Williamson B. Strum

Effect of combined anticoagulation and low-dose aspirin treatment on upper gastrointestinal bleeding.

Multiple studies link the use of nonsteroidalantiinflammatory drugs (NSAIDs) with severe uppergastrointestinal bleeding (UGIB); the incidence of suchbleeding is 2-4%. One common regimen to assure patency after intracoronary stent placement requires ananticoagulant (warfarin) combined with aspirin as anantiplatelet agent. However, a 13-fold increase in therisk of UGIB occurs with long-term use of oral anticoagulants and NSAIDs. We retrospectivelyassessed the rate of UGIB in 138 patients who hadreceived coronary stents (group I, receiving heparinfollowed by warfarin in combination with aspirin) and 109 angioplasty patients without stents (groupII, receiving aspirin alone) between 1990 and 1994. UGIBwas identified by hematemesis or melena, which led togastrointestinal consultation. Patients were analyzed for multiple risk factors. UGIBoccurred in 28 of 138 group I patients (20%; 95% CI13.3-26.7%) and 0 of 109 group II patients (P ≤0.0001). Esophagogastroduodenoscopy (EGD) findings onthe 28 patients with UGIB included 13 patients with esophagitisor gastritis, 7 patients with gastric or duodenalulcers, and 8 patients with no identifiable source ofbleeding. UGIB occurred within a mean of 2.5 days of initiation of combination therapy. Ofpatients with UGIB, 10 required blood transfusion (meannumber of units 5.3). Previous history of peptic ulcerdisease, smoking, and use of antiulcer medication did not significantly differ between the twogroups. The concurrent use of anticoagulant and aspirinin patients with coronary stents creates a significantpotential for UGIB and should be used only with extreme caution.

Enzymatic reduction and methylation of folate following pH-dependent, carrier-mediated transport in rat jejunum

Intestinal transport of [3H] folate was studied using everted sacs of rat jejunum. The proximal small intestine transports folate against a concentration gradient by a system which is saturable, pH-dependent, energy-dependent, sodium-dependent, sensitive to temperature, and appears to be a common transport system for folate compounds. Chromatographic analysis of folate compounds in the serosal compartment after a 60 min incubation with folate in the mucosal medium in sodium phosohate buffer indicated that metabolism of folate to 5-methyltetrahydrofolate was extensive at pH 6.0 and negligible at pH 7.5. The percent conversion of folate to 5-methyltetrahydrofolate at pH 6.0 was reduced by increasing the concentration of folate in the mucosal medium, thus indicating saturation of the reduction and methylation process. These findings indicate that folate transport in rat jejunum occurs by an energy-dependent, carried-mediated system and that both folate transport and intestinal conversion of folate to 5-methyltetrahydrofolate are pH-dependent.

Hepatic uptake, intracellular protein binding and biliary excretion of amethopterin.

Abstract Transport of the folate antagonist, amethopterin, from plasma to bile was studied in the isolated rat liver. The hepatic uptake of amethopterin was a saturable process with a K m of 1.3 mM and V max of 11.1 μmoles/hr/g liver. The uptake process was energy dependent and was inhibited by folate. The drug was bound to a soluble protein in the liver which was identified as dihydrofolate reductase. After an initial delay the biliary excretion of amethopterin paralleled the hepatic uptake and 80 per cent of the drug was recovered in the bile after a 5-hour perfusion. Chromatography of bile revealed no conjugation or metabolism of amethopterin during transcellular transport. The drug was 70–120 times more concentrated in the bile than in the perfusion medium; in separate experiments the amethopterin in bile was available for intestinal absorption and 25 per cent of the drug was excreted in the urine 48 hr after peroral administration. These studies suggest that hepatic uptake and biliary excretion of amethopterin is an active carrier-mediated process and may be dependent on two separate energy-requiring systems for the uptake and biliary excretion of the drug.

