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עמוד בית
Mon, 25.11.24

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July 2002
Paul E. Slater, MD, MPH, Emilia Anis, MD, MPH and Alex Leventhal, MD, MPH, MPA

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.

Raymond Kaempfer, PhD, Gila Arad, PhD, Revital Levy, BA and Dalia Hillman, BA

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.
 

Eyal Robenshtok, MD, Shay Luria, MD, Zeev Tashma, PhD and Ariel Hourvitz, MD

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.

Amir Vardi, MD, Inbal Levin, RN, Haim Berkenstadt, MD, Ariel Hourvitz, MD, Arik Eisenkraft, MD, Amir Cohen, MD and Amital Ziv, MD

With chemical warfare becoming an imminent threat, medical systems need to be prepared to treat the resultant mass casualties. Medical preparedness should not be limited to the triage and logistics of mass casualties and first-line treatment, but should include knowledge and training covering the whole medical spectrum. In view of the unique characteristics of chemical warfare casualties the use of simulation-assisted medical training is highly appropriate. Our objective was to explore the potential of simulator-based teaching to train medical teams in the treatment of chemical warfare casualties. The training concept integrates several types of skill-training simulators, including high tech and low tech simulators as well as standardized simulated patients in a specialized simulated setting. The combined use of multi-simulation modalities makes this maverick program an excellent solution for the challenge of multidisciplinary training in the face of the looming chemical warfare threat.

Ronen Rubinshtein, MD, Eyal Robenshtok, MD, Arik Eisenkraft, MD, Aviv Vidan, MD and Ariel Hourvitz, MD

Recent events have significantly increased concern about the use of biologic and chemical weapons by terrorists and other countries. Since weapons of mass destruction could result in a huge number of casualties, optimizing our diagnostic and therapeutic skills may help to minimize the morbidity and mortality. The national demands for training in medical aspects of nuclear, biologic and chemical warfare have increased dramatically. While Israeli medical preparedness for non-conventional warfare has improved substantially in recent years especially due to extensive training programs, a standardized course and course materials were not available until recently. We have developed a core curriculum and teaching materials for a 1 or 2 day modular course, including printed materials.

Jehuda Hiss, MD, Maya Freund, PhD, Uzi Motro, PhD and Tzipi Kahana

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.

Gidon Almogy, MD, Arnon Makori, MD, Oded Zamir, MD, Alon J. Pikarsky, MD and Avraham I. Rivkind, MD
Dorith Shaham, MD, Tamar Sella, MD, Arnon Makori, MD, Liat Appelbaum, MD, Avraham I. Rivkind, MD and Jacob Bar Ziv, MD
Adi Yagur, MD, Alexander Grinshpoon, MD and Alexander Ponizovsky, MD, PhD

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.

Alina Weissman-Brenner, MD, Avi David, Avi Vidan, MD and Ariel Hourvitz, MD

Background: Organophosphates (OP) are frequently used as insecticides in the household and in agricultural areas, thus posing a risk for accidental exposure.

Objectives: To describe the characteristics, clinical course and outcome of 97 patients admitted to emergency rooms with a diagnosis of acute OP poisoning.

Methods: The clinical details of 97 patients were collected from 6 different hospitals in Israel. Diagnosis of intoxication was based on clinical findings, butyrylcholinesterase levels and, in several cases, the material brought to the hospital. Demographic, intoxication and clinical data were analyzed.

Results: The study group comprised 64 men and 33 women whose age range was 1–70 years old (mean 19.8 ± 17.1); more than one-third of the patients were less than 10 years old. Accidental exposure was the cause of intoxication in 51.5% of the patients, and suicide in 20.6% of exposures. Intoxication occurred at home in most patients (67%), and the route of intoxication was oral in 65% of them. The patients arrived at the hospital 20 minutes to 72 hours after intoxication. Nine patients were asymptomatic; 53 presented with mild intoxication, 22 with moderate, and 13 had severe intoxication, 5 of whom died. There was a direct correlation between the degree of inhibition of butyrylcholinesterase levels and the severity of intoxication. Treatment included decontamination and antidotal medication. Duration of hospitalization ranged between 1 and to 14 days (average 2.9 days).

Conclusions: Organophosphates may cause severe morbidity and mortality. Medical staff should therefore be aware of the clinical manifestations and the antidotal treatment for this poisoning.
 

June 2002
E. Michael Sarrell, MD, Avigdor Mandelberg, MD, Herman Avner Cohen, MD and Ernesto Kahan, MD, MPH

Background: Primary care physicians' adherence to accepted asthma guidelines is necessary for the proper care of asthma patients.

Objectives: To investigate the compliance of primary care physicians with clinical guidelines for asthma treatment and their participation in related educational programs, and to evaluate the influence of their employment status.

Methods: A questionnaire was administered to a random sample of 1,000 primary care practitioners (pediatricians and family physicians) in Israel.

Results: The response rate was 64%. Of the physicians who participated, 473 (75%) had read and consulted the guidelines but only 192 (29%) had participated in an educational program on asthma management in the last 12 months. The younger the responding physician (fewer years in practice), the more likely his/her attendance in such a program (P<0.0001). After consulting the guidelines 189 physicians (40%) had modified their treatment strategies. Significantly more self-employed than salaried physicians had read the guidelines and participated in educational programs; physicians who were both self-employed and salaried fell somewhere between these groups. This trend was not influenced by years in practice.

Conclusions: All primary care physicians should update their knowledge more often. The publication of guidelines on asthma must be followed by their proper dissemination and utilization. Our study suggests that major efforts should be directed at the population of employed physicians.

Nurit Rosenberg, PhD, Ariella Zivelin, PhD, Angela Chetrit, PhD, Rima Dardik, PhD, Nurit Kornbrot, MSc, Dov Freimark, MD and Aida Inbal, MD

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.






[1] AMI = acute myocardial infarction


Gabriel Izbicki, MD, David Shitrit, MD, Dan Aravot MD, Gershon Fink, MD, Milton Saute, MD, Leonid Idelman, MD, Ilana Bakal, BA, Jaqueline Sulkes, PhD and Mordechai R. Kramer, MD

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. 

Alexander Guber, MD, Eyal Morris, MD, Baruch Chen MD and Shaul Israeli, MD

Background: Ventilator-dependent patients represent an increasing clinical, logistic and economic burden.  An alternative solution might be monitored home care with high-tech ventilatory support systems. 

Objectives: To explore the implications of such home-care management, such as its impact on quality of life and its cost-effectiveness, and to assess the practical feasibility of this mode of home care in Israel.

Methods: We surveyed 25 partly or fully home-ventilated patients (17 males and 8 females), average age 37.6 years (range 1–72), who were treated through a home-care provider during a 2 year period.

Results: Most patients (n=18) had a neuromuscular respiratory disorder.  The average hospital stay of these patients prior to entry into the home-care program was 181.2 days/per patient.  The average home-care duration was 404.9 days/per patient (range 60–971) with a low hospitalization rate of 3.3 ± 6.5 days/per patient.  The monthly expenditure for home care of these patients was one-third that of the hospital stay cost ($3,546.9 vs. $11,000, per patient respectively).  The patients reported better quality of life in the home-care environment, as assessed by the Sickness Impact Profile questionnaire. 

Conclusions: Home ventilation of patients in Israel by home-care providers is a practical and attractive treatment modality in terms of economic benefits and quality of life.
 

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