Bayes theorem and conditional dependence of symptoms: different models applied to data of upper gastrointestinal bleeding.
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Biomedical subjects
Publications and source records attributed to C Ohmann.
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Perioperative risk research with biomedical (biochemical, physiological) methods must grow up as a main topic in surgical research. However, operative risk has also to be analysed with methods of clinimetrics, such as formal (objective) decision making and epidemiology. Only by this way a convincing practical dimension is added to basic scientific statements. ASA-classification of the preoperative physical status is a global index for estimating the operative risk. It contains objective findings, subjective impressions and the final clinical judgement. For this reason it is so flexible. For a multicentre trial on perioperative risk and histamine an empirical index was constructed using both the ASA-classification and the Mannheim-Munich risk check list.
In this paper standardized and quantitative definitions of perioperative risk and risk factor using probabilities are given. A calculation of risk and risk factors is performed using data from a study on perioperative risk in colon resection and a study on a preoperative risk check in general surgery. The problem of one risk factor, a combination of two risk factors and the use of many risk factors to quantify preoperative risk is discussed. Confidence intervals are recommended as a standard method for presenting statistical results on perioperative risk.
Histamine, among various "biologic-physiologic" abnormalities, is considered as a pathogenetic factor in chronic duodenal ulcer disease. The 10-30 per cent difference between its concentration in gastric and duodenal mucosa of patients compared to healthy controls, however, has to be demonstrated to be specific for the disease. It has to be shown to be neither a methodological artefact nor a common effect, concomitant factor or consequence. This study, after a series of pathogenetic trials examines systematic errors (biases) in the fluorometric-fluoroenzymatic histamine assay under the conditions of field studies including tests on specificity over a time period of 10 years. It concentrates on sensitivity (detection limits) and specificity of a standard technique described herein. A modified Shore procedure for large scale assays in human biopsies was developed including reference luminescence values for all reagents, cleaning material and glassware, reduction of OPD concentration to 0.05%, purification of n-heptan, omission of centrifugation steps in the extraction procedure and use of 2 ml 1 M HClO4 in the homogenization step to prevent losses of histamine due to adherence to the mechanical homogenizer. This assay was sensitive enough to measure histamine without difficulty in any biopsy taken. The detection limit was 3 ng/biopsy, but the smallest quantities of the amine ever obtained were 10.6 and 18.3 ng/biopsy (depending on both histamine content and biopsy weight). A series of problems had to be solved both in achieving and demonstrating specificity. It had to be defined not only for the assay in general, but also for assessing the difference in histamine content between ulcer patients and healthy controls. Exogenous more than endogenous fluorescing material interfering with the determination had to be excluded. A series of pitfalls were detected which had to be overcome in demonstrating the specificity of the assay by physicochemical and enzymatic tests. The specificity of the identification tests was more often impaired than the histamine assay itself. Fluorescing material interfering with the assay occurred in the homogenization, extraction and condensation steps, was found in water, OPD, the organic solvents, the cleaning material and in all kinds of plastic vessels. Plasticizers were shown by physicochemical characteristics including fluorescence spectra to be most likely responsible for this interfering material. Rules were developed to exclude such hazards in specificity in longterm pathobiochemical studies. Enzymatic identification test were applied to exclude endogenous fluorecing substances interfering with the standard technique. Simil
In surgery, risk research is of great importance at the present time but is controversely discussed with contradictory definitions, calculations and applications. In this paper standardized and quantitative definitions of risk and risk factors using probabilities are given. A calculation of risk, risk factors and risk rates is performed using data from studies on bleeding duodenal ulcers. Possible applications of risk and risk factor research (risk analysis) in suitable treatment policies are demonstrated using data from patients with bleeding duodenal ulcers. The utility of this type of approach, using decision tree analysis, clearly manifests itself in the reduction of lethality. Objective and quantitative surgical risk research and its application as risk analysis using probabilities can improve patient care in standard surgical situations.
Several types of clinical studies provide important decision aids for surgical indications. They include quantitative data on outcomes and utility analysis, graphic illustration of the various possibilities for decisions by decision trees, controlled clinical trials with data used in decision trees and--if these trials fail for several reasons--carefully conducted and documented prospective and retrospective trials. Items for defining the term "surgical indication" were illustrated by constructing a decision tree for treatment of chronic duodenal ulcer.
