Increased colonic motility during exposure to a stressful situation.

Colonic smooth muscle spike potentials and contractility were recorded during the periods of stress by a bipolar electrode-perfused catheter apparatus placed in the rectosigmoid colon. Healthy subjects and patients with the irritable colon syndrome (ICS) were exposed to three standardized stressful conditions: (1) ice-water immersion, (2) Stroop stimulus differentiation test, and (3) ball sorting. In healthy controls, colonic motility increased after the first exposure to ice-water immersion (P less than 0.05), Stroop test (P less than 0.05), or ball sorting. Respiratory frequency also increased after exposure to the stressful stimuli. However, repeat exposures to the stress tests did not stimulate colonic motility. An increase in colonic motility occurred in patients with the irritable colon syndrome pretreated with a placebo after exposure to ice water (P less than 0.05), Stroop Test, or ball sorting (P less than 0.05). However, after exposure to the stressful situations patients pretreated with chlordiazepoxide had a diminished increase in colonic motility or in respiratory frequency. These studies suggest: (1) in healthy controls habituation reduces the stress-related increase in colonic motility, and (2) in patients with the irritable colon syndrome, chlordiazepoxide decreases the stress-related increase in colonic motility.

Disorders of colonic motility in patients with diabetes mellitus.

Motility disturbances of the colon can give significant symptoms in patients with diabetes mellitus. Constipation is a common complaint in these patients. Diarrhea associated with a generalized autonomic neuropathy can be very troublesome. There is a disturbance in the gastrocolonic response to eating in patients with diabetes mellitus who have constipation. These patients have no postprandial increase in colonic motility. However, their colonic smooth muscle contracts normally to the exogenous administration of neostigmine or metoclopramide. Stool softeners used in combination with the smooth muscle stimulants (neostigmine or metoclopramide) are helpful in treating constipation in patients with diabetes mellitus. Diarrhea can be treated with loperamide or diphenoxylate. Biofeedback may be useful in treating incontinence associated with diarrhea in these patients.

Alpha-1-antitrypsin deficiency--a cause of cryptogenic liver disease in the elderly.

We report a 73-year-old woman with homozygous ZZ alpha-1-antitrypsin deficiency (AATD), micronodular cirrhosis, cholestatic jaundice, and emphysema. An elevated SGOT/SGPT ratio was noted in the absence of chronic alcoholism. ERCP demonstrated a normal extrahepatic biliary system and suggested obstruction of the intrahepatic ducts. An operative liver biopsy demonstrated periodic acid-Schiff-positive, diastase resistant intracytoplasmic inclusion bodies. This patient reminds us that metabolic causes of cryptogenic liver disease need to be considered, even in the elderly. We review briefly the literature concerning AATD and liver disease.

Metoclopramide to treat gastroparesis due to diabetes mellitus: a double-blind, controlled trial.

Ten patients with diabetic gastroparesis were selected for a randomized, double-blind, controlled trial of metoclopramide. Each patient had longstanding insulin-requiring diabetes mellitus and symptoms of gastric stasis. The patients were evaluated for the symptoms of gastric stasis and radionucleotide gastric emptying was measured before the patients entered the study and after they were given either metoclopramide or placebo treatment. Metoclopramide, 10 mg orally, stimulated an increase in the rate of gastric emptying (56.8% +/- 7.4%) in contrast to the response to placebo (37.6% +/- 7.7%) (p less than 0.01). The overall symptoms and symptoms of vomiting were markedly reduced during metoclopramide treatment in contrast to those during placebo treatment. Before the study five patients were constipated (less than three bowel movements per week); during metoclopramide treatment the patients' bowel habits were improved. There was a poor correlation between improved gastric emptying and decreased symptoms. Metoclopramide may improve symptoms of diabetic gastric stasis through two mechanisms: its peripheral effect on gastric smooth muscle, which increases gastric emptying; and its central effects on the chemoreceptor vomiting zone, which decrease nausea.

Abnormal colonic motility in progressive systemic sclerosis.

