Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn's disease with low rate of side effects: results of double blind Phase II clinical trial.

Therapy for Crohn's disease (CD) with thiopurines is limited by systemic side effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR-6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR-6MP in patients with moderately severe CD compared to systemically delivered 6-mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week, double-blind controlled trial. The primary end-point was the percentage of subjects with clinical remission [Crohn's Disease Activity Index (CDAI) < 150] or clinical response (100-point CDAI reduction). Twenty-six (56·5%) and 13 (54·2%) subjects from the DR-6MP and Purinethol cohorts, respectively, completed the study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12 weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a decrease of CD62(+) expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR-6MP was safer than Purinethol, with significantly fewer adverse events (AEs). There was no evidence of drug-induced leucopenia in the DR-6MP group; the proportion of subjects who developed hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects.

Treatment of hepatitis C in patients with haemophilia - the Israeli National Hemophilia Center experience.

Treatment with pegylated interferon (Peg-IFN) and ribavirin, now the standard of care, has been shown to achieve sustained viral response (SVR) in up to 60% of patients with hepatitis C (HCV). Studies of response to this combination in HCV-infected haemophilia patients are scarce. The aim of the study was to report the results and safety of interferon/ribavirin treatment in HCV and HCV-/HIV-infected patients at the Israeli National Hemophilia Center. A retrospective observational cohort study was conducted on haemophilia patients infected with HCV or HCV/HIV. Patients received combination of Peg-IFN and ribavirin. Few were still treated with standard interferon. The primary end-point was sustained viral response (SVR). The secondary end-point was safety, with emphasis on increased bleeding episodes. Some 18/43 (42%) HCV mono-infected haemophilia patients achieved SVR. Relapse occurred in 14 (33%), while 11 patients (25%) were non-responders. SVR was achieved among 17/37 (46%) naïve patients receiving Peg-IFN and ribavirin. Among patients with genotype-1, SVR was achieved in 12/36 (33%) and 11/30 (37%) in the whole group and Peg-IFN treated naïve patients, respectively. In HCV/HIV co-infected patients only 1 patient achieved SVR. Severe anaemia occurred in 14/50 (28%) patients, four received erythropoietin. None maintained stable haemoglobin levels. Two patients had significant bleeding episodes. In our cohort of haemophilia patients, SVR was achieved in a lower than expected rates. A relatively high relapse rate in the HCV mono-infected patients and a very high non-response rate in the HCV/HIV co-infected patients were observed as anticipated. Anaemia was a major side effect and the use of growth factors seemed unrevealing.

[Primary gastric tuberculosis].

Intestinal tuberculosis (TB) comprises 5% of all cases of TB and may be a major problem in immigrant communities, although the incidence of pulmonary TB is declining. Gastric TB is rare, constituting 0.1-2% of all cases of TB. Gastric TB usually develops secondary to other tuberculous lesions, most commonly pulmonary. On endoscopy antral infiltrative lesions are found. Primary gastric TB is very rare, only 8 cases having been reported in the English literature. We report a case of primary gastric TB in a 55-year-old woman who presented with abdominal pain and gastric outlet obstruction. The diagnosis was confirmed by endoscopic biopsies which showed granulomas, but no acid-fast bacilli. The Mantoux test was positive, acid-fast bacilli were found in the gastric juice, and a positive culture for TB was obtained on gastric lavage. There was an excellent response to antituberculous chemotherapy. With the relative rate of extra-pulmonary TB increasing, primary gastric TB should be taken into account in the differential diagnosis of infiltrative lesions of the antrum.

Prevalence of markers of infection with hepatitis B and C viruses in immigrants of operation Solomon, 1991.

Sera of 200 recent Ethiopian immigrants (less than 1 year in Israel) were tested for the presence of antibodies against hepatitis B and hepatitis C viruses. The prevalence of the various markers was: anti-hepatitis B core antigen (anti-HBc) 52%, and hepatitis B surface antigen (HBsAg) 11.5%. None of the HBs-positive sera tested positive for IgM-anti core. Sixty-eight sera from nonvaccinated subjects were tested for anti-HBs, and 12 of them were anti-HBc negative/anti-HBs positive (the only positive marker was anti-HBs). Four of 23 HBsAg-positive sera were HBcAg positive (17%), and only 1 of 18 HBeAg-negative sera was positive for anti-e antibodies. Antibodies to hepatitis C were positive in 6/200 sera (3%).

Anti-histone antibodies in SLE and other autoimmune diseases.

The frequency of IgG and IgM anti-total histones and anti-histone subfractions were studied in 63 patients with SLE and 257 patients with other autoimmune conditions employing the ELISA. IgG anti-histone antibodies were found in 17 of 63 (25%) sera of lupus patients and in only 16 of 257 (6%) sera of patients with other autoimmune conditions. The latter incidence did not differ statistically from that of 115 healthy control subjects. Furthermore, the concomitant appearance of both IgG and IgM anti-histone antibodies was observed only in SLE patients. Anti-histone subfraction (H1, H2A, H2B, H3, H4) activity was determined in sera containing anti-total histone antibodies. There was a higher preponderance for antibodies to H1, H2A, H2B in SLE. We conclude that anti-histone antibodies seem to be a marker for lupus and its variants (e.g. drug induced lupus) and should be routinely looked for in SLE patients.

Detection of antibodies to total histones and their subfractions in systemic lupus erythematosus patients and their asymptomatic relatives.

Sera drawn from 75 patients with systemic lupus erythematosus, 141 healthy relatives (from the families of 51 patients), and 115 healthy control subjects were examined, by enzyme-linked immunosorbent assay, for IgG and IgM antibodies to total histones and their subfractions. Compared with the controls, statistically significant numbers of patients and their relatives had antihistone antibodies of both isotypes. Among the relatives, the sera from females, notably sisters of the patients, contained the highest levels of anti-total histone antibody. Anti-H2A/H2B and H3 antibodies were most prevalent among the lupus patients, but many of the relatives had IgM anti-H4 antibodies. These findings indicate that antihistone antibodies can serve as a genetic marker in patients with systemic lupus erythematosus.