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עמוד בית
Thu, 18.07.24

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June 2000
Guillermo Ruiz-Irastorza, MD, PhD, Munther A. Khamashta, MD, MRCP, PhD and Graham R.V. Hughes, MD, FRCP
May 2000
Ziona Haklai MSc, Shimon Glick MD and Jochanan Benbassat MD

Background: The increasing utilization of general internal medicine hospital wards in Israel during the last decade is a source of concern for health policy makers.

Objectives: To report on the distribution of selected main and secondary diagnoses among GIM inpatients, and to estimate the proportion of disorders for which appropriate care in the community will reduce the need for hospital admissions and re-admissions.

Methods: Data from the Health Information and Computer Services of the Israel Ministry of Health (national hospitalization database) for a one year period were analyzed by distribution of diagnostic entities (ICD-9-CM) in GIM and in medical subspecialty wards.

Results: Of the 313,824 discharges from hospital divisions of medicine in 1995, 256,956 (81.9%) were from GIM and 56,868 (18.1%) from specialty wards. Main and secondary discharge diagnoses were available for 188,807 GIM and 35,992 specialty patients. Of all main diagnoses in GIM wards, 27% were coded as "general or systemic symptoms and signs" or as "abnormal laboratory or ill defined manifestations" (ICD-9-CM codes 780-799, 276,277), and heart diseases comprised another 27%. The remaining main diagnoses covered almost all medical conditions. The combined proportion of "ambulatory care sensitive hospital admissions" (bronchial asthma, hypertension, congestive heart failure, chronic obstructive pulmonary disease, diabetes) constituted 12% of all main diagnoses in GIM, and respiratory symptoms or signs comprised another 11%. A by-product of this analysis was an insight into the experience of undergraduate medical students in GIM.

Conclusions: Assuming that 12-75% of admissions for "ambulatory care sensitive disorders" are preventable, an improved review before hospital discharge and a closer outpatient follow-up may reduce the load on GIM wards by 1-17%. This wide range justifies controlled trials to determine the effect of improved community care on hospital utilization. GIM wards offer valuable learning opportunities, but they cannot be a substitute for primary care clinics. The unexplained high proportion of GIM inpatients who were discharged with an unspecified main diagnosis could be detrimental for the accuracy of hospitalization statistics, and justifies investigation by chart audits into physicians' habits of documentation.

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GIM= general internal medicine

Perla Werner PhD and Iris Vered MD

Background: Osteoporosis is the most common human bone disease. It affects millions of persons throughout the world and its prevalence will increase as the population ages worldwide.

Objective: To assess Israeli physicians' attitudes and knowledge with regard to management of osteoporosis.

Methods: A questionnaire was mailed to 1,900 Israeli physicians concerning their attitudes to the management of osteoporosis, their prescribing habits, and their knowledge on the pharmacological treatment of the disease.

Results: Replies were received from 19% of the physicians. The respondents encouraged physical activity and cessation of smoking for all women, and prescribed estrogen replacement as the main treatment for 50-year-old women. A relatively low level of knowledge was found regarding the adequate dosage of several of the pharmacological treatments.

Conclusions: The findings of the present study stress the need to provide clear guidelines and to extend physicians' knowledge regarding the management of osteoporosis.

April 2000
chondrocyte transplantation, joint cartilage, articular surface, bioengineering, cartilage repair, dror robinson, hana ash, david aviezer, gabriel agar, nahum halperin, zvi nevo, robinson, ash, aviezer, agar, halperin, nevo

Background: Articular cartilage is incapable of undergoing self-repair since chondrocytes lose their mitotic ability as early as the first year of life. Defects in articular cartilage, especially in weight-bearing joints, will predictably deteriorate toward osteoarthritis.  No method has been found to prevent this deterioration. Drilling of the subchondral bone can lead to fibrocartilage formation and temporary repair that slowly degrades. Animal experiments indicate that introducing proliferating chondrocytes such as cultured articular chondrocytes can reliably reconstruct joint defects.

Objectives: To describe our clinical experience in culturing and transplanting autologous chondrocytes. 

