Fecal incontinence in a 39-year-old man.
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Biomedical subjects
Publications and source records attributed to R J May.
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Previous studies indicated that Alcaligenes eutrophus H850 attacks a different spectrum of polychlorinated biphenyl (PCB) congeners than do most PCB-degrading bacteria and that novel mechanisms of PCB degradation might be involved. To delineate this, we have investigated the differences in congener selectivity and metabolite production between H850 and Corynebacterium sp. strain MB1, an organism that apparently degrades PCBs via a 2,3-dioxygenase. H850 exhibited a superior ability to degrade congeners via attack on 2-, 2,4-, 2,5-, or 2,4,5-chlorophenyl rings in PCBs but an inferior ability to degrade congeners via attack on a 4-chlorophenyl ring. Reactivity preferences were also reflected in the products formed from unsymmetrical PCBs; thus MB1 attacked the 2,3-chlorophenyl ring of 2,3,2',5'-tetrachlorobiphenyl to yield 2,5-dichlorobenzoic acid, while H850 attacked the 2,5-chlorophenyl ring to yield 2,3-dichlorobenzoic acid and a novel metabolite, 2',3'-dichloroacetophenone. Furthermore, H850 oxidized 2,4,5,2',4',5'-hexachlorobiphenyl, a congener with no adjacent unsubstituted carbons, to 2',4',5'-trichloroacetophenone. The atypical congener selectivity pattern and novel metabolites produced suggest that A. eutrophus H850 may degrade certain PCB congeners by a new route beginning with attack by some enzyme other than the usual 2,3-dioxygenase.
5-Aminosalicylic acid (5-ASA), the presumed active moiety of sulfasalazine, has shown clinical efficacy when administered per rectum as initial therapy to patients with distal ulcerative colitis. We report the results of a randomized double-blind trial comparing nightly retention of a 4-g 5-ASA enema with continued administration of hydrocortisone enemas in 18 patients with persistent active distal ulcerative colitis after at least a 3-wk course of treatment with 100-mg hydrocortisone enemas with or without oral sulfasalazine. Continuation of hydrocortisone enemas rather than placebo was used in the control group to reflect the realistic alternative therapy likely to be employed in current practice. Response to therapy was assessed after 3 wk by comparing pretreatment and posttreatment point scores of clinical, sigmoidoscopic, and histological severity. Improvement in clinical score was achieved in seven of nine 5-ASA enema-treated patients versus one of nine hydrocortisone enema-treated patients (p less than 0.05). Sigmoidoscopic and histological improvement generally paralleled clinical improvement. We conclude that in patients with distal ulcerative colitis unresponsive to standard therapy, treatment with 5-ASA enemas results in significant short-term clinical and sigmoidoscopic improvement in a majority of cases. Moreover, a significantly greater number of refractory patients improve when switched to 5-ASA enemas than when continued on standard therapy.
While deficiences of trace metals and essential fatty acids are rare in humans fed orally, the widespread use of total parenteral nutrition (TPN) has increased the likelihood of encountering these deficiences. A 14-year-old boy, with total villous atrophy of the small intestine, suffered from severe malnutrition and was placed on a conventional TPN regimen. Although not immediately recognized, he rapidly developed deficiencies of zinc, copper and essential fatty acids. Careful monitoring of the course of the illness and the responses to sequential treatments with zinc, lipid, and copper given intravenously allowed examination of the effects of the deficiencies on skin, intestine, liver, and hemopoietic systems and helped to establish normal requirements for the metals. The progress of the illness suggested that patients with intestinal malabsorption may be especially at risk of developing some of these lesser known complications of TPN.
In dispersed acinar cells prepared from guinea pig pancreas, peptides isolated from amphibian skin (caerulein, bombesin, litorin, and physalaemin) as well as eledoisin, a peptide isolated from the posterior salivary gland of a Mediterranean octopod, increased outflux of 45Ca, release of bound 45Ca, accumulation of cyclic GMP, and release of amylase. In addition, bombesin, litorin, physalaemin, and eledoisin each increased the initial uptake of 45Ca by dispersed acinar cells, whereas C-terminal octapeptide of porcine cholecystokinin (CCK-OP) and carbamylcholine did not increase the initial uptake of 45Ca but, rather, abolished the increase caused by the other agents. None of the actions of these amphibian peptides was altered by concentrations of atropine sufficient to abolish the effects of muscarinic cholinergic agents. None of the amphibian peptides altered cellular cyclic AMP or the increase caused by secretin or porcine vasoactive intestinal peptide (VIP). Acinar cells preincubated with 45Ca plus bombesin showed the same rate of release of 45Ca as did control cells and this rate was not altered by adding bombesin but was increased fivefold by adding CCK-OP. In terms of their chemical structures as well as the potency and efficacy with which they alter acinar cell function, the amphibian peptides plus CCK-OP can be grouped into three pairs: caerulein with CCK-OP, bombesin with litorin, and physalaemin with eledoisin.
H2-Histamine receptor blocking agents metiamide and cimetidine were assessed in seven patients with Zollinger-Ellison syndrome (serum gastrin greater than 300 microgram/ml, basal acid output greater than 15 meq/h, ratio of basal acid output to maximal acid output greater than 0.5). Intravenous or oral administration of the drugs lowered acid secretion by at least 70% in all cases. Subsequent treatment of six patients for 3 to 15 months (oral therapy) and one patient for 1 month (intravenous therapy) showed that the drugs abolished symptoms in all seven, abolished diarrhea in five, allowed ulcer healing in six, and were well tolerated without adverse effects in seven. No patient failed to respond to the drug, although one died from tumor progression and two required total gastrectomy for complex reasons. The results indicate that patients with Zollinger-Ellison syndrome can be managed medically and, in light of current mortality trends, gain little from the extra risks attending total gastrectomy.
The activity of hexokinase was examined in brush-border membranes purified from rat intestine. Compared with homogenates, purified membranes exhibited a 20-fold increase in sucrase specific activity and a 15-fold decrease in hexokinase specific activity, which argues against the structural localization of hexokinase within the brush-border membrane.