A comparative study of the effects of four motor-stimulating agents on canine jejunal spike bursts. The use of a computer program to analyze spike burst spread

The intestinal myoelectric effects of four motor-stimulating drugs were compared in conscious dogs. Dogs were fed a standardized 400-kcal meal, and the myoelectric activity was monitored before and after drug administration. Graded doses of metoclopramide, cisapride, bethanechol, and cholecystokinin (CCK) were compared by means of a computer program to identify spike bursts and determine their frequency, duration, and length of migration. Bethanechol and CCK produced the greatest increase in myoelectric activity in terms of spike burst frequency and duration but the least in terms of length of spike burst spread. Metoclopramide had minimal measurable myoelectric effects. Cisapride had the greatest effect on the length of spike burst migration but little effect on spike burst frequency and duration. The results suggest that cisapride is a more efficient prokinetic agent than bethanechol, CCK, or metoclopramide. The greater length of spike burst spread caused by cisapride was associated with a more rapid rate of transit along the monitored segment of bowel when compared with control. This confirms the correlation between length of spike burst spread and propulsive efficiency.     

A single night time dose of ranitidine in the acute treatment of gastric ulcer: a European multicentre trial.

Four hundred and twenty eight patients with endoscopically diagnosed gastric ulcers, randomly allocated to treatment with ranitidine 300 mg at night or ranitidine 150 mg twice daily, were evaluated in a double blind multicentre trial conducted in 10 European countries. After four weeks, complete ulcer healing was observed in 138 of 211 patients (65%) treated with ranitidine 300 mg nocte and in 155 of 217 patients (71%) receiving 150 mg bd. Cumulative healing rates at eight weeks were 90% and 93%, respectively. There was no statistically significant difference between the healing rates at either four or eight weeks. The treatment regimens were equally effective at rapidly reducing the incidence of ulcer related symptoms. Adverse events reported were minor and equally distributed between the two groups. The results of this trial show that 300 mg of ranitidine administered at night is an effective and safe alternative to the current twice daily regimen for the short term treatment of gastric ulcer.     

Two Epstein-Barr viral nuclear neoantigens distinguished by gene transfer, serology, and chromosome binding.

We recently identified, by means of cotransformation of LTK- cells, a region of the Epstein-Barr virus (EBV) genome (the BamHI K fragment) that encodes or induces an EBV nuclear neoantigen (EBNA) serologically related to the EBNA found in lymphoid cells carrying the entire EBV genome. We now find that a second EBV DNA fragment, BamHI M, is also able to give rise to cotransformed LTK- cells with stable expression of a nuclear antigen. The BamHI K and M fragments have no apparent DNA homology. Many human sera that are reactive to EBNA in Raji cells detect both antigens; however, certain anti-EBNA-positive human sera are discordant and react only with the BamHI M or only with the BamHI K nuclear antigen. Every Raji cell appears to express both "M" and "K" antigens; D98 Raji cells, a somatic cell hybrid, express only "K" antigen. The K antigen is found on metaphase chromosomes of LTK cells and Raji cells. The M-induced antigen is not located on chromosomes when the cells are in metaphase but is present as granules within the nucleus.     

Decreased expression of phospholipase C-beta 2 isozyme in human platelets with impaired function

Platelets from a patient with a mild inherited bleeding disorder and abnormal platelet aggregation and secretion show reduced generation of inositol 1,4,5-trisphosphate, mobilization of intracellular Ca2+, and phosphorylation of pleckstrin in response to several G protein mediated agonists, suggesting a possible defect at the level of phospholipase C (PLC) activation (see accompanying report). A procedure was developed that allows quantitation of platelet PLC isozymes. After fractionation of platelet extracts by high-performance liquid chromatography, 7 out of 10 known PLC isoforms were detected by immunoblot analysis. The amount of these isoforms in normal platelets decreased in the order PLC- gamma 2 > PLC-beta 2 > PLC-beta 3 > PLC-beta 1 > PLC-gamma 1 > PLC- delta 1 > PLC-beta 4. Compared with normal platelets, platelets from the patient contained approximately one-third the amount of PLC-beta 2, whereas PLC-beta 4 was increased threefold. These results suggest that the impaired platelet function in the patient in response to multiple G protein mediated agonists is attributable to a deficiency of PLC-beta 2. They document for the first time a specific PLC isozyme deficiency in human platelets and provide an unique opportunity to understand the role of different PLC isozymes in normal platelet function.     

