Israel Medical Association Journal

Background: Decreased heparan sulfate proteoglycan content of the glomerular basement membrane has been described in proteinuric patients with diabetic nephropathy. Heparanase is an endo-b-D-glucuronidase that cleaves negatively charged heparan sulfate side chains in the basement membrane and extracellular matrix.

Objectives: To investigate whether urine from type I diabetic patients differs in heparanase activity from control subjects and whether resident glomerular cells could be the source of urinary heparanase.

Methods: Using soluble ³⁵S-HSPG[1] and sulfate-labeled extracellular matrix we assessed heparanase activity in human glomerular epithelial cells, rat mesangial cells, and urine from 73 type I diabetic patients. Heparanase activity resulted in the conversion of a high molecular weight sulfate-labeled HSPG into heparan sulfate degradation fragments as determined by gel filtration analysis.

Results: High heparanase activity was found in lysates of both epithelial and mesangial cells. Immunohistochemical staining localized the heparanase protein to both glomeruli capillaries and tubular epithelium. Heparanase activity was detected in the urine of 16% and 25% of the normoalbuminuric and microalbuminuric diabetic patients, respectively. Urine from 40 healthy individuals did not posses detectable heparanase. Urinary heparanase activity was associated with worse glycemic control.

Conclusion: We suggest that heparanase enzyme participates in the turnover of glomerular HSPG. Hyperglycemia enhances heparanase activity and/or secretion in some diabetic patients, resulting in the loss of albumin permselective properties of the GBM[2].

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[1] HSPG = heparan sulfate proteoglycan

[2] GBM = glomerular basement membrane

The threat of a disease outbreak resulting from biologic warfare has been of concern for the Israeli health system for many years. In order to be prepared for such an event the health system has formulated doctrines for various biologic agents and defined the logistic elements for the procurement of drugs. During the last 4 years, and especially after the West Nile fever epidemic in 2000, efforts to prepare the healthcare system and the relevant organizations were accelerated. The Director-General of the Ministry of Health nominated a Supreme Steering Committee to fill in the gaps and upgrade the preparedness of the health system for an unusual disease outbreak. This committee and its seven subcommittees established appropriate guidelines, communication routes among different organizations, and training programs for medical personnel. The anthrax outbreak in the United States found the healthcare system in the hub of the preparation process, and all modes of action were intensified. Further work by hospitals, primary care clinics and all other institutes should be initiated to maintain a state of proper preparedness.

Background: Concern about the side effects of allogeneic blood transfusion has led to an increased interest in methods of minimizing peri-operative transfusion. Technologies to minimize allogeneic transfusion include drugs such as aprotinin, desmopressin, tranexamic acid and erythropoietin, and techniques such as acute normovolemic hemodilution, cell salvage and autologous pre-donation.

Objective: To survey the current use in Israel of these seven technologies used to minimize allogeneic blood transfusion.

Methods: Our survey was conducted in 1996–97 in all hospitals in Israel with more than 50 beds and at least one of the following departments: cardiac or vascular surgery, orthopedics, or urology. All departments surveyed were asked: a) whether the technologies were currently being used or not, b) the degree of use, and c) the factors influencing their use and non-use. The survey was targeted at the heads of these departments.

Results: Pharmaceuticals to reduce allogeneic blood transfusion were used in a much higher proportion in cardiac surgery departments than in the other three departments. Pre-operative blood donation was used in few of the cardiac, urologic and vascular surgery departments compared to its moderate use in orthopedic departments. The use of acute normovolemic hemodilution was reported in a majority of the cardiac departments only. Moderate use of cell salvage was reported in all departments except urology where it was not used at all.

Conclusion: There is considerable practice variation in the use of technologies to minimize exposure to peri-operative allogeneic blood transfusion in Israel.
 

Background: Appropriateness of hospital admission has both clinical and economic relevance, especially in light of the growing pressure for increased efficiency of health services utilization. In Israel, the number of referrals and use of the emergency room continue to rise along with an increase in hospital admissions and the number of inappropriate admis­sions. Using evaluation protocols, such as the Pediatric Appropriateness Evaluation Protocol, international studies have shown that 10-30% of hospital admissions are medically unnecessary. Inappropriate hospitalizations have an economic impact as well as medical and psychological effects on the child and the family.

Objectives: To assess the extent and characteristics of inappropriate pediatric admissions to a tertiary care facility in Israel.

Methods: We conducted a prospective study using chart review of pediatric admissions to Soroka University Medical Center on 18 randomly selected days in 1993, and evaluated the appropriateness of admissions using the PAEP.

Results: Of the 221 pediatric admissions 18% were evaluated as inappropriate. The main reason for such an evaluation was that the problem could have been managed on an ambulatory basis. Inappropriate admissions were asso­ciated with hospital stays of 2 or less days, children older than 1 year of age, Jewish children, and self-referrals to the pediatric emergency room.

Conclusions: The assessment and identification of characteristics of inappropriate hospital admissions can serve as indicators of problems in healthcare management and as a basis for improving quality of care and developing appropriate medical decision-making processes.

Background: The pattern of diabetes and ischemic heart disease among emigrants from pre-industrialized societies to more developed countries may be explained by both genetic and environmental factors.

Objectives: To describe and interpret the pattern of diabetes and ischemic heart disease among Yemenite immigrants in Israel and their second-generation offspring.

Methods: Medical record charts of adult Yemenites were surveyed in a primary care health center, and the data were compared with prevalence rates derived from a non-Yemenite population.

Results: There was a marked excess of non-insulin dependent diabetes mellitus among Yemenite immigrants over 45 years of age, but not of hypertension or ischemic heart disease. Yemenites with diabetes were far less likely to develop ischemic heart disease than non-Yemenites with diabetes (odds ratio for non-Yemenites compared with Yemenites, 3.5; confidence interval 1.54<OR<7.77).

