Israel Medical Association Journal

The ubiquitin-proteasome pathway has a central role in selective degradation of intracellular proteins. Among the key proteins degraded by the system are those involved in the control of inflammation, cell cycle regulation and gene expression. With numerous important cellular pathways affected, derangements in the ubiquitin system were shown to result in a variety of human diseases including malignancies, neurodegenerative diseases and hereditary syndromes, and proteasome inhibition was implicated as a potential treatment for cancer and inflammatory conditions. Two proteasome inhibitors are currently under clinical evaluation for multiple myeloma and acute ischemic stroke. The ubiquitin system also has an important function in the immune and inflammatory response. It is involved in antigen processing and presentation to cytotoxic T cells, and the activation of nuclear factor-kappa B – the central transcription factor of the immune system. Since the proteasome is the central source of antigenic peptides that are presented to the immune system, some viruses, such as the Epstein-Barr virus, developed escape mechanisms that manipulate the ubiquitin-proteasome system in order to persist in the infected host. Understanding the mechanisms underlying the production of viral antigens by the ubiquitin-proteasome system may have therapeutic applications such as future development of vaccines.

Background: Laryngeal obstruction due to bilateral vocal cord immobility in adduction may cause dyspnea, hoarseness and dysphagia and can lead to dependence on a tracheostomy. Treatment poses a challenge because of the opposing functions of the larynx and the risk of neck and laryngeal tissue damage.

Objectives: To describe our experience with endoscopic CO₂-laser-assisted posterior ventriculocordectomy without tracheostomy for the treatment of bilateral vocal cord immobility in adduction.

Method: The study group consisted of five male and five female patients aged 17–81 years. The procedure was performed with an endoscope and operating microscope connected to a CO₂ laser. A C-shaped incision was made, and the posterior third of one vocal cord, the vocal process of the arytenoid, and the posterior third of the false vocal cord were excised. Tracheostomy was not performed.

Results: The technique allowed for a convenient approach to the difficult-to-view areas of the larynx. The procedure was short and bloodless, with minimal damage to laryngeal tissue and no local edema. Hospitalization time was short. Postoperatively, patients had sufficient breathing and mostly fair to good voice quality. None of the patients had severe aspirations and only three patients had mild aspirations.

Conclusions: We recommend this procedure for patients with bilateral vocal cord immobility prior to tracheostomy. Delaying surgery beyond the time of possible re-innervation may place the patient at risk of decompensation, which requires tracheostomy.

Background: Contralateral exploration of the groin has been common practice among pediatric surgeons for nearly 50 years, based on the high incidence of patent processus vaginalis on the contralateral side with the potential for the subsequent development of a hernia.

Objectives: To evaluate transinguinal laparoscopic examination of the contralateral side during repair of inguinal hernia in children in order to reach a decision regarding exploration of the contralateral side.

Methods: Over a of 21 month period 124 children with unilateral inguinal hernia underwent laparoscopic evaluation of the contralateral groin. The operations were performed under general anesthesia as ambulatory procedures.

Results: Transinguinal contralateral laparoscopic exploration was positive (patent processus vaginalis) in 26 children (21%) and negative (closed processus vaginalis) in 88 (71%). Failure to introduce the telescope occurred in 10 patients (8%) due to a friable or narrow hernia sac. Twenty-five children below 2 years of age were spared exploration of the contralateral side as a result of the negative laparoscopic examination. On the other hand, 15 children aged 2–17 had their contralateral groin explored because of a positive finding at laparoscopy.

Conclusions: Transinguinal laparoscopic examination of the contralateral side during repair of inguinal hernia in children is a simple, safe and quick method to avoid systematic bilateral explorations and should be part of every pediatric surgeon's experience.

Background: The external approach is the golden standard for sinonasal tumor removal but it is associated with several side effects, including facial scars, intracranial and extracranial complications, a long hospitalization period and high costs. Endoscopic sinus surgery enables resection of benign and selected malignant sinonasal tumors and has the advantages of no facial scars, better functional and structural preservation of the sinonasal complex, minimal trauma to surrounding tissue, a shorter hospitalization stay and lower costs.

