Israel Medical Association Journal

Background: The contribution of the abnormal DNA mismatch repair system to non-small cell lung cancer tumorigenesis is controversial and has not been reported in Jewish Israeli patients. Similarly, the involvement of 3p deletions in NSCLC[1] in the same population has not been assessed.

Objectives: To assess the contribution of the DNA-MMR[2] system to NSCLC pathogenesis by analyzing microsatellite instability, and evaluate loss of heterozygosity at 3p rates in Israeli NSCLC patients.

Methods: Paired DNA from tumorous and non-tumorous tissue was extracted, and genotyping for MSI[3] determination was carried out using the five Bethesda markers and for determining LOH[4] two 3p markers were used. Genotyping was performed using polymerase chain reaction amplification and size separation on an ABI semiautomatic DNA sequencer, and the allelic patterns of tumorous and non-tumorous tissue were compared.

Results: Forty-four NSCLCs from 35 smokers and 9 non-smokers were analyzed, with 26 of the 44 (59%) at stage I disease. Using five microsatellite markers (D17S250, D5S346, D2S123, BAT-25, BAT-26) (known as Bethesda markers) for MSI determination, 6 of the 44 tumors (13.6%) exhibited MSI in at least one marker. Similarly, genotyping for LOH at chromosome 3p was performed using two markers (D3S4103, D3S1234) located at 3p14.2 l. With D3S4103, 33 of the 44 patients successfully analyzed were homozygous and therefore non-informative with respect to LOH. Using D3S1234, 33 of 36 patients (91.7%) were heterozygous, and 23 of these individuals' tumors (69.7%) displayed LOH. Unexpectedly, 4 of 33 tumors (12.1%) genotyped by D3S4103, and 16 of 36 tumors (44.5%) genotyped by D3S1234 showed a pattern of MSI, even though only one of these tumors showed a similar pattern when genotyped with the five consensus markers. Overall, 23 of 44 tumors (52.3%) demonstrated MSI on at least one marker, and 5 of these 23 tumors (21.7%) had MSI on two or more markers.

Conclusions: MSI using 3p markers and not the Bethesda markers occurs at a high rate and in early stages in Jewish NSCLC patients.

Background: The suspicion of child abuse and neglect may arise from manifestations such as physical or psychosomatic symptoms, eating disorders, suicidal behavior, impaired parental functioning, etc. Thus the arrival of an abused or neglected child at the hospital provides an opportunity for detecting the problem and beginning a process of change. Optimal utilization of this potential depends on the awareness, diagnostic ability and cooperation of the staff.

Objectives: To assess knowledge about hospital policy, attitudes and actual behavior of hospital staff in cases of SCAN[1].

Methods: The questionnaire was adapted and distributed to a convenience sample of personnel at a children’s hospital. The questionnaire included items on knowledge of hospital policy regarding SCAN, attitudes towards inquiring about cases that appear suspicious, and behaviors in cases in which the respondent was involved. The comparison of responses to specific questions and among members of different professions was analyzed by chi-square test.

Results: Eighty-two staff members completed the questionnaires. Most of the respondents were aware of hospital policy regarding suspected abuse (86.6%), with fewer regarding suspected neglect (77.2%). Physicians were the least aware of these policies, as compared to medical students, nurses and social workers. Although most considered the issue of SCAN a responsibility of members of their own profession, 35.4% considered it primarily the responsibility of the welfare or judicial systems. Over 40% felt uncomfortable discussing suspicions with the child and nearly half felt uncomfortable discussing them with parents. The most often reported reason for this was the sense that they lacked skills or training for dealing with the issue. Despite this, when asked about actual behavior, 94.7% responded that they do try to clarify the circumstances related to the suspicious symptoms. Respondents were more likely to contact the hospital social worker than community resources (91.5% vs. 47.2%).

Conclusions: The findings highlight the need to encourage awareness, discourse and training of medical personnel about issues related to SCAN in order to maximize their potential contribution to identifying children at risk.

The role of skin substitutes in burn surgery and in the treatment of chronic wounds is constantly evolving. New products are regularly being developed and approved for clinical use. Studies on existing products demonstrate their effectiveness in different clinical scenarios. However, cost-related concerns, inadequate physician education, and the drawbacks that still accompany every skin substitute have resulted in limited application of these modalities. Today, burn surgeons still rely mostly on old-fashioned skin grafts. Only a few burn centers in the world actually use some of these products in their routine treatment of wounds. This review provides an up-to-date overview of the latest developments in the field of skin substitutes. We examine the major commercially available skin substitute products and their performance, and briefly review the technologies and products that are under development but have not yet become widely available.

Background: Lipoid pneumonia is a pneumonitis resulting from the aspiration of lipids, and is commonly associated with the use of mineral oil as a laxative. LP[1] is relatively unfamiliar to clinicians and is probably underdiagnosed.

Objectives: To increase physicians' awareness of LP, its diagnosis and prevention.

