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This article is an attempt to clarify a confusion in the brain death literature between logical sufficiency/necessity and natural sufficiency/necessity. We focus on arguments that draw conclusions regarding empirical matters of fact from conceptual or ontological definitions. Specifically, we critically analyze arguments by Tom Tomlinson and Michael B. Green and Daniel Wikler, which, respectively, confuse logical and natural sufficiency and logical and natural necessity. Our own conclusion is that it is especially important in discussing the brain death issue to observe the distinction between logical and natural sufficiency/necessity in a strict fashion.

Single input, single output experiments can result in nonunique solutions for the rate constants to a linear compartmental model used to describe the pharmacokinetics. Where a finite number of solutions exists, a priori knowledge has to be used to distinguish between the solutions. Where there is a infinite number of solutions, assumptions have to be made about the values of some rate constants in order to obtained a unique solution for the other. This paper considers such experiments and determines whether either the addition of an extra input (simultaneously with the first input) or the taking of an extra measurement would result in a unique solution. It is found that perturbing a second input can be useful, but only if the perturbation is of different shape from the first input. Measurements of drug in urine and metabolite in plasma are generally not helpful in resolving identifiability of the drug dynamic model. If a radioactive tracer is used, through, the second measurement (for example, by externally scanning the radioactivity of the liver) can prove useful, but only if the gain of the measuring device is known.

A separate role for water activity in the conversion of sugars to ethanol by two strains of yeast is identified. During fermentation of both single and mixed sugar substrates, the water activity was shown to remain constant during the logarithmic growth phase. This is despite the changes in concentration of substrates and product, the constancy reflecting the fact that the greater influence of ethanol on the solution activity is counterbalanced, in the early stages of the fermentation, by its low yield. The end of the log phase of growth coincides with the start of a period of gradually decreasing water activity. For the more ethanol-tolerant strain UQM66Y, growth was found to cease at a constant value of water activity while that for the less tolerant strain UQM70Y depended on both ethanol concentration and water activity. It is argued that water activity is a more appropriate variable than ethanol concentration for describing some of the nonspecific inhibitory effects apparent in ethanol fermentations. A straightforward method for the calculation of water activity during such fermentations based on the use of solution osmolality is presented.

A system of routine interrogation of patients using a computer has been developed. It includes a visual display unit with a specially designed response keyboard, and the program has been designed to adapt to the individual patient. The system was evaluated objectively, using the criteria of accuracy in eliciting symptoms, acceptability to the patient, and cost. While doctors will always take the ultimate management decisions, it seems that machines can be programmed to undertake the routine interrogation of patients, elicit evidence accurately and acceptably, and calculate the probabilities of disease as effectively as doctors.

In 3 cases of simultaneous bilateral anterior dislocation of the shoulders, considering the forces which predispose to anterior dislocations, it is postulated that in each case forced abduction and external rotation or abduction with hyperextension causes these injuries to occur.

We conducted serial neurologic examinations on 500 patients in nontraumatic coma to identify factors predicting recovery. Overall, 81 patients (16%) led an independent life at some point within the first year; the remainder either died without recovery from coma (61%), never improved beyond the vegetative state (12%), or regained consciousness but remained dependent on others for daily activities (11%). Functional recovery did not depend on age but was to some degree related to the cause of coma (subarachnoid hemorrhage and other cerebrovascular disease having the worst recovery; hypoxia-ischemia, intermediate; and hepatic and miscellaneous causes, best) and especially to early clinical signs of brain dysfunction. Even within hours of the onset of coma, only one of 120 patients lacking two of corneal, pupillary, and oculovestibular responses ever regained independent function. The study identifies clinical features of comatose patients that appear within the first week and that are important for predicting recovery and designing future therapeutic trials.

The management of individual patients with subarachnoid hemorrhage depends greatly on assessment of the patient's clinical condition. Difficulty in applying current grading systems prompted the authors to conduct studies of observer variability and to attempt to identify sources of inconsistency. Observers graded 15 patients by both the Hunt and Hess and Nishioka systems. Considerable observer variability was found, with up to four different grades being selected for the same patient. Kappa statistics were used to evaluate the data. This method determines observer agreement occurring in excess of chance. Kappa values for each grading system showed observer agreement to be significantly better than chance, yet revealed marked observer variation. Most variation occurred when Grade 3 was selected, irrespective of the system used. In a further study where observers graded clinical summaries, similar variation occurred; therefore, inconsistency was due mainly to difficulty in matching patients with levels described in the grading system, rather than to fluctuation in the patient's clinical condition or difference in the observers' examination technique. Variability was high when patients with systemic disease or vasospasm on angiography were graded with the Hunt and Hess system. The studies show that a simpler and more reliable grading system is required, and emphasize and need for caution when interpreting the results from different published series.

