Clinical studies with low-lactose milk.

A low-lactose milk was evaluated for taste acceptance and clinical symptomatology by means of a double-blind control study in two groups of individuals. One group consisted of nine milk intolerant individuals, while the other consisted of five milk tolerant individuals. Each week for 9 wk the participants were given a coded sample of skim milk, lactose hydrolyzed milk, skim milk plus glucose, or sweet acidophilus milk. Each participant was asked to consume four liters of milk during a week and keep a daily log of symptoms (pain, bloating, nausea, flatus, emesis, bowel frequency) along with taste acceptability. After assigning a numerical value to the intensity of symptomatology a X2 analysis was performed on the data. In the milk intolerant population lactose hydrolyzed milk produced significantly milder (p < 0.05) pain and gas symptoms than the nonhydrolyzed milks. Bowel frequency was not altered between the types of milk in both groups. The lactose hydrolyzed milk did not reduce the symptoms of lactose intolerance in the milk intolerance population to the response of the control group. Although both study populations found decreased taste acceptability to the lactose hydrolyzed milk, a taste panel assessment did not show any significant differences in the milks.

Utilization of a low-lactose milk.

This study was undertaken to determine if a milk containing prehydrolyzed lactose, yet affording full nutritional benefits, could be ingested by a milk intolerant (MI) population without the symptoms of lactose intolerance. MI was defined by the failure of serum glucose to rise greater than 20 mg/100 ml after ingestion of 50 gm of lactose as well as by subjective and objective symptoms and signs after consumption of both 12.5 gm of lactose in water and 250 ml of skim milk. Lactose tolerance (LT) was evidenced by both lack of symptoms and a concomitant rise in serum glucose of greater than 20 mg/100 ml after ingestion of 50 gm lactose in water. A series of four, two hr tolerance tests were given to 12 MI patients and 12 LT controls. The following solutions were employed: 12.5 gm lactose, 250 ml skim milk. 250 ml low-lactose skim milk, and 6 gm glucose plus 6 gm galactose. In the MI group, significant differences were apparent between the tolerance test utilizing skim milk and that using low-lactose skim milk; no such differences were observed in the LT group. These observations indicate that in the MI population the lactose in skim milk was poorly absorbed or tolerated, but after hydrolysis the low-lactose skim milk was well tolerated. A MI individual then, appears able to absorb the monosaccharides of the prehydrolyzed milk and can, furthermore, tolerate the low-lactose skim milk without suffering from symptoms normally associated with lactose intolerance.

Inflammatory bowel disease. The case for an infectious etiology.

The infectious hypothesis for IBD is certainly not new. The evidence for an infectious agent is tantalizing but not yet convincing. A failure to demonstrate a specific agent in the inflammatory process could mean that many different organisms are involved, or several organisms that, by themselves, do not cause disease interact. All candidate organisms proposed thus far are compatible with either hypothesis. Nevertheless, interaction between an agent(s) in a host modified by immunologic and genetic factors is still an attractive hypothesis for the cause of these illnesses.

The use of antimycobacterial agents in Crohn's disease.

Seventy-five years ago, a Scottish surgeon, Dalziel, clearly described Crohn's disease (CD) and suggested that it might be caused by a mycobacteria. However, mycobacteria were not isolated from CD tissue until 1978 and 1984. Since then several investigators, using sophisticated polymerase chain reaction (PCR) techniques, found Mycobacterium paratuberculosis sequences in cultures of Crohn's disease tissue in approximately two thirds of patients. Because of a possible mycobacterial etiology, Rutgeerts et al. (J Clin Gastroenterol 1992;15:24-8) treated resected ileocolonic CD patients who had early evidence of recurrence with ethambutol and rifabutin. Patients were followed by colonoscopy to observe changes in the intestinal lesions, but no improvement was noted. Rutgeerts et al. concluded that antimycobacterial therapy did not affect the course of CD. Failure of these antibiotics does not necessarily negate the mycobacterial theory of CD, however. The study population of Rutgeerts et al. was too small, and the treatment period too short. Furthermore, ethambutol shows little or no activity against the proposed Crohn's organism, Mycobacterium paratuberculosis; use of only one active agent (rifabutin) can lead to drug resistance and failure of antibiotic therapy. We hope that Rutgeerts et al. will continue these important studies, but with a more active combination of antimycobacterial drugs for a longer time.

