Israel Medical Association Journal

Background: Splanchnic nerve stimulation evokes adrenomedullary catecholamine secretion via acetylcholine release and occupation of nicotinic cholinergic receptors on chromaffin cells.

Objectives: To assess whether among cultured adrenomedullary cells there exists a population that tonically secretes acetylcholine. If so, then blockade of enzymatic breakdown of acetylcholine by addition of a cholinesterase inhibitor to the medium would increase occupation of nicotinic receptors by endogenous acetylcholine and thereby induce catecholamine release.

Methods: Primary cultures of bovine adrenomedullary cells in 24-well plates (1 million cells per well) were incubated after 48–72 hours with fresh incubation medium (control), medium with added secretagogues (nicotine, angiotensin II, or K+) or the acetylcholinesterase inhibitor, edrophonium (10-7 to 10-³ M), for 1–20 minutes. Fractional release rates of epinephrine, norepinephrine and dopamine were compared to a control. We also examined whether co-incubation with edrophonium enhanced the effects of the secretagogues. All experiments were performed in quadruplicate and repeated three times.

Results: Nicotine, angiotensin II, and K+ each elicited time-related release of epinephrine, norepinephrine and dopamine by up to fourfold compared to the control. At all tested concentrations, edrophonium had no such effect. Co-incubation with edrophonium also failed to augment the secretory responses to nicotine, angiotensin II, or K+.

Conclusion: Bovine adrenomedullary cells in primary culture do not include a population of tonically active cholinergic cells.

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: Dysphagia is a common disorder among the elderly population. As many as 50% of nursing home residents suffer from dysphagia. It is important to identify patients at increased risk for colonization of dental and denture plaque by pathogenic organisms for prevention of associated disease.

Objectives: To quantify the prevalence and evaluate the effect of dental and denture plaque colonization by Candida albicans in hospitalized elderly dysphagic patients as a complication of stroke, as well as the effect of systemic antimicrobial therapy on C. albicans colonization in these patients.

Methods: We evaluated dysphagia and antibiotic therapy as risk factors for dental and denture plaque colonization by C. albicans in elderly stroke rehabilitating patients with dysphagia, as compared to elderly non-dysphagic stroke and non-stroke rehabilitating patients on days 0, 7 and 14 following admission to the Fliman Geriatric Rehabilitation Hospital.

Results: The risk of C. albicans colonization of dental plaque was greater in dysphagic patients than in those without dysphagia on day 0 (50% vs. 21%, P = 0.076), day 7 (58 vs. 15.2%, P = 0.008) and day 14 (58 vs. 15.2%, P = 0.08). Similarly, patients on antibiotic therapy were at greater risk for C. albicans colonization of dental plaque on day 0 (56 vs. 11%, P = 0.002), day 7 (44 vs. 14.8%, P = 0.04) and day 14 (39 vs. 19%, P = 0.18). The risk of C. albicans colonization of denture plaque as opposed to dental plaques in non-dysphagic patients was significantly greater on day 0 (45.7 vs. 21.2%, P = 0.03), day 7 (51.4 vs. 15.1%, P = 0.0016) and day 14 (54.3 vs. 15.1%, P = 0.0007). Dysphagia did not increase the risk of denture plaque colonization by C. albicans.

Conclusiona: Both dysphagia and antibiotic therapy are risk factors for C. albicans colonization of dental plaque, and although dysphagia does not significantly increase colonization of denture plaque, denture wearers are at greater risk of such colonization.

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: Hypertrophic pyloric stenosis classically presents as projectile vomiting during the third to fourth week of life associated with good appetite. Additional classical presenting findings include palpation of the pyloric tumor, described as olive-shaped, a visible gastric peristaltic wave after feeding, and hypochloremic, hypokalemic metabolic alkalosis. It was recently claimed that this presentation has changed due to the easier access to gastrointestinal imaging.

Objective: To validate this contention and discuss possible reasons.

Methods: We conducted a retrospective chart review of all patients who underwent pyloromyotomy for HPS[1] between 1990 and 2000. Only patients with confirmed HPS at the time of surgery were included. We also performed a comprehensive review of older studies for comparison.

Results: Seventy patients underwent pyloromyotomy over the 10 year period. Overall, 81% of patients were male infants and the mean age at diagnosis was 40 days. The mean duration of symptoms was 8 days. A firstborn child was noted in 43% of the cases. The classical symptom of projectile vomiting was absent in one-third of the patients, a pyloric tumor was not palpated in one-half of the cases, bicarbonate was higher than 28 mEq/L in 20% and a pH of above 7.45 was present in 25% of patients. Hypochloremia was noted in about one-third. We found a good correlation between ultrasonographic width and length of the pylorus and the intraoperative findings. Pylorus length ≥ 24 mm correlated with significantly longer duration of symptoms. When compared with previous studies, the main findings were not significantly different; namely, mean age at diagnosis, percentage of male gender and duration to diagnosis. The decrease in the number of pyloric tumors palpated paralleled the increase in the use of upper gastrointestinal series and ultrasonography in particular.

Conclusions: The clinical presentation of HPS has not actually changed despite the easier accessibility of GI imaging studies. However, the one significant change is the low percentage of pyloric tumors palpated, probably due to declining clinical skills, accompanied by earlier utilization of imaging studies. The use of imaging and laboratory studies did not change the age at diagnosis but may have shortened the time for diagnosis and reduced the postoperative stay. Imaging and laboratory studies may be helpful for the subgroup with a non-classical clinical presentation.

Background: Intravenous recombinant tissue plasminogen activator therapy within 3 hours of stroke onset is a proven effective treatment for acute ischemic stroke.

Objectives: To assess the feasibility and safety of rt-PA[1] therapy for reperfusion in routine clinical practice in Israel, in a setting of a dedicated stroke unit.

