Israel Medical Association Journal

Background: Gaucher disease results from the accumulation of glucosylceramide (glucocerebroside) in tissues of affected persons. Patients sharing the same genotype present with widely varying degrees of lipid storage and of clinical manifestations.

Objectives: To determine whether variation in the glucosylceramide synthase (UDPGlucose ceramide glucosyltransferase) gene, which encodes the enzyme that regulates the synthesis of glucocerebroside, could account for the variability and clinical manifestations.

Methods: Patients homozygous for the 1226G (N370S) mutation, the most common in the Ashkenazi Jewish population, were investigated. The exons and flanking sequences of the gene were sequenced using DNA derived from five very mild Gaucher disease patients and four patients with relatively severe Gaucher disease. Results: One polymorphism was found in the coding region, but this did not change any amino acids. Seven other polymorphisms were found in introns and in the 5' untranslated region. Some of these were single nucleotide polymorphisms; others were insertions. The mutations appear to be in linkage equilibrium and none were found with a significantly higher frequency in either severe or mildly affected individuals.

Conclusions: Mutations in the glucosylceramide synthase gene do not appear to count for the variability in expression of the common Jewish Gaucher disease mutation.
 

The etiology of inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, is uncertain. Studies of specific environmental factors and immune dysfunction have provided limited insight into disease pathogenesis. There is ample evidence that these diseases are in part the result of genetic predisposition. The early search for candidate genes focused on genes involved in the regulation of immune function.

Recent genome wide searches reported several susceptibility loci for Crohn’s disease and ulcerative colitis. The recent identification of the IBD1 gene (NOD2) with mutations that are associated with susceptibility to Crohn’s disease will have a major impact on the understanding of the genetics of this disease.
 

Background: Celiac disease is common in both children and adults. Small intestinal biopsy is mandatory for establishing a diagnosis. Anti-endomysial antibodies, detected by immunofluorescence, have a sensitivity and specificity close to 100% in the diagnosis of CD[1]. Recently, tissue transglutaminase has been identified as the target autoantigen of antibodies against endomysium, and TTG[2] antibodies are comparable to EMA-IMF[3] in the diagnosis of CD.

Objective: To evaluate a new enzyme-linked immunosorbent assay kit for EMA, compared to EMA-IMF and TTG antibodies in the diagnosis of CD.

Methods: Our study population included all subjects with positive EMA-IMF who underwent intestinal biopsy (n=21). From the same sera, TTG antibodies and EMA-ELISA[4] were determined, and all antibody results were compared to the biopsy findings.

Results: EMA-IMF was able to predict biopsy findings of CD in 19 of 21 cases (90.5%). When patients with biopsy findings compatible with CD and positive EMA-IMF (n=19) were tested for EMA-ELISA and TTG antibodies, 18 of the 19 were positive for both EMA-ELISA and TTG antibodies. A significant correlation was found between EMA-ELISA and TTG antibody titers (r = 0.74, P < 0.001).

Conclusions: Our study demonstrates that EMA-ELISA is comparable to TTG antibodies in the diagnosis of CD, and supports the use of EMA-ELISA as a serologic marker for this disease.

Background: The treatment of patients with recurrent ovarian carcinoma after failure of first and second-line chemotherapy is still debated. Chemical agents used for third and fourth-line therapy usually yield poor results with severe toxic side effects.

Objective: To summarize our experience with goserelin in the treatment of patients with recurrent ovarian cancer.

Methods: From September 1996 to June 1999 we administered goserelin, 3.6 mg subcutaneously every 4 weeks, to 15 patients with advanced and recurrent epithelial ovarian cancer (median age 59.0, median performance status 3.0).

Results: Seven of 15 eligible patients relapsed after platinum-based chemotherapy (3 of them also received paclitaxel and another 2 received tamoxifen). Four patients relapsed after carboplatin and paclitaxel, one of whom was treated with topotecan thereafter. Two patients relapsed after single-agent paclitaxel. Two patients with advanced disease and poor performance status without previous treatment received only goserelin. There was one complete response (6.7%) and 1 partial response (6.7%) lasting 8 and 14 months respectively (overall response rate 13.4%). In addition, the disease stabilized in three patients (20%) for a median of 7.5 months. In 10 patients the disease progressed. There was no significant toxicity. Median survival of all patients was 5.8 months.

Conclusion: Goserelin was helpful in one-third of our patients with advanced and refractory ovarian cancer. It is an easy and non-toxic option for treating very ill or previously heavily treated patients.
 

The threat of a disease outbreak resulting from biologic warfare has been of concern for the Israeli health system for many years. In order to be prepared for such an event the health system has formulated doctrines for various biologic agents and defined the logistic elements for the procurement of drugs. During the last 4 years, and especially after the West Nile fever epidemic in 2000, efforts to prepare the healthcare system and the relevant organizations were accelerated. The Director-General of the Ministry of Health nominated a Supreme Steering Committee to fill in the gaps and upgrade the preparedness of the health system for an unusual disease outbreak. This committee and its seven subcommittees established appropriate guidelines, communication routes among different organizations, and training programs for medical personnel. The anthrax outbreak in the United States found the healthcare system in the hub of the preparation process, and all modes of action were intensified. Further work by hospitals, primary care clinics and all other institutes should be initiated to maintain a state of proper preparedness.

