Thrombolytic Therapy or Primary Coronary Angioplasty in Acute Myocardial Infarction?

David Pereg, Shlomo Behar, Alexander Battler, Valentina Boyko, Shmuel Gottlieb, Jonathan Leor: Israel Thrombolytic Survey Group

Cardiology Division, Soroka Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba; Neufeld Cardiac Research Institute, Tel Hashomer and Tel Aviv University; and Cardiology Dept., Rabin Medical Center, Petah Tikva

There has been continuous debate over the superiority of primary percutaneous, transluminal, coronary angioplasty (PTCA) over thrombolysis for acute myocardial infarction (AMI). It was questioned whether this advantage of primary PTCA reported in selected populations by experienced centers can be replicated in our clinical practice.

We compared demographic and clinical variables, therapies and outcome in AMI treated with primary PTCA vs thrombolytic therapy. Clinical and demographic variables of 1,678 unselected AMI patients (admitted January/February and May/July 1996) were analyzed in 16 cardiac care units with on-site catheterization facilities and ability to perform PTCA. Of these 803 (48%) were treated by thrombolysis and 99 (6%) by primary PTCA.

The prevalence of adverse prognostic variables, such as anterior wall MI, heart failure on admission or during hospital stay, pulmonary edema, and ventricular tachycardia or fibrillation, was higher in the PTCA group. The 7-day, 30-day and 1-year mortality rates were similar in the 2 groups: 4%, 7.2% and 12.8%, respectively, in the PTCA group and 5%, 7.2% and 11.1% in the thrombolysis group. There was a trend toward lower mortality in subgroups of high-risk patients: those with heart failure on admission (Killip class >1), the elderly (>65 years), and those with previous MI treated with PTCA. After adjusting for confounders, treatment with primary PTCA was not found to be associated with lower mortality.

Only a small proportion of AMI patients in Israel were treated with primary PTCA in 1996. The frequency of adverse prognostic factors among them was higher but their short and long term outcomes were similar to those of high risk patients treated with thrombolysis.

Prolonged Neuromuscular Damage following Cortico-Steroids and Muscle-Relaxants

Yehonatan Sharabi, Eran Segal, Ehud Grossman

Dept. of Medicine D and ICU, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

Many patients mechanically ventilated for acute respiratory failure, are treated with medication that includes a combination of cortico-steroids and non-depolarizing neuromuscular-blocking agents (NNBa). A third of them can be expected to develop delayed neuromuscular damage, which may be severe and prolonged.

We describe a 50-year-old man who suffered from acute myeloid leukemia and was ventilated due to pneumonia. He was treated with pancuronium and cortico-steroids, and during recovery suffered quadriparesis that lasted several months.

Typically this damage is purely motor and is accompanied by absent tendon-reflexes, sometimes with elevated creatin-kinase. Muscle biopsy usually shows deletion and degeneration of thick myosin filaments. The phenomenon is related to the duration of NNBa treatment, and probably results from an adverse synergistic effect on muscle tissue of the cortico-steroids and cortico-steroid-like NNBa given the immobilized patient.

Awareness of this adverse effect of steroids and pancuronium, the use of passive mobilization, shortening the use of NNBa and early rehabilitation would minimize disability due to this phenomenon.

רונית חיימוב-קוכמן¹, ראובן ברומיקר², אריאל מילויצקי¹

¹מחלקת נשים ויולדות ²והמחלקה לטיפול נמרץ בילוד, בי"ח הדסה הר הצופים, הפקולטה לרפואה, האוניברסיטה העברית, ירושלים

Israel Naval Medical Institute: 20 Years of Applied Research, and Future Goals 

Ran Arieli, Avi Shupak

Israel Naval Medical Institute, Medical Corps, Israel Defense Forces

The Israel Naval Medical Institute (INMI) is unique as a research center located in a naval base and having close inter-relations with naval underwater units. It is ideal for applied research, and for mutual exchange of needs and of ideas and instructions.

Factors making this institute so suitable for applied research include: direct personal communication with combat divers, professional naval divers, submariners, civilian recreational divers and professional civilian divers, as well as naval vessel crews prone to seasickness; hyperbaric oxygen therapy is administered in cooperation with a large neighboring hospital.

Close spatial and personal relations with an academic institution (the Technion, with its Faculties of Medicine, Biology and Biophysics) provide a basis for cooperative research which expands research capabilities, and allows access to extensive expertise, instrumentation and equipment. Close ties with physicians who served at the INMI in the past also bring them into this research community.

