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: Metastatic melanoma is an aggressive and highly malignant cancer. The 5 year survival rate of patients with metastatic disease is less than 5% with a median survival of only 6–10 months. Drugs like dacarbazin (DTIC) as a single agent or in combination with other chemotherapy agents have a response rate of 15–30%, but the duration of response is usually short with no impact on survival. Interleukin-2-based immunotherapy has shown more promising results. The National Institutes of Health recently reported that lymphodepleting chemotherapy, followed by an adoptive transfer of large numbers of anti-tumor specific tumor-infiltrating lymphocytes, resulted in an objective regression in 51% of patients.

Objectives: To introduce the TIL[1] technology to advanced metastatic melanoma patients in Israel.

Methods: We generated TIL cultures from tumor tissue, choosing those with specific activity against melanoma and expanding them to large numbers.

Results: TIL cultures from nine patients were established and examined for their specific activity against the patients' autologous tumor cells. Twelve TIL cultures derived from 5 different patients showed the desired anti-tumor activity, making those 5 patients potential candidates for the therapy.

Conclusions: Pre-clinical studies of the TIL technology in a clinical laboratory set-up were performed successfully and this modality is ready for treating metastatic melanoma patients at the Sheba Medical Center's Ella Institute.

Background: We recently published preliminary evidence on the effectiveness of hypertonic saline in infants with viral bronchiolitis.

Objective: To further establish the efficacy of nebulized hypertonic saline in these infants

Methods: In a continuing, second-year randomized, double-blind controlled trial, an additional 41 infants (age 2.6 ± 1 months) hospitalized with viral bronchiolitis were recruited during the winter of 2001–2002. The infants received inhalation of 1.5 mg epinephrine dissolved either in 4 ml normal (0.9%) saline (Group I, n=20) or 4 ml hypertonic (3%) saline (Group II, n=22). The therapy was repeated three times daily until discharge. Pooling our 2 years of experience (2000–2002), a total of 93 hospitalized infants with viral bronchiolitis were recruited; 45 were assigned to Group I and 48 to Group II.

Results: The clinical scores at baseline were 7.6 ± 0.7 for Group I vs. 7.4 ± 1.3 for Group II (P = NS). However, the clinical scores at days 1 and 2 after inhalation differed significantly between the two groups, invariably favoring Group II: 7 ± 1 vs. 6.25 ± 1.1 (P < 0.05), 6.45 ± 1 vs. 5.35 ± 1.35 (P < 0.05), respectively. Adding aerosolized 3% saline to 1.5 mg epinephrine reduced the hospitalization stay from 3.5 ± 1.7 days in Group I to 2.6 ± 1.4 in Group II (P < 0.05). The pooled data of both years revealed that adding 3% saline to the inhalation mixture decreased hospitalization stay from 3.6 ± 1.6 to 2.8 ± 1.3 days (P < 0.05).
Conclusions: This second-year experience and our 2 year pooled data analysis strengthen the evidence that the combination of 3% saline/1.5 mg epinephrine benefits hospitalized infants with viral bronchiolitis

Background: Peritoneal dialysis is a widely accepted route for renal replacement. With the advent of endoscopy, many surgical techniques for the prevention of catheter failure have been proposed.

Objectives: To evaluate the outcomes of patients undergoing laparoscopic Tenckhoff catheter implantation, using the pelvic fixation technique.

Methods: Data analysis was retrospective. All procedures were performed under general anesthesia. A double-cuffed catheter was inserted using two 5 mm trocars and one 10 mm trocar, fixing its internal tip to the dome of the bladder and its inner cuff to the fascia. Catheter failure was defined as persistent peritonitis/exit-site/tunnel infection, severe dialysate leak, migration or outflow obstruction.

Results: LTCI[1] was performed in 34 patients. Mean patient age was 65 ± 17 years. In 12 of the 34 patients the indication for LTCI was end-stage renal failure combined with NYHA class IV congestive heart failure. Operative time was 35 ± 15 minutes. A previous laparotomy was performed in 9 patients. Hospital stay was 1.5 ± 0.6 days. The first continuous ambulatory peritoneal dialysis was performed after 20 ± 12 days. Median follow-up time was 13 months. There were several complications, including 5 (14%) exit-site/tunnel infections, 27 episodes (0.05 per patient-month) of bacterial peritonitis, 3 (9%) incisional hernias, 1 case of fatal intraabdominal bleeding, 2 (5.8%) catheter migrations (functionally significant), and 10 (30%) cases of catheter plugging, 8 of which were treated successfully by instillation of urokinase and 2 surgically. A complication-mandated surgery was performed in 8 patients (23.5%). The 1 year failure-free rate of the catheter was 80.8%. One fatal intraabdominal bleeding was recorded.
Conclusions: LTCI is safe, obviating the need for laparotomy in high risk patients. Catheter fixation to the bladder may prevent common mechanical failures

Endometrial polyps are a frequent finding in infertile patients. Little is known about the true prevalence of polyps in infertile patients. It is unproved whether polyps are causative of infertility, or whether surgical polypectomy by hysteroscopy improves the likelihood of successful conception. This article reviews endometrial polyps in reproductive-age fertile and infertile women.