Objectives: To evaluate the advantages and limitations of endoscopic resection of benign and malignant sinonasal tumors, their recurrence and complication rates.

Methods: The medical and radiology records of 56 patients who underwent endonasal endoscopic resection of benign and malignant sinonasal tumors between 1996 and 2003 were retrospectively reviewed. Tumors located in the center of the nose and sinuses were endoscopically resected.

Results: Six cases of malignant tumor and 50 cases of benign tumor underwent resection by ESS[1]. One of the patients with malignant tumor died, the remainder showing no evidence of disease on follow-up of 3–60 months (mean 26.8 months). Inverted papilloma was the most common benign tumor (40 patients). Seven patients (18%) had recurrence followed by endonasal resection. No major complications were recorded. Hospitalization stay was 2–7 days (mean 3.6 days).

Conclusions: Endoscopic resection of benign sinonasal tumors that are centrally located in the nose and sinuses should be considered before the external approach is used. In very carefully selected cases of malignant tumors ESS is oncologically acceptable, but more experience is needed for discerning the indications for endoscopic resection of malignant tumors. The complication rate for endoscopic resection is low, there are no facial scars, hospitalization stay is short, and costs are low.

Background: Hyperhomocysteinemia is a well-recognized risk factor for accelerated atherosclerosis in hemodialysis patients.

Objectives: To examine the effects of two doses of vitamins B6 and B12 and folic acid on homocysteine levels in hemodialysis patients and assess the functional impact of the methylenetetrahydrofolate reductase genotype on the response to treatment.

Methods: In a randomized prospective study, we assessed the effects of folic acid and two doses of B-vitamins in 50 hemodialysis patients with hyperhomocysteinemia. Patients were divided into two groups: 26 patients (group A) who received 25 mg of vitamin B₆ daily and one monthly injection of 200 µg vitamin B12, and 24 patients (group B) who received 100 mg of vitamin B6 daily and one monthly injection of 1,000 µg vitamin B12. In addition, both groups received 15 mg folic acid daily. Patients were evaluated for homocysteine levels as well as for coagulation and a thorough lipid profile. Baseline Hcy[1] levels were determined after at least 4 weeks washout from all folic acid and B-vitamins that were given. MFTHR[2] alleles were analyzed, as were activated protein C resistance, von Willebrand factor and lupus anticoagulant.

Results: Basal plasma Hcy levels were significantly elevated in hemodialysis patients compared with normal subjects (33.8 ± 4.3 vs. 4.5 to 14.0 mmol/L). Following treatment, Hcy levels were significantly reduced to 21.2 ± 1.6 in group A and 18.6 ± 1.4 mmol/L in group B (P < 0.01). There was no difference in Hcy reduction following the administration of either high or low dosage of vitamins B6 and B12 utilized in the present study. There was no correlation between Hcy levels or thrombophilia and high incidence of thrombotic episodes in hemodialysis patients. Genotypic evaluation of MTHFR revealed that the presence of homozygous thermolabile MTHFR (n = 5) was associated with higher Hcy levels and better response to treatment (Hcy levels decreased by 58%, from 46.2 ± 14.6 to 19.48 ± 4.1 mmol/L following treatment). In patients with heterozygous thermolabile MTHFR (n = 25), Hcy levels decreased by 34%, from 31.2 ± 3.7 to 18.1 ± 1.1 mmol/L following treatment. The efficacy of high and low doses of B-vitamins on the reduction of homocysteine levels was comparable.

Conclusions: Treatment with B-vitamins in combination with folic acid significantly decreased homocysteine levels in hemodialysis patients, independently of the tested doses. In addition, mutations in MTHFR were associated with elevated plasma levels of Hcy. Neither vascular access nor.

Background: The highly tissue-specific trafficking of normal and malignant lymphocytes to particular organs is mediated by adhesion molecules, or “homing receptors.” Among our patients with B cell chronic lymphocytic leukemia 15% demonstrate predominantly splenic manifestations and are classified as stage II(S).