Methods: We present two illustrative cases of LP and review the literature.

Results: Two cases of LP were diagnosed within half a year in an internal medicine ward. Both cases were elderly patients, and LP was associated with the use of mineral oil as a laxative agent. Computerized tomography revealed bilateral low attenuation infiltrates, associated with a "crazy paving" pattern in one case. Sudan Black staining was diagnostic in both cases – in one on a transbronchial biopsy specimen, and in the other on sputum cytologic examination. Both patients suffered from neurologic diseases and were at risk of aspiration. In both cases clinical symptoms and signs continued for several months prior to diagnosis but resolved after the mineral oil was discontinued.

Conclusions: LP often occurs in elderly patients who are at risk of aspiration. The condition may be underdiagnosed. Since in most cases mineral oil cathartics are the causative agent, an effort at primary prevention is indicated. It is suggested that the licensing of mineral oil for internal use be changed.

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 evaluate the outcome of this procedure and to compare the complication rate following circumcisions performed by ritual circumcisers and by physicians.

Methods: In 2001, of the 19,478 males born in four major medical centers in Israel 66 had circumcision-related complications. All the children were circumcised in non‑medical settings within the community. The patients were medically evaluated either urgently due to immediate complications or electively in outpatient clinics later on. Upon the initial assessment a detailed questionnaire was filled to obtain data regarding the procedure, the performer and the subsequent complications.

Results: All the circumcisions were performed during the early neonatal life, usually on day 8 of life (according to Jewish law). In 55 cases (83%) it was part of a ritual ceremony conducted by a ritual circumciser (Mohel), while in 11 babies (17%) physicians were involved. Acute bleeding after circumcision was encountered in 16 cases (24%), which required suturing in 8. In addition, we found two cases of wound infection and one case of partial amputation of glans penis in which the circumcision was performed by a ritual circumciser. Among the late complications, the most common was excess of skin in 38 cases (57%); 5 children (7.5%) had penile torsion and 4 children (6%) had shortages of skin, phimosis and inclusion cyst. The overall estimated complication rate of circumcision was 0.34%.

Conclusions: Complications of circumcision are rare in Israel and in most cases are mild and correctable. There appears to be no significant difference in the type of complications between medical and ritual circumcisions.

Objectives: To describe the dynamic changes of the coronary sinus during the cardiac cycle.

Methods: The angiographic feature of the coronary sinus was evaluated in 30 patients undergoing diagnostic and therapeutic coronary angiography.

Results: Prolonged angiographic imaging following coronary injections permitted accurate demonstration of the coronary sinus in all 30 patients. We report, for the first time, that the coronary sinus can be divided into two angiographic functional/anatomic portions, upper and lower. The lower part is prone to a highly dynamic contraction/relaxation pattern, observed in 12 of the 30 patients, while 10 patients had normal and 8 had low contractile pattern on angiography. Clinical assessment of these patients did not identify an association with this motion pattern.

Conclusions: The coronary sinus is an important anatomic/functional structure that should be further investigated in patients with various forms of heart disease.

Background: Road traffic accidents are the leading cause of accidental injury and death for persons under the age of 35. The medical literature presents surprisingly little information on the general characteristics of such accidents in the urban setting.

Objectives: To characterize RTA[1] patients arriving at an urban trauma center.

Methods: We prospectively examined the charts of all patients admitted to the Tel Aviv Sourasky Medical Center due to RTA injuries during two periods in 1995.

Results: Of the 1,560 patients examined, the male:female ratio was 1:1 and median age was 27 years (47% aged 20–30 years); 51% of the accidents took place between 8 a.m. and 4 p.m. and on working week days; automobiles comprised 47.1% of the vehicles involved, motorized two-wheel vehicles 37.1%, bicycles 3.8%, and pedestrians 12%. The Glasgow Coma Scale was 15 on arrival in 98.7% of the patients. The trunk was the most commonly injured body part (84.7%); whiplash injury to the neck was diagnosed in 343 patients (22%), and brain concussion in 183 (11.7%). Computed tomography studies were performed in 34 patients (2.2%). The vast majority of patients (1,438, 92.2%) was discharged home; 14 (0.9%) were admitted to the intensive care unit, and 2 (0.13%) died during hospitalization. The average time spent in the emergency department in the morning shift was 2.1 hours.

Conclusions: We could identify distinguishing factors of this population: equal gender distribution, peak RTA incidence in the young adult working population during working hours, automobile drivers being the most injured subgroup, a disproportionate number of motorcycle and motor scooter involvement, and a relatively extensive amount of time and resources spent treating these injuries despite their generally minor nature.



