Israel Medical Association Journal

Background: Advanced glycation end products, formed by the non-enzymatic glycation of proteins with reducing sugars, are thought to play a pathogenetic role in the vascular complications of diabetes, uremia and atherosclerosis. β2-microglobulin is a major constituent of amyloid fibrils in dialysis-related amyloidosis. AGE[1]-modified β2m[2] has been found in amyloid deposits of long-term hemodialysis patients. AGE-modified β2m has also been shown to enhance chemotaxis and increase tumor necrosis factor-alpha and interleukin-1 beta secretion by circulating and tissue monocytes/macrophages.

Objectives: To investigate the effect of AGE-modified β2m and AGE-human serum albumin on TNF-α[3] and IL-1β[4] secretion by human peritoneal macrophages derived from patients on continuous ambulatory peritoneal dialysis.

Methods: Human PMØ[5] were isolated from peritoneal dialysis effluent of stable CAPD[6] patients and were incubated for 24 hours with AGE-modified β2m, β2m, AGE-HSA[7], HSA or lipopolysaccharide. TNF-α or IL-1β secretion was measured by enzyme-linked immunosorbent assay in cell-free culture supernatants.

Results: Both AGE-modified β2m and AGE-HSA significantly increased TNF-α and IL-1β secretion by human PMØ in a dose-dependent manner (50–200 μg/ml). In contrast, β2m or HSA had no such stimulatory effect on TNF-α secretion but had a small significant increase in IL-1β secretion.

Conclusions: AGE-modified β2m promotes in vitro TNF-α and IL-1β secretion by human PMØ of CAPD patients. Activation of these macrophages by AGE-modified β2m may be a contributory factor to the morphologic changes and altered permeability of the peritoneal membrane in long-term CAPD. 

We present the case of a 14 day old baby in whom we observed the evolution of idippathic hypertrophic pyloric stenosis.

Background: Heat shock proteins are highly conserved immunodominant antigens found in various species. Humoral immune responses to mycobacterial HSP65[1] and human HSP60 have been established in a number of human autoimmune diseases.

Objective: To assess the prevalence of antibodies to HSP60 kDa and HSP65 kDa in patients with Sjogren's syndrome as compared to normal subjects.

Methods: Thirty-seven patients with SS[2] were compared with normal controls. The antibodies against human HSP60 were measured by the Anti-Human (IgG/IgM) HSP60 ELISA kit. IgGs[3] and IgMs to mycobacterial HSP65 were determined using an enzyme-linked immunosorbent assay with mycobacterial recombinant HSP65 antigens.

Results: The levels of both anti-HSP60 and -HSP65 were lower among patients compared with controls. IgG autoantibodies to HSP60 were significantly different between groups: 162 ± 55.1 ng/ml in controls versus 112.3 ± 30.6 ng/ml in SS patients (P < 0.001). The levels among controls of anti-HSP65 IgM isotype were also significantly higher than among patients: 111.6 ± 33.4 U/ml versus 96.1 ± 8.9 U/ml (P = 0.01).

Conclusions: The results of the present study show that the levels of different isotypes of anti- HSP60 and HSP65 antibodies were lower in patients with SS than in normal subjects. Additional studies on larger patient populations are required to evaluate the prevalence of these autoantibodies in SS patients.

Objective: To assess the effect of establishing a new dedicated acute stroke unit within a department of neurology on indicators of process of care and outcome of acute stroke in a routine clinical setting in Israel.

Methods: Stroke patients admitted to the Sheba Medical Center during the period March 2001 to June 2002 were included in a prospective study according to selection criteria. Data on demographics, risk factors, co-morbidities and stroke severity were collected. Indicators of process of care and outcome were assessed at hospital discharge and 30 days follow-up. Comparison between outcome variables by hospitalization ward was conducted using logistic regression analysis adjusting for confounders.

Results: Of 616 acute stroke patients (mean age 70 years, 61% men, 84% ischemic stroke), 353 (57%) were admitted to general wards and 263 (43%) to the stroke unit. Diagnostic procedures were performed more often, and infection rate was lower in the setting of the stroke unit. Poor outcome (modified Rankin scale ≥3 or death) was present less often in patients managed in the stroke unit both at hospital discharge (adjusted odds ratio 0.5, 95% confidence interval 0.3–0.8) and at 30 day follow-up (adjusted OR[1] 0.6, 95%CI[2] 0.3–0.9). A Functional Independence Measure score ≤90 or death at 30 day follow-up was less frequent among patients managed in the stroke unit than in general wards (adjusted OR 0.5, 95%CI 0.2–0.8).

Conclusions: Improved outcomes and higher adherence to guidelines were observed in patients treated in a stroke unit within a department of neurology. The results suggest that patients with acute stroke should have access to treatment in a dedicated stroke unit.

Objectives: To use pelvic fractures as a test case for the efficiency of the Israeli trauma system, as reflected in the experience of our medical center.

Methods: Data were obtained from the medical charts of all cases of pelvic fractures admitted to our medical center between 1987 and 1999. We obtained demographic data, information on the cause of injury, fracture classification, co-injuries and Injury Severity Score, treatment strategies, and mortality rate.

Results: Altogether, 808 patients with pelvic injuries were treated in our medical center. The most common cause of injury was motor vehicle accidents (51%). Pelvic fractures without acetabular involvement were diagnosed in 58% of patients and isolated acetabular fractures in 32%, while 10% sustained combined injuries to the pelvic ring and the acetabulum. The overall rate of operative stabilization was 34%. The majority of patients had associated injuries, mostly additional musculoskeletal injuries. Altogether, 13% were referred from Level II/III trauma centers. We observed an increase in the total number of local admissions, in the percentage of referred patients and in the percentage of operated patients during the study period. The observed mortality rate was 5%.

