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עמוד בית
Sat, 03.12.22

September 2001

Original Articles
Irit Gil-ad, PhD, Blana Shtaif, MSc, Rina Eshet, PhD, Rachel Maayan, PhD, Moshe Rehavi, PhD and Abraham Weizman, MD

Background: The neurosteroids dehydroepiandrosterone (DHEA) and its sulfated metabolite (DHEAS) have been reported to possess neuroprotective as well as anti-tumoral activity in vitro and in vivo.

Objectives: To compare the effect of the two neurohor­mones on cell viability in primary whole-brain fetal mouse culture and isolated neuronal culture, as well as in a human neuroblastoma cell line (SK-N-SH).

Methods: Cell viability and cell proliferation were deter­mined with the neutral red and 3H-thymidine uptake methods, Apoptosis in propidium iodide-stained neuroblastoma cells was determined using flow cytometry.

Results: DHEA (1 nM-10 ìM) decreased the viability of selected primary neuronal cells (33-95% after 24 and 72 hours) but not of whole-brain cultured cells (neuron+glia). DHEAS did not significantly modify cell viability in either primary culture. In a human neuroblastoma cell line, DHEA (1 nM- 1 ìM) decreased 3H-thymidine uptake (30-60%) and cell viability (23-52%) after 24 hours. DHEAS did not significantly modify, or only slightly stimulated, cell viability and uptake of  3H-thymidine (132% of controls). The combination of DHEA and DHEAS neutralized the toxic effect of DHEA in both primary neuronal culture and neuroblastoma cell line. Flow cytometric analysis of DNA fragmentation in neuroblastoma cells treated with 100 nM DHEA/DHEAS for 24 hours showed an increase in apoptotic events (31.9% and 26.3%. respec­tively, vs. control 2.54%).

Conclusions: Our results do not confirm a neuroprotective role for DHEA and suggest that DHEA and DHEAS have a differential role: DHEA possesses a neurotoxic (expressed only in isolated neurons) and anti-proliferative effect DHEAS demonstrates only a slight neuroprotective effect.

Gabriel Kenet, MD, Joram Wardi, MD, Yona Avni, MD, Hussein Aeed, PhD, Haim Shirin, MD, Liliana Zaidel, MD, Rami Hershkovitz, MD and Rafael Bruck, MD

Background: Rectal administration of iodoacetamide induces colitis by blocking sulphhydryl groups and generating inflammatory mediators. Thalidomide, a non-barbiturate hyp­notic, also has an anti-inflammatory effect, presumably by suppressing the production of tumor necrosis factor alpha. In patients with Crohn’s disease, neutralization or suppression of TNFá reduces inflammation.

Objectives: To evaluate the effects of thalidomide in a model of experimental colitis.

Methods: Colitis was induced in rats by intracolonic administration of 3% iodoacetamide. In the treatment group, thalidomide 50 mg/kg was given daily by gavage and continued for 7 days until the rats were sacrificed. Their colons were then processed for wet weight, lesion area, weight of mucosal scraping, myeloperoxidase activity and histology. Serum levels of TNF were determined.

Results: Colonic wet weight, lesion area, myeloperoxidase activity and serum levels of TNFá were significantly lower (P<0.05) in the treatment group (iodoacetamide + thalido­mide) than the control group (iodoacetamide only). Histologi­cally, colonic inflammation in the treated group was markedly decreased.

Conclusions: Thalidomide effectively decreases colitis induced by iodoacetamide. The mechanism is probably associated with inhibition of TNFá, and should be further studied.

by Allan I. Bloom, MD, Talia Sasson, MD, Anthony Verstandig, MD, Yehuda G. Wolf, MD, Haim Anner, MD, Yakov Berlatzky, MD, Inna Akopnick, MD, Chaim Lotan, MD, Richard Lederman, MD and Pinchas D. Lebensart, MD
Carin Hagberg, MD, Tiberiu Ezri, MD and Ezzat Abouleish, MD

Background: The incidence of spinal failure necessitating general anesthesia and endotracheal intubation following spinal anesthesia for cesarean section is extremely low. Aspiration prophylaxis prior to spinal anesthesia is often recommended in case of spinal failure or excessive spinal block requiring the emergency administration of general anesthesia.

Objectives: To determine the incidence of endotracheal intubation following spinal anesthesia for cesarean section.

Methods: We retrospectively reviewed the pen-operative course of parturients undergoing cesarean section under spinal anesthesia at our institution from February 1991 to December 1993. If spinal failure occurred, 10 ml of sodium bicarbonate was administered by mouth prior to induction of general anesthesia.

Results: Among the 743 cases that we reviewed, spinal failure occurred in 15 patients (2%) because of inadequate analgesia in 14 patients (1.9%) and unexpected prolonged surgery for hysterectomy in one patient (0.1%). No patient required intubation due to excessive spinal block. In none of the patients was a record of pulmonary aspiration identified.

Conclusions: The extremely low incidence of spinal failure or excessive block necessitating endotracheal intuba­tion suggests that routine aspiration prophylaxis may not be necessary prior to spinal anesthesia. However, these results should be confirmed by a prospective, controlled study on larger populations. An antacid should be readily available and administered whenever general anesthesia is required.

David S. Blondheim, MD, Orna Blondheim, MD and S.H. Blondheim, MD

Background: Fasting is required by the Jewish and Islamic religions, and may sometimes be necessary for non­religious reasons as well. Very little empiric data are available on the effect of 24 hours of food and water deprivation.

Objectives:  To compare the effects of the dietary composition of different pre-fast meals on subjective discom­fort and various other parameters of a 24 hour food and water fast.

Methods: Thirteen volunteers of both genders participated in a non-randomized crossover study. Each consumed three different equicaloric pre-fast meals in which the main source of calories was protein (49% of calories), carbohydrate (86%), or fat (69%). Weight, heart rate, blood pressure, blood and urine were tested before and after 24 hours of fasting, and the subjective evaluations of the discomfort during the three fasts were compared.

Results: After the protein-rich meal greater discomfort and more side effects were reported. Weight and blood pressure decreased at the end of the fasts that followed each of the three meals heart rate increased after the high fat and carbohydrate meals but not after the protein meal. The main laboratory findings were a 40% increase in blood urea nitrogen and higher urine osmolarity after the protein-rich meal than after the other meals.

Conclusion: A protein-poor pre-fast meal is likely to be followed by easier fasting.

Slomo Vinker, MD, Boris Kaplan, MD, Sasson Nakar, MD, Gita Samuels, MD, Gidon Shapira, MD and Eliezer Kitai, MD

Background: Urinary incontinence in older women is common. Its characteristics and impact on quality of life is not well established since these women are usually reluctant to tell their healthcare providers about the problem.

Objective: To determine the characteristics of urinary incontinence in women and the manner in which it affects patients quality of life.

Methods: Twenty family physicians were requested to distribute a questionnaire to the first 25 consecutive women aged 30 to 75 years who visited their clinic for any reason. The questionnaire covered general health issues, symptoms of urinary incontinence, and quality of life.

Results: A total of 418 women, mean age 50.0 ± 11.8 years, completed the questionnaire (84% response rate). Of these, 148 (36%) reported having episodes of urinary incontinence. Urinary incontinence was found to be associated with older age, menopause, obesity and coexisting chronic disorders. Sixty percent of the women with urinary incon­tinence found it to be a disturbing symptom, and 44% reported that it had a detrimental effect on their quality of life. Only 32% of the affected women had sought medical advice, half of them from their family physician. Treatment was recommended to 66% of those who sought help, and in about two-thirds of these it brought some measure of relief.

Conclusions: Urinary incontinence is a common com­plaint among women attending primary care clinics, but it does not receive appropriate attention, Though it often adversely affects quality of life, only a small proportion of women seek medical advice. Family physicians should raise the issue as a part of the routine general health check-up.

Auli Toivanen, MD and Paavo Toivanen, MD

Reactive arthritis is a disease affecting mostly young adults. Owing to a greater general awareness the diagnosis has become more common during recent years. It is well established that ReA is caused by an infection, mostly in genetically susceptible individuals. The pathogenetic mechan­isms are still poorly understood, and the treatment rests mainly on anti-inflammatory drugs or steroids. Vigorous and early treatment of the triggering infection may prevent the develop­ment of ReA but this is rarely possible in everyday clinical practice. Despite its name, the disease should be considered as a general disorder that affects not only the joints. The prognosis is not as good as earlier believed, and relapses or chronic development are not unusual.

Larry W. Moreland, MD

There is accumulating evidence that tumor necrosis factor plays a major role in the pathogenesis of rheumatoid arthritis. Recent biotechnological advances have allowed for the development of agents that directly target TNF, a pro-inflammatory cytokine. In the last 2 years, the U.S. Food and Drug Administration and the European Union’s Commission of the European Communities have approved two biological agents for the treatment of refractory RA, etanercept and infliximab. Etanercept is a fusion protein, composed of the Fc portion of immunoglobulin G1 and the extracellular domain of a TNF receptor (p75). Infliximab is a chimeric monoclonal antibody composed of murine variable and human constant regions. In placebo-controlled trials, both agents have proven to be effective and well tolerated in PA patients.

Reuven Rabinovici, MD

Red cell substitutes are currently under development for use in a variety of surgery and trauma-related clinical conditions. The need for artificial oxygen-carrying fluids continues to be driven by the shortage of donor blood, the complex logistics of blood banking, the risk of virally transmitted diseases, current transfusion practices, and the projected increased demand for blood products in the future. The effort to develop a replacement for the red cell component has evolved over the last century and has presented a number of significant challenges including safety and efficacy concerns. Recent progress in understanding the fundamental interactions of hemoglobin with the body at the molecular, cellular and tissue levels has led to the production of improved red cell substitutes suitable for clinical testing. Currently, seven products are being tested for a variety of applications including trauma, surgery, sepsis, cancer and anemia. Although some of these trials were unsuccessful, the majority of the available products exert no toxicity or only low level side effects. Encouraging results in early clinical trials with oxygen-carrying fluids support further development of these products and have increased the hope that a usable oxygen-carrying fluid will soon be available in the clinic. The purpose of this review is to provide up-to-date information on the status of these products with special emphasis on pre-clinical and clinical experience.

Case Communications
Daniel Schapira, MD, DSc, Alexandra Balbir-Gurman, MD, Alicia Nachtigal, MD and Abraham Menachem Nahir, MD, PhD
Rafik Masalha, MD, Bella Chudakov, MD, Mohammed Morad MD, Inna Rudoy, MD, Ilia Volkov, MD and Itzhak Wirguin, MD
Clinical Views
Alexander Lowenthal, M Med Sci and Mark N. Lowenthal, MB, BCh, FRCPE
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