Israel Medical Association Journal

The 50th anniversary of the Israel Diabetes Association this year is a time less for celebration than for concern. The prevalence of diabetes is rapidly and alarmingly increasing in Westernized and developing countries around the world. Unfortunately, the majority of patients with diabetes do not meet their treatment goals – i.e., glucose, blood pressure or lipid levels. Moreover, our clinical experience and large longitudinal studies have taught us that the mean glucose levels of diabetic patients tend to increase over the years regardless of their treatment modalities. The appropriate answer to these somewhat frustrating data is that the medical community responsible for the integrated health of our diabetic patients – namely, physicians, researchers, nurses and dieticians – must use its combined resources and available therapeutic tools to optimize treatment for these patients. We should also deepen our understanding of the mechanisms underlying the various forms of diabetes and its complications in order to devise more efficient preventive measures for this prevalent devastating chronic disease.

This issue of IMAJ dedicated to diabetes provides some glimpses into these approaches. It contains relevant clinical management debates such as how and when insulin therapy should be instituted and which antihypertensive drugs are more appropriate in the treatment of diabetic nephropathy; a current state-of-the-art review of gestational diabetes as well as how to recognize and manage the diabetic Charcot foot. It exposes the reader to modern prevention strategies against type 1 and type 2 diabetes, to the search for alternative insulin-producing tissue, to advanced understanding of diabetic dermopathy, and more. It also includes selected abstracts of ongoing studies to be presented at the 2004 annual meeting of the Israel Diabetes Association. Most of all, the high quality of the clinical and basic research presented herein strengthens our hope for a better future for our diabetic patients.

Micha Rapoport MD (Guest Editor)

Department of Internal Medicine C and the Diabetes Service, Assaf Harofeh Medical Center, Zerifin, Israel

Editorial Committee

Hilla Knobler MD (Debate Editor)

Eleazar Shafrir PhD

Efrat Wertheimer MD PhD

Background:  One of the major reasons for the shortage of organs for transplantation in Israel is the failure to identify potential donors. According to the World Health Organization, the expected number of potential donors in Israel is 300 per year. In recent years an average of only 200 donors (2/3) has been identified.

Objective: To identify the reasons for the gap between the potential and the actual number of organ donors.

Methods: We reviewed the medical records of all potential donors at the Soroka University Medical Center between October 1997 through September 1999.

Results: The total of 183 death records was consistent with the minimal inclusion criteria for potential organ donation, of which 41 were suspected to be potential brain death (PBD) In 31 cases an ad hoc committee had declared brain death, and the patients were evaluated for organ donation. However, in 10 cases no committee was formed. We found that 24.4% (10/41) of the potential donors had not been designated as such by their medical team.

Conclusion: We believe that a comprehensive education program for medical and nursing staff might increase awareness for organ donation and may eliminate the gap between the potential and actual number of organ donors.

Background: Revision of total knee arthroplasties are performed with increasing frequency due to the increasing numbers of primary arthroplasties.

Objectives: To retrospectively analyze 71 patients who underwent 78 revision total knee arthroplasties during the years 1991 to 1999

Methods: We evaluated the revised knees using the Knee Society Clinical Rating System after an average follow-up period of 3 years and 9 months (2–10 years). The indications for revision included pain and instability, deep infection of the joint, complaints linked to the patella, or post-trauma to the operated knee.

Results: The average knee score (evaluation of the knee joint itself) calculated after the revision was 74.5. The results on the knee score were excellent (>85) in 48% of patients and poor (<60) in 22%. The functional results (patients’ ability to walk and climb stairs) were only 48.3.

Conclusion: Although the revision of total knee replacements is known to be problematic, most patients show good results on knee examination, and reasonable functional results given the factors involved.

Background: Although the preferred management of a patient presenting with an acute myocardial infarction is in a coronary care unit, data based on discharge diagnoses in Israel indicate that many of these patients are treated outside such units.

Objectives: To compare the demographic and clinical characteristics, treatment and mortality of AMI[1] patients treated inside and outside a CCU[2].

Methods: We compiled a registry of all patients admitted to three general hospitals in Haifa, Israel during January, March, May, July, September and November 1996.

