Major abdominal operations on elderly patients.
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Biomedical subjects
Publications and source records attributed to M Daly.
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Previous reports have observed a fall in antithrombin III (AT III) concentration in patients receiving L-asparaginase as part of acute lymphatic leukaemia (ALL) induction therapy. The aim of this study was to define any qualitative changes in AT III that might arise during the course of L-asparaginase therapy and predispose to coagulopathy. Serial AT III profiles were studied in 12 patients with ALL receiving a course of L-asparaginase for 21 consecutive days as part of induction therapy. AT III isoforms were examined by isoelectric focusing in polyacrylamide gels (IEF/PA) and immunoblotting, and no changes were observed throughout the study period. Contrary to expectation, AT III antigen was significantly increased on treatment, while AT III activity remained unchanged. Fibrinogen levels, in contrast, fell considerably by 1 week of therapy and had not reverted to pre-treatment values 1 week after completion of asparaginase. No coagulation or bleeding disorders were observed during or after the study period.
We have demonstrated the value of immunoblotting techniques for the examination of the variant forms of plasma proteins. Furthermore, by preincubation of samples with the appropriate enzymes or ligands it is possible, using immunoblotting, to examine the molecular basis and functional significance of plasma protein microheterogeneity.
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The antithrombin III (ATIII) isoform pattern of a number of serum and plasma samples was analysed by isoelectric focusing and immuno-blotting. A novel ATIII isoform pattern which was observed in 4/80 children with acute lymphatic leukaemia (ALL) and in 1/4 children with Ewing's sarcoma, has been shown by family studies to be due to a mutant form of ATIII (AT Dublin) in the heterozygous state. The coagulation properties of AT Dublin heterozygotes were normal. In addition the immunological and activity levels of their ATIII were normal. The effects of thrombin and heparin on the mutant ATIII were similar to controls. Neuraminidase treatment reduced the ATIII isoforms to one in controls and two in the mutant. Two-dimensional gel analysis showed the mutant ATIII to have an identical molecular size distribution to the normal form. This mutant is, thus, most likely due to an amino acid substitution giving a more basic molecule that is clinically silent (at the coagulation level). It may be of interest that the frequency of AT Dublin in the ALL group is significantly higher than in the control group (3/430) studied (P less than 0.001).
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In a study involving three centers, 105 patients with duodenal ulcer proven by endoscopy were randomly assigned to treatment with either the H+, K+, ATPase inhibitor omeprazole (20 mg or 40 mg taken as a single morning dose), or ranitidine (150 mg morning and night). It was a double-blind study using a double-dummy technique. Clinical assessment and laboratory investigations were carried out at 2, 4, and 8 weeks; endoscopy was done at 2 weeks, and if not healed, at 4 and 8 weeks. The patients in the three treatment groups were well matched. Significantly more patients treated with omeprazole healed compared with ranitidine at 2 weeks (p = 0.007) and at 4 weeks (p = 0.007), but there was no statistically significant difference between the two omeprazole groups. Pain was of similar severity at the start in all groups, but patients treated with omeprazole had fewer days with pain (median values being omeprazole 20 mg: 2 days; omeprazole 40 mg: 1 day; ranitidine: 7 days). The difference between the combined omeprazole groups and ranitidine was significant (p less than 0.02). There was also a tendency towards less severe daytime pain on omeprazole during the first week. The difference was statistically significant between omeprazole (40 mg) and ranitidine for days 2-7 (p less than 0.01). No change in laboratory screen attributable to drug treatment occurred. After healing, 79 patients entered a 6-month follow-up study with endoscopy at 3 and 6 months or whenever symptoms occurred. After 6 months relapses occurred in 14/24, 19/23, and 15/25 after 20 mg omeprazole, 40 mg omeprazole, and ranitidine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
The non-fatal deliberate taking of overdoses in Cork city during 1982 was investigated from records in the general hospitals. In one of the hospitals, those attending after an overdose were personally interviewed. For both sexes, the greatest incidence of overdoses was in the younger groups; for females, there was a seasonal variation. Those taking overdoses were grouped by electoral wards, and the social characteristics of these wards determined. The frequency varied greatly throughout the city; some wards, particularly in corporation northern estates and part of the city centre, showed a rate of up to three times the average; these areas were the most likely to show social deprivation.
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Microheterogeneity of antithrombin III (ATIII) was examined in pooled normal human plasma and serum by IEF/PA and immunoblotting techniques. A pattern consisting of 8 bands varying in isoelectric point from 4.7 to 5.2 was observed in citrated plasma following IEF in a pH range of 4-6. A similar pattern was observed in all 149 healthy adults examined. The reactivity of ATIII with heparin or, thrombin was investigated using this technique. Characteristic shifts of the banding pattern to the anode or, cathode respectively were observed.