Hemochromatosis associated with chronic cimetidine therapy?

We report a patient in whom hemochromatosis with high transferrin saturation developed during long-term cimetidine administration. Prior reports have noted impaired iron absorption to be associated with short-term cimetidine use. The effect of chronic cimetidine administration on iron absorption and metabolism has not been studied. We believe this to be the first, and so far the only report of increased iron absorption with long-term cimetidine use.

Effects of sulfasalazine on selected lymphocyte subpopulations in vivo and in vitro.

Sulfasalazine has proven to be an effective agent in the therapy of inflammatory bowel disease (IBD). Despite long and widespread usage, the mechanism of action of this drug is still not understood. Several investigators have suggested that the drug might act as an immunosuppressant. To examine this possibility, an in vivo study was undertaken to ascertain any quantitative change in the circulating T cells, Ig-bearing B cells, and complement receptor-bearing lymphocytes (CRL) of patients before and during therapy with sulfaslazine. Concomitant responses to skin test antigens were also evaluated. In vitro studies with control cells were performed to determine the influence of sulfasalazine and its components (sulfapyridine or 5-aminosalicylic acid) on the extent of antibody-dependent cellular cytotoxicity (ADCC), as well as on the number of T cells and CRL. Results indicate that neither sulfasalazine nor either of its components quantitatively alters those subpopulations of circulating mononuclear cells studied in vivo or in vitro--nor are these compounds responsible for any functional inhibition of ADCC.

Circulating Clq binding complexes in inflammatory bowel diseases.

To determine whether circulating immune complexes are present in the sera of patients with inflammatory bowel disease (IBD), a 125I-Clq binding assay was performed. Of the 55 IBD serum samples tested, the 24 ulcerative colitis samples demonstrated significant binding (33.1 +/- 8.3%, p = 0.02), whereas the 31 Crohn's samples bound essentially normal amounts (29.2 +/- 7.4%). A positive control group consisting of 27 patients with rheumatoid arthritis was also studied. Sera from 4 patients wiht IBD and colonic cancer when tested, bound 40.2 +/- 8.0% of the available 125I-Clq, while 10 patients with previous colectomies and ileostomies gave results similar to those of 15 healthy controls and 11 patients with irritable colon.

The alternate complement pathway in inflammatory bowel disease. Quantitation of the C3 proactivator (factor B) protein.

A component of the complement system's alternate pathway was investigated in ulcerative colitis and Crohn's disease. The mean C3PA (Factor B) titer in normals was 74 +/- 15%; in ulcerative colitis, 92 +/- 18%; and in Crohn's disease, 119+/- 24%. Significance was at the P less than 0.001 level when the mean values for the ulcerative colitis and the Crohn's disease groups were compared to normal subjects. Titers did not change significantly with exacerbation or amelioration of the diseases or when patient groups were analyzed according to the mode of treatment received.

Use of rifabutin in treatment of systemic Mycobacterium paratuberculosis infection in mice.

BALB/c mice were infected intraperitoneally with Mycobacterium paratuberculosis and, after allowing the infection to progress for 30 days, were treated with rifabutin at 0, 12.5, 25, and 50 mg/kg of body weight. Rifabutin was administered in drinking water under conditions of water deprivation, whereby the entire daily dose was delivered within a 1-h period. Animals were killed at biweekly intervals from time zero of treatment to 180 days. Spleens and livers from each animal were examined by quantitative bacteriologic culture and histopathology. Restricted water availability was found to be a viable alternative to daily gavage for single-dose bolus administration. Infection, as assessed by bacterial counts, was reduced only in animals that received 50 mg of rifabutin per kg. In these animals, bacterial counts in the liver and spleen were reduced from 7.2 x 10(5) +/- 4.1 x 10(4) and 6.5 x 10(5) +/- 4.1 x 10(4) to 3.0 x 10(3) +/- 1.8 x 10(2) and 3.1 x 10(3) +/- 2.2 x 10(2), respectively, over the 6-month treatment period. Rifabutin may be an appropriate chemotherapeutic drug for long-term treatment of M. paratuberculosis infection and should be considered in any multidrug regimen.