Methods: Biopsies were obtained from 10 patients, aged 18–45, undergoing a routine arthroscopy in which a cartilage defect was identified with indications for cartilage transplantation. The biopsies were further processed to establish chondrocyte cultures. ACT was performed in 8 of the 10 patients because of persistent symptoms for at least 2 months post-arthroscopy. All patients (6 men and 2 women) had a grade IV cartilage defect in the medial or lateral femoral condyle, and three had a defect in the trochlear region as well. Biopsies were removed from the lateral rim of the superior aspect of the femur, and cells were cultured in a clean room. Following a 2 order of magnitude expansion, cells were implanted under a periosteal flap.

Results: The eight patients implanted with autologous cells were followed for 6 months to 5 years (average 1 year). Complaints of giving-way, effusion and joint locking resolved in all patients, and pain as assessed by the visual analogue score was reduced by an average of 50%. Follow-up magnetic resonance imaging studies in all patients revealed that the defects were filled with tissue having similar signal characteristics to cartilage.

Conclusions: Chondrocyte implantation is a procedure capable of restoring normal articular cartilage in cases with isolated joint defects. Pain can be predictably reduced, while joint locking and effusion are eliminated. The effect on osteoarthritis progression in humans has not yet been elucidated.

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ACT = autologous chondrocyte transplantation

Hagit Cohen PhD, Moshe Kotler MD, Mike Matar MD and Zeev Kaplan MD

Background: Spectral analysis of heart rate variability has been shown to be a reliable non-invasive test for quantitative assessment of cardiovascular autonomic regulatory responses, providing a window reflecting the interaction of sympathetic and parasympathetic tone. Alterations in autonomic function are associated with a variety of physiologic and pathophysiologic processes and may contribute substantially to morbidity and mortality. Our previous study shows that patients with post-traumatic stress disorder have significantly lower HRV compared to controls, reflecting a basal autonomic state characterized by increased sympathetic and decreased parasympathetic tone.

Objectives: To apply this tool to PTSD patients treated with selective serotonin re-uptake inhibitors in order to assess the impact of such treatment on the autonomic dysregulation characterizing these patients.

Methods: Standardized heart rate analysis was carried out in nine PTSD patients treated with SSRI agents and compared to that in a matched control group of nine healthy volunteers and in nine untreated PTSD patients, based on a 15 minute resting electrocardiogram.

Results: Our preliminary results show that the HRV parameters indicating autonomic dysregulation, which characterize PTSD patients at rest, are normalized in responding patients by use of SSRIs. Neither the clinical implications of these findings nor their physiological mechanisms are clear at present, although we presume that they reflect a central effect, since the peripheral autonomic effects of SSRIs are relatively negligible.   

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HRV = heart rate variability

PTSD = post-traumatic stress disorder

SSRI = selective serotonin re-uptake inhibitor

Shahar Zimand, MD, Patricia Benjamin, Mira. Frand, MD, David Mishaly, MD and Julius Hegesh, MD
March 2000
Michael A. Weingarten MA BM BCh, Irene Katzir MD, Elliot Sprecher PhD,Svetlana Kobzantsev MD, Cara Zelzer MD and Ernesto Kahan MD

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

Joseph Meyerovitch MD, Trevor Waner BVSc PhD, Joseph Sack MD, Juri Kopolovic MD and Joshua Shemer MD

Background: Despite current treatment protocols, the long-term complications of insulin-dependent diabetes mellitus have prompted the investigation of strategies for the prevention of IDDM.

Objectives: To investigate the effect of oral vanadate in reducing diabetes type I in non-obese diabetic mice.

Methods: Sodium metavanadate, 3.92 mmol/L, was added to the drinking water of 8-week-old female NOD mice. Blood glucose levels, water consumption and body weight were measured, and the end point of the study was judged by the appearance of hyperglycemia in the mice.