Results: The non-CCU admission rate was 22%. CCU patients were younger (61.6 vs. 65.5 years), less likely to report a past AMI (18% vs. 34%), and arrived earlier at the emergency room. Non-CCU patients were more likely to present with severe heart failure (30 vs. 11%). Non-CCU patients received less aspirin (81 vs. 95%) and beta-blockers (62 vs. 80%). Upon discharge, these patients were less frequently prescribed beta-blockers and cardiac rehabilitation programs. CCU-treated patients had lower unadjusted mortality rates at both 30 days (odds ratio=0.35) and in the long term (hazards ratio=0.57). These ratios were attenuated after controlling for gender, age, type of AMI, and degree of heart failure (OR[3]=0.91 and HR[4]=0.78, respectively).

Conclusions: A relatively high proportion of AMI patients were treated outside a CCU, with older and sicker patients being denied admission to a CCU. The process of evidence-based care by cardiologists was preferable to that of internists both during the hospital stay and at discharge. In Israel a significant proportion of all AMI admissions are initially treated outside a CCU. Emphasis on increasing awareness in internal medicine departments to evidence-based care of AMI is indicated.

Micronutrient deficiencies have reoccupied the center stage of public health policy with the realization that folic acid deficiency results in neural tube defects and possibly other birth defects as well as ischemic heart disease. These, in turn, have raised an older debate on food fortification policy for the elimination of iodine, iron and vitamin D deficiencies. Data from the First Israeli National Health and Nutrition Survey (MABAT 2000) provided an impetus to develop an active national nutrition policy aimed to improve the nutritional status of iodine, iron, vitamins A and D and B-vitamins, including folate. In this paper we examine some of the MND[1] issues in Israel and their implications for public health, and suggest options for the formulation of policy.

Behavioral genetics is the identification of behavioral traits that are genetically determined, the identification of the genes that are involved, and the discovery of modes of intervention to alter the expected course of the disease. Unlike the classical Mendelian traits, many specific aspects of behavior are, in part, determined by several genes. The corresponding abnormalities of behavior or deficiencies are therefore polygenic. New genetic techniques are leading to the discovery of these genes, and the techniques and knowledge developed in the Human Genome Project make it possible to screen the genome of any individual for the presence of known polymorphisms. This raises great hopes for diagnosis and the individualization of therapy. However, the genetic prediction of unacceptable behavior can further lead to social and occupational discrimination and enforced therapy. This raises serious concerns about how this information will be collected and who will have access to it.

Background: The ¹³C-urea breath test is the best non-invasive test to validate Helicobacter pylori eradication. Serology is unreliable for this purpose due to the slow and unpredictable decline in the antibodies titer.

Objectives: To characterize a specific group of patients who were treated for H. pylori and tested for successful eradication by ¹³C-UBT[1] in our central laboratory and to correlate the eradication success rate with specific drug combinations, and to evaluate other factors that may influence eradication success.

Methods: ¹³C-UBT for H. pylori was performed in the central laboratory of Clalit Health Services. The breath test was performed by dedicated nurses in 25 regional laboratories and the samples were analyzed by a mass spectrometer (Analytical Precision 2003, UK). The physician who ordered the test completed a questionnaire computing demographic data (age, gender, origin), indication, use of non-steroidal anti-inflammatory drugs or proton pump inhibitor, and combination of eradication therapy.

Results: Of the 1,986 patients tested to validate successful H. pylori eradication, 539 (27%) had a positive test (treatment failure group) and 1,447 (73%) had a negative test (successful treatment group). Male gender, older age and European-American origin predicted better eradication rates. Dyspeptic symptoms and chronic PPI[2] therapy predicted treatment failure. Combination therapy that included clarithromycin had a higher eradication rate than a combination containing metronidazole. The combination of omeprazole, amoxicillin and clarithromycin achieved an eradication rate of 81.3%, which was better than the combination of omeprazole, metronidazole and clarithromycin (77.2%) (not significant), or of omeprazole, amoxicillin and metronidazole (66.1%) (P < 0.01).

Conclusion: Gender, age, origin, dyspepsia and PPI therapy may predict H. pylori eradication results. Our findings also support an increase in metronidazole resistance of H. pylori strains in Israel, as described in other countries. We recommend combination therapy with omeprazole, amoxicillin and clarithromycin and avoidance of metronidazole as one of the first-line eradication drugs.

