intoxication and has been used for this indication for several decades. Adverse reactions to atropine may occur, and are of two types: toxic and allergic. Toxic reaction, the most common form, results from the anti-muscarinic effects of the drug. Since it is most probably related to interpersonal variation in sensitivity to atropine, toxic effects may appear at the usual therapeutic doses. The second type, allergic reaction, includes local manifestations, usually after the administration of eyedrops, and systemic reaction in the form of anaphylaxis. Since most patients manifest only a mild reaction, allergy testing is not performed and the prevalence of allergy to atropine is therefore not known. Severe allergic reaction to atropine is rare, as evidenced by the small number of case reports in the literature despite the drug's extensive use. Alternative anti-muscarinic drugs recommended for OP poisoning include glycopyrrolate and scopolamine. Glycopyrrolate is a peripheral anti-muscarinic drug that has been studied in comparison to atropine for many clinical indications, while scopolamine is an anti-muscarinic drug with both peripheral and central effects. An acceptable alternative regimen for patients with proven allergy to atropine is a combination of glycopyrrolate with centrally active drugs such as benzodiazepines or scopolamine.

Background: The majority (n = 445) of the Israeli and Palestinian fatal victims of the El Aqsa Intifada was examined at the National Center of Forensic Medicine in Tel Aviv. Analysis of the trauma sustained and the anthropologic profile of both the victims and the perpetrators elucidates the trends and contrasts them with the phenomenon in the past.

Objectives: The purpose of the forensic investigation of mass casualty incidents is manifold: establishing the minimal number of individuals involved, identifying the victims and perpetrators, collecting material evidence, and determining the modus operandi.

Methods: The postmortem examination includes external description of the bodies and their injuries, photo-documentation, and sampling of tissues. Radiography, dental examination, and a ten-print card of each cadaver are also recorded.

Results: The modus operandi of the current Intifada is somewhat different from that of the previous wave of terrorism and includes more road shootings and vehicular terrorism. In addition, three suicide bombers using explosive devices detonated within crowded areas were young women, and the age of the perpetrators has increased from up to 35 years to individuals as old as 47, thus greatly enlarging the potential number of suicide terrorists. Virologic and biologic tests have been introduced to examine the tissues of the suicide bombers since they are possible sources of contagion to the wounded victims.

Conclusion: The results of the medico-legal investigation of victims and perpetrators of terrorism enable us to establish the modus operandi and the profile of potential perpetrators, which can help in the prevention of similar attacks. Documentation of the different types of injuries in fatal victims of explosion and shooting contributes to improving the awareness of the medical staff treating the wounded of similar attacks. Further investigation into the reliability of virologic and biologic tests conducted on postmortem tissue is recommended.

Background: The ear is the most frequent organ affected during an explosion. Recognition of possible damage to its auditory and vestibular components, and particularly the recovery time of the incurred damage, may help in planning the optimal treatment strategies for the otologic manifestations of blast injury and preventing deleterious consequences.   

Objective: To report the results of the oto-vestibular initial evaluation and follow-up of 17 survivors of a suicidal terrorist attack on a municipal bus.

Methods: These 17 patients underwent periodic ear inspections and pure tone audiometry for 6 months. Balance studies, consisting of electronystagmography (ENG) and computerized dynamic posturography (CDP) were performed at the first time possible.

Results: Complaints of earache, aural fullness and tinnitus resolved, whereas dizziness persisted in most of the patients. By the end of the follow-up, 15 (55.6%) of the eardrum perforations had healed spontaneously. Hearing impairment was detected in 33 of the 34 tested ears. Recovery of hearing was complete in 6 ears and partial in another 11. ENG and CDP were performed in 13 patients: 5 had abnormal results on CDP while the ENG was normal in all the patients. The vertigo in seven patients resolved in only one patient who was free of symptoms 1 month after the explosion.

Conclusion:  Exposure to a high powered explosion in a confined space may result in severe auditory and vestibular damage. Awareness of these possible ear injuries may prevent many of the deleterious consequences of such injuries.
 

Background: The threat to the individual’s physical integrity and well-being as well as to those of significant others, the disruption of normal patterns of life, and property losses make wartime a highly stressful condition.

Objectives: To assess the level of psychological distress in primary care attenders in a district of Jerusalem (Gilo) that experienced long-term exposure to gunfire.

