EuroQol: the current state of play

The EuroQol Group first met in 1987 to test the feasibility of jointly developing a standardised non-disease-specific instrument for describing and valuing health-related quality of life. From the outset the Group has been multi-country, multi-centre, and multi-disciplinary. The EuroQol instrument is intended to complement other forms of quality of life measures, and it has been purposefully developed to generate a cardinal index of health, thus giving it considerable potential for use in economic evaluation. Considerable effort has been invested by the Group in the development and valuation aspects of health status measurement. Earlier work was reported upon in 1990; this paper is a second 'corporate' effort detailing subsequent developments. The concepts underlying the EuroQol framework are explored with particular reference to the generic nature of the instrument. The valuation task is reviewed and some evidence on the methodological requirements for measurement is presented. A number of special issues of considerable interest and concern to the Group are discussed: the modelling of data, the duration of health states and the problems surrounding the state 'dead'. An outline of some of the applications of the EuroQol instrument is presented and a brief commentary on the Group's ongoing programme of work concludes the paper.     

Blood lead levels in sheep exposed to automotive emissions

Summary The lead content of whole blood of 62 sheep grazed continuously for 6 months near a major highway was compared with 38 sheep from a nearby uncontaminated area. Mean values of 0.90 and 0.20 g/ml were obtained. Four sheep from the contaminated area were placed in an uncontaminated paddock and the lead content of the blood decreased rapidly during the first 10 days and thereafter more slowly. After 185 days, blood lead levels had still not quite reached normal levels.Animals from an uncontaminated area showed an immediate rise in the blood lead levels when placed near a major highway. Sheep placed in a concrete pen away from motor vehicle exhaust emissions showed a rise in lead levels when fed with, forage cut from the verges of a busy highway. Sheep placed near a highway and fed with forage from an uncontaminated area showed an increase of lead levels in the blood, comparable to that of the previous experiment. It was concluded that lead uptake by ingestion of polluted forage and by inhalation of airborne particulates are both mechanisms responsible for enhanced lead levels in ovine blood.     

Gastric pseudolymphoma. Its three subtypes and relation to lymphoma

Three separate histologic types of gastric pseudolymphoma (GPL) are described: (1) the common "inflammatory" type usually accompanied by ulceration and extensive fibrosis; (2) the entity known as "nodular lymphoid hyperplasia," which was associated with multiple intestinal lesions; and (3) the third reported case of angiofollicular lymphoid hyperplasia of the stomach (one with nodal involvement). Criteria for the common type were developed and, in general, confirm previous studies. However, the importance of evaluating nuclear cytology and mitotic rate are stressed. Organ infiltration by chronic lymphocytic leukemia should be excluded by the absence of an absolute peripheral lymphocytosis. In addition to the ten cases presented, the literature on 175 previous cases is summarized. GPL is estimated to account for 10-15% of all gastric lymphoid tumors. In comparison to gastric lymphoma, GPL is usually smaller in size and occurs a decade earlier on the average. Since an associated focal lymphoma was documented in an additional five cases, this study proposes that pseudolymphoma be considered a precursor lesion with malignant potential. Extensive pathologic sampling and total surgical excision are recommended.     

Personality and behavioural change after severe blunt head injury--a relative''s view.

A close relative of 55 severely head injured adults rated the personality of the patient at 3, 6 and 12 months after injury, using a Yes/No judgement, and analogue scales comprising bipolar adjectives. The relative assessed the "current" as well as the "premorbid" personality at each time. Personality change was associated with many negative scores on the analogue scale, and increasing negative scores were associated with high "subjective burden" on the relative. Severity of injury (post-traumatic amnesia) was of no significance in predicting the extent or pattern of personality change.     

Statistical "biases" in respiratory disability determinations

The manner in which pulmonary function test results are employed in the assessment of respiratory disability may be affected by 4 statistical choices: (1) choice of prediction equation(s), (2) adjustment factors (such as sex and race), (3) criterion values, and (4) method of comparison of observed to predicted normal test values. The records of 900 respiratory disability applicants were employed to estimate the direction and magnitude of the effect of these choices on the overall number of persons who would be declared "disabled" and upon the manner in which personal characteristics (e.g., sex, race, height, age) affect the likelihood of being declared "disabled." Choice of prediction equation had minor effects, and adjustment for race and sex had more significant effects. Choice of criterion value affected the overall number and, in certain instances (e.g., Social Security Disability Insurance), the distribution of "disability" declarations. Method of comparison (percent of predicted, difference of predicted minus observed or minimal value criterion) had major effects upon the distribution of "disability" declarations between population subgroups. Preliminary analysis therefore suggests that these statistical choices should be carefully manipulated in the design of a disability system to facilitate achievement of the system's goals.     

Defective acidification of endosomes in Chinese hamster ovary cell mutants "cross-resistant" to toxins and viruses.

Like many physiological ligands, several viruses and toxins enter mammalian cells through receptor-mediated endocytosis. Once internalized, the nucleic acids of several viruses and the toxic subunit of diphtheria toxin gain access to the cytosol of the host cell through an acidic intracellular compartment. In this report, we present evidence that one class of mutants of Chinese hamster ovary (CHO)-K1 cells, which is "cross-resistant" to Pseudomonas exotoxin A, diphtheria toxin, and several animal viruses, has a defect in acidification of the endosome. Cells were allowed to internalize fluorescein isothiocyanate-conjugated dextran before subcellular fractionation. Fluorescence measurements on subcellular fractions permitted measurement of the internal pH of the isolated endosomes and lysosomes. Our results show that (i) endosomes and lysosomes from CHO-K1 cells maintain an acidic pH, (ii) acidification of both endosomes and lysosomes is mediated by a Mg2+/ATP-dependent process, (iii) GTP can satisfy the ATP requirement for acidification of lysosomes but not of endosomes, and (iv) at least one class of mutants that is cross-resistant to toxins and animal viruses has a defect in the ATP-dependent acidification of their endosomes. These studies provide biochemical and genetic evidence that the mechanisms of acidification of endosomes and lysosomes are distinct and that a defect in acidification of endosomes is one biochemical basis for cross-resistance to toxins and viruses.     

Diabetic mastopathy: a distinctive clinicopathologic entity.

Insulin-dependent diabetics may manifest evidence of autoimmune diseases involving endocrine or other organs. Rare cases of a peculiar fibrous and inflammatory lesion of the breast in diabetic patients have been previously described; however, the pathologic and clinical features that uniquely characterize these cases have not been defined or distinguished from other chronic inflammatory and fibrosing conditions in the breast. We studied eight patients with breast masses and longstanding insulin-dependent diabetes and compared them with 36 nondiabetic or short-duration diabetic patients with fibrosis and chronic mastitis. The longstanding diabetic patients presented with clinical breast masses ranging in size from 2 to 6 cm. Six of the eight patients had documented diabetic nephropathy, retinopathy, or neuropathy. Pathologically, these lesions showed lymphocytic lobulitis and ductitis, lymphocytic vasculitis (predominantly B cell), and dense keloid-like fibrosis that in many cases (six of eight) contained peculiar epithelioid cells embedded in dense fibrous stroma. We have provisionally labeled these cells "epithelioid fibroblasts" (EFBs). Although the features of lymphocytic lobulitis, ductitis, and/or vasