Israel Medical Association Journal

Background: Repaglinide, a new insulin secretagogue, is purported to be as effective as sulphonylurea but is less hypoglycemic-prone.

Objectives: To assess the efficacy of repaglinide and its proclivity for hypoglycemia in a post-marketing study.

Methods: The study group comprised 688 patients, aged 26–95 years, clinically diagnosed with non-insulin-dependent type 2 diabetes. The patients were divided into three groups based on previous therapy: a) sulphonylurea-treated (group 1, n=132); b) metformin with or without sulphonylurea where sulphonylurea was replaced with repaglinide. (group 2, n=302); and c) lifestyle modification alone (drug-naïve) (group 3, n=254). At initiation of the study, all patients were transferred from their current treatment to repaglinide. Only patients in group 2, with combined sulphonylurea plus metformin, continued with metformin plus repaglinide. Fasting blood sugar, hemoglobin A1c and weight were measured at study entry and 4–8 weeks following repaglinide therapy. A questionnaire documented the number of meals daily and the presence of eating from fear of hypoglycemia.

Results: The fasting blood sugar level of the entire cohort dropped from 191 ± 2.4 to 155 ± 2.0 mg/dl (P < 0.0001); HbA1c from 8.8 ± 0.1 to 7.7 ± 0.1% (P < 0.0001). The drop of HbA1c in groups 1, 2 and 3 respectively were: 1.04 ± 0.22% (P < 0.0001), 1.14 ± 0.24% (P < 0.0001), and 1.51 ± 0.31% (P = 0.0137). Weight dropped from 81 ± 0.7 to 80.2 ± 0.7 kg (P < 0.0001), and eating from fear of hypoglycemia from 157 to 97 (P < 0.001). The daily number of meals decreased from 2.9 ± 0.4 to 2.4 ± 0.4 (P < 0.001). No serious adverse reactions occurred during the study.

Conclusions: Repaglinide is an effective oral hypoglycemic agent taken either as monotherapy or combination therapy. There is less eating to avoid hypoglycemia, fewer meals consumed, and weight loss.

Background: Restorative proctocolectomy eliminates the risk of colorectal cancer in patients with familial adenomatous polyposis. Complications and extra‑intestinal manifestations are inherent to the procedure.

Objectives: To evaluate operative procedures, complications, early and late results and long-term functional outcome in FAP[1] patients operated in our department.

Methods: The study group included all patients with FAP who were operated between 1988 and 2003. Demographic data, length of follow‑up, complications, colorectal cancer, pouch function and extracolonic manifestations were recorded.

Results: Median age at surgery was 33 years (range 13–61 years). The final operative breakdown was: 48 proctocolectomies, 41 ileal pouch-anal anastomoses, 2 Kock’s pouch, 5 permanent ileostomies, and 2 colectomies with ileorectal anastomosis. There was no perioperative mortality. Early and late complications occurred in 20 and 9 patients, respectively. Twelve patients required re‑operation. Colorectal carcinoma was diagnosed in eight patients, three of whom were in an advanced stage. The mean follow‑up was 74 months (range 3–288 months). Four patients were lost to follow‑up. Extracolonic manifestations developed in 38 patients, including desmoid tumors (in 12), duodenal adenomas (in 9), pouch adenomas (in 5), and rectal stump adenomas (in 3). Two patients died (4%) because of desmoid tumor and malignant fibrous histiocytoma. At last follow‑up, 37 IPAA[2] patients have (median) six bowel movements/24 hours and good fecal control.

Conclusions: Restorative proctocolectomy can be performed with low mortality, acceptable morbidity, and good functional results. Patients should be closely followed after surgery for development of other manifestations of the syndrome. Relatives of the affected patients should be referred to a specialist multidisciplinary clinic.

Background: Involvement of the liver by lymphoma is almost always secondary. A definite diagnosis can be made only after histologic examination. Recently, there has been a trend to replace surgical biopsies with percutaneous core-needle biopsies for the diagnosis of lymphoproliferative disorders.

Objectives: To describe our experience with percutaneous image-guided needle biopsies of the liver in 15 cases of primary and secondary hepatic lymphoma.

Methods: Between 1997 and 2002, 15 of all the percutaneous computerized tomography-guided core-needle liver biopsies performed at our institution yielded the diagnosis of lymphoma. We retrospectively reviewed the medical records of these patients.

Results: Seven patients had primary hepatic lymphoma (all non-Hodgkin’s lymphoma), and eight had secondary (three Hodgkin`s disease and five non-Hodgkin’s lymphoma). No major complications were caused by the percutaneous biopsies, and all biopsies were diagnostic. The imaging findings were non-specific but were characteristic and similar to previously described series. Imaging demonstrated hypodense lesions by CT, or hypoechoic or anechoic lesions by ultrasound in all but two cases in which hilar lesions resulted in biliary dilatation, both demonstrated by ultrasound

Conclusions: Review of our primary cases indicated no association with cirrhosis or AIDS in contradistinction to the worldwide experience. There were no significant complications in the 15 patients in the study, and a definite diagnosis of lymphoma was made in all the cases with no need to proceed to surgical biopsy. We highly recommend image-guided core-needle biopsy of the liver as a reliable and useful tool for the diagnosis of hepatic lymphoma.

Background: Ultrasound is useful in detecting acromioclavicular pathologies in cases of trauma, inflammations and degenerative changes.

Objectives: To describe the sonographic findings of the acromioclavicular joint pathology in patients with anterior shoulder pain.

Methods: Sonographic examination of the ACJ[1] was used to examine 30 adults with anterior shoulder pain. As a control group we studied 30 asymptomatic patients and compared the findings to plain radiographs of the symptomatic group.

Results: The pathologic findings consisted of swelling of the joints, bone irregularities, widening and/or narrowing of the ACJ, soft tissue cyst formation, excessive fluid collection, and calcification. All these signs represent degenerative changes compatible with early osteoarthritis. We encountered one case of septic arthritis that required joint aspiration and antibiotic treatment.

Conclusions: It is our belief that ultrasonography should be used routinely in cases of anterior shoulder pain since it demonstrates various pathologies undetected by plain radiographs.

Background: Heterotopic ossification is a common complication of hip surgery and musculoskeletal or brain traumas.

Objectives: To confirm by in vivo study that colchicine inhibits osteoblast cell proliferation with marked decrease in tissue mineralization.

Methods: Heterotopic ossification was induced in three groups of New Zealand white rabbits (females, 6 months old, weight 3–3.5 kg) by injecting 2 ml bone marrow drawn from the iliac crest into their right thigh muscle. To prevent heterotopic ossification, colchicine (0.25 mg/day) was administered orally for 4 weeks to two groups of adult rabbits: group A (preload group) – 1 week preceding bone marrow injection; group B – on day of injection; and group C – control group.

Results: After 4 weeks the rabbits were evaluated by radiographs and ultrasound for evidence of heterotopic ossification. At the end of the study histologic samples were taken from all the thighs. Imaging and histologic studies showed, with statistical significance, almost complete prevention of heterotopic ossification formation in group A (preload) and a marked decrease in group B, when compared with the controls in whom large new bone had formed at the injection site. These results indicated the inhibitory effects of colchicine on a bone-forming process in soft tissue such as heterotopic ossification.

Conclusions: The role of colchicine in preventing heterotopic ossification in other bone-forming conditions, such as hip arthroplasty or pelvic trauma, and after brain trauma, remains to be evaluated in a clinical setting.

Background: Many medical school curricula include training for ethical considerations, legal comprehension, implementation of patients' rights, awareness of cultural differences and communication skills (ELCE).

Objectives: To explore medical students' perceptions of their ELCE training during the clinical phase as well as the relationship between humanistic practice skills' experiences and the quality of clinical training.

Methods: A cross-sectional survey was carried out in two cohorts during their clinical year period at Tel Aviv University's Sackler Faculty of Medicine at the end of their internal medicine and surgery clerkships in the 2002 academic year. The research tool was an 18 item Likert-type questionnaire (ELCEQ), based on the literature of biomedical ethics, legal aspects and behavior of practice skills. The content validation of the questionnaire was established by consulting experts among the school's faculty. It was circulated among the students by representatives of the Unit of Medical Education.

