Israel Medical Association Journal

Fanconi anemia is a rare autosomal recessive disorder characterized clinically by congenital abnormalities, progressive bone marrow failure, and a predisposition to malignancy. FA cells are sensitive to DNA cross-linking agents. Complementation analysis of FA cells using somatic cell fusion has facilitated the identification of eight complementation groups, suggesting that FA is a genetically heterogeneous disorder. Six genes (FANCA, FANCC, FANCD2, FANCE, FANGF, FANCG) have been cloned so far. The majority of affected patients belong to FA group A. Of the 32 unrelated Israeli patients with FA that we studied, 6 carried the FANCC mutations and 15 the FANCA mutations. Among the Jewish patients, ethnic-related mutations were common. Recent cumulative evidence suggests that the FA proteins are repair proteins. FANCC, FANCA and FANCG bind and interact in a protein complex found in the cytoplasm and nucleus of normal cells. FANCD2 exists in two isoforms; the long active form, FANCD2-L, is absent from FA cells of all complementation groups. FANCD2 co-localized with BRCA1 in unclear foci, probably as part of a large genomic surveillance complex. Studies using FANCA and FANCC knockout mice suggest that bone marrow precursors express interferon-g hypersensitivity and show progressive apoptosis. The definition of the molecular basis of FA in many affected families now enables prenatal diagnosis.

Background: Current treatment for the eradication of Helicobacter pylori in patients with peptic disease is based on the combination of antibiotic and anti-acid regimens. Multiple combinations have been investigated, however no consensus has been reached regarding the optimal duration and medica­tions.

Objectives: To assess the efficacy of two treatment regimens in patients with peptic ulcer disease and non-ulcer dyspepsia, and to determine the need for gastric mucosal culture in patients failing previous treatment.

Methods: Ninety patients with established peptic ulcer and NUD (with previously proven ulcer) were randomly assigned to receive either bismuth-subcitrate, amoxycillin and metrnida­zole (8AM) or lansoprasole, clarithromycine and metronida­zole (LCM) for 7 days. Patients with active peptic disease were treated with ranitidine 300 mg/day for an additional month.

Results: Eradication failed in 8 of the 42 patients in the 8AM group and in 2 of the 43 patients in the LCM group, as determined by the ¹³C urea breath test or rapid urease test (19% vs. 5%, respectively, P=0.05). Five of these 10 patients were randomly assigned to treatment with lansoprazole, amoxycillin and clarithromycin (LAC) regardless of the culture obtained, and the other 5 patients were assigned to treatment with lansoprazole and two antibacterial agents chosen according to a susceptibility test. Eradication of H. pylon was confirmed by the ‘³C urea breath test. The same protocol (LAC) was used in all patients in the first group and in four of the five patients in the second group. The culture results did not influence the treatment protocol employed.

Conclusions: Combination therapy based on proton pump inhibitor and two antibiotics is superior to bismuth-based therapy for one week. Gastric-mucosal culture testing for sensitivity of H. pylon to antibiotics is probably unnecessary before the initiation of therapy for patients with eradication failure.

Background: The preconception and intraconception parameters that are relevant to outcome in women with underlying renal disease remain controversial.  

Objectives: To analyze the types and frequencies of short- and long-term (2 years after delivery) maternal and neonatal complications in 38 patients with primary renal disease (46 pregnancies), most of them with mild renal insufficiency.  

Methods: Logistic regression models were formulated to predict successful outcome.  

Results: Successful pregnancy outcome (live, healthy infant without severe handicap 2 years after delivery) was observed in 98% of the patients with primary renal disease. Factors found to be significantly predictive of successful outcome were absence of pre-existing hypertension, in addition to low preconception serum uric acid level.

Conclusions: Most women with primary renal disease who receive proper prenatal care have a successful pregnancy outcome. Worse pregnancy outcome was observed in women with moderate or severe renal failure. Fitted logistic models may provide useful guidelines for counseling women with preexisting renal disease about their prospects for a successful pregnancy in terms of immediate and long-term maternal and neonatal outcome.
 

Objectives: To report the characteristics of liver injury induced by nimesulide.

Patients and Methods: We report retrospectively six patients, five of them females with a median age of 59 years, whose aminotransferase levels rose after they took nimesulide for joint pains. In all patients nimesulide was discontinued, laboratory tests for viral and autoimmune causes of hepatitis were performed, and sufficient follow-up was available.

Results: One patient remained asymptomatic. Four patients presented with symptoms, including fatigue, nausea and vomiting, which had developed several weeks after they began taking nimesulide (median 10 weeks, range 2–13). Hepatocellular injury was observed with median peak serum alanine aminotransferase 15 times the upper limit of normal (range 4–35), reversing to normal 2–4 months after discontinuation of the drug. The remaining patient eveloped symptoms, but continued taking the drug for another 2 weeks. She subsequently developed acute hepatic failure with encephalopathy and hepatorenal syndrome and died 6 weeks after hospitalization. In none of the cases did serological tests for hepatitis A, B and C, Epstein-Barr virus and cytomegalovirus, as well as autoimmune hepatitis reveal findings.

Conclusions: Nimesulide may cause liver damage. The clinical presentation may vary from abnormal liver enzyme levels with no symptoms, to fatal hepatic failure. Therefore, monitoring liver enzymes after initiating therapy with nimesulide seems prudent.