Israel Medical Association Journal

Background: The primary diagnosis of functional dyspepsia (FD) is made on the basis of typical symptoms and by excluding organic gastrointestinal diseases that cause dyspeptic symptoms. However, there is difficulty reaching a diagnosis in FD.

Objectives: To assess the efficiency of the Usefulness Index (UI) test and history-taking in diagnosing FD.

Methods: A study on acute abdominal pain conducted by the World Organizati­on of Gast­roentero­logy Research Committee (OMGE) included 1333 patients presenting with acute abdo­minal pain. The clinical history-taking variables (n=23) for each pa­tient were recorded in detail using a prede­fined structured data collection sheet, and the collected data were compared with the final diagnoses.

Results: The most signifi­cant clinical history-taking variables of FD in univa­riate analysis were risk ratio (RR): location of pain at diagnosis (RR = 5.7), location of initial pain (RR = 6.5), previous similar pain (RR = 4.0), duration of pain (RR = 2.9), previous abdominal surgery (RR = 4.1), previous abdominal diseases (RR = 4.0), and previous indigestion (RR = 3.1). T­he sensi­tivity of the physicians’ initial de­cisi­on in detecting FD was 0.44, speci­fi­city 0.99 and effi­ciency 0.98; UI was 0.19 and RR 195.3. In the stepwise multivariate logistic regression analysis, the independent predictors of FD were the physicians’ initial decision (RR = 266.4), location of initial pain (RR = 3.4), duration of pain (RR = 3.1), previous abdominal surgery (RR = 3.7), previous indigestion (RR = 2.2) and vomiting (RR = 2.0).

Conclusions: The patients with upper abdominal pain initially and a previous history of abdominal surgery and indigestion tended to be at risk for FD. In these patients the UI test could help the clinician differentiate FD from other diagnoses of acute abdominal pain.

Background: Removal of retained placental tissue postpartum and retained products of conception (RPOC) abortion is done by uterine curettage or hysteroscopy. Trauma to the endometrium from surgical procedures, primarily curettage, can cause intrauterine adhesions (Asherman's syndrome) and subsequent infertility. The incidence of malpractice claims relating to intrauterine adhesions is rising, justifying reevaluation of the optimal way of handling these complications. 

Objectives: To review malpractice claims regarding intrauterine adhesions, and to explore the clinical approach that might reduce those claims or improve their medical and legal outcomes.

Methods: We examined 42 Asherman's syndrome claims handled by MCI, the largest professional liability insurer in Israel. The clinical chart of each case was reviewed and analyzed by the event preceding the adhesion formations, timing and mode of diagnosis, and outcome. We also assessed whether the adverse outcome was caused by substandard care and it it could have been avoided by different clinical practice. The legal outcome was also evaluated.

Results: Forty-seven percent of the cases occurred following vaginal delivery, 19% followed cesarean section, 28% were RPOC following a first-trimester pregnancy termination, and 2% followed a second-trimester pregnancy termination.

Conclusions: It is apparent that due to a lack of an accepted management protocol for cases of RPOC, it is difficult to legally defend those cases when the complication of Asherman syndrome develops. 

Objective: To study the mechanism of platelet function inhibition in a patient with acquired thrombasthenia.

Methods: Aggregation assays of platelets from the patient and healthy controls were performed. In addition, anti-glycoprotein (GP) IIbIIIa antibodies binding to normal platelets in the presence or absence of the patient’s serum was studied by flow cytometry.

Results: Aggregation of normal platelets in the presence of patient's plasma was inhibited four- and 2.5-fold in the presence of ADP and arachidonic acid respectively, while collagen-induced aggregation was completely abolished. Ristocetin-induced aggregation was normal. The patient's serum inhibited binding of commercial anti-glycoprotein IIbIIIa antibodies to normal platelets twofold by flow cytometry. Treatment with anti-CD20 monoclonal antibody (rituximab) normalized the patient's platelet aggregation.

Conclusions: These results suggest that the patient developed inhibitory anti-GPIIbIIIa autoantibodies that caused acquired thrombasthenia. 

Objectives: To determine the properties of HAM as an antigenic substrate for the detection of autoantibodies in pemphigus vulgaris and bullous pemphigoid.

