Clostridium difficile colitis secondary to intravenous vancomycin.

Nearly every known antibiotic has been implicated as a cause of Clostridium difficile colitis. We report the first case resulting from monotherapy with intravenous vancomycin. The patient was on chronic hemodialysis and was treated with intravenous vancomycin for presumed cervical osteomyelitis. After 29 days of therapy he developed abdominal pain and diarrhea and his stool was found to contain both C. difficile and cytotoxin. The patient responded with symptomatic and microbiological recovery to withdrawal of the drug and treatment with oral metronidazole. The prolonged elevation of serum vancomycin levels in patients with renal failure may predispose them to the development of C. difficile colitis.

The advantages of the 30-cm flexible sigmoidoscope over the 60-cm flexible sigmoidoscope.

To determine the optimal length of the flexible fiberoptic sigmoidoscope we performed a randomized, blinded comparison study of the standard 60-cm instrument with a prototype 30-cm instrument with identical design features. Ninety-six male patients referred for symptom evaluation underwent examination with both instruments in random order by different examiners; positive examinations were followed by colonoscopy or surgery. Performance of the 30-cm sigmoidoscope compared with the 60-cm instrument revealed that the former was significantly more likely to yield a complete examination (74 vs. 32 examinations, p less than 0.002), took less time to perform (6.4 vs. 9.8 min, p less than 0.0001), and was more acceptable to patients and physicians. The 30-cm instrument was not significantly less effective than the 60-cm instrument in detecting polyps (21 vs. 25), adenocarcinoma (six for each), and inflammatory lesions. For these reasons, we conclude that the 30-cm flexible sigmoidoscope has a role in the evaluation of colorectal complaints.

Failure of cimetidine in Zollinger-Ellison syndrome.

Both the pharmacokinetics and the pharmacodynamics of cimetidine were investigated in three patients with Zollinger-Ellison syndrome, who were unresponsive to conventional dosing regimens. Doses employed in these patients ranged from 2400 to 5400 mg daily. The poor response to oral cimetidine, as measured by acid secretion and gastric pH, was associated with subtherapeutic and unreliable cimetidine serum concentrations. The response to intravenous cimetidine was only a transient suppression of gastric secretion. The failure of cimetidine to control gastric hypersecretion in these patients was attributed to both a diminished oral bioavailability and a decreased pharmacologic response to the drug.

H2-Histamine receptor blocking agents in the Zollinger-Ellison syndrome. Experience in seven cases and implications for long-term therapy.

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.

Hyperhistaminemia and hyperchlorhydria in basophilic granulocytic leukemia.

A patient with basophilic granulocytic leukemia had hyperhistaminemia, hyperchlorhydria and gastroduodenal ulceration. Because the patient's whole blood, plasma, and urinary histamine levels were increased and the serum gastrin was normal, it was concluded that endogenous hyperhistaminemia was responsible for an ulcerogenic diathesis clinically indistinguishable from that seen in the Zollinger-Ellison syndrome.

Intestinal folate absorption. II. Conversion and retention of pteroylmonoglutamate by jejunum.

These studies were designed to determine whether pteroylmonoglutamic acid (PGA) at physiologic concentrations is transported across the small intestine unaltered or is reduced and methylated to the circulating folate form (5-methyltetrahydrofolate [5-MeFH(4)]) during absorption. [(3)H]PGA was incubated in vitro on the mucosal side of rat jejunum. Of the folate transferred to the serosal side, the percent identified as 5-MeFH(4) by DEAE-Sephadex chromtography was inversely related to the initial mucosa PGA concentration: at 7, 20, and 2,000 nM, 44%, 34%, and 2%, respectively, was converted to 5-MeFH(4). In contrast, less than 4% of the folate transferred across ileal mucosa was 5-MeFH(4) when the initial mucosa concentration was 20 nM. Specific activity of dihydrofolate (DHF) reductase, the enzyme responsible for converting PGA to tetrahydrofolic acid, was measured in villus homogenates and was significantly greater in the jejunum than in the ileum. 1,000 nM methotrexate (MTX), a DHF reductase inhibitor, markedly inhibited PGA conversion to 5-MeFH(4) by the jejunum. Studies of transmural flux, initial rate of mucosal entry (influx) and mucosal accumulation (uptake) of folate were also performed. Although MTX did not alter the influx of PGA, MTX decreased jejunal mucosal uptake but increased transmural movement. Transmural folate movement across ileal mucosa was greater than across jejunal mucosa although mucosal uptake was greater in the jejunum than in the ileum. These results could explain previous studies which have failed to identify conversion of PGA to 5-MeFH(4) when intestinal preparations have been exposed to higher and less physiologic concentrations of PGA. Further, these studies suggest that 5-MeFH(4) may be retained by the jejunal mucosa.