Conclusions: There was less of an association between diabetes and ischemic heart disease among Yemenites. This finding requires further investigation of the relative roles of genetic and environmental factors. 

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OR= odds ratio

Background: Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital malformation that presents a diagnostic challenge to the pediatrician and pediatric cardiologist. Although surgical repair is always indicated, the optimal technique has yet to be determined.      

Objectives: To review our experience with the diagnosis of children with ALCAPA and to assess short to midterm surgical results.

Methods: Between 1992 and 1998, 13 infants and children (2 months to 15 years) were treated for ALCAPA at our medical center. Eight were diagnosed during the first year of life; all were symptomatic and had severe dysfunction of the left ventricle. The five patients diagnosed at an older age had normal myocardial function. Diagnosis was established by echocardiography alone in seven patients; six required catheterization (one infant and all older patients). Surgery was performed in 12 patients to establish dual coronary artery system: 7 underwent the Takeuchi procedure and 5 had re-implantation of the anomalous left coronary artery.

Results: One infant died shortly after diagnosis before surgical repair was attempted, and one died postoperatively. Four patients required additional surgery: three for late complications of the Takeuchi procedure and one valve replacement for mitral insufficiency. Recent evaluation revealed good global left ventricle function in all patients except for one, who is still within the recovery phase and shows gradual improvement. However, most patients who presented with severe myocardial dysfunction upon diagnosis still display abnormal features such as echo-dense papillary muscles or evidence of small akinetic segments. In this group, early repair was associated with faster myocardial recovery.

Conclusions: The diagnosis of ALCAPA remains a clinical challenge to the pediatrician and cardiologist. Diagnosis can be established echocardiographically, and early diagnosis and treatment may lead to faster myocardial recovery. The preferred surgical method appears to be re-implantation of the ALCA. The chance for good recovery of global ventricular function is high even in the sickest patients, nonetheless abnormal myocardial features can be identified even years after surgery.

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ALCAPA= anomolous origin of the left coronary artery from pulmonary artery.

Background: The need for aortic valve replacement in children and young adults poses a special problem to cardiologists and surgeons. Replacing the sick aortic valve with the patient’s pulmonary valve as described by Ross has proven to be a good option in this special age group.

Objective: To review our initial experience in order to assess the short-term results.

Methods: From January 1996 to June 1999, 40 patients (age 8 months to 41 years) underwent aortic valve replacement with pulmonary autograft. Indications for surgery were congenital aortic valve disease in 30 patients, bacterial endocarditis in 5, rheumatic fever in 3, and complex left ventricular outflow tract obstruction in 3. Trans-esophageal echocardiography was performed preoperatively and post-bypass in all patients, and transthoracic echocardiography was done prior to discharge and on follow-up.

Results: There was no preoperative or late mortality. All patients remain in functional class I (New York Heart Association) and are free of complications and medication. None showed progression of autograft insufficiency or LVOT obstruction. Homograft insufficiency in the pulmonary position has progressed from mild to moderate in one patient, and three developed mild homograft stenosis.

Conclusions: The Ross procedure can be performed with good results in the young population and is considered an elegant surgical alternative to prosthetic valves and homografts.

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LVOT = left ventricular outflow tract

Background: Previous studies have documented an increased incidence of cardiac mortality and sudden death during winter months.

Objectives: To evaluate seasonal variation in sudden death in a hot climate such as the desert region of southern Israel.

Methods: We analyzed the files of 243 consecutive patients treated for out-of-hospital sudden death by the Beer Sheva Mobile Intensive Care Unit during 1989-90. Daily, monthly and seasonal incidence of sudden death was correlated with meteorological data, including temperature, heat stress, relative humidity and barometric pressure.

Results: The seasonal distribution of sudden death was 23% in spring, 21% in summer, 25% in autumn and 31% in winter (not significant). In patients with known heart disease there were more episodes of sudden death in cold weather (<15.4°C) than hot (>34.2°C) (16 vs. 3, P<0.05). Resuscitation was less successful in cold compared with hot weather (28 vs. 11, P<0.05). Of patients older than 65 years, 11 sustained sudden death when heat stress was below 12.4°C compared to 2 patients when heat stress was above 27.5°C (P=0.05).

Conclusion: Despite the warm desert climate, there were more cases of sudden death in older patients and in those with known heart disease during the winter season and on particularly cold days.
 

Background: Prenatal lead exposure (umbilical cord blood lead concentration 10 (μg/dl) may impair cognitive development. Childhood lead poisoning is infrequent in Israel, and there are no data on lead exposure in immigrants to Israel from the former Soviet Union.

Objectives: To evaluate prenatal blood lead concentrations in Israeli newborns whose mothers were born in Israel and in those whose mothers recently immigrated from Russia, and to compare data of prenatal lead exposure in Israel with those reported from other countries.

Methods: We compared the UCBLC of 35 newborns of new immigrants from Russia with a group of 35 newborns whose mothers were born in Israel. Venous BLC was also measured in 50 mothers. Data are compared with similar reports on prenatal lead exposure internationally.

Results: The UCBLC in all 70 newborns (mean±SD) was 3.53±1.6 μg/dl, and mothers' BLC (mean±SD) was 3.90±1.39 μg/dl. UCBLC and BLC in the 50 mother-newborn pairs correlated (γ=0.36, P<0.01). All newborns except one had UCBLC<8.0 μg/dl. There was no significant difference between UCBLC in the two groups.

Conclusions: Prenatal lead exposure among the study subjects in both groups was low. In this sample the newborns of mothers born in Israel and those whose mothers recently immigrated from Russia were not found to be at risk for lead poisoning. Prenatal lead exposure in this sample was low compared to that reported from various parts of the world.