Methods: Immunomapping and tandem liquid chromatography mass spectrometry were used to delineate the antigenic structure of HAM in 25 pemphigus patients, 41 pemphigoid patients, and 36 controls. Immunoblotting and indirect immunofluorescence were used to study the diagnostic utility of HAM, and the results were compared to those of indirect immunofluorescence on monkey esophagus, immunoblotting using normal human skin, and enzyme-linked immunosorbent assay (ELISA).

Results: Immunomapping demonstrated the presence of all the antigens known to be targeted in autoimmune bullous skin diseases, in both normal human skin and HAM, except for the absence of BP230, and low threshold levels of Dsg1, Dsg3 and Dsc3 in HAM. HAM indirect immunofluorescence demonstrated anti-basement membrane zone antibodies in 48.7% of the pemphigoid patients, and anti-intercellular space antibodies in 72.0% of the pemphigus patients. HAM immunoblotting did not demonstrate anti-BP230 antibodies, but detected anti-BP180 antibodies in 53.6% of the pemphigoid patients. It did not demonstrate anti-Dsg1 and/or anti-Dsg3 antibodies in any of the pemphigus patients. These results were inferior to those of ELISA and monkey esophagus indirect immunofluorescence.

Conclusions: Compared to other studied methods, HAM does not offer advantages in detecting autoantibodies in bullous pemphigoid and pemphigus vulgaris. 

Objectives: To investigate whether the change in protocols over the years resulted in an outcome difference at two hospitals in Israel.

Methods: We thoroughly reviewed the records of 153 patients from Sheba Medical Center and Soroka Medical Center, of whom 106 comprised the study group. The patients were divided into two groups according to the treatment protocol used: 40 patients with the 1989/93 protocol and 66 with the 1999/2003 protocol. Outcome was analyzed for the two groups.

Results: We found a significant difference in disease-free survival (DFS) between the two groups for B cell-ALL (B-ALL) patients who achieved complete remission after induction. There was no difference in overall survival. We did not find any difference in outcome for T cell-ALL patients or for CD20-positive patients.

Conclusions: In our retrospective analysis, GMALL 99/2003 led to a better DFS for B-ALL patients who were in complete remission after induction. This is possibly related to the differences in medications between the protocols, but may also be due to better supportive care. Despite the proven advantage of the newer protocols regarding overall survival, in our experience there was no other significant difference between the two regimens. 

Objectives: To examine the effect of meloxicam, a selective COX-2 inhibitor, or low dose aspirin on the development of experimental atherosclerosis in apoE knockout (KO) compared to wild-type (WT) mice. We aimed to test the hypothesis that meloxicam, a potential vasculitis inducer, would exacerbate atherosclerotic lesions while aspirin, which is known to reduce the incidence of thrombosis occlusive events, would increase protection in this model.

Methods: We randomly divided 36 male apoE KO and 36 WT mice, 8 weeks old. Mice were treated for 10 weeks with 0.1 mg/ml aspirin, or 0.05 mg/ml meloxicam, dissolved in their drinking water. Control groups received regular drinking water. At sacrifice, the hearts were removed for histochemical staining and plaque size and composition were examined.

Results: Aspirin-treated animals displayed a decreased atherosclerotic lesion area compared to the untreated control mice, while meloxicam had a null effect on the extent of atherosclerosis in Apo E KO mice.

Conclusions: These results suggest that low dose aspirin reduces early atherosclerosis, while inhibition of COX-2 by meloxicam is not associated with an increase in atherosclerotic plaque size in this mouse model.

Objectives: To describe the results of nerve conduction studies in patients with anogenital pruritus, brachioradial pruritus and scalp dysesthesia, and compare these sites to typical sites of lichen simplex chronicus (LSC).

Methods: The study summarizes previously published data combined with unpublished data of patients with scalp dysesthesia. Nerve conduction studies included measurements of distal sensory and motor latency, conduction velocity and F-responses.

Results: A neuropathy was demonstrated in 29 of 36 patients with anogenital pruritus (80.5%), 8/14 with brachioradial pruritus (57.1%) and 4/9 with scalp dysesthesia (44.4%). The typical sites overlapped with some but not all LSC sites.