Possible effect of secretor locus on plasma concentration of factor VIII and von Willebrand factor

A significant fraction (30%) of the genetically determined variance in plasma concentration of the von Willebrand factor antigen (vWf:Ag) has been shown to be related to ABH determinants. Individuals with blood group O, who have the highest amounts of blood group H substance, have the lowest concentration of vWf:Ag. The Lewis substances, Le(a) and Le(b), are biochemically closely related to the ABH substances as both can be produced from the same precursor substance. We studied the effect of the presence of the Lewis antigens on the plasma concentration of vWf:Ag and factor VIII antigen (VIII:Ag) in 323 individuals of different ABO groups from a series of twins and in 58 blood donors of blood group O. Among persons belonging to blood group O, those with the Le(a) antigen had a higher concentration of both vWf:Ag and VIII:Ag than individuals lacking Le(a). Le(a+b-) people are nonsecretors and Le(a-b+) people are secretors of ABH substance. Thus, the lowest concentration of vWf:Ag and VIII:Ag was found in group O secretors. The effect is most likely due to an effect of the secretor locus. This finding may be of importance for the detection of carriers of hemophilia A and for the diagnosis of type I von Willebrand disease.     

Colorectal cancer in patients under close colonoscopic surveillance

BACKGROUND & AIMS: Colonoscopic polypectomy is considered effective for preventing colorectal cancer (CRC), but the incidence of cancer in patients under colonoscopic surveillance has rarely been investigated. We determined the incidence of CRC in patients under colonoscopic surveillance and examined the circumstances and risk factors for CRC and adenoma with high-grade dysplasia. METHODS: Patients were drawn from 3 adenoma chemoprevention trials. All underwent baseline colonoscopy with removal of at least one adenoma and were deemed free of remaining lesions. We identified patients subsequently diagnosed with invasive cancer or adenoma with high-grade dysplasia. The timing, location, and outcome of all cases of cancer and high-grade dysplasia identified are described and risks associated with their development explored. RESULTS: CRC was diagnosed in 19 of the 2915 patients over a mean follow-up of 3.7 years (incidence, 1.74 cancers/1000 person-years). The cancers were located in all regions of the colon; 10 were at or proximal to the hepatic flexure. Although most of the cancers (84%) were of early stage, 2 participants died of CRC. Seven patients were diagnosed with adenoma with high-grade dysplasia during follow-up. Older patients and those with a history of more adenomas were at higher risk of being diagnosed with invasive cancer or adenoma with high-grade dysplasia. CONCLUSIONS: CRC is diagnosed in a clinically important proportion of patients following complete colonoscopy and polypectomy. More precise and representative estimates of CRC incidence and death among patients undergoing surveillance examinations are needed.     

Desensitization for sulfasalazine skin rash

Thirteen patients with inflammatory bowel disease and a documented allergy to sulfasalazine, manifested by skin rash with or without fever, were enrolled in a sulfasalazine-desensitization protocol. Twelve patients were successfully desensitized by using two concentrations of a liquid suspension of sulfasalazine. Four of thirteen patients developed a rash during the protocol. Although one patient refused further attempts at desensitization, the remainder completed the regimen successfully, despite recurrence of the rash on two occasions in one patient. No predilection to either fast or slow acetylator phenotype was found. This simple and convenient tolerance induction regimen may be used safely to desensitize most patients with sulfasalazine allergy manifested by skin rash with or without fever, despite recurrence of the rash during tolerance induction. Patients with serious reactions to sulfasalazine, such as agranulocytosis, toxic epidermal necrolysis, or fibrosing alveolitis, are not candidates for desensitization.