Although constipation is a well-known side effect of calcium channel blockers such as verapamil, this side effect has not been evaluated in a quantitative manner. In a double-blind, randomized, crossover trial, the effect of verapamil (240 mg/day) was compared to placebo in 15 normal male volunteers. Subjects recorded their bowel movements and any side effects. Scintigraphy was used to quantitate gastric emptying, small intestinal transit, and colonic transit. In the study period of four days, verapamil did not change the frequency, consistency, or passage of bowel movements. A significantly increased number of side effects was noted during verapamil treatment--notably abdominal pain and dry mouth. The slope of gastric emptying was not significantly different for verapamil (0.012 +/- 0.02) than for placebo (0.013 +/- 0.001). Distal ileum filling was also not different for verapamil (0.41 +/- 0.13%/min) than placebo (0.33 +/- 0.05%/min). Progression of the colonic geometric center was significantly delayed at 48 hr by verapamil (5.2 +/- 0.4 vs 6.2 +/- 0.23; P less than 0.01). This study suggests that the constipating effect of verapamil is due to a delay of colonic transit and not due to an effect on upper gastrointestinal transit.
We have shown that the contact (kallikrein-kinin) system is involved in the pathogenesis of experimental enterocolitis. We now investigate activation of the contact and coagulation pathways, platelets, and neutrophils in active and inactive ulcerative colitis patients as compared to normal controls. In active ulcerative colitis patients, a significant decrease of plasma prekallikrein, high molecular weight kininogen, and C1 inhibitor levels was observed as compared with controls, as well as prekallikrein activation on western blots. Significant elevation of prothrombin fragment (F1 + 2), which indicates thrombin generation, and elastase-alpha 1-antitrypsin complexes, reflecting neutrophil activation, were found in patients with active disease. Plasma beta-thromboglobulin, a marker of platelet activation, was elevated in both active and inactive disease and appears to be a feature of ulcerative colitis. Activation of contact and coagulation pathways, as well as neutrophils, may mediate inflammation in the active phase of ulcerative colitis.
The fibrinolytic system was studied in 46 patients with acute leukaemia at diagnosis. Untreated patients (with the sole exception of the M3 subgroup) showed an inhibition of fibrinolytic activity, measured by the euglobulin lysis time and area. This inhibition was accompanied by reduced t-PA antigen and t-PA inhibitor activity. No correlation was found between the above-mentioned fibrinolytic parameters and the biochemical haematological values considered, nor with clinical and/or laboratory features of DIC, fever, liver failure. The decrease in immunological plasminogen and functional alpha 2-antiplasmin, showed a significant correlation with the presence of clinical and/or laboratory signs of DIC, as diagnosed on the basis of concomitant increase in fibrin monomers, plasmatic fibrinopeptide A and serum FDP.
Aspirin and nonsteroidal antiinflammatory drugs have been implicated in the pathogenesis of gastrointestinal hemorrhage. To evaluate their impact on inpatients, charts from Temple University Hospital with a discharge ICD-9 code which included upper gastrointestinal hemorrhage during a one-year period were reviewed. Aspirin and/or nonaspirin nonsteroid antiinflammatory drug (NSAID) use was identified in 34 patients (19 daily users and 15 intermittent users). Sixty-seven patients who bled, but did not use these agents, served as controls. Daily NSAID users were older than intermittent users and controls (P < 0.05). A higher frequency of bleeding ulcers was associated with NSAID use. Patients using NSAIDs spent more time in intensive care than controls (median 1 day vs 0 days). Daily users had a higher transfusion requirement (4 units) than non-users (0 units; P < 0.05). This study suggests that NSAID use has a substantial impact on health care resource utilization in patients admitted to an urban hospital for upper gastrointestinal hemorrhage.
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