Effect of Ethanol and Other Aliphatic Alcohols on the Intestinal Transport of Folates

The effect of ethanol and other aliphatic alcohols on the intestinal transport of 5-methyltetrahydrofolate and folic acid was examined using everted sacs from rat jejunum. Ethanol added to the mucosal medium inhibited the transport of both folate compounds in a parallel manner, and the inhibition increased with increasing ethanol concentration (0.5-10% v/v). Ethanol at 3% v/v in the mucosal medium caused: depression in the pH dependency of the active transport of 5-methyltetrahydrofolate; higher inhibition in the transport of low concentration (0.1 microM) than high concentration (10 microM) of 5-methyltetrahydrofolate, and inhibition in the active accumulation against a concentration gradient of 5-methyltetrahydrofolate and L-leucine. Methanol, propanol and butanol also inhibited the transport of the folate compounds; and in general, the inhibitory effect increased with the increase in the number of carbon atoms in the hydrophobic chain. This study indicates that ethanol and other alcohols inhibit the intestinal transport of folates, that the degree of inhibition is related to the concentration and chain length of the alcohol, that the inhibition is not specific for folates and finally that the mechanism of inhibition is multifactorial.

Effects of haem infusion on biliary secretion of porphyrins, haem and bilirubin in man

Abstract. Employing a continuous bile collection, we measured the bile secretion of porphyrins, haem (iron protoporphyrin IX regardless of oxidation state) and bilirubin in five healthy subjects. The baseline values for the flow of porphyrins in the bile were: 4·7 pL 1·9 nmol/h uroporphyrin, 27·3 pL 3·8 nmol/h coproporphyrin and 39·2 pL 11·7 nmol/h protoporphyrin. Bile haem flow was 59·7 pL 12·6 nmol/h, and that of bilirubin 23·8 pL 8·2 μmol/h. Following haem injection (6·4 μmol/kg) the flow of protoporphyrin but not of the other porphyrins was reduced, and the bile haem flow increased (232 pL 109·5 nmol/h), while the flow of bilirubin did not increase significantly. A few patients with representative porphyrias showed the expected increase in copro‐ and protoporphyrin in the bile. The patient with coproporphyria exhibited a bile flow of coproporphyrin of 1470 pL 133 nmol/h and of protoporphyrin of 334 pL 29 nmol/h; haem infusion significantly reduced the bile flow of both porphyrins (to 649 pL 101 for copro‐ and 215 pL 36 nmol/h for protoporphyrin). The patient with protoporphyria had an increased protoporphyrin flow, yet haem infusion caused no reduction in protoporphyrin flow (106 pL 7 after v. 81·4 pL 13 nmol/h before haem).

Endoscopic techniques in the diagnosis of gastric adenocarcinoma

At endoscopic examination of 7 exophytic, 20 infiltrative, and 11 ulcerating gastric carcinomas, correct visual diagnosis was made in 82%. Guided biopsy and brushing cytology together yielded a positive pathologic diagnosis in 84%. When endoscopic appearance, biopsy, and cytology were collated, a correct diagnosis was achieved in 97% of cases. Infiltrative and ulcerated lesions required the most assiduous study.

Incidence of advanced adenomas of the rectosigmoid colon three years and five years after negative flexible sigmoidoscopy in 4010 patients.

Flexible sigmoidoscopy is recommended for persons at average risk for colorectal cancer. A follow-up is advised in 3 to 5 years, although the outcomes are not well established. We designed a large, prospective study of an unselected population to measure the incidence of advanced adenomas at flexible sigmoidoscopy 3 and 5 years after an initial negative examination. Adenomas were considered advanced if they were villous, tubulovillous, high-grade dysplasia, adenocarcinoma, or ≥10 mm in size. We evaluated 8121 patients referred for flexible sigmoidoscopy and 4010 met the inclusion criteria. Group 1 had flexible sigmoidoscopy between 3 and 4 years and Group 2 between 5 and 6 years after a negative examination. Group 1 included 1300 patients with an incidence rate for advanced adenomas of 0.9% (12/1300) and Group 2 included 2710 patients with an incidence rate for advanced adenomas of 1.1% (30/2710). When the two group were subdivided by the presence or absence of a family history of a first-degree relative with sporadic colorectal cancer, the incidence rates for advanced adenomas between the populations were not different. Our data indicate incidence rates of 0.9 and 1.1% for advanced adenomas at flexible sigmoidoscopy 3 and 5 years, respectively, after a negative flexible sigmoidoscopy, with no impact from a family history.

