Israel Medical Association Journal

Classic anticoagulant drugs, such as heparin and warfarin, are very effective. Although in use for more than 50 years, they have some clinical drawbacks. Heparin, now better termed unfractionated heparin, can only be used intravenously and its laboratory control is complicated. Warfarin is orally administered, but its therapeutic window is very narrow and patients need repeated laboratory tests. Moreover, both drugs are non-specific, as they inhibit the coagulation cascade at several steps. Pharmaceutic research has developed new drugs, some of which are already on the market, such as fondaparinux, a pentasaccharide that can interact with antithrombin, thus inhibiting factor Xa. This pentasaccharide is part of the parent heparin molecule and can be chemically synthesized, with the advantage of avoiding extractive compounds. Fondaparinux has a half-life compatible with once-a-day administration; modification of its structure (idraparinux) has led to more stable binding with antithrombin and to an increase in its half-life to allow once-a-week administration. Alternatives to oral anticoagulants have been developed following the study of some compounds like hirudin, which directly binds thrombin and blocks its catalytic site. One of these molecules, ximelagatran, is in advanced clinical development. Ximelagatran is converted into its active form, melagatran, in the circulation, and thrombin activity can be blocked by oral administration twice daily. There is no need for laboratory control and phase II and phase III studies are encouraging. The next few years should bring great changes in the treatment of patients with thromboembolic disorders.

Background: Reports from Europe and North America indicate that significant changes have occurred in the practice of cardiac surgery in the last two decades.

Objectives: To examine the trends and case-mix in cardiac surgery in Israel and their relationship with changes in invasive cardiology.

Methods: We analysed data collected by the Ministry of Health from all cardiac centers in Israel from 1985 to 2002.

Results: Three periods were identified: the 1980s, when a relatively small number of operations were performed; 1990–1994, characterized by a dramatic rise in the number of operations; and 1994–present, characterized by a small decline and stabilization in the rate of operations. The percentage of valve procedures increased significantly from 15% of all cardiac surgeries in 1991 to 21% in 2002 (P = 0.002). In addition, the chance of a diagnostic coronary angiography being followed, in the same patient, by an interventional procedure such as percutaneous transluminal coronary angioplasty or by a coronary artery bypass graft increased dramatically from 42% in 1991 to 69% in 2002. At Rabin Medical Center, there was a constant decline in the percent of repeated CABGs[1] out of the total CABGs performed, from 6.7% in 1996 to 1.3% in 2002.

Conclusions: Despite the rise in the rate of percutaneous coronary interventions since 1991, there has been no significant decline in the rate of CABGs performed. However, there is a significant shift to more complex operations. The number of repeated CABG operations has significantly decreased and, in view of the growing use of arterial grafts and further improvements in invasive cardiology techniques, we expect this decline to continue.

Background: Reperfusion practices have changed markedly over the last few years with the introduction of primary percutaneous coronary intervention. This technique has gained growing popularity in Israel, but little published data are available regarding the delays to primary PCI[1] in real life in this country.

Objectives: To examine temporal trends in time to reperfusion achieved in a large tertiary center over 6 years.

Results: Between 1997 and 2002, 1,031 patients were admitted to our hospital with ST elevation myocardial infarction. Of these, 62% underwent thrombolysis and 38% primary PCI. The proportion of patients referred for primary PCI increased steadily, from 14% in 1997 to 68% in 2002. Door to treatment time among patients referred for thrombolysis or primary PCI was 54 ± 42 and 117 ± 77 minutes, respectively (P < 0.00001). The door to needle time in patients given thrombolysis remained virtually unchanged during the study period at around 54 minutes. In contrast, the door to balloon time has progressively and substantially decreased, from 175 ± 164 minutes in 1997 to 96 ± 52 minutes in 2002.

Conclusions: There is a steady increase in the proportion of patients referred for primary PCI than for thrombolysis. The door to needle delay in patients given thrombolysis substantially exceeds the recommended time. The door to balloon time has declined considerably but still slightly exceeds the recommended time. Given the inherent delay between initiation of lysis and arterial recanalization, it appears from our experience that PCI does not substantially delay arterial reperfusion as compared to thrombolysis. Efforts should continue to minimize delays to reperfusion therapy.

Background: Which medical specialties do Israeli medical graduates choose? Answers to this question can serve as an essential means of evaluating both Israeli medical education and the healthcare system.

Objectives: To determine the distribution of medical specialty choice, its change over time and the posible influence of the medical school on the choice; to study the graduates’ gender, gender variability in specialty choice of family medicine as a career among the graduates as a group, by medical school, gender, and time trends.

Method: The study population comprised all graduates of the four medical schools in Israel during 16 years: 1980-1995 inclusive. Data were obtained from the four medical schools, the Israel Medical Association’s Scientific Council, and the Ministry of Health. Data allowed for correct identification of two-third of the graduates.