During their specialization, physicians may spend up to 6 months working with us on a research project. Undergraduate, graduate and post-graduate students may complete their research at our institute with the agreement of their parent academic institutions.

Much of the research can be released to the international community. However, some is classified, serves only internal needs or is not of public interest. The number of published papers has stabilized since 1991 at about 16 a year.

Studies of gas exchange and oxygen toxicity originate mainly in the Hyperbaric Research Unit, research on motion sickness in the Motion Sickness and Human Performance Laboratory, and work on hyperbaric and diving medicine in the Clinical Section of the INMI.
 

Jet Lag Causing or Exacerbating Psychiatric Disorders

Gregory Katz, Rimona Durst, Josef Zislin, Hilla Knobler, Haim Y. Knobler

Kfar Shaul Mental Health Center, Jerusalem (Affiliated with the Hebrew University-Hadassah Medical School, Jerusalem)

Desynchronization of circadian rhythmicity resulting from rapid travel through at least 4 time zones leads to symptoms of jet lag syndrome. The most commonly experienced symptoms in normal individuals are sleep disorders, difficulties with concentrating, irritability, mild depression, fatigue, and gastrointestinal disturbances.

There is strong evidence relating affective disorders to circadian rhythm abnormalities, such as occur in jet lag. Less convincing suggestions relate jet lag to psychosis. We presume, relying on the literature and our accumulated experience, that in predisposed individuals jet lag may play a role in triggering exacerbation of, or de novo affective disorders, as well as, though less convincing, schizophreniform psychosis or even schizophrenia. An illustrative case vignette exemplifies the possible relationship between jet lag following eastbound flight and psychotic manifestations.

Tacrolimus does not Accentuate Hepatic Damage due to Hypoperfusion 

Ron Ben Abraham, Ivgeni Isartal, Richard Nakache, Vallery Rudick, Daniel Ogorek, Gideon Paret, Avi Weinbroum

Dept. of Anesthesiology and Critical Care Medicine, Organ Transplantation and Postoperative Care Units, Tel Aviv-Sourasky Medical Center; and Pediatric Intensive Care Units, Sheba Medical Center, Tel Hashomer; and Sackler Faculty of Medicine, Tel Aviv University

Deterioration of hepatic function following liver transplantation is a known complication, sometimes attributed to the use of cyclosporin A. Reaction to tacrolimus (Prograf), a relatively new and effective immunosuppressant drug, is thought to result in a much lower grade of organ dysfunction, especially in the transplanted liver.

Using the ex-vivo rat model of isolated perfused liver, we evaluated hepatocellular damage and oxygen extraction when tacrolimus was administered following liver hypoperfusion. Tacrolimus did not worsen hepatic dysfunction caused by the hypoperfusion. Therefore using tacrolimus in the perioperative period might be safer than cyclosporin A, which tends to worsen hepatic damage in the presence of hypoperfusion.

Mitral Valve Repair in Ischemic Cardiomyopathy with Severeleft Ventricular Dysfunction

Dani Bitran, Ofer Merin, Jeffrey Fisher, Nadiv Shapira, Marc W. Klutstein, Shuli Silberman

Depts. of Cardiothoracic Surgery, Anesthesiology and Cardiology, Shaare Zedek Medical Center, Jerusalem

Patients with ischemic mitral insufficiency and poor left ventricular function are high operative risks. We present 101 patients who had mitral valve repair in our department: 21 had severely reduced left ventricular function, 19 were in NYHA functional Class IV, and 2 in Class III. All had concomitant coronary artery bypass.

There was no early operative mortality, but there were 2 late deaths (9.6%). At follow-up (3-36 months) all valves were functioning normally, 9 patients (43%) were in NYHA functional Class I, and 4 (19%) in Class II.

Our experience shows that repair of ischemic mitral insufficiency in the presence of severe left ventricular dysfunction can be performed with good results, and is preferable to mitral valve replacement. Late follow-up showed significant symptomatic improvement.

Israel Hospital Pharmaceutical Services: A National Survey 

S. Livny, A. Hammerman, S. Shani, J. Shemer

Hiliel Yaffe Medical Center, Hadera; Israel Center for Technology Assessment in Health Care; Gertner Institute, Tel HaShomer; Dept. of Internal Medicine, Sheba Medical Center, Tel HaShomer; and Sackler School of Medicine, Tel Aviv University

Results of a 1996 survey of hospital pharmaceutical services in Israel are presented. A questionnaire was mailed to 46 pharmacy directors in Israel hospitals of which a total of 33 were returned (72%).