Objective: To investigate whether expression of cell surface adhesion molecules can distinguish stage II(S) patients from stage 0 or stage 0 and I CLL[1] patients.

Methods: Expression of adhesion molecules belonging to different families was studied in CD19-positive cells isolated from the blood of 42 patients by dual color flow cytometry. The families included: immunoglobulin superfamily (CD54, CD58), integrin family (β1, β2 and β3 chains, CD11a, CD11c CD49d), selectin family (L-selectin), and lymphocyte homing receptor family (CD44).

Results: The average percentage of leukemic cells expressing CD11c in the 23 patients with stage II(S) was 25.7 compared with 13.2% in the 14 patients with stage 0 disease (P = 0.047). The average percentage of leukemic cells expressing CD44 in patients with stage II(S) was 90.5 compared with 77.2% in patients with stage 0 (P = 0.007) and 80% in patients with stages 0 and I together (n=19, P = 0.008). Other adhesion molecules tested did not show a statistically significance difference in expression between the different disease stages.

Conclusions: The higher expression of CD44 and CD11c in cells of CLL patients with predominantly splenic manifestations may account for the tendency of their lymphocytes to home to the spleen.

Background: Iodine intake is necessary to maintain normal thyroid function and prevent iodine deficiency disorders. In 1990, a resolution calling for universal salt iodination to eliminate iodine deficiency worldwide was taken by the World Health Organization and endorsed by some 130 countries. As of today, very little is known about iodine intake and the prevalence of iodine deficiency disorders in Israel, and iodine enrichment of regular salt has not been authorized.

Objectives: To assess the current level of iodine intake in an unselected group of residents from the Israeli costal area.

Methods: Spot urine samples were collected from three groups: Group A comprising 51 pregnant women attending the Women s Health Clinic at our institution, with a mean age of 32 years and at gestational week 28; group B consisting of 35 healthy subjects, mean age 38; and group C consisting of 16 euthyroid subjects harboring nodular goiters. Tap drinking and mineral water were also analyzed for iodine content. Iodine concentration was measured using the catalytic reduction of ceric ammonium sulfate method.

Results: When considering all groups together the median urinary iodine concentration was 143 µg/L, with 27% of the study population having concentrations under 100 µg/L and 7.8% under 50 µg/L. Values were distributed similarly between sites of residency, and no significant differences were seen between groups. The mean iodine concentration for tap drinking water was 22.8 µg/L (range 0.5–53.5 µg/L) and for mineral water 7 µg/L (range 0–15 µg/L).

Conclusions: Overall, iodine intake appeared to be satisfactory in our study population, however mild deficiency may exist in up to 26% of this group. A nationwide survey is needed to better determine the status of iodine intake in Israel, allowing for recommendations on salt-iodine enrichment in the future.

Background: Complementary and alternative medical care has gained increasing popularity in western societies in recent years.

Objectives: To provide a cross-sectional and temporal (2000 vs. 1993) analysis of the use of complementary and alternative medicine in Israel.

Methods: The subjects studied represented the Israeli Jewish urban population aged 45–75 years. Full sit-down interviews were conducted with 2,003 respondents in 1993 and 2,505 respondents in 2000.

Results: For 1993, 6% of the population reported on consultations with CAM[1] providers during the previous year. For 2000, that proportion increased to 10%. Being a woman, having higher education, enjoying better economic status, being younger, living in a big city, and being dissatisfied with specialists’ care were all positively related to the use of non-conventional medicine, particularly in 2000. In both years, more than 50% of the consultations were with acupuncturists and homeopaths. However, chiropractors have doubled their market shares, and lower back pain became the leading problem for which care was sought. The main reason for consulting CAM was a reluctance to use too many drugs or to undergo an invasive procedure. However, a significant proportion of the users continue to use conventional medicine concurrently. Seventy-five percent in 2000 and 60% in 1993 reported that the treatment helped.

Conclusions: Between 1993 and 2000, CAM in Israel changed from an infant industry into a mainstream medical commodity, reflected in both prevalence and different patterns of consumption.