Results: The response rate was 88%. Students reported only a few opportunities for gaining experience in humanistic practice skills. A weak correlation was found between students' assessment of the quality of clinical training and their experiences in humanistic practice skills.

Conclusions: A wider and more relevant range of active experiences in humanistic practice skills should be available to students during the clerkships. Correspondingly, there is a need for the clinical faculty to find innovative ways to internalize their task as role models and ensure that students acquire and are able to practice those skills.
 

Background: Food intake has an immediate effect on the cardiovascular system. However, the effect of a large meal as an immediate trigger for the acute coronary syndrome has not been assessed.

Objectives: To assess the relative risk for an ACS[1] within a few hours after the ingestion of a heavy meal.

Methods: In a case-crossover study 209 patients were interviewed a median of 2 days after an ACS. Ingestion of a large meal in the few hours immediately before the onset of ACS was compared with the comparable few hours the day before and with the usual frequency of large meals over the past year. Large meals were assessed by a 5 level scale.

Results: The relative risk of an acute coronary event during the first hour after a heavy meal ingestion was RR[2] = 7 (95% confidence interval 0.75–65.8) when the day before the ACS served as the control data and RR = 4 (95% CI[3] 1.9–8.6) when the usual frequency of heavy meals ingestion during the previous year served as the control data. 

Conclusions: The ingestion of heavy meals can trigger the onset of an ACS. Education of the population to avoid heavy meals, especially in people at high risk for coronary heart disease, should be included in the prevention of ACS. Research on specific nutrients that may act as potential triggers for ACS should be considered.

Background: Oral anticoagulation with warfarin can lead to life-threatening events as a result of either over-anticoagulation or undertreatment. One of the main contributors to an undesirable warfarin effect is the need to adjust its daily dose for a specific patient. The dose is adjusted empirically based on the experience of the clinician, a method that is often imprecise. There is currently no other well-accepted method for predicting the maintenance dose of warfarin.

Objective: To describe the application of an artificial neural network to the problem of warfarin maintenance dose prediction.

Methods: We designed a neural network that predicts the maintenance dose of warfarin. Data on 148 patients attending a large anticoagulant clinic were collected by file review. Using correlational analysis of the patients' data we selected the best input variables. The network was trained by using the back-propagation algorithm on a subset of our data and the results were validated against the rest of the data. We used a multivariate linear regression to create a comparable model.

Results: The neural network generated reasonable predictions of the maintenance dose (r = 0.823). The results of the linear regression model were similar (r = 0.800).

Conclusion: Neural networks can be applied successfully for warfarin maintenance dose prediction. The results are promising, but further investigation is needed.
 

Background: The relationship between the amount of rehabilitation therapy and functional outcome in stroke patients has not been established.

Objectives: To evaluate the effectiveness of inpatient rehabilitation for post-acute stroke, and examine the relationship between intensity of therapies and functional status at discharge.

Methods: We evaluated 50 first-stroke patients, average age 63 years, in a prospective, descriptive study. The impairment and Functional Independence Measurement were assessed both at admission to rehabilitation and at discharge. Patients were monitored weekly during their stay by means of discipline-specific measures of activity level. Predictor variables included intensity of physical, occupational and speech therapies; demographic characteristics; length of stay; and time since the stroke.

Results: A significant reduction in impairment was observed at discharge. The predictors of gains and activity level at discharge as well as motor vs. cognitive components of the FIM[1] were neither consistent nor did they occur in the same trend of functional improvement. Greater FIM motor level at discharge was associated with younger age, higher admission motor and cognitive level, and receipt of any speech therapy, while greater FIM cognitive level was associated with higher cognitive level at admission, shorter interval from onset to admission, and more intense occupational therapy. More intense OT[2] was associated with greater and more cognitive improvement during the hospitalization.   

Conclusion: Since the sample was relatively small and heterogeneous in terms of the patients’ functional abilities, the findings cannot be generalized to the whole population of stroke patients. Further efforts to identify the best timing, modalities, intensity and frequency of the various treatments are needed to improve the cost-benefit equation of rehabilitation in stroke patients.