The main services provided at hospital pharmacies are production of pharmaceuticals and inventory management. The pharmacy directors estimated that more then half of their pharmacists' time was spent on technical work that did not need their academic, professional knowledge. In Israel general hospitals there are on the average 1.23 full time pharmacist positions per 100 hospital beds and 1.09 positions for other pharmacy employees.

A similar survey carried out in the United States showed an average of 7.4 pharmacists per 100 hospital beds. Pharmacists there have broad clinical roles which, in general Israeli pharmacists do not have.

Computer systems are used in our pharmacies mainly for inventory management. About half of the directors did not think that the location, structure and furnishings of their pharmacy were appropriate for its role.

Under current conditions, Israel hospital pharmacies are not organized to provide pharmaceutical services beyond inventory management and pharmaceutical production. Appropriate budgets and personnel are required to develop clinical pharmacy services at Israel hospitals. This would lead to improved quality of drug treatment and cost-containment and would allow pharmacists to exploit their knowledge, skills and training that under the current system, are only partially utilized.

Military Psychiatry in Israel: a 50-Year Perspective 

Avi Bleich

Tel Aviv-Souraski Medical Center and Sackler Faculty of Medicine, Tel Aviv University

The history of military psychiatry in Israel may be divided into 2 main periods. The first extended from the War of Independence in 1948, through the Sinai, Six Day and Yom Kippur Wars. Its outstanding feature was avoidance of the issue of combat stress reaction (CSR). The Yom Kippur War made the recognition of CSR inescapable, assisted in breaking up denial, and served as a stimulus for development of the next phase of the system.

This second phase was characterized by impressive progress in all areas of military psychiatry. The rich experience accumulated during the wars, together with the assimilation of a research culture which began blooming, especially in the wake of the Lebanon War, aided the development and crystallization of concepts related to combat and non-combat military psychiatry alike. The build-up of the mental health organization overlapped field deployment of the Medical Corps.

The Gift of Breastfeeding 

Dorit Nitzan Kaluski, Alex Leventhal

Dept. of Nutrition, Public Health Services, Israel Ministry of Health, Jerusalem

Breast milk is the optimal food for infant growth and development, the prevention of infectious diseases and mother- child bonding. From the economic perspective, breastfeeding is cost-effective both for the family and society as a whole. The Israeli Ministry of Health encourages breastfeeding as the exclusive source of nutrition for infants in the first 4-6 months of life, with gradual addition of complementary foods thereafter. The promotion of breastfeeding in Israel requires comprehensive national activity with involvement of all the stakeholders. This includes implementation of the International Code of Marketing of Breast Milk Substitutes and joining the international "Baby Friendly Hospitals" project. Knowledge of breastfeeding should be spread, health professionals should be encouraged to become agents of change, support by breast counselors should be encouraged, post-delivery vacations from work should be prolonged and empowerment of women implemented.

Acetaminophen Toxicity in Children - A Therapeutic "Misadventure"

Sarit Shahroor, Yigal Shvil, Mely Ohali, Esther Granot

Dept. of Pediatrics, Hadassah University Hospital and Hebrew University Hadassah Medical School, Jerusalem; and Dept. of Pediatrics, Barzilai Medical Center, Ashkelon

Acetaminophen toxicity after repeated administration of amounts that only moderately exceed recommended doses, is being increasingly reported in alcoholic or fasting adults. Pediatric experience with this pattern of acetaminophen toxicity is sparse.

We present 2 children who developed severe hepatic damage, with renal insufficiency as well in 1, after 15-20 mg/kg of acetaminophen, given at 4-hour intervals for 3-4 days during an intercurrent febrile illness. When given in doses as low as 20 mg/kg at frequent intervals for a number of days, the drug puts children who are vomiting or have sharply reduced caloric intakes at increased risk for severe toxicity.

Increased caution and awareness of the toxic effects of acetaminophen are needed, and it should be dispensed with appropriate package-label warnings.

Cilazapril for Essential Hypertension Treated in the Community 

Reuven Zimlichman

Dept. of Medicine and Hypertension Institute, Wolfson Medical Center and Sackler Faculty of Medicine, Tel Aviv University

In a multicenter study in community clinics, 413 patients with mild to moderate essential hypertension were treated with cilazapril (Vasocase), 2.5 mg daily. Patients had either been untreated or had developed side-effects from previous antihypertensive treatment. When response was inadequate the dose was either increased to 5 mg or another antihypertensive medication was added, or both.