Impact of a family history of colorectal cancer on age at diagnosis, anatomic location, and clinical characteristics of colorectal cancer

Background: Among the risk factors for colorectal cancer (CRC) is a family history of colorectal cancer. Reliable evidence is needed regarding the clinical characteristics of cancer in patients with this history to determine if a change in the diagnostic approach is needed.Aim of the Study: This study set out to determine specific clinical outcomes in patients with CRC with a family history of one first-degree relative with sporadic colorectal cancer compared to control patients with colorectal cancer but without the family history.Methods: We designed a case-control study of colorectal cancer registry data between 1988 and 1999. Patients with a family history of one first-degree relative with colorectal cancer were compared to those without the history with regard to four characteristics: age at cancer diagnosis, anatomic location of the cancer, presence of distal adenomas with proximal cancer, and stage of disease at diagnosis.Results: Nine hundred and twenty-one patients met the inclusion criteria. Family history was positive in 124 patients. The demography of the populations was similar, except for mean age, which was 65 yr for men with a family history and proximal cancer compared to 70 yr for their counterparts without the family history (p=0.03). The anatomic location of the cancer, presence of distal benign neoplasia when the cancer was proximal, and disease stage at diagnosis were not different between the groups.Conclusions: Men with a family history of sporadic colorectal cancer and proximal colon cancer were younger than men without the family history and proximal colon cancer. The overall results do not indicate that a change in the diagnostic approach is needed.

Impact of a family history of colorectal cancer on the prevalence of advanced adenomas of the rectosigmoid colon at flexible sigmoidoscopy in 3147 asymptomatic patients.

Flexible sigmoidoscopy is advised as a screening test for colorectal cancer for persons with a family history of late-onset colorectal cancer. The expected outcome for this approach is not well established. We designed a large, prospective study of an unselected population to assess the impact of a family history of one first-degree relative with colorectal cancer on the prevalence of advanced adenomas at screening flexible sigmoidoscopy. We evaluated 8121 patients referred for flexible sigmoidoscopy between 1997 and 1999 and 3147 patients met the inclusion criteria. The 3147 patients were divided into 210 with a family history of colorectal cancer and 2937 without a family history and analyzed for differences in the prevalence of advanced adenomas. Of the 210 with a family history, 3 had an advanced adenoma of the rectosigmoid colon (1.4%) Of the 2937 without a family history, 52 had an advanced adenoma of the rectosigmoid colon (1.8%), including 2 cancers. These differences were not significant. In conclusion, a family history of colorectal cancer had no impact on the prevalence of advanced adenomas in asymptomatic patients at screening flexible sigmoidoscopy. The prevalence rates for advanced adenomas and carcinomas of the rectosigmoid colon were low.

Electronic image of the monthSpontaneous Rectal Passage of a Colonic Angiolipoma After Colonoscopy With Forceps Biopsy

75-year-old man presented with a week-long hisAtory of constipation and left lower quadrant abdominal pain thatwas preceded by aweek of diarrhea and scant bright red blood per rectum. Initial work-up demonstrated anormal physical exam, completebloodcount, and comprehensive metabolic panel. Three view abdominal x-ray showed mild colonic dilatation. Subsequent computed tomography scan of the abdomen showed a 4.3 3.1 4.9 cm, well-defined, heterogeneous mass projecting into the lumenof thedescending colon (FigureA, arrow). This lesion was thought to be causing the patient’s symptoms with intermittent intestinal obstruction. Colonoscopy was performed, revealing a polypoid lesion with a surface nipple measuring 3.0 cm in the distal descending colon (Figure B). The surface appeared fibrous and was biopsied extensively. India ink was injected to mark the area. The biopsies showed colonic mucosa with focal ulceration and granulation tissue. The next day, the patient passed a fleshy mass per rectum while having a spontaneous bowel movement. He retrieved the specimen, and it was submitted for pathologic analysis. The specimen measured 6.7 5.2 2.0 cm and had the gross appearance of fat with focal hemorrhage. Microscopic analysis revealed an angiolipoma (Figure C). Follow-up sigmoidoscopy 1 week later showed an amorphous mass at the location of the pedicle (Figure D). At the last flexible sigmoidoscopy 3 months later, the mass was completely resolved, with no intervention in the interim (Figure E). Angiolipomas are common, benign subcutaneous masses that usually present on the trunk and limbs and are painful. Angiolipomas are distinguished from lipomas by the increased groups of small capillaries in the lipoma that resemble hemangiomas. They are quite rare in the gastrointestinal tract, with only 7 cases of angiolipomas involving the colon having previously been reported in the literature. Because of their benign nature, colonic angiolipomas are typically left untreated unless they are causing symptoms.