Use of allopurinol with low-dose 6-mercaptopurine in inflammatory bowel disease to achieve optimal active metabolite levels: a review of four cases and the literature.

BACKGROUND: At least one-third of patients with inflammatory bowel disease do not respond or are intolerant to therapy with 6-mercaptopurine (6-MP). A subgroup fails to attain optimal levels of 6-thioguanine nucleotide (6-TGN) and instead shunts to 6-methylmercaptopurine nucleotide (6-MMPN). PATIENTS AND METHODS: A retrospective chart review was conducted, and four patients are described who had been previously unable to achieve optimal 6-TGN metabolite levels until allopurinol was added to their treatment. RESULTS: All four patients achieved optimal 6-TGN levels and undetectable 6-MMPN with a mean 6-MP dose of 0.49 mg/kg. Three achieved steroid-free clinical remission. Two of those three patients had normalization of liver enzymes; one patient had baseline normal liver enzymes despite an initial 6-MMPN level of 27,369 pmol/8 x 10(8) red blood cells. Two patients experienced reversible leukopenia. CONCLUSIONS: Combination allopurinol and low-dose 6-MP is an effective means to achieve optimal metabolite levels and steroid-free clinical remission in previously refractory patients. Caution is advised.

Placebo-controlled trial of ulcerative colitis with oral 4-aminosalicylic acid.

Forty patients with active ulcerative colitis were randomly assigned to receive either 4 g of oral enterically coated 4-aminosalicylic acid (para-aminosalicylic acid) or placebo. The duration of treatment was 12 weeks. Disease activity was assessed by grading clinical symptoms of blood, mucus, urgency, sigmoidoscopic findings, and degree of histological inflammation in rectal biopsy specimens. At 12 weeks, 11 of 20 patients (55%) who received 4-aminosalicylic acid showed improvement in clinical and sigmoidoscopic variables. In contrast, only 1 of 20 patients (5%) who had received placebo showed improvement (P less than 0.005). Eighteen of the 19 patients in the placebo group who showed no improvement were treated subsequently with open-label 4-aminosalicylic acid. Of the 18, 11 showed clinical and sigmoidoscopic improvement. Patients allergic or intolerant to sulfasalazine with extensive disease were more likely to respond to 4-aminosalicylic acid.

Topical salicylate therapy (4-ASA and 5-ASA enemas).

Topical therapy with amino salicylate enemas is the treatment of choice for proctitis, proctosigmoiditis, and left-sided ulcerative colitis. Adjunctive sulfasalazine therapy is often required. Relapse rates of 80 per cent can be expected within 3 months of discontinuing therapy.

Treatment of left-sided ulcerative colitis with 4-aminosalicylic acid enemas. A double-blind, placebo-controlled trial.

Twenty-five patients with active left-sided ulcerative colitis were randomly assigned to receive either 2 g of 4-aminosalicylic acid (para-aminosalicylic acid) or placebo in a 60-mL volume as a nightly retention enema. The duration of treatment was 8 weeks. Disease activity was assessed by grading clinical symptoms of blood, mucus, urgency, sigmoidoscopic findings, and degree of histologic inflammation in rectal biopsies. At 8 weeks, 10 of 12 patients (83%; 95% confidence interval [CI], 55% to 97%) who received 4-aminosalicylic acid showed improvement in clinical, sigmoidoscopic, and histologic variables. In contrast, only 2 of 13 patients (15%, 95% CI, 4% to 38%) who had received placebo showed clinical improvement (P less than 0.005). The 11 patients in the placebo group who showed no improvement were treated subsequently with open-label 4-aminosalicylic acid enemas. Of the 11, 9 showed clinical, sigmoidoscopic, and histologic improvement. No adverse effects were seen. 4-Aminosalicylic acid enemas are a safe and effective means of treating left-sided ulcerative colitis.

Turcot's syndrome. Evidence for autosomal dominant inheritance.

A case of Turcot's syndrome (colonic polyposis plus a malignant central nervous system tumor) occurring in a kindred with autosomal dominant colonic polyposis is presented. It is proposed that Turcot's syndrome patients can be classified into Type I where only siblings are affected and Type II where two or more generations have colonic polyposis. A third nonfamilial group cannot be classified into Type I or II based on available information. Evidence is presented suggesting Turcot's syndrome is best considered an additional phenotype of familial polyposis and is most likely inherited in an autosomal dominant manner.

The hazard of drug-induced esophagitis.

The importance of differentiating between underlying esophageal pathology and drug-induced esophagitis is stressed by the authors. The underdiagnosis of the latter is particularly unfortunate because it is usually reversible if recognized early.

Marked elevation in serum alkaline phosphatase activity as a manifestation of systemic infection.

Jaundice of severe bacterial infection is well known. Marked elevation of the alkaline phosphatase has not previously been emphasized as a manifestation of severe bacterial infection. We report 4 patients with bacterial infection manifested chemically by a markedly elevated serum alkaline phosphatase and a minimally elevated serum bilirubin.

Risk factors in transmission of non-A, non-B posttransfusion hepatitis. The role of hepatitis B antibody in donor blood.

Risk of developing icteric hepatitis in a transfusion study involving cardiac surgery patients was 0.2 per cent per unit of blood transfused with the ratio of icteric to anicteric cases being 1:4. Risk of developing hepatitis was proportional to the number of units transfused: one to four units, 4 per cent; six to ten units, 8 per cent; 11 to 20 units, 19 per cent; greater than 21 units, 42 per cent. The prevalence of type B hepatitis was low (6 per cent), with the vast majority of patients being shown to have non-A non-B hepatitis. However, a greater incidence of hepatitis type B serologic events was observed among recipients of anti-HBs positive blood than those transfused only with units not containing antibody (p = 0.04. A significantly greater incidence of non-A, non-B hepatitis was observed among patients transfused with blood containing anti-HBs when compared with a group who received blood without antibody (p less than 0.01). Caution should be exercised in interpretation of this difference because patients transfused with blood containing anti-HBs received significantly more units of blood. However, utilization of stepwise regression analysis to unconfound the two dependent variables suggest that the use of blood containing anti-HBs increases the hepatitis risk (p = 0.06) although the number of units transfused was the more significant factor (p less than 0.001). Additional data from carefully designed studies are needed to determine if donor blood containing anti-HBs significantly increases the risk of transmitting non-A, non-B hepatitis.

Efficacy of prophylactic gamma-globulin in preventing non-A, non-B post-transfusion hepatitis.

Of 279 cardiac-surgery patients receiving a mean of twelve transfusions, 47 had significantly increased transaminase concentrations 14 to 180 days postoperatively and 10 were icteric. Preoperatively, each patient randomly received high-titre HbsAb gamma-globulin, normal gamma-globulin, or placebo and was followed at intervals for 9 months. Only 3 patients had serological evidence of hepatitis-B infection. 3 additional patients had serological evidence of cytomegalovirus infection, while none had evidence of hepatitis-A or Epstein-Barr infection. Less icteric hepatitis occurred in patients receiving the gamma-globulin preparations (P = 0-003), and the overall frequency of hepatitis was significantly reduced when compared with recipients of placebo. The protective effects of the two gamma-globulin preparations were not significantly different. Most post-transfusion hepatitis tody is neither viral hepatitis type B nor type A, and its severity and transmission are reduced by pre-transfusion gamma-globulin.