Treatment significantly reduced systolic and diastolic blood pressures. Pulse rate decreased significantly from the second month of treatment onwards. At the end of the 3rd month of treatment blood pressure was normalized or had decreased by more than 10 mmHg in 91.9% of patients. Physicians' evaluations revealed improvement in 62%; patients' self-evaluations suggested improvement in 61%. Efficacy was equal in all age groups and in both obese and nonobese patients. Antihypertensive response was superior in those with normal renal function. Side-effects were rare and similar to those reported in the literature.

Family Physicians' Attitudes to Clinical Guidelines for Treatment of Diabetes 

Sasson Nakar, Shlomo Vinker, Tal Baro-Aloni, Eliezer Kitai

Dept. of Family Medicine, Rabin Medical Center and Sackler Faculty of Medicine, Tel Aviv University

Clinical guidelines are systematically developed statements designed to help practitioners and patients make decisions about appropriate health care for specific clinical states. Attitudes of family physicians to clinical guidelines for treating diabetes and guidelines in general were evaluated from anonymous questionnaires answered by physicians participating in continuous medical education throughout the country (May-June 1998). The questionnaire dealt with attitudes to the recently published specific guidelines for treating the diabetic patient and overall perception of the efficacy of clinical guidelines.

293 family physicians, aged 40.2‏7.0 responded (83%). 93.5% appreciated the guidelines and thought them applicable. Most (83.7%) reported the guidelines to be of help in their daily work; 31.4% said they were oversimplified; a quarter said they aimed main at containing costs. Most respondents preferred written guidelines of up to 5 pages.

In view of our results, attention can now be turned to developing ways to implement the guidelines. To improve adherence, they need to be short and the rate of publication of new clinical guidelines should be slowed.

Relationship Between Preterm Birth and Exertion During Pregnancy

S. Gazit-Nissim, E. Sheiner, M. Mazor, I. Shoham-Vardi

Depts. of Obstetrics and Gynecology, Epidemiology and of Health Services Evaluation, Soroka-University Medical Center, and Ben-Gurion University of the Negev, Beer Sheba

The relationship between physical activity at home and at work during pregnancy and preterm birth was studied. Using a case-control design, 99 women who delivered preterm were compared with 189 women who had term deliveries. The risk of preterm birth was tested in relation to characteristics of work in and outside the home. All women were interviewed post-partum before discharge.

There were no statistically significant differences between the groups in relation to sociodemographic and obstetrical factors, but level of education was significantly lower in the study group versus the control group (p=0.001).

Women who delivered preterm had devoted less time 3 months prior to delivery to household chores (mean of 3.7 hours vs. 4.8 hours in the control group, p=0.002). They also had spent less time walking around the home than the controls (1.2 vs. 1.5 hours, p=0.02). There were no differences between the groups in relation to physical activity outside the home, not during working hours, nor in duration of work. Significantly fewer women who delivered preterm were active in sports (odds ratio 0.22; 95% confidence interval 0.50-0.65; p=0.002).

A low level of education was significantly related to the risk of preterm birth, which may have resulted from lesser compliance with their physician's recommendations. It appears that in women not used to significant physical activity but who had access to adequate prenatal care, physical effort during pregnancy was not related to a higher risk of preterm birth.

Introduction of Routine Hepatitis Immunization in Israel 

Emilia Anis, Alex Leventhal, Malvina Roitman, Paul E. Slater 

Notification of hepatitis A, which is endemic in Israel, has been compulsory since the establishment of the State. From 1992-98 an average of 2,600 cases were reported annually. Many infections are asymptomatic and mild, especially in children. In general, severity increases with age; in Western countries the case fatality rate is 1.5/1,000 among children less than 5 years old and 27/1,000 among those over 50. Until 1987 incidence in Israel was higher in Jews than in non-Jews, but since 1988 incidence has been about 50% higher in non-Jews.

Among Jews highest age specific rates shifted from children 1-4 years old to children 5-9 years old in 1970, and in non-Jews in 1989. Improved sanitary conditions and personal hygiene have reduced very early childhood exposure and hence increased the proportion of susceptible older children and adults, in whom symptomatic disease is more prevalent.

Israel is the first country in the world to include hepatitis A vaccine in its routine immunization schedule. The vaccine is given in 2 doses: at 18 months and 24-30 months of age, and there will be epidemiologic and serologic follow-up. A significant decrease in hepatitis A morbidity is expected in small children within 5 years. The percentage of reported cases in older children and in adults is expected to increase, although the absolute incidence among these groups will decrease.
 

Dept. of Epidemiology and Public Health Services, Israel Ministry of Health, Jerusalem