A computer-assisted model for diagnosing jaundice has been adapted for use on the University of London C.D.C. 7600 computer via an on-line terminal at King's College Hospital to provide a rapid turn-round time. The model was used prospectively in the diagnosis of 219 patients--135 seen in a specialized liver unit and 84 seen in one of four district hospitals in south-east London--with an overall accuracy in distinguishing among 11 different causes of jaundice of 69% and 62% respectively. These figures rose to 77% and 88% respectively when only those patients in whom the final diagnosis reached a "certain" probability were considered. When used to distinguish between a medical and a surgical cause of jaundice the accuracy was 86% in the liver unit and 77% in the district hospitals, rising to 95% in both series for those with a diagnosis of certain probability. The proposed improvements to the model--namely, the use of two deparate data bases and more diagnoses within the matrix--should be improve the accuracy even further. In practice the rapid feedback to the clinicians looking after patients provided help in managing difficult cases.

Five observers each examined 20 jaundiced patients, recording clinical signs and symptoms on a form which also gave the definitions used for the study. The balanced design of the study allowed examination for order effects, but none were found, except for a tendency for agreement on indicants with more than two categories to improve as the study progressed. Chance agreement was corrected by the use of kappa statistics which showed that 80% of the indicants showed agreement significantly greater than expected by chance. Certain indicants (dark urine, variability of jaundice, abdominal pain, character of liver edge and presence of spleen) showed no evidence of significant agreement, even though the indicants were frequently observed in both states - present or absent. The percentage of correct clinical diagnoses reached by the observers (without biochemical or any other information) varied between 65% and 84%. The consensus diagnosis was correct in 80% of cases. Agreement was higher if the diagnosis was simplified to a 'Medical' or 'Surgical' diagnosis, the observers' accuracy being between 90 and 100%.

A computer system for probabilistic diagnosis of jaundice was tested on a patient sample from a geographical area different from that for which it was first constructed. 144 consecutive patients with jaundice seen in two Stockholm hospitals were interviewed and examined to record a total of 82 indicants from history, demographic details, physical findings and laboratory tests. Data were compared with those of 319 jaundiced patients previously interviewed and examined at different London hospitals. It was found that disease incidences were different in the two patient samples. There were more patients with acute viral hepatitis, chronic active hepatitis and primary biliary cirrhosis in the London data base whereas the Stockholm data base included significantly more patients with Gilbert's syndrome and alcoholic cirrhosis. Indicant frequencies, standardised for disease incidence, differed with respect to age (Stockholm patients were on average six years older), time from onset of first symptom to hospital admission (Stockholm patients had on average a two-week shorter history of disease) and a number of symptoms such as nausea, vomiting, anorexia, weight loss, itching, pale stools and dark urine which were more frequent among the London patients. Differences in hospital admission policy was regarded as an important reason for the differences in indicant frequency. The results of probabilistic diagnosis were poor. Only 49% of the cases were correctly classified into twelve diagnostic groups. In particular the computer model was poor at separating different causes of malignant bile duct obstruction and at differentiating between malignant and benign bile duct obstruction. However, all cases of acute viral hepatitis were correctly classified and the computer model was 87% accurate in differentiating between medical and surgical jaundice. Reclassification of the 144 patients on their own data showed the computer system to be well calibrated and 97% of the cases were correctly classified according to this procedure. In conclusion, the computer system could not be directly transferred for use in a Swedish hospital but the results of reclassification were sufficiently encouraging to warrant prospective studies.

The derivation of a predictive index is illustrated using 14 simple questions to assess the chance of the presence of an ulcer. The evaluation and use of such a 'calculated-risk' is briefly described.

Two patients with primary hepatic malignancy were treated by hepatectomy and orthotopic liver transplantation. In both cases the donor liver was infused with cold solutions and kept chilled without continuous perfusion. There was immediate satisfactory hepatic function in both transplants.The first patient died after 11 weeks from overwhelming bacterial and fungal infections probably secondary to hepatic infarction due to thrombosis of the recipient hepatic artery. The thrombus occurred at the site of the arterial clamp. In an attempt to control the growth before transplantation, the patient had been treated with large doses of chlorambucil, which resulted in extreme marrow depression and septicaemia.The second patient developed cholestatic jaundice during the second and third weeks after transplantation, with histological evidence of mild rejection, which was controlled by increasing the dose of immunosuppressive agents. He is now well, having returned to work six weeks after the operation.Though the first patient showed no evidence of rejection, it is concluded that patients receiving liver allografts should receive immunosuppressive therapy.

The effects of 5 mg of diazepam intravenously were assessed in 23 patients with liver disease, 10 of whom had clinical evidence either in the past or at the time of study of hepatic encephalopathy. Transient drowsiness occurred in all patients, but prolonged deterioration in conscious level was not observed. Serial electroencephalographic recordings showed the development of activity at faster frequencies, similar to that found in normal subjects, a change which is different from that usually observed in cirrhotic patients after administration of chlorpromazine and morphine when slow-wave activity is increased.