The aim of this study was to evaluate the influence of postoperative iodide-substitution on the function of thyroid remnants of different quality and quantity in order to define the appropriate prophylaxis (iodide or thyroid hormone) to prevent recurrent goitre. In a prospective, randomized clinical trial, the following patients were examined: group I: simple, non-autonomous nodular goitre, bilateral thyroidectomy (n = 40); group II: simple, non-autonomous nodular goitre, "selective" (unilateral) thyroidectomy (n = 40); group III: autonomous nodular goitre, bilateral thyroidectomy (n = 40); group IV: autonomous nodular goitre, "selective" (unilateral) thyroidectomy (n = 35). The following parameters were measured 6 and 12 weeks postoperatively. Serum-total-T4, -T3, -TSH, TRH-test, 99mTc-Thyroid-Uptake (TcTU). Six weeks postoperatively the 4 groups were separately randomized into controls and treatment groups, who received 200 micrograms iodide/day orally. Six weeks postoperatively, patients in group I had lower T4 levels and both basal and stimulated TSH were higher than in the other groups, however no significant differences were observed in T3, T4/T3 ratio and TcTU. Twelve weeks postoperatively patients from groups I, II and III, who had been treated with iodide, had lower T3 and TcTU values but higher T4 and T4/T3 than the appropriate controls. Basal and stimulated TSH showed no differences between controls and iodide-treated patients in these groups. In group IV, T4 and T3 showed a tendency to elevation (n.s.), and basal and stimulated TSH as well as TcTU were lower in patients with iodide.(ABSTRACT TRUNCATED AT 250 WORDS)
Asymptomatic recurrent ulcers following drugs and surgical therapy are true failures of treatment (Visick IV). Several types of bias at present do not allow any conclusion whether medical treatment and maintenance increase the rate of ulcer complications. The mechanisms of action for medical treatment with cimetidine and operative treatment with SPV are similar, but not identical. Bad compliance and incomplete vagotomies mainly account for success of mutual exchange between the two types of therapy. Using a decision tree with mortality as outcome recommendations are developed for a step-wise therapeutic concept in peptic ulcer patients.
Changes in histamine storage in the oxyntic mucosa of duodenal ulcer patients and their reversal by vagotomy and the histamine H2-antagonist cimetidine supported the hypothesis that histamine could be a causal factor in peptic ulcer pathogenesis. The specificity of these findings was impaired by problems in biopsy taking, however, and in the preparative steps before measuring the actual histamine contents in all parts of the gastric mucosa and in the duodenum. A prospective trial was carried out in 190 patients to identify these sources of bias and to overcome them by appropriate study designs. Usually a direct correlation was found between weight of biopsy and mucosal histamine content. This problem was solved by selecting a biopsy forceps producing smaller variations in sample size, by limiting the time of cold ischaemia to four to five minutes only and by taking three biopsy specimens for each single histamine value. The actual histamine content of mucosal biopsies remained constant for about four to five minutes only. The 'disappearance' rate was faster in control subjects than in duodenal ulcer patients. Hence by variation of the cold ischaemia time any artefacts of differences between mucosal histamine levels in controls and duodenal ulcer patients could be produced. Using the optimised sample taking procedure mucosal histamine contents of several gastric regions and the duodenal bulb were measured in 24 patients with duodenal ulcer, after selective proximal vagotomy without drainage and in control subjects without any stomach disease (randomised controlled trial). The histamine content was lower in all parts of the upper gastrointestinal tract in duodenal ulcer patients than in controls and was raised again in all regions after selective proximal vagotomy. As the most likely hypothesis it is suggested that vagal reflexes with afferent fibres coming from the oxyntic mucosa stimulate histamine release in duodenal ulcer patients by efferent peptidergic neurones to all parts of the stomach and the duodenum where the ulcer lesion is situated.
Cytostatic treatment with anthracyclines lines can lead to acute or chronic myocardial insufficiency. A cumulative dose of less than 500 mg/m2 body surface area can in general be regarded as safe. A case of acute cardio-circulatory insufficiency during induction of anesthesia is described, in which the total cumulative dose did not exceed 250 mg/m2 body surface area. The pathophysiological mechanisms occurring and the diagnostic and therapeutic measures necessary are discussed.