Results: A total of 4,578 physicians graduated during this period. There was a significant growth trend in the proportion of women graduates from 22.6% in 1980 (lowest: 20.0% un 1981) to 35.3 in 1995 (highest: 41.5% in 1991). Overall, 3,063 physicians (66.8%) started residency and 1,714 (37.4%) became specialists. The four most popular residencies were internal medicine. Ten percent of Israeli graduates choose family medicine.

Conclusions: The overall class size in Israel was stable at a time considerable population change. Women’s place in Israeli medicine is undergoing significant change. Family medicine is one of the four most popular residencies. Amonitoring system for MSC in Israel is imperative.
 

Objectives: To assess mortality causes and trends over time and identify target groups with excessive mortality rates among Israeli youth aged 10-24, in order to formulate an intervention policy for prevention of adolescent mortality.

Methods: Mortality data for Israeli residents aged 10-24 were extracted from the Central Bureau of Statistics compu­terized death certificate file for the period 1984-95. Trends were evaluated by cause of death and demographic char­acteristics.

Results: The crude mortality rate among Israeli youth aged 10-24, during 1993-1995, was 39.6 per 100000. Rates were 2.7 times higher among males, increased with age, and reached a peak among 18-21 year olds. Rates were 1.4 times higher among Arabs than among Jews. The sharp increase in mortality among Jewish males of military service age (18-21 years) was due mainly to motor vehicle crashes and suicide. Although overall mortality decreased by 9.4% from 1984-86 to 1993-95, the gap between the subgroups increased. MVC­related mortality increased over time by 100% among Arab males. The rate of completed suicide among Jewish males increased by 110%. Although injury-related mortality is lower in Israel compared with the U.S., similar demographic differen­tials and trends were found in both countries.

Conclusions: Suicide among Jewish males of military service age, as well as MVC fatalities among Arab males, present a growing public health issue. Intervention strategies should therefore be targeted towards these subgroups in order to minimize the rates of preventable death.

Cancer is a multi-step disease involving a series of genetic alterations that result in the loss of control of cell proliferation and differentiation. Such genetic alterations could emerge from the activation of oncogenes and the loss or malfunctioning of tumor suppressor gene activity. Our understanding of cancer has greatly increased through the use of DNA tumor viruses and their transforming proteins as a biological tool to decipher a cascade of events that lead to deregulation of cell proliferation and subsequent tumor formation. For the past ten years our laboratory has focused on the molecular biology of the human neurotropic papovavirus, JCV. This virus causes progressive multifocal Ieukoencephalopathy, a fatal neuro­degenerative disease of the central nervous system in immunocompromised patients. JCV is a common human virus that infects more than 80% of humans but does not induce any obvious clinical symptoms. The increased incidence of acquired immune deficiency syndrome and the use of immunosuppressive chemotherapy have dramatically raised the incidence of PML. The coincidental occurrence of malignant astrocytes and oligodendrocytes in PML patients, coupled with the induction of glioblastoma in JCV-intected non­human primates, provides intriguing speculation on the association between JCV and CNS malignancies. In this report we discuss clinical data and laboratory observations pointing to the direct involvement of JCV in cancer.

Objectives: To analyze the incidence of mesothelioma in Israel during the years 1960-96, and to project its trend for the following years.

Methods: We conducted a population-based study of the incidence of mesothelioma reported to the Israel Cancer Registry during 1960-96. Time trends were analyzed from data on the annual import of asbestos to Israel, which may indicate the magnitude of past exposure. Based on these findings, trends in the incidence of mesothelioma in Israel were projected for the subsequent years.

Results: A total of 327 cases of mesothelioma were reported to the Israel Cancer Registry during the study period. The incidence in Jews was higher than in Arabs (age-standardized incidence rate 2.64 vs. 1.35 per million/year, respectively). Among the Jewish population, Israeli-born males and males born in Europe and America showed the highest incidence (ASR 4.23 and 4.15 per million/year, respectively). Israeli-born males were 20 years younger than Jewish males born elsewhere. The incidence was twice as high among males than females and increased sevenfold from its nadir (1.17 per million/year) in 1978--80 to its peak (8.5 per million/year) in 1993-96. During a similar period the incidence among females increased from 0.33 to 2.56 per million/year. The incidence in both sexes does not appear to level off. The large wave of immigration from the former Soviet Union that began in 1989 only partly accounts for the increased incidence in 1993-96. The time trend in the incidence of mesothelioma in both sexes parallels the use of asbestos in Israel, which peaked in the years 1976-78.

Conclusions: The incidence of mesothelioma in Israel has increased sharply in recent years, unrelated to a wave of immigration from East Europe, and is predicted to continue to rise for another 10-15 years.