Background: Concomitant mitral valve regurgitation is often present in patients with aortic stenosis. The additional MV[1] replacement is associated with high operative risk. Previous studies have shown an amelioration of MV regurgitation after aortic valve replacement but most of the patient groups were heterogenous.

Objectives: To determine whether AV[2] replacement for aortic stenosis has any effect on MV regurgitation.

Methods: We reviewed two-dimensional echocardiography and color flow Doppler assessment of both aortic stenosis and MV regurgitation severity in 30 patients. Patients with previous MV surgery, organic MV disease, occlusive carotid artery disease, ejection fraction < 50%, and coexisting significant AV regurgitation were excluded. Preoperatively, MV regurgitation was mild in 23 patients (77%) and moderate in 7 (23%); in no patient was the condition severe. All patients had severe atrial stenosis (peak average aortic gradient was 86  ± 22 mmHg in the mild MV regurgitation group, and 83 ± 26 mmHg in the moderate group). The patients were divided into two groups according to the severity of MV regurgitation (associated mild, and moderate). Group 2, with moderate MV regurgitation, was the most problematic in terms of decision making for concomitant MV surgery. Therefore, additional assessment of several parameters was required.

Results: There was a significant decrease in MV regurgitation area (7.6 ± 1.9 vs. 3.0 ± 1.2 cm², P £ 0.012) and percent (28 ± 5% vs. 12 ± 6%, P £ 0.001) between pre- and postoperative evaluation. Thus, the severity of the condition in all patients with moderate MV regurgitation decreased after AV replacement; in the mild group it remained unchanged in 53% or improved in 47%. There was no association between the preoperative gradient on the aortic valve and the degree of MV regurgitation.

Conclusions: In our population of patients with severe atrial stenosis there were no patients with coexisting severe MV regurgitation. The decision to repair or replace a severely leaking mitral valve is an easy one, as in mild MV regurgitation. The clinical problem often presents in patients with severe aortic stenosis and moderate MV regurgitation. We believe that additional MV surgery is not necessary, at least in patients with preserved left ventricular function and without organic MV disease.

Background: Imaging-guided core needle biopsy is a well-established technique for the diagnosis of bone and soft tissue tumors and tumor-like lesions in specialized orthopedic oncology centers.

Objective: To present our results of computed tomography-guided core needle biopsy with assessment of the accuracy of the technique.

Methods: Between July 1998 and October 2000, 215 CT-guided core needle biopies were performed and histologically examined in the Unit of Bone and Soft Tissue Pathology, Tel Aviv Sourasky Medical Center. There were 80 soft tissue and 135 bony lesions. All biopsies were performed by the same radiologist and the histologic examination by the same pathologist.  To assess the accuracy of the procedure, we compared the diagnosis at biopsy with the diagnosis after definitive surgery (when available).

Results: Bone core needle biopsy (n = 135) showed malignancy in 89 cases (primary or recurrent bone sarcoma, lymphoma, myeloma, metastatic carcinoma or melanoma). There were 29 benign lesions. In 17 cases the result was inconclusive and an open incisional biopsy was performed. Of the 80 soft tissue biopsies, 35 were malignant (25 soft tissue sarcomas, 6 lymphomas, 4 metastatic carcinomas); 40 were benign (myositis ossificans, neurofibroma, desmoid tumor, schwannoma, hematoma and others), and 5 were inconclusive and followed by an open incisional biopsy. The core needle biopsy histologic diagnosis was compared with that of the definitive surgery and the diagnostic accuracy was 90%. Only three samples initially diagnosed as benign turned out to be malignant. No significant complications occurred during the procedures.

Conclusions: CT-guided CNB[1] of musculoskeletal lesions is a safe and effective procedure that assures sufficient and proper material for histologic examination. The accuracy of this method in our center was 90%. Tumor sampling is extremely important, especially in soft tissue sarcomas, and cores should be taken in different directions, including areas of necrosis. The processing is quick, especially for bone CNB, and diagnosis can be achieved within 24 hours. The material undergoes excellent fixation and the immunostains are reliable.