The adult human heart has limited regenerative capacity and, therefore, functional restoration of the damaged heart presents a great challenge. Despite the progress achieved in the pharmacological and surgical treatment of degenerative myocardial diseases, they are still considered a major cause of morbidity and mortality in the western world. Repopulation of the damaged heart with cardiomyocytes represents a novel conceptual therapeutic paradigm but is hampered by the lack of sources for human cardiomyocytes. The recent derivation of pluripotent human embryonic stem cell lines may provide a solution for this cell sourcing problem. This review will focus on the derivation of the hESC[1] lines, their mechanism of self-renewal, and their differentiation to cardiomyocytes. The possible signals and cues involved in the commitment and early differentiation of cardiomyocytes in this model will be discussed as well as the molecular, structural and electrophysiologic characteristics of the generated hESC-derived cardiomyocytes. Finally, the hurdles and challenges toward fully harnessing the potential clinical applications of these unique cells will be described.

Background: Diabetic macular edema causes visual loss in almost one-third of diabetic patients. There is currently no treatment for the accompanying cystoid foveal changes.

Objectives: To assess the clinical outcome, i.e., change in visual acuity, in patients treated with steroids for long-standing diabetic macular edema with foveal cystoid changes.

Methods: In the ophthalmology department of a tertiary care university‑affiliated medical center and the ophthalmology service of a health management organization, 46 diabetic subjects (56 eyes) who had diabetic macular edema with cystoid foveal changes received one intravitreal injection of 4 mg triamcinolone acetonide.

Results: The mean baseline (pre‑injection) visual acuity of 0.21 increased to 0.31 and 0.48 at 1 and 3 months, respectively, after which it decreased to 0.33 at 6 months. The mean intraocular pressure was 15.07 mmHg at baseline, 15.83 at day 1, gradually rising to 17.16, 18.38 and 18.57 mmHg at 1, 3 and 6 months respectively. Three patients suffered immediate visual decline after the injection.

Conclusions: Intravitreal triamcinolone acetonide may be a therapeutic option for long‑standing diabetic macular edema with foveal cystoid changes.
 

Background: Magnetic resonance imaging is a diagnostic tool of growing importance. Since its introduction, certain medical implants, e.g., pacemakers, were considered an absolute contraindication, mainly due to the presence of ferromagnetic components and the potential for electromagnetic interference. Patients with such implants were therefore prevented from entering MRI systems and not studied by this modality. These devices are now smaller and have improved electromechanical interference protection. Recently in vitro and in vivo data showed that these devices may be scanned safely in the MRI.

Objectives: To report our initial experience with three patients with pacemakers who underwent cerebral MRI studies.

Methods: The study included patients with clear clinical indications for MRI examination and who had implanted devices shown to be safe by in vitro and in vivo animal testing. In each patient the pacemaker was programmed to pacing-off. During the scan, continuous electrocardiographic telemetry, breathing rate, pulse oximetry and symptoms were monitored. Specific absorption rate was limited to 4.0 W/kg for all sequences. Device parameters were assessed before, immediately after MRI, and 1 week later.

Results: None of the patients was pacemaker dependent. During the MRI study, no device movement was felt by the patients and no episodes of inappropriate inhibition or rapid activation of pacing were observed during the scan. At device interrogation here were no significant differences in device parameters pre-, post-, and 1 week after MRI. Image quality was unremarkable in all imaging sequences used and was not influenced by the presence of the pacemaker.

Conclusion: Given appropriate precautions, MRI can be safely performed in patients with a selected permanent pacemaker. This may have significant implications for current MRI contraindications.  

Background: The contribution of drugs and alcohol to current trauma‑related morbidity and mortality in Israel is not known. Identification of these factors in the fast-changing demographics of the Israeli population might lead to better care and, no less importantly, to targeted prevention measures.

Objectives: To determine the incidence of alcohol‑related trauma, and to specify the time of day, the cause of trauma, and the morbidity and mortality rates as compared to non-alcohol‑associated trauma in the tertiary trauma unit of a large medical center in Tel Aviv.

Methods: Data were obtained from the Israel National Trauma Registry, based on patient records in our institution (Tel Aviv Sourasky Medical Center) from January 2001 to December 2003.

Results: Of the 5,529 patients who were enrolled in the study, 170 had high alcohol blood levels (> 50 mg/dl). Patients intoxicated with alcohol had higher rates of road accident injuries (35% versus 24% non‑intoxicated) and stab wounds (29% vs. 7%). The Injury Severity Score of the alcohol‑intoxicated patients was higher (32% ³ 16 vs. 12% ³ 16). The alcohol‑intoxicated patients were more likely to be non-Jewish (34% vs. 9%), young (82% aged 15–44 years) and males (91%). Most of the alcohol‑related injuries occurred during the weekend (47%) and during evening‑late night hours (from 7 a.m. to 11 p.m.; 55%).

Conclusions: Alcohol‑associated trauma differs from non-alcohol‑associated trauma in many ways. Since the population at risk can be identified, it is important that legislative, social, enforcement and educational measures be adopted to reduce the extent of alcohol abuse and thereby improve the level of public safety.