Progressive systemic sclerosis alters smooth muscle function throughout the gastrointestinal tract. In 10 consecutive patients with the disease, colonic spike activity and contractile activity were measured after a 1000-kcal meal, intramuscular injection of neostigmine, or intravenous injection of metoclopramide. The 1000-kcal meal stimulated a significant increase in spike and contractile activity in normal subjects. Nine of the 10 patients had no increase in motility after eating. Neostigmine or metoclopramide stimulated colonic spike (p less than 0.01) and contractile (p less than 0.02) activity in normal subjects and stimulated colonic motility (p less than 0.01) in four of 10 patients with less severe systemic manifestations of the disease (Group 1). The drugs had no effect on patients with severe progressive systemic sclerosis (Group II). The patients with severe scleroderma had significant gastrointestinal roentgenographic abnormalities and severe cardiac, renal, or pulmonary dysfunction. Four of six Group II patients died from the disease; all four had marked smooth muscle atrophy in the colonic wall. These findings suggest that the gastrocolonic response is absent early in the disease process and that the smooth muscle atrophy occurring with progression of the disease may lead to a more severe colonic motor disturbance.

Colonic dysfunction in diabetes mellitus.

Colonic myoelectrical and motor activity were measured in 12 patients with diabetes mellitus. Diabetic patients with severe constipation were compared to diabetics with mild or no constipation. Gastric emptying and peripheral nerve conduction studies were performed in all patients. Normal subjects had a rapid increase in colonic spike and motor activity (P < 0.001) within the first 30-min postprandial period. Diabetic patients with mild constipation had a postprandial increase in colonic motility; however, the response was delayed to 60-90 min after eating. Diabetic patients with severe constipation had no postprandial increase in colonic motility. There was no correlation between colinic motility and gastric emptying of a liquid meal (r = 0.23) (P > 0.05) or peripheral nerve conduction (r = 0.36) (P > 0.05). Neostigmine (0.5 mg, intramuscularly) or metoclopramide (20 mg, intravenously) increased colonic spike (P < 0.005) and motor (P < 0.005) activity in all diabetic subjects regardless of their symptoms. These studies suggest that patients with diabetes mellitus and severe constipation may have an autonomic neuropathy which leads to an absent postprandial gastrocolonic response.

Inhibition of postprandial colonic motility after ingestion of an amino acid mixture.

Previous studies suggested that the ingestion of a mixture of amino acids inhibited the fat-stimulated increase in colonic motility. This study determine the effect of the ingestion of an amino acid mixture on the postprandial distal colonic spike potential (SP) response to a standard 1000-calorie meal in normal subjects and in patients with the irritable bowel syndrome. The distal colonic response was measured following a standard meal with and without the preadministration of a protein hydrolysate solution. After the meal, normal subjects had their maximum response within the first 30-min postprandial period (41.0 +/- 6.3 SP/30 min). Spike activity returned to fasting activity by 60 min. Most patients with irritable bowel syndrome did not have a significant early postprandial distal colonic spike response (P > 0.05), but all patients had a large late increase in spike activity occurring 60-90 min postprandially (50.0 +/- 5.0 SP/30 min) (P < 0.001). Ingestion of the protein hydrolysate solution prior to the meal resulted in suppression of the early colonic spike response in normal subjects (P < 0.01) and the late colonic spike response in the irritable bowel patients (P < 0.01). This study suggests that amino acids can modulate postprandial colonic motility and that dietary alteration may be beneficial in the irritable bowel syndrome.

The gastrocolic response: evidence for a neural mechanism.

The aim of this study is to determine the effect of anticholinergic therapy on the gastrocolonic response to a standard meal or its major constituent fat. A rapid increase in rectosigmoidal spike activity occurs after ingesting the standard meal or the fat meal (P less than 0.01). Distal colonic motility returns to fasting levels 50 min after both meals. There is no further increase in spike activity after the 1000-calorie meal, but spike activity increases again 70 min after ingesting the fat (P less than 0.02). The anticholinergic drug, clidinium bromide, inhibits the early increase in spike activity after both meals. However, the anticholinergic has no effect on the delayed peak of activity following the ingestion of fat. This study suggests that (a) the early gastrocolic response to a standard meal and a fat meal is cholinergically mediated and (b) the late increase in rectosigmoidal motility occurs only after fat ingestion and may be controlled by other neural mediators or possibly the gastrointestinal hormones.

Adenocarcinoma of the stomach with common variable immunodeficiency syndrome.

Two patients had adenocarcinoma of the stomach in association with common variable immunodeficiency syndrome. There has been an increased prevalence of malignancy in this late-onset immunodeficient state. Similar to five previously reported cases, our patients had gastric carcinoma as a late complication. Further documentation of this association stresses the need for long-term follow-up in this premalignant condition.