Antitumor effects of inhibitors of arachidonic acid cascade on experimentally induced intestinal tumors

The antitumor action of inhibitors of cyclooxygenase (indomethacin) and lipoxygenase activity (nordihydroguaiaretic acid) of arachidonic acid cascade was investigated in the chemically induced large bowel tumors in Sprague-Dawley rats. Indomethacin treatment completely prevented the carcinogenic effect of methylazoxymethanol. Thus, no tumors were found in the 14 rat test group, compared with 13 of 14 tumor-bearing rats in the unteated control group. Although nordihydroguaiaretic acid treatment does not abolish prostaglandin synthesis, it does reduce the effect of the carcinogen and tumors were found in only five of 14 treated rats. From this study it can be postulated that not only is reduction in prostaglandin formation responsible for the inhibition of tumor growth, but also leukotrienes may play some role. This work was supported partially by a grant from the Chief Scientist of the Ministry of Health Israel.     

The significance of an early (premature) rise of plasma progesterone in in vitro fertilization cycles induced by a “long protocol” of gonadotropin releasing hormone analogue and human menopausal gonadotropins

Objective: Our purpose was to assess and clarify the mechanism of whether an early progesterone rise in cycles with gonadotropin-releasing hormone agonist (GnRH-a) is associated with an impairment of IVF outcome Methods: Seven hundred eighty-six cycles were induced with GnRH-a and human menopausal gonodotropin (hMG) (long protocol). Plasma progesterone (PP) levels on the day of human chorionic gonadotropin (hCG) administration were divided into three groups: <0.9 ng/ml (Group A), 1–2 ng/ml (Group B), and >2 ng/ml (Group C). We also analyzed the pregnancies achieved in our egg donation protocol in relation to the PP levels of each donor on the day of hCG administration. Results: Group A involved 525 cycles, Group B had 223, and Group C had 38. The overall pregnancy rate per egg transfer was 19.2%, with the highest for Group A (22.3%), declining for Groups B (14.3%) and C (7.9%) (A = B = C; P<0.005). The embryo implantation rate was found to be negatively correlated with the PP levels on the day of hCG administration. In contrast, there was an opposite trend between PP levels and the chance of conception in 30 pregnancies achieved by egg donation. Conclusions: Since premature luteinization is very unlikely to occur under the conditions of this study, our findings suggest that an early PP rise has a negative impact on endometrial receptivity but not on egg and embryo quality.     

The role of a human chorionic gonadotropin burst in in vitro fertilization

Findings: No oocytes were found during four ovum pickups (OPU), despite a satisfactory ovarian response to controlled ovarian hyperstimulation. After the first attempt failed in the fourth case, five eggs were retrieved, fertilized, and cleaved after cycle rescue with hCG. Conclusions: Whenever oocytes are not aspirated during OPU due to a lack of hCG administration, the cycle may be rescued if 10,000 IU of hCG is injected immediately and OPU planned for 33–36 hr later.     

Lessons learned from chlorine intoxications in swimming pools: the challenge of pediatric mass toxicological events

INTRODUCTION: The classical doctrine of mass toxicological events provides general guidelines for the management of a wide range of "chemical" events. The guidelines include provisions for the: (1) protection of medical staff with personal protective equipment; (2) simple triage of casualties; (3) airway protection and early intubation; (4) undressing and decontamination at the hospital gates; and (5) medical treatment with antidotes, as necessary. A number of toxicological incidents in Israel during the summer of 2005 involved chlorine exposure in swimming pools. In the largest event, 40 children were affected. This study analyzes its medical management, in view of the Israeli Guidelines for Mass Toxicological Events. METHODS: Data were collected from debriefings by the Israeli Home Front Command, emergency medical services (EMS), participating hospitals, and hospital chart reviews. The timetable of the event, the number and severity of casualties evacuated to each hospital, and the major medical and logistical problems encountered were analyzed according to the recently described methodology of Disastrous Incident Systematic Analysis Through-Components, Interactions, Results (DISAST-CIR). RESULTS: The first ambulance arrived on-scene seven minutes after the first call. Emergency medical services personnel provided supplemental oxygen to the victims at the scene and en route when required. Forty casualties were evacuated to four nearby hospitals. Emergency medical services classified 26 patients as mildly injured, 13 as mild-moderate, and one as moderate, suffering from pulmonary edema. Most children received bronchodilators and steroids in the emergency room; 20 were hospitalized. All were treated in pediatric emergency rooms. None of the hospitals deployed their decontamination sites. CONCLUSIONS: Event management differed from the standard Israeli toxicological doctrine. It involved EMS triage of casualties to a number of medical centers, treatment in pediatric emergency departments, lack of use of protective gear, and omission of decontamination prior to emergency department entrance. Guidelines for mass toxicological events must be tailored to unique scenarios, such as chlorine intoxications at swimming pools, and for specific patient populations, such as children. All adult emergency departments always should be prepared and equipped for taking care of pediatric patients.     

Oral solution of levodopa ethylester for treatment of response fluctuations in patients with advanced Parkinson's disease.

Levodopa ethylester (LDEE), a highly soluble prodrug of levodopa, may overcome the impaired absorption of regular levodopa, due mainly to a combination of levodopa's poor solubility and delayed gastric emptying. We conducted a double-blind, levodopa-controlled, multicenter study of oral LDEE solution compared with standard levodopa-carbidopa (LD-CD) tablets. Sixty-two patients with Parkinson's disease who had "delayed on" and "no-on" subtypes of response fluctuations were randomly assigned for treatment with LDEE-CD or LD-CD 250/25 mg for 4 weeks (phase A). Only the first morning and first post-lunch dose of LD were replaced. This was followed by a 2-week extension with a supplementation of carbidopa (25 mg) to each replaced dose (phase B). Patients filled home diaries 2 weeks before and during the trial period in which times of turning on and off for the two doses were reported. In phase A, mean latency to turning on was reduced by 21% (morning dose) and 17% (post-lunch dose) in the LDEE-CD group. Percentage of no-on episodes after the post-lunch dose was decreased by 21% in the LDEE-CD group but increased by 36% in the LD-CD group (P < 0.01). In phase B, LDEE-CD decreased latencies to on after the morning and post-lunch doses and no-on episodes after the post-lunch dose. The beneficial effects of LDEE were supported by the pharmacokinetic data. Results indicate that LDEE solution is beneficial in ameliorating delayed on and no-on response fluctuations. This effect of LDEE is due to more rapid levodopa absorption.