Biomedical subjects
Publications and source records attributed to D M McCarthy.
Rhizopus oryzae was the causative organism in a fatal case of rhinocerebral and then pulmonary mucormycosis in a patient cured of her underlying leukaemia by bone marrow transplantation. We discuss the risk factors involved and the need for maintaining a high index of suspicion of fungal infection in the late post-transplant period.
Physicians using nonsteroidal anti-inflammatory drugs (NSAIDs) are concerned that effective anti-inflammatory doses cause few gastrointestinal side effects. Among the causes of discontinuing therapy, upper gastrointestinal symptoms and the development of 'ulcer' complications are major concerns; endoscopic findings in asymptomatic users are not. Initial symptoms, poorly correlated with endoscopic findings, are relieved by anti-ulcer drugs and ameliorate with time of NSAID use in most patients. Symptoms accompanied by epigastric tenderness, or unrelieved by H2 antagonists, or resulting in cessation of NSAID therapy are more predictive of underlying ulcers. Complications probably arise in several ways, including as hemorrhages due to interference with platelet function, and as complications due to exacerbations of underlying ulcer disease or of ulcers caused by the NSAIDs. Pathogenesis and effective prophylaxis (yet to be established) may therefore vary in different patients, a clinical dilemma.
Eight autistic patients with steatorrhoea, hypocalciuria, and alleged behavioural improvements on gluten restriction, were fed ordinary diets plus 20 g gluten/day for 4 weeks. None of the patients had any significant change in body-weight or bowel habit as a result of gluten challenge, nor were any histological abnormalities detected on jejunal biopsy. The data suggest that the steatorrhoea and hypocalciuria seen in some autistic subjects cannot be accounted for by the presence of coeliac disease. Furthermore, these patients should not be confined to gluten-free diets, unless rigorous behavioural studies demonstrate a statistically significant improvement in behaviour as a result of the diet, or deterioration during challenge.
Diabetes mellitus, steatorrhea, cholelithiasis and a tumor distorting the duodenum prompted a work-up for somatostatinoma in a 52-year-old man. The responses of pancreatic B-cells but not of A-cells to nutrient stimuli were inhibited, and growth-hormone release was suppressed, suggesting somatostatin resistance in some target tissues. Plasma somatostatin-like immunoreactivity ranged from 9000 to 13,000 pg per milliliter (normal: 88+/-8, mean +/- S.E.M.) and was distributed in four molecular forms, including free somatostatin. The primary tumor contained 5 microgram of somatostatin-like immunoreactivity per milligram of wet tissue, distributed in three of the molecular forms noted in plasma. Plasma calcitonin was also elevated (4650 pg per milliliter; normal: less than 120). Immunocytochemical studies showed that cells of the primary tumor contained somatostatin and calcitonin but no other peptide hormones. Only somatostatin was present in the metastases. Somatostatin was localized electron microscopically in all secretory granules, irrespective of size and shape, whereas calcitonin was present only within a single subpopulation of small granules in the same cells.
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Controlled studies indicate that both high-dose antacids and cimetidine can be highly effective. Thus, the choice must rest on other considerations--acceptability, compliance, side effects, and cost. The problem of recurrence is addressed.
Of 20 patients with the Zollinger-Ellison syndrome who underwent visceral angiography, only 3 had unequivocally positive studies for primary pancreatic tumors; another 5 patients had equivocal diagnoses based on adequate studies. Eight patients had no abnormalities of any kind detected by angiography (except for an obstructed splenic vein in one patient). Five patients were shown to have hypervascular liver metastases. These results contrast with most reports of findings in islet cell tumors in general and specifically with the findings in several small series of the Zollinger-Ellison syndrome.
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Creatine kinase (CK), lactic dehydrogenase (LDH), and more recently their isoenzyme determinations (CK-MB and LDH1) have been useful adjuncts in verification of myocardial injury. To determine whether DC cardioversion affects these serum enzyme levels, we recorded total CK, total LDH, CK-MB, and LDH1 levels serially during 24 hours following elective DC cardioversion in 18 patients without cardiac ischemia. New postcardioversion elevations in total CK and total LDH levels were small and occasional: CK (one of 18 patients), LDH (four of 18 patients). Elevations of CK-MB or LDH1 following cardioversion did not develop in any of the patients. Therefore, new CK-MB or LDH1 elevations associated with arrhythmias must result from myocardial damage to DC cardioversion.
