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Biomedical subjects

W R Thayer

Publications and source records attributed to W R Thayer.

13 recordsLinked to original sources

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.

Antitubercular Agents

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.

Antibody-Dependent Cell Cytotoxicity

K-Cell activity in lamina proprial lymphocytes from the human colon.

Using an enzymatic method for their isolation, it has been shown that human colonic lamina proprial lymphocytes, isolated from patients with various colonic diseases and depleted of polymorphonuclear leukocytes and macrophages, demonstrated K-cell activity in two antibody-dependent cell-mediated cytotoxicity assays in vitro. No differences were found between the activities of lamina proprial lymphocytes isolated from colonic specimens involved by Crohn's disease, chronic ulcerative colitis, or colonorectal carcinoma. K-cell activity was demonstrable using lymphoid cells isolated from the colons of patients receiving steroid therapy at the time of the therapeutic resections. These findings indicate the need for further investigation of possible roles for K-cells in local immune responses in the human bowel mucosa in inflammatory and neoplastic diseases.

B-Lymphocytes

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.

Antigen-Antibody Complex

Skin test reactivity in inflammatory bowel disease in the United States and Czechoslovakia.

Inflammatory bowel disease (IBD) patients in the United States of America (USA) and Czechoslovakia (CSSR) were categorized by clinical, pathological, and radiological criteria as having Crohn's disease (CD) or ulcerative colitis (UC) and were tested with five skin test antigens [Candida, mumps, purified protein derivative (PPD), streptokinase-streptodornase (SK-SD), and trichophytin] at two different dilutions in an attempt to elicit some evidence of anergy. No significant differences were encountered between the USA and CSSR populations or between any patient group and its controls.

Allergens

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.

Animals

The subpopulations of circulating white blood cells in inflammatory bowel disease.

A detailed analysis of the species of lymphocytes was carried out in 58 patients with inflammatory bowel disease (IBD). These individuals were further divided into 31 with Crohn's disease (CD) and 27 with ulcerative colitis (UC). There were 13 CD patients with only small bowel involvement called "regional enteritis" and 18 who had some degree of colonic involvement called "ileocolitis". Similarly, the UC group was subdivided into 9 patients with disease confined to the rectosigmoid area called "proctosigmoiditis" and 18 with more extensive involvement called "universal colitis". We also studied 13 patients who had undergone previous colectomy and ileostomy and 78 healthy age- and sex-matched controls. Although there was no increase in the absolute number of lymphocytes in patients with ileocolitis and universal colitis, the percentage of these cells was decreased because of an increase in both polymorphonuclear leukocytes and monocytes. In IBD and its subgroups, mean T lymphocytes, determined by the sheep red blood cell rosette technique, were not significantly different from the controls either in percentage or absolute number. Furthermore, no difference was noted between UC and CD. However, there seems to be a subpopulation of patients with UC or CD whose T cells are reduced below 1 SD of the mean. There was also no difference in the number of immunoglobulin-bearing B cells in both diseases; however, when the B cells were enumerated by their ability to rosette with antibody-complement-coated sheep cells (EAC), we found a marked decrease in percentage (P less than 0.001) and absolute number (P less than 0.0005) relative to the control population. The decrease bore a direct relation to the severity of the disease process and, although more marked in patients with UC, was present in CD also.

B-Lymphocytes

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.

Blood Proteins