Regional myocardial perfusion was measured in 32 patients with the xenon-133 washout technique at rest and after 5 mg of intracoronary papaverine. Areas of decreased perfusion and/or decreased vasodilation were identified visually from computer-generated functional images. The locations of arteries and stenoses, obtained from identically positioned cineangiograms, were overlaid on the functional images. Perfusion rates for 62 myocardial regions were calculated and correlated with the percentage of stenosis. There was no association between degree of stenosis and perfusion at rest. Regional myocardial perfusion increased after papaverine in regions supplied by coronary arteries without stenoses (0% to 25%), 88.6 +/- 4.7 ml/min/100 gm. This increase was significantly greater (p less than 0.001) than the increase in regions supplied by 51% to 75% stenoses (23.7 +/- 6.3 ml/min/100 gm), or 76% to 99% stenoses (12.9 +/- 6.3 ml/min/100 gm), or 100% stenoses (2.5 +/- 3.8 ml/min/100 gm). Thus there was an inverse relationship between the increase in myocardial perfusion stimulated by papaverine and the degree of coronary artery stenosis measured angiographically. In regions supplied by two stenoses in series, vasodilation produced less of an increase than a single stenosis of a similar degree.
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Three hundred male Irish alcoholics were selected from 508 consecutive alcoholic admissions to hospital. Using well defined diagnostic criteria, they were divided into three subgroups (1) primary alcoholics, (2) alcoholics with secondary affective disorder and (3) those with primary affective disorder and secondary alcoholism. Although the three groups reported differences in past history and family history of affective disorder and in time spent in hospital for both alcoholism and affective disorder, there was little to distinguish them in behaviour associated with alcoholism or in family history of alcoholism. The implications of these findings and their significance for the relationship of affective disorder and alcoholism are discussed.
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Six patients with extensive polyostotic Paget's disease were treated for 3 months with dichloromethane diphosphonate (CL2MDP; 1600 mg/day, orally). Serum alkaline phosphatase and urinary hydroxyproline excretion decreased 60-80% in each patient. Blood ionized calcium (ca++) and immunoreactive PTH (iPTH) were measured weekly during the first month of therapy and monthly thereafter. As an index of parathyroid function, PTH secretory reserve was assessed by EDTA infusions before treatment, at the end of treatment, and 3 months after Cl2 MDP therapy was stopped. Before therapy, iPTH and Ca++ were normal in all patients. During treatment, Ca++ decreased and iPTH increased in all patients; mean iPTH approximately doubled (95% confidence limits, 1.5- to 2.7-fold increase). At the end of 3 months of treatment, EDTA infusion raised iPTH in each patient to a level higher than that in the control infusion, indicating augmented PTH secretory reserve. Ca++, iPTH, and the iPTH response to EDTA-induced hypocalcemia returned toward baseline by 3 months after the end of CL2MDP treatment. The results indicate that secondary hyperparathyroidism developed as a result of Cl2MDP therapy. The cause of the parathyroid-gland adaptation is not known; the hyperparathyroidism is, however, at least partly reversible. Cl2MDP inhibits bone resorption while allowing bone mineralization to continue; this differential effect could lead to the hypocalcemia and parathyroid hyperfunction.
Gated blood pool radionuclide ventriculography provides a means for obtaining repeated studies of both cardiac ventricles with a single dose of radionuclide. Quantitative assessment of right ventricular (RV) function using this technique has been complicated by several technical problems. We describe a new method of RV blood pool analysis which attempts to solve these problems using well-established concepts for left ventricular (LV) blood pool analysis: (1) variable regions of interest; (2) computer edge detection with operator intervention; and (3) computer selected background. Results showed a strong linear correlation between gated first pass RV ejection fraction (RVEF) and the gated blood pool RVEF (n = 22; r = 0.93; blood pool RVEF = 0.03 + 0.89 X first pass RVEF; Sy.x = 0.04). There was also a strong linear correlation between LV and RV stroke counts in patients without valvular regurgitation, intracardiac shunts, or ventricular aneurysms (n = 19; r =0.86; RV counts = 72 + 0.94 X LV counts; Sy.x = 116). In terms of both of these validation standards this method proved superior to three published methods of RV blood pool analysis that used hand-drawn regions, and is suitable for analysis of rest, exercise, and intervention studies of RV function.