While deficiences of trace metals and essential fatty acids are rare in humans fed orally, the widespread use of total parenteral nutrition (TPN) has increased the likelihood of encountering these deficiences. A 14-year-old boy, with total villous atrophy of the small intestine, suffered from severe malnutrition and was placed on a conventional TPN regimen. Although not immediately recognized, he rapidly developed deficiencies of zinc, copper and essential fatty acids. Careful monitoring of the course of the illness and the responses to sequential treatments with zinc, lipid, and copper given intravenously allowed examination of the effects of the deficiencies on skin, intestine, liver, and hemopoietic systems and helped to establish normal requirements for the metals. The progress of the illness suggested that patients with intestinal malabsorption may be especially at risk of developing some of these lesser known complications of TPN.
Thallium-201 myocardial perfusion scintigraphy was performed after exercise, 4 hours after exercise (redistribution) and after a separate rest injection in 87 patients undergoing coronary arteriography. Significant coronary lesions were present in 62 of the patients. Interpretation of the rest and redistribution scintiscans was the same in 69 patients, 45 of whom had coronary artery disease (CAD). In 16 of the 17 patients with CAD and differing interpretations, defects were present on redistribution scintiscans but not on rest scintiscans; 11 of these patients had evidence of prior transmural myocardial infarction and the other five had an occluded coronary artery supplying the region of the defect. Redistribution scintiscans were more sensitive than rest scintiscans for the detection of prior myocardial infarction (93% vs 54%; P less than 0.01). The increased sensitivity was confined to the detection of prior inferior myocardial infarctions. In 36 of 38 patients with persistent perfusion defects on 4-hour redistribution scintiscans, either a prior infarction or an occluded coronary vessel was present. Exercise scintiscans were compared with rest scintiscans or with redistribution scintiscans for the detection of CAD. The sensitivity was not significantly different with either technique (90% and 89%, respectively), but both scintigraphic techniques were more sensitive than exercise electrocardiography (66%, P less than 0.01). These data demonstrate that redistribution thallium-201 scintiscans may be substituted for conventional rest scintiscans, resulting in reduced cost and radiation exposure to the patient.
Sixty-one cases of the Zollinger-Ellison syndrome, encountered over a 2-year period, have been treated with cimetidine, half of them for over 1 year. Two-thirds of the patients responded to 300 mg of the drug every 6 hr by mouth. Others required up to 600 mg every 6 hr. In adequate doses the drug was highly effective: it controlled pain and dyspepsia, restored weight, abolished diarrhea, and allowed healing of ulcers and other inflammatory conditions. Missed or reduced doses led to rapid return of symptoms. Progression of the basic neoplastic process, with associated secretory drive, was unimpeded. Patient acceptance of the drug was 100 percent, and apart from minor transient abnormalities, gynecomastia (5 cases) and liver dysfunction (3 cases), which resolved while treatment continued, no serious adverse effects were seen. Of 61 patients 48 are still on the drug, 3 who were well controlled were treated surgically, 5 died for reasons unrelated to therapy, and 5 had significant problems. The drug provides an alternative to total gastrectomy and can be recommended with confidence for the suitably selected patients. The drug was also beneficial in some cases of the short bowel syndrome, systemic mastocytosis, and endogenous hyperhistaminemia due to leukemia.
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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.
In rats fed equal amounts of isocaloric high-protein (HPR) and low-protein (LPR) diets, studies were performed on the mucosal activities of enterokinase and alkaline phosphatase and on the activities of these enzymes and of trypsin in washings obtained from the contents of two standard 5 cm. segments of duodenum, located proximal (Segment I) and distal (Segment II) to the main pancreatic duct. Mean mucosal weights and tissue protein per segment were 1.3-fold higher in rats fed HPR diets. In Segment I, but not Segment II, mucosal activities per segment were higher in HPR for enterkinase (threefold) and alkaline phosphatase (twofold). In luminal washings trypsin did not differ between the two groups; in HPR luminal levels of enterkinase were significantly higher in Segment II and those of alkaline phosphatase were similarly elevated in Segment I. Irrespective of diet the major activity of both enzymes was in mucosal fractions. Studies of total activity of each enzyme showed that the enzymes behave rather similarly, with the major differences between the dietary groups discernible in Segment I. These data stress the importance of dietary protein content in intestinal enzyme adaptation and reveal regional variation in the responses of the different enzymes.
The activity of hexokinase was examined in brush-border membranes purified from rat intestine. Compared with homogenates, purified membranes exhibited a 20-fold increase in sucrase specific activity and a 15-fold decrease in hexokinase specific activity, which argues against the structural localization of hexokinase within the brush-border membrane.