Conclusions: A considerable proportion of patients with brachioradial pruritus, anogenital pruritus and scalp dysesthesia have abnormal nerve conduction findings, suggesting a neuropathic origin. The skin sites overlap with some common LSC sites, suggesting that in some cases of LSC a local neuropathy could be a possible cause.

Objectives: To retrospectively analyze the results of a screening program for C-CMV performed at the Sheba Medical Center, Tel Hashomer, during a 1 year period, using real-time polymerase chain reaction (rt-PCR) from umbilical cord blood.

Methods: CMV DNA was detected by rt-PCR performed on infants’ cord blood. C-CMV was confirmed by urine culture (Shell-vial). All confirmed cases were further investigated for C-CMV manifestations by head ultrasound, complete blood count, liver enzyme measurement, ophthalmology examination and hearing investigation.

Results: During the period 1 June 2009 to 31 May 2010, 11,022 infants were born at the Sheba Medical Center, of whom 8105 (74%) were screened. Twenty-three (0.28%) were positive for CMV and 22 of them (96%) were confirmed by urine culture. Two additional infants, who had not been screened, were detected after clinical suspicion. All 24 infants were further investigated, and 3 (12.5%) had central nervous system involvement (including hearing impairment) and were offered intravenous ganciclovir for 6 weeks. Eighteen (82%) infants would not otherwise have been diagnosed.

Conclusions: The relatively low incidence of C-CMV detected in our screening program probably reflects the low sensitivity of cord blood screening. Nevertheless, this screening program reliably detected a non-negligible number of infants who could benefit from early detection. Other screening methods using saliva should be investigated further.

Mesenchymal stem cells, or mesenchymal stromal cells, have emerged as a major new cell technology with a diverse spectrum of potential clinical applications. MSCs[1] were originally conceived as stem/progenitor cells to rebuild diseased or damaged tissues. Over the last 14 years, since the first report of MSC infusions in patients, the cells have been shown to suppress graft vs. host disease, stimulate linear growth in a genetic disorder of bone, and foster engraftment of haplo-identical hematopoietic stem cells. In all cases, few, if any, MSCs were identified at the site of clinical activity. This experience suggests a remarkable clinical potential, but a different general mechanism of action. Systemically infused MSCs seem to exert a therapeutic effect effect through the release of cytokines that act on local, or perhaps distant, target tissues. Rather than serving as stem cells to repair tissues, they serve as cellular factories that secrete mediators to stimulate the repair of tissues or other beneficial effects. Since both the tissue source of MSCs and the ex vivo expansion system may significantly impact the cytokine expression profile, these parameters may be critically important determinants of clinical activity. Furthermore, cell processing protocols may be developed to optimize the cell product for a specific clinical indication. For example, MSC-like cells isolated from placenta and expanded in a three-dimensional bioreactor have recently been shown to increase blood flow in critical limb ischemia. Future efforts to understand the cytokine expression profile will undoubtedly expand the range of MSC clinical applications.

Background: In the western world, trauma is the leading cause of disability and mortality in the 1–39 years age group. Road accidents constitute the most frequent cause of mortality among children older than 1 year and falls from a height are the most frequent cause of injuries requiring hospitalization.

Objectives: To analyze the epidemiology and characteristics of severe pediatric trauma due to falls from a height in northern Israel. This analysis should aid in planning an effective intervention plan.

Methods: This observational study included all patients aged 0–14 who died or were admitted to an intensive care unit in northern Israel following a steep fall. Demographic and clinical data were collected retrospectively for 3 years and prospectively for 1 year.

Results: A total of 188 children were severely injured or died following such a fall, with an annual rate of 11.4 per 100,000 children. Over 85% of severe injuries due to falls occurred among non-Jewish children, with an incidence rate 6.36 times higher than among Jewish children (20.17 and 3.17 per 100,000 children, respectively). In the non-Jewish sector 93.7% of the falls occurred at or around the child’s home, mainly from staircases, balconies and roofs.

Conclusions: A very high incidence of severe trauma due to domestic falls from a height was found among non-Jewish children in northern Israel. Domestic falls represent an important epidemiological problem in the non-Jewish pediatric sector, and an effective prevention plan should include measures to modify parents’ attitudes towards safety issues and the creation of a safe domestic environment.