Conclusions: Our results show a more than twofold increase in the percentage of referred patients following the designation of a Level I trauma center. These referrals result not only from the designation as a Level I trauma center, but also from the presence of a dedicated team of pelvic fracture specialists, available 24 hours a day. In addition, a larger percentage of patients undergo surgery for internal fixation of pelvic fractures, in accordance with current worldwide trends.

Objectives: To examine whether hostility, anxiety and autobiographical memory (a correlate of depression) are associated with IIH[1].

Methods: Using a case-control cross sectional design, 20 patients with IIH were compared with 9 healthy controls of similar age, weight and height, and 11 headache controls. Patients were assessed for hostility and anxiety. The Autobiographical Memory Test was used to assess episodic memories.

Results: The IIH group reported significantly more anxiety and more general episodic memories than the healthy controls, but not the headache control group. The headache control patients reported more general memories than did the healthy controls.

Conclusions: Patients with headaches, whether of general origin or related to IIH, have a poor psychosocial profile. While the study design does not permit any conclusions regarding causality, our results support the need to consider psychological factors in evaluating and treating IIH and headache patients. 

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[1] IIH = idiopathic intracranial hypertension

Objectives: To review the current status of MAS[1] in a pediatric tertiary care center in Israel, in terms of feasibility, safety, and effect on standard practices.

Methods: We reviewed the files of all children who underwent a MAS procedure in our department during the period April 2002 to July 2004, and compared the findings with those of children treated by standard practices.

Results: A total of 301 procedures were performed in 271 patients: 107 thoracoscopic and 194 laparoscopic. There were no major intraoperative complications. The total conversion rate was 3.65%: 0 for thoracoscopy and 5.6% for laparoscopy (11/194). Twenty-four types of procedures were performed during the study period. The thoracoscopies accounted for 92.24% of all thoracic procedures in the department (107/116), and routine abdominal laparoscopic procedures replaced open surgery in 30–100% of cases (total 44.8%, 194/433).

Conclusions: MAS procedures appear to be safe for a wide range of indications in children. In our center they currently account for a significant percentage of pediatric surgeries. We suggest that the integration of MAS training in the residency programs of pediatric surgeons be made a major long-term goal. The creation of a pediatric MAS study group, which would allow for multi-institutional studies, is especially important in Israel where a relatively large number of pediatric surgery departments handle a small annual number of patients.

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[1] MAS = minimal access surgery

Objectives: To examine whether a military medic, using a structured questionnaire and an algorithm, can appropriately triage patients to receive over-the-counter medications and refer more complicated cases to a physician.

Methods: The study group comprised 190 consecutive soldiers who presented to a military primary care clinic with symptoms of ARVI. Using a questionnaire, a medic recorded the patient's history and measured oral temperature, pulse rate and blood pressure. All patients were referred to a doctor. Physicians were “blind” to the medic’s anamnesis and to the algorithm diagnosis. We compared the medic’s anamnesis and therapeutic decisions to those of the doctors.

Results: Patients were young (21.1 ± 3.7 years) and generally healthy (93% without background illness). They usually had a minor disease (64% without fever), which was mostly diagnosed as viral ARVI (83% of cases). Ninety-nine percent were also examined by a physician. According to the patients' data, the medics showed high overall agreement with the doctors (83–97.9%). The proposed algorithm could have saved 37% of referrals to physicians, with a sensitivity of 95.2%. Had the medics been allowed to examine the pharynx for an exudate, the sensitivity might have been 97.6%.

Conclusions: Medics, equipped with a questionnaire and algorithm but without special training and without performing a physical examination, can appropriately triage patients and thereby reduce the number of referrals to physicians.

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[1] ARVI = acute respiratory viral infection

Objectives: To investigate the spectrum of findings in 32 consecutive patients with chest pain who underwent CT coronary angiogram in order to determine the clinical situations that will benefit most from this new technique.

Methods: Thirty-two patients with chest pain were studied by MDCT[1] using 4 x 1 mm cross-sections, at 500 msec rotation with pitch 1–1.5, intravenous non-ionic contrast agent and a retrospectively ECG-gated reconstruction algorithm. The heart anatomy was evaluated using multi-planar reconstructions in the axial, long and short heart axes planes. Coronary arteries were evaluated using dedicated coronary software and the results were compared to those of the conventional coronary angiograms in 12 patients. The patients were divided into four groups according to the indication for the study: group A – patients with high probability for coronary disease; group B – patients after CCA[2] with undetermined diagnosis; group C – patients after cardiac surgery with possible anatomic derangement; and group D – symptomatic patients after coronary artery bypass graft, before considering conventional coronary angiography.

Results: Artifacts caused by coronary motion, heavy calcification and a lumen diameter smaller than 2 mm were the most frequent reasons for non-evaluable arteries. Assessment was satisfactory in 83% of all coronary segments. The overall sensitivity of 50% stenosis was 74% (85% for main vessels) with a specificity of 96%. Overall, the CTCA[3] results were critical for management in 18 patients.

Conclusions: Our preliminary experience suggests that CTCA is a reliable and promising technique for the detection of coronary artery stenosis as well as for a variety of additional cardiac and coronary structural abnormalities.