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Histamine assays can be unreliable in individual subjects or samples even though the particular method is in general working very well. Therefore the specificity and accuracy of histamine determination in the gastric aspirate of individual duodenal ulcer patients was thoroughly examined and shown to be satisfactory. Pitfalls of the fluorometric assay were investigated. A native (non-histamine) fluorescence in gastric aspirate which occurs before the addition of OPT was not removed by the original Shore procedure. In the combined assay (Dowex 50 + butanol extraction) this fluorescence no longer interferes with the assay. For the identification of histamine in a single gastric aspirate of an individual duodenal ulcer patient, the reversed blank (3 M HCl added to the reaction mixture before OPT instead after OPT), excitation and fluorescence spectra, the heating test with spectra recorded and the HMT test were found to be reliable. The formaldehyde test and the heating test without recording the spectra were useless since they gave false negative results. Since the HMT test was regarded as a reference method it was thoroughly investigated both by theoretical considerations (enzyme kinetics) and by a series of measurements in a single patient as well as in a group of nine subjects. Samples from the period of peak acid output in response to pentagastrin showed an average histamine concentration of about 8 ng/ml and a histamine output of 1.5 microgram/30 min.
Anaphylactoid reactions in man following administration of drugs solubilized with cremophor El (polyethylenglycolglycerol riconoleate) are a considerable clinical problem. Since these reactions occur in dogs on first exposure and in pigs on second exposure, the 'dog model' was used in this communication to analyse components and chemical modifications of cremophor El and its components for their clinical effects, their hypotensive actions and their histamine-releasing capacity. Two series of experiments in 1978 and 1980 were performed in 144 adult mongrel dogs of both sexes. In these studies histamine release was not related to the effect of the solubilizing agents as tensides and was elicited by rather low doses (about 10--100 mg/kg i.v.). The effect of these substances on blood pressure and on blood histamine levels was connected with distinct chemical features: the most potent compounds were oxethylated and additionally esterified unsaturated or hydroxylated fatty acids. Several phases in hypotensive reactions were observed, including an immediate response, a delayed blood pressure response and a late response about 15--20 min after injection. Only the delayed response was associated with histamine release. The combination of cardiovascular effects and histamine release was fatal on some occasions indicating that histamine release can be dangerous. Compared to cremophor El, the tenside effect was equal, but the toxicity was reduced in oxethylated 12-hydroxystearic acid. It is recommended that this solubilizer should be used in further extended studies in animals and - if these are successful - in clinical trials.
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It has been suggested that histamine contributes to lethal circulatory collapse after acute superior mesenteric artery occlusion. The activity of the histamine inactivating enzyme diamine oxidase, the release of the amine, and the effect of histamine receptor antagonists was therefore studied in rabbits. The main results were: (a) Diamine oxidase activity decreased by 60% after intestinal ischemia and reperfusion. A monoexponential dose-response relationship was found between the specific diamine oxidase inhibitor aminoguanidine and reduced survival time. (b) Plasma histamine levels in the right atrium rose only slightly after ischemia, but considerably during reperfusion of the gut, and remained high for at least 20 min. In sham-operated animals the plasma histamine concentration was unchanged throughout the experiment. The histamine content in the intestinal wall did not fall significantly at any time after mesenteric artery occlusion and reperfusion. (c) The aminoguanidine-induced reduction in survival time was completely reversed by pre-treatment of the animals with the H1-receptor antagonist dimethylpyridine and the H2-receptor antagonist cimetidine. This study provides strong evidence for the protective role of intestinal diamine oxidase in intestinal ischemia.
Of three groups of anaesthetized and intubated patients (n = 7) under controlled ventilation two received fresh gas flows of 70 ml/kg . min, 100 ml/kg . min and 130 ml/kg . min either in increasing or in decreasing amounts via a Bain circuit, while the third group was ventilated via a conventional semi-closed anaesthesia circuit. Blood gas analyses and cardiovascular parameters were recorded. In one patient temperatures and relative humidities of in- and expired gases were obtained by psychrometry. A modification of the Bain system afforded control of respiratory minute volumes and airway pressures. CO2-elimination proved to be adequate at a fresh gas flow of 130 ml/kg. min. At 100 ml/kg. min it was acceptable still, however pH values were outside normal range. With 70 ml/kg . min mean capillary pCO2 values (42.6 mmHg and 43.2 mmHg) and mean pH values (7.32 and 7.33) in the two respective groups proved a respiratory acidosis. Capillary pO2 was above 100 mmHg in all groups. Temperature and relative humidity of inspired gases were 24 degrees C and 40 per cent, 23 degrees C and 25 per cent, 22 degrees C and 3 per cent at fresh gas flows of 70, 100 and 130 ml/kg . min respectively.