Israel Medical Association Journal

Background: Nitrofurantoin is a commonly prescribed urinary antiseptic. Hepatic injury has been associated with its use.

Objectives: To present three patients in whom long-term exposure to the drug resulted in chronic active hepatitis, and review the epidemiology, clinical immunology, histopathology, pathogenetic features and treatment of previously reported cases.

Findings: Withdrawing nitrofurantoin once the diagnosis was suspected did not lead to remission of the liver disease and glucocorticoids had to be administered. One patient died of liver failure.

Conclusions: Awareness of this unusual side effect of nitrofurantoin is important and caution should be exerted before prescribing it. Over the past years new insight into the immune nature of this drug has emerged.
 

Background: Primary aldosteronism is a common cause of non-renal secondary hypertension. A correct diagnosis results in curing the hypertension or targeting appropriate pharmacotherapy. In patients with low renin resistant hypertension (after treatment with three or more different anti-hypertensive drugs the blood pressure remains above 140/90 mmHg), screening for aldosteronism is mandatory.

Objectives: To demonstrate that normal blood levels of potassium in resistant hypertensive patients do not exclude the possible presence of hyperaldosteronism, and to suggest the use of the plasma aldosterone concentration (ng/dl)/plasma renin activity (ng/ml/hour) ratio in screening for hyperaldosteronism.

Methods: Blood tests, suppression and stimulation tests (2 L normal saline IV/4 hours and 20 mg furosemide IV for 60 minutes in a standing position) were systematically performed in 20 low renin normokalemic resistant hypertensive patients. None had renal disorders, known endocrine abnormalities or heart failure. They did not receive anti-hypertensive drugs affecting PAC[1] or PRA[2]. Basal PRA and PAC were measured twice: PAC after saline infusion and PAC/PRA after stimulation.

Results:. PAC/PRA above 50 was used to denote hyperaldosteronism. Serum K was 4 ± 0.07 mM/L, PAC 22.8 ± 1.8 ng/dl, PRA 0.13 ± 0.02 ng/ml/hour, PAC/PRA 190 ± 22 (above 100 in 17). After suppression PAC decreased from 25 ± 1.8 to 11 ± 1 ng/dl (normal <5 ng/dl). Stimulation did not affect PRA and PAC/PRA. Abdominal computed tomography scan revealed normal adrenal glands in 15 patients. Spironolactone (116 ± 60 mg/day) normalized blood pressure in all patients; it was used as a single therapy in 8, and in association with only one anti-hypertensive drug in the remaining 12 patients. In one patient the treatment was discontinued due to the presence of hyperkalemia.

Conclusions: Low renin resistant hypertension associated with normokalemia may be due to hyperaldosteronism. Normal aldosterone levels in the basal condition do not exclude the possibility of hyperaldosteronism. Using a PAC/PRA ratio above 50 as a screening test can aid the physician in deciding when to perform dynamic tests, thus increasing the sensitivity of the diagnosis of hyperaldosteronism. CT scan is frequently normal. Targeted pharmacotherapy leads to a normalization of blood values.

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.
 

Background: About one-third of patients with severe ulcerative colitis do not respond to conventional therapy and require urgent colectomy. It was recently shown that cyclosporin is effective in some of these patients.

Objectives: To review the current experience of six hospitals in central Israel that used cyc-losporin in patients with severe ulcerative colitis.

Methods: The files of all 32 patients treated with cyclosporin for corticosteroid-resistant ulcerative colitis were reviewed. Activity of disease was measured by a clinical activity, index colonoscopy and laboratory tests.

Results: The average duration of treatment with intravenous cyclosporin was 12.7 days (range 9–28) after which the disease activity index dropped from an average of 14.22 to 4.74. The mean time for response was 7.5 days (4–14). Twelve patients (40%) required surgery within 6 months and another 6 patients (18.8%) were operated on after more than 6 months. Twelve patients (37%) maintained remission for at least 6 months and did not require surgery. In one patient treatment was stopped because of non-compliance and one was lost to follow-up. There were numerous side effects, but in only one case with neurotoxicity was treatment withdrawn.

Conclusions: Cyclosporin is a relatively safe and effective treatment for severe ulcerative colitis. It induced long-term remission in 37% of the patients, and in those who required surgery the treatment resulted in an improved clinical condition before the operation.

Background: Chickenpox is a highly contagious childhood infection caused by varicella zoster virus, a virus of the herpes family. Although a mild and self-limiting disease in otherwise healthy children, chickenpox can be a complicated and even life-threatening disease in adults, pregnant women and immunosuppressed individuals. Among infants whose mothers had varicella during the first trimester of pregnancy, 2-3% will develop a congenital VZV syndrome that includes a combination of scarring, limb deformation, central nervous system impairment and ocular injury. In 1974, a live attenuated virus vaccine against VZV was developed in Japan and has been thoroughly tested for safety, efficacy and long-term effects. In March 1995 the vaccine was licensed in the U.S. for use in healthy children only.

Objectives: To determine the rate of immunity to VZV in young Israeli adults.

Methods: On the assumption that a randomly picked sample of 18-year-old army recruits in Israel is representative of the general Jewish population, 900 sera samples were taken for 3 years (1985,1988,1992). The sera were analyzed for IgG to VZV with a commercial ELISA kit using microwells coated with VZV antigens.

Results: A total of 98% of the samples tested positive for VZV antibodies. The difference in serologic values between the recruitment years was not statistically significant.

Conclusion: The majority of the Israeli population reaches adulthood already immunized against VZV, with immigrants having slightly lower immunity rates. Nonetheless, a few dozen cases of chickenpox are diagnosed in the IDF annually. These data should be taken into account when a vaccination program is devised. Should such a program be implemented, it would be interesting to repeat the serosurvey for comparison. A shift in the peak occurrence age might necessitate the administration of a booster vaccine at an older age.

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VZV= varicella zoster virus

IDF= Israel Defense Forces

Background: DHEAS, the most abundant steroid secreted by the adrenal cortex, is suggested to have an important role in the development of immune reaction by activating T cell function and increasing antibody response, and has been tried as a vaccine adjuvant in elderly people.

Objectives: We examined the correlation between endogenous DHEAS and antibody response in the neonatal period by comparing the serum DHEAS levels with the amount of antibody response against hepatitis B vaccination in neonates.

Methods: Vaccine was administered to 12 healthy infants within 24 hours of birth (day 0), and blood specimens were obtained on days 0 and 30 for determination of anti-hepatitis B surface antibody concentration and DHEAS levels.

Results: DHEAS levels varied widely (range 0.38-3.70 μg/ml, mean±SD 2.14±0.98). While we could identify two groups of patients - those with high DHEAS levels (2.90±0.56) and those with lower levels (1.30±0.56) - there was no correlation between DHEAS levels and the antibody response to hepatitis B vaccine (γ=-0.05).

Conclusions: In neonates, antibody response to hepatitis B vaccine does not correlate with DHEAS serum levels. These results do not support the usage of DHEAS as a vaccine adjuvant in neonates.

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DHEAS= dehydepiandrosterone sulphate

Objectives: To present a case series of foyr patients with phenytion-induced severe CDRs, including toxic epidermal necrolysis (2 patients), exanthematous eruption (1 patient) and hypersensitivity syndrome (1 patient). In all patients the reactions appeared following the combined intake of phenytion, corticosteroids and H2 blockers.

Conclusions: Our case series may imply the role of drug interactions between phenytion, corticosteroids and H2 blockers in the induction of severe CDRs.