Recent events have drawn world attention to “mythological diseases” such as anthrax, plague and smallpox, which have been out of the spotlight for some decades. Much of our current knowledge of epidemic intervention and disease prevention was acquired over history through our experience with these very diseases, such that the sudden panic over the re-emergence of these historically well-known entities is perplexing. Over time, changes in the balance of the epidemiologic triangle have driven each of these disease systems towards a new equilibrium with which we are not familiar. While the pathogens may be similar, these are not the diseases of the past. These new disease systems are insufficiently described by the classic epidemiologic triangle, which lacks a dimension necessary for providing a valid model of the real-world effects of bioterror-related disease. Interactions within the classic epidemiologic triangle are now refracted through the prism of the global environment, where they are mediated, altered, and often amplified. Bioterror-associated diseases must be analyzed through the epidemiologic pyramid. The added dimension represents the global environment, which plays an integral part in the effects of the overall disease system. The classic triangle still exists, and continues to function at the base of the new model to describe actual agent transmission, but the overall disease picture should be viewed from the height of the fourth apex of the pyramid. The epidemiologic pyramid also serves as a practical model for guiding effective interventional measures.

Background: The ear is the most frequent organ affected during an explosion. Recognition of possible damage to its auditory and vestibular components, and particularly the recovery time of the incurred damage, may help in planning the optimal treatment strategies for the otologic manifestations of blast injury and preventing deleterious consequences.   

Objective: To report the results of the oto-vestibular initial evaluation and follow-up of 17 survivors of a suicidal terrorist attack on a municipal bus.

Methods: These 17 patients underwent periodic ear inspections and pure tone audiometry for 6 months. Balance studies, consisting of electronystagmography (ENG) and computerized dynamic posturography (CDP) were performed at the first time possible.

Results: Complaints of earache, aural fullness and tinnitus resolved, whereas dizziness persisted in most of the patients. By the end of the follow-up, 15 (55.6%) of the eardrum perforations had healed spontaneously. Hearing impairment was detected in 33 of the 34 tested ears. Recovery of hearing was complete in 6 ears and partial in another 11. ENG and CDP were performed in 13 patients: 5 had abnormal results on CDP while the ENG was normal in all the patients. The vertigo in seven patients resolved in only one patient who was free of symptoms 1 month after the explosion.

Conclusion:  Exposure to a high powered explosion in a confined space may result in severe auditory and vestibular damage. Awareness of these possible ear injuries may prevent many of the deleterious consequences of such injuries.
 

Background: Primary care physicians' adherence to accepted asthma guidelines is necessary for the proper care of asthma patients.

Objectives: To investigate the compliance of primary care physicians with clinical guidelines for asthma treatment and their participation in related educational programs, and to evaluate the influence of their employment status.

Methods: A questionnaire was administered to a random sample of 1,000 primary care practitioners (pediatricians and family physicians) in Israel.

Results: The response rate was 64%. Of the physicians who participated, 473 (75%) had read and consulted the guidelines but only 192 (29%) had participated in an educational program on asthma management in the last 12 months. The younger the responding physician (fewer years in practice), the more likely his/her attendance in such a program (P<0.0001). After consulting the guidelines 189 physicians (40%) had modified their treatment strategies. Significantly more self-employed than salaried physicians had read the guidelines and participated in educational programs; physicians who were both self-employed and salaried fell somewhere between these groups. This trend was not influenced by years in practice.

Conclusions: All primary care physicians should update their knowledge more often. The publication of guidelines on asthma must be followed by their proper dissemination and utilization. Our study suggests that major efforts should be directed at the population of employed physicians.

Background: Historically, donor age above 55 years has been considered to be a relative contraindication for organ transplantation. The shortage of organs for transplantation has led to the expansion of the donor pool by accepting older donors. 

Objectives: To compare the 1 year follow-up in patients after lung transplantation from older donors (>50 years old) and in patients after transplantation from younger donors (± 50 years).

Methods: The study group comprised all adult patients who underwent lung transplantation at the Rabin Medical Center between May 1997 and August 2001. Donors were classified into two groups according to their age: ≤ 50 years (n=20) and > 50 years (n=9). Survival, number and total days of hospitalization, development of bronchiolitis obliterans syndrome, and pulmonary function tests, were examined 1 year after transplantation.     

Results: We performed 29 lung transplantations in our center during the observed period. Donor age had no statistically significant impact on 1 year survival after lung transplantation. There was no statistically significant effect on lung function parameters, the incidence of hospitalization or the incidence of bronchiolitis obliterans between both donor age groups at 1 year after transplantation.

Conclusions: Donor age did not influence survival or important secondary end-points 1 year after lung transplantation. By liberalizing donor criteria of age up to 65 years, we can expand the donor pool, while assessing other possible mechanisms to increase donor availability. 

Background: Femoral hip fractures are a common occurrence in the elderly. Of the various fracture patterns, intertrochanteric injuries have the lowest rate of complications. Case reports of ensuing subcapital fracture have all been linked to incorrect placement of fixation devices or to osteomyelitis, while cases of avascular necrosis have only been reported rarely in the literature and are considered to occur at the rare rate of 0.8%.

Objectives: To check the incidence and outcome of AVN[1] in intertrochanteric hip fractures.

Methods and Results: In a retrospective analysis of patients who had surgical treatment for intertrochanteric fractures, 10 patients (0.5%) underwent dynamic hip screw fixation for intertrochanteric fractures and subsequently developed painful AVN as their primary presentation. Three of these patients were also found to have subcapital fractures. On revision of the primary fixation no fault was found with nail placement.

Conclusions: The reported rate of AVN may be understated since many patients have limiting factors that prevent them from consulting a physician when in pain, and one-third of these patients die within 2 years. Therefore, we suggest that hip pain following fixation of an intertrochanteric fracture should prompt the clinician to consider the rare possibility of AVN or subcapital fracture.

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[1] AV = avascular necrosis