Methods: A self-administered questionnaire exploring emotional distress (anxiety and depression symptoms), fire exposure, patterns of help-seeking behavior, and prescription of sedative or hypnotic drugs was administered to a sample of 125 consecutive attenders to a general practitioner during a 10 week period in the autumn of 2001. Eighty-four attenders residing in Gilo were compared with 41 attenders residing in neighborhoods that had not been under fire. T-tests and Mann-Whitney two-sample tests were used to determine statistical significance of differences.

Results: The mean distress score was significantly higher among the Gilo residents than among their counterparts in other neighborhoods (1.1 ± 0.8 vs. 0.8 ± 0.5, t = 1.73, P <0.01); 15.5% of the former reported probable clinically significant distress. Emotional distress was associated with periods of intensive gunfire exposure, psychological care-seeking behavior, and the prescription of sedative or hypnotic drugs. No significant differences in distress levels were found between those living in zones of Gilo that were at differential gunfire risk, nor between those whose houses and cars were or were not damaged.

Conclusions: War-related life events would seem to be associated with elevated emotional distress. A motivated primary care physician could easily and reliably ascertain the attenders’ psychological status and identify those requiring psychological support. These identification and intervention stages are facilitated if the specialized services are community-based.

Background: Platelet adhesion and aggregation are mediated by specific platelet membrane glycoproteins GPIa/IIa, GPIba, and GPIIb/IIIa, and are essential steps in thrombus formation and development of acute myocardial infarction.

Objective: To evaluate the risks exerted by each of the following polymorphisms: HPA-1a/b in GPIIIa; 807C/T in GPIa; and HPA-2a/b, VNTR and Kozak C/T in GPIba in young males with AMI[1]..

Methods: We conducted a case-control study of 100 young males with first AMI before the age of 53 and 119 healthy controls of similar age. All subjects were tested for the above polymorphisms.

Results: The allele frequencies of each of the platelet polymorphism were not significantly different between the young men with AMI and the controls. Smoking alone was associated with a 9.97-fold risk, and the presence of at least one metabolic risk factor resulted in a 2.57-fold risk of AMI.

Conclusion: These results indicate that platelet glycoproteins polymorphisms are not an independent risk factor for AMI.

Background: Historically, donor age above 55 years has been considered to be a relative contraindication for organ transplantation. The shortage of organs for transplantation has led to the expansion of the donor pool by accepting older donors. 

Objectives: To compare the 1 year follow-up in patients after lung transplantation from older donors (>50 years old) and in patients after transplantation from younger donors (± 50 years).

Methods: The study group comprised all adult patients who underwent lung transplantation at the Rabin Medical Center between May 1997 and August 2001. Donors were classified into two groups according to their age: ≤ 50 years (n=20) and > 50 years (n=9). Survival, number and total days of hospitalization, development of bronchiolitis obliterans syndrome, and pulmonary function tests, were examined 1 year after transplantation.     

Results: We performed 29 lung transplantations in our center during the observed period. Donor age had no statistically significant impact on 1 year survival after lung transplantation. There was no statistically significant effect on lung function parameters, the incidence of hospitalization or the incidence of bronchiolitis obliterans between both donor age groups at 1 year after transplantation.

Conclusions: Donor age did not influence survival or important secondary end-points 1 year after lung transplantation. By liberalizing donor criteria of age up to 65 years, we can expand the donor pool, while assessing other possible mechanisms to increase donor availability. 

Background: Multiple factors are involved in the pathogenesis of hypertension in the obese individual.

Objective: To evaluate the role of a decrease in sympathetically mediated thermogenesis and the effect of the correlation between the plasma leptin and daily urinary nitric oxide levels on obesity-related hypertension.

Methods: We evaluated three groups: 25 obese hypertensive patients (age 45.7±1.37 years, body mass index 34.2±1.35 kg/m², systolic/diastolic blood pressure 155±2.9/105±1.3, mean arterial pressure 122±1.50 mmHg); 21 obese normotensive patients (age 39.6±1.72, BMI[1] 31.3±0.76, SBP/DBP[2] 124±2.1/85.4±1.8, MAP[3] 98.2±1.80); and 17 lean normotensive subjects (age 38.1±2.16, BMI 22.1±0.28, SBP/DBP 117±1.7/76.8±1.5, MAP 90.1±1.50). We determined basal resting metabolic rates, plasma insulin (radioimmunoassay), norepinephrine (high performance liquid chromatography) in all subjects. Thereafter, 14 obese hypertensives underwent a weight reduction diet. At weeks 6 (n=14) and 14 (n=10) of the diet the above determinations were repeated. Plasma leptin (enzyme-linked immunosorbent assay) and UNOx[4] (spectrophotometry) were assayed in 17 obese hypertensives and 17 obese normotensives, and in 19 obese hypertensives versus 11 obese normotensives, respectively.