Results: Treatment with vanadate did not significantly reduce the incidence of type I diabetes as compared to the control group. However, oral vanadate therapy significantly reduced the blood glucose levels after the fourth week of treatment compared to the control group (3.83±10.67 vs. 4.44±10.83 mmol/L, P<0.03). There was a consistent and significant increase in body weight of the vanadate-treated pre-diabetic NOD mice compared to the controls. Diabetic mice treated with vanadate had significantly lower levels of serum insulin as compared to control diabetic mice (104±27 vs. 151±36 mol/L, P<0.03). Histologically, no significant differences were found in inflammatory response of the islets of Langerhans between the control and treated groups.

Conclusions: This study suggests that the post-receptor insulin-like effect induced by vanadate is not sufficient to prevent the development of diabetes and insulitis in pre-diabetic NOD mice.

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IDDM= insulin-dependent diabetes mellitus

NOD= non-obese diabetic

Anabel Aharon-Maor, MD and Yehuda Shoenfeld, MD
Rolando Cimaz, MD, Luca Catelli, MD, Cristina Luzzana, MD, Paola Panzerei, PhD and Pierluigi Meroni, MD
Israel Hodish, MD, David Ezra, MD, Hanan Gur, MD, Rephael Strugo, MD and David Olchovsky, MD
Elias Toubi, MD, Johana E. Naschitz, MD, Aharon Kessel, MD and Milo Fradis, MD
February 2000
Ilan Zahavi MD, Olga Rosezki MD, Yerah Stolkarts MD, Raanan Shamir MD, Bruria Heckelman BSc, Hedva Marcus MSc and Gabriel Dinari MD

Background: Cholestasis is a frequent problem in patients on total parenteral nutrition. Cisapride has a prokinetic effect on the biliary system, but its effect on hepatic excretory function is unknown.

Objectives: To study the effect of cisapride on TPN-induced cholestasis in a rat model.

Methods: Bile flow and bile salt secretion rate were measured in rats given TPN. There were four groups of 8 to 13 animals each. After a one hour baseline period during which all four groups received i.v. saline infusion, two groups received a TPN solution for another 2 hours, while saline was infused in the two control groups.

At the beginning of the second hour, 2 mg/kg cisapride was injected i.v. as a bolus into one experimental and one control group. Bile was collected from the common bile duct.

Results: At the end of the third hour, TPN caused a significant reduction in bile flow (P<0.02) and bile salt secretion rate (P<0.001) (61.24 vs. 50.74 µl/min/kg, and 1.173 vs. 0.799 µmol/min/kg, respectively). Addition of cisapride abolished the cholestatic effect of TPN.

Conclusions: Cisapride has a protective effect against TPN-associated cholestasis. This may have clinical significance, and further studies are warranted.

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TPN= total parenteral nutrition
 

Arie Levine MD, Yoram Bujanover MD, Shimon Reif MD, Svetlana Gass, Nurit Vardinon, Ram Reifen MD and Dan Lehmann PhD

Background: Anti-endomysial antibodies are sensitive and specific markers for celiac disease. This antibody has recently been identified as an antibody to tissue transglutaminase, an enzyme that cross-links and stabilizes extracellular matrix proteins.

Objectives: To evaluate the clinical usefulness of an enzyme-linked immunoassay for anti-transglutaminase antibodies, and to compare the results with those of AEA, the current gold standard serological test for celiac disease.

Methods: Serum samples were collected from 33 patients with biopsy-proven celiac disease and AEA tests were performed. Control samples for anti-transglutaminase were obtained from 155 patients. An ELISA test for immunoglobulin A anti-transglutaminase utilizing guinea pig liver transglutaminase was developed and performed on all sera.  Cutoff values for the test were performed using logistic regression and receiver operating curves analysis.

Results: An optical density cutoff value of 0.34 was established for the assay. The mean value was 0.18±0.19 optical density for controls, and 1.65±1.14 for patients with celiac disease (P<0.001). Sensitivity and specificity of the assay were both 90%, while AEA had a sensitivity and specificity of 100% and 94%, respectively.

Conclusions: A tissue transglutaminase-based ELISA test is both sensitive and specific for  detection of celiac disease.

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AEA = anti-endomysial antibody

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