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[1] RTA = road traffic accidents

Melanoma is the leading cause of death from skin tumors worldwide, with an annual increase in incidence over the past decade. The molecular mechanisms involved in melanoma pathogenesis are beginning to be unraveled. While a family history of melanoma and exposure to ultraviolet irradiation have been known for years as risk factors in melanoma development, the precise genes involved in inherited predisposition were defined only in the past decade. Germline mutations in two genes that play a pivotal role in controlling cell cycle and division – CDKN2A and cyclin-dependent kinase 4 (CDK4) – have been detected in autosomal, dominant, high penetrance familial melanoma cases. In addition to these two highly penetrant genes, germline mutations and polymorphisms in a few low penetrance genes have been reported in familial melanoma cases: melanocortin-1 receptor, epidermal growth factor, glutathione s-transferase M1, cytochrome p450 debrisoquine hydroxylase locus (CYP2D6) and vitamin D receptor.

The world now faces the dreadful possibility of biological weapons attacks by terrorists. Healthcare systems would have to cope with such emergencies should all preemptive measures fail. Information gained from the Global Mercury exercise and the SARS outbreak has shown that containing an outbreak at the start is more effective than reacting to it once it has spread and that containment should be treated both nationally and internationally. On the national level this entails developing rapid and effective methods to detect and identify infected cases, and implementing isolation and control measures to lower the risk of further transmission of the disease while assuring the safety of medical teams and laboratory workers. Strategic contingency plans should incorporate well-defined procedures for hospitalization and isolation of patients, providing regional backup of medical personnel and equipment and maintaining close cooperation between the various bodies in the healthcare system. Quarantine is an effective containment measure, especially if voluntarily imposed. Modern communication systems can help by sending professional teams timely instructions and providing the public with information to reduce panic and stress during quarantine procedures. Informing the public poses a dilemma: finding a balance between giving advance warning of an imminent epidemic outbreak and ascertaining the likelihood of its occurrence. Containment of international bioterrorist attacks depends entirely on close international cooperation to implement national and international strategic contingency plans with free exchange of information and recognition of procedures.

Background: Preoperative radiotherapy is standard treatment for rectal cancer and is often combined with 5-fluorouracil-based chemotherapy. UFT, a new oral 5FU[1] derivative, given daily during a course of radiotherapy mimics the effect of continuous-infusion 5FU.

Objectives: To determine the maximum tolerated dose of oral UFT and leucovorin with preoperative pelvic irradiation for rectal cancer, and assess tumor response.

Methods: In this phase 1 trial, 16 patients aged 42–79 years with tumors within 12 cm of the anal verge received radiotherapy, 45 Gy over 5 weeks, an escalating dose of oral UFT, and a fixed dose of 30 mg/day leucovorin. UFT and leucovorin were given for 28 consecutive days concomitant with the first 4 weeks of radiotherapy. Surgery was scheduled for 4–6 weeks after completion of radiotherapy. The surgical procedure was determined by the surgeon at the time of surgery.

Results: No grade III toxicity was seen at 200 mg/m²/day UFT. Of eight patients who received 240 mg/m²/day UFT, one developed grade IV diarrhea; of four patients who received 270 mg/m²/day UFT, one was hospitalized with grade IV diarrhea and leukopenic fever and died during hospitalization. Of the 15 evaluable patients, 9 had pathologic tumor down-staging including 4 patients with complete response. Only one patient required a colostomy.
Conclusions: The MTD[2] of UFT together with leucovorin and preoperative radiotherapy for rectal cancer is 240 mg/m². The major toxicity was diarrhea. Down-staging was noted in 60% of patients, allowing sphincter-preserving surgery even in patients with low tumors.

Background: Major efforts are being directed at the early diagnosis of breast cancer. The diagnosis rate of non-palpable tumors is steadily growing as a result of increased screening by mammography. In most patients with non-palpable lesions, percutaneous image-guided biopsies have replaced wire localization with surgical excision for obtaining tissue diagnosis. In recent years the Israel Ministry of Health initiated a mammograpy screening program. Percutaneous image-guided biopsies have also become widely available.

Objective: To assess the impact of these changes on breast cancer surgical treatment in our hospital.

Methods: The charts of 483 patients operated on in our department for primary breast carcinoma during the years 1997 to mid-2001 were reviewed. Data on the mode of diagnosis, tumor stage, resection margins, and number and types of operations were recorded and analyzed. The term non-palpable tumors relates to tumors necessitating wire localization for surgical excision.

Results: The percentage of patients diagnosed with non-palpable tumors rose from 16.2% in 1997 to 47.4% in 2001, with an average size of 2.6 cm for palpable and 1.7 cm for non-palpable tumors. The rate of preoperative diagnosis for non-palpable tumors rose from 6.2% in 1997 to 96.4% in 2001. The rate of involved or very close margins was reduced by 73% in the patient group diagnosed preoperatively as compared to those without a preoperative diagnosis (10.6% vs. 39.4%). Finally, the percentage of patients who had two operations fell from 56.2% in 1997 to 11.1% in 2001.

Conclusions: The mammography screening program in Jerusalem in 1997–2001 was effective in increasing the relative percentage of non-palpable breast cancers with reduced tumor size at diagnosis. The improved availability of preoperative tissue diagnosis in these patients reduced the number of surgical procedures needed.