Results: Obese hypertensive patients had significantly higher basal RMR[5] and plasma NE[6] levels. Insulin levels were lower in the lean group, with no difference between the hypertensive and normotensive obese groups. At weeks 6 and 14, BMI was significantly lower, as were insulin and NE levels. RMR decreased to values of normotensive subjects. MAP normalized but remained significantly higher than that of obese normotensives. Leptin blood levels and the leptin/UNOx ratio were significantly higher in the obese hypertensive compared to the obese normotensive patients. Both these parameters were strongly correlated to BMI, MAP⁵, RMR, and plasma NE and insulin .Obese hypertensive patients excreted less urinary NO metabolites. A strong correlation was found between MAP and the leptin/UNOx ratio.  

Conclusions: A reduction of sympathetically mediated thermogenesis, as reflected by RMR, results in normalization of obesity-related hypertension. In contrast, insulin does not seem to play a major role in the pathogenesis of hypertension associated with obesity. Increased leptin levels in conjunction with decreased NO production in the presence of enhanced sympathetic activity may contribute to blood pressure elevation in the obese.

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[1] BMI = body mass index

[2] SBP/DBP = systolic blood pressure/diastolic blood pressure

[3] MAP = mean arterial pressure

[4] UNOx = urinary nitric oxide

[5] RMR – resting metabolic rate

[6] NE = norepinephrine

The complex genetic nature of many common diseases makes the identification of the genes that predispose to these ailments a difficult task. In this review we discuss the elements that contribute to the complexity of polygenic diseases and describe an experimental strategy for disease-related gene discovery that attempts to overcome these factors. This strategy involves a population-based case-control paradigm and makes use of a highly informative, homogeneous founder population, many of whose members presently reside in Israel. The properties of single nucleotide polymorphisms, which are presently the markers of choice, are discussed, and the technologies that are currently available for SNP[1] genotyping are briefly presented.

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[1] SNP = single nucleotide polymorphism

This review summarizes the clinical, metabolic and genetic characteristics of early-onset type 2 diabetes in Mexico. Early-onset type 2 diabetes is both a clinical challenge and a public health problem. It is calculated that almost 300,000 Mexican diabetics are diagnosed between the ages of 20 and 40. The large Mexican family structure and the high prevalence of the disease provide a unique opportunity to identify the genes and the metabolic abnormalities involved in this form of the disease. In a hospital-based population, our group found that insulin deficiency was the main defect in this form of diabetes. Mutations in the HNF-1α or HNF-4α genes or autoimmunity to the beta cell were found in a small proportion of cases, leaving unexplained the majority of cases. Also discussed are the epidemiologic and therapeutic implications of early-onset type 2 diabetes, and the possible role of genetic testing for prevention.

Background: Clinical studies showing an association between immigration and increased prevalence of coronary risk factors or mortality rate in patients immigration is associated with greater risk among immigrants from the Soviet with coronary artery disease are scarce.

Objectives: To compare the risk profile and mortality of coronary patients born in Israel with those who immigrated to Israel, and to determine whether recent Union.

Methods: Demographic, clinical, and laboratory data were collected on chronic coronary artery disease patients from 18 Israeli medical centers during the screening period of the Bezafibrate Infarction Prevention Study in the early 1990s. Data on mortality after a mean 7.7 year follow-up were obtained from the Israel Population Registry.

Results: While significant differences in mortality (14.7% vs. 18.5%, P < 0.001) were observed between Israeli-born patients and immigrants respectively, the mortality in these groups was similar when compared within specific age groups. Immigrants suffered more from hypertension and angina pectoris, and their New York Heart Association functional limitation class was higher, as compared to their Israeli-born counterparts. A multivariate analysis of mortality comparing patients from the Soviet Union who immigrated after 1970 with those who immigrated before 1970 showed an increased risk for newer immigrants, with a hazard ratio of 1.69 (95% confidence interval 1.19-2.40) for those immigrating between 1970 and 1984, and 1.68 (95% CI[1] 1.01-2.28) for those immigrating between 1985 and 1991.

Conclusion: The worse profile and prognosis observed among patients who recently emigrated from the Soviet Union cannot be explained by traditional risk factors for CAD[2] such as smoking, diabetes, hypertension, and lipid disorders. Further investigation, including variables such as psychological stress to which immigrants are more exposed than others, is needed.

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