Methods: Consecutive patients presenting within less than 3 hours of stroke onset were evaluated by an emergency physician and the neurology stroke team. After brain computerized tomography eligible patients were treated with intravenous rt-PA (0.9 mg/kg; maximum dose 90 mg) according to an in-hospital protocol corresponding to recommended criteria. Patients were admitted to the acute stroke unit. Safety and clinical outcome were routinely assessed. Re-canalization was assessed by serial transcranial Doppler.

Results: The study group comprised 16 patients, mean age 61 years (range 47–80 years), male to female ratio 10:6, whose median baseline National Institutes of Health stroke scale was 13 (range 6–24). They were treated within a mean door-to-CT time of 39 minutes (range 17–62 min), door-to-drug time 101 minutes (range 72–150), and stroke onset-to-drug time 151 minutes (range 90–180). There was an early improvement within 24 hours (of ≥ 4 points in the NIHSS[2] score) in 7 patients (44%) and no early deteriorations. There were no protocol deviations, no symptomatic intracranial hemorrhages, and no major systemic hemorrhage within 36 hours of rt-PA treatment. Three asymptomatic hemorrhagic transformations of the infarct were noted on routine follow-up brain CT associated with neurologic improvement. Outcome data were comparable to the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study.

Conclusion: Intravenous rt-PA treatment within 3 hours of stroke onset in routine clinical practice in Israel is feasible and appears safe in the setting of a neurology stroke unit and team. Careful implementation of rt-PA therapy for selected patients in Israel is encouraged.

Background: The lack of lactobacilli in the vagina of postmenopausal women due to estrogen deficiency plays an important role in the development of bacteriuria. In the last few years, the use of lactobacilli for the prevention of genitourinary infections has been explored using different probiotic strains.

Objectives: To evaluate the vaginal colonization by Lactobacillus rhamnosus GG in postmenopausal healthy women following oral administration of the bacteria in a yogurt base for 1 month, as a first step in evaluating the potential probiotic role of LGG[1] in the prevention of recurrent urinary tract infections.

Methods: One or two doses per day of yogurt containing 10⁹ colony forming units of LGG were administered orally to 42 postmenopausal healthy women for 1 month. Vaginal and rectal swabs were cultured at the beginning and end of the study.

Results: At the end of the study, the vaginas of only four women (9.5%) were colonized with LGG, at a very low number of bacteria, despite the fact that the gastrointestinal tracts of 33 women (78.6%) were colonized. There were no significant differences between one or two doses daily.

Conclusions: LGG should not be considered as a probiotic agent in urinary infections since it does not attach well to the vaginal epithelium.

Background: A high total plasma homocysteine level is an independent risk factor for cardiovascular and cerebrovascular disease, but the evidence connecting plasma tHcy level with hypertension is inconsistent.

Objective: To determine the association between plasma tHcy level and some common risk factors for cerebrovascular disease (recurrent  stroke, diabetes mellitus, hypertension, ischemic heart disease and hyperlipidemia) in patients presenting with primary or recurrent acute ischemic strokes.

Methods: This retrospective cross-sectional chart analysis was conducted in a university-affiliated referral hospital. During an 18 month period we identified 113 acute ischemic stroke patients (mean age 71.2), 25 of whom had a recurrent stroke. Plasma tHcy[1] level, obtained 2–10 days after stroke onset, was determined by the high performance liquid chromatography method with fluorescence detection. A multivariate logistic regression model was used to determine the independent relationship between each potential risk factor and tHcy level above or below the 75th percentile.

Results:  Hypertension was more frequent among patients with plasma tHcy level above than below the 75th percentile (51.7% vs. 80.8%, respectively, P = 0.012). After adjusting for demographic and clinical variables, the odds ratio for recurrent stroke and hypertension, with tHcy above or below the 75th percentile, was 3.4 (95% confidence interval 1.01–10.4, P = 0.037) and 4.02 (95% CI[2] 1.2–13.9, P = 0.028), respectively.

Conclusions: A high plasma tHcy level is associated with history of hypertension and recurrent stroke among patients presenting with acute ischemic stroke. These results were independent of other risk factors such as atrial fibrillation, diabetes and hyperlipidemia. Hypertensive stroke patients with hyperhomocysteinemia should be identified as high risk patients as compared to non-hypertensive stroke patients, and may warrant more vigorous measures for secondary prevention.

Background: Seroepidemeliogic surveys have provided valuable information on the prevalence and incidence of herpes simplex virus-2 infection in general and in selected populations.

Objective: To review the reliability of traditional diagnostic approaches in herpes simplex virus-2 infection.

Methods: In this cross-sectional study, 472 patients attending a clinic for sexually transmitted disease in 1998-1999 were evaluated for HSV-2 infection through collection of epidemiologic and clinical data.

HSV-2 infection was confirmed by the presence of specific Viral glycoprotein, gG-2, antibody in sera.

Results: The seroprevalence of HSV-2 among clinic attendees was 9.33%. Of these attendees only 22% presented with or reported a history of typical vesicular lesions in the genital area. Infection rate was  higher in patients with multiple sex partners (20.8% vs. 8.7%, P< ( 0.0023 in individuals aged 30 or older (12.6 vs. 6.4%, P = 0.03) and  in the Israeli Jewish population as compared to the Israeli Arab population (11.1% vs. 2.4%, P ~ 0.01). Females with multiple sex partners exhibited higher rates of infection than did their male counterparts (50 vs. 16.1%, P < 0.0275(.

Conclusion: The findings support the need for HSV-2 serologi  testing in patients presenting to STD clinics even when typical genital  lesions are not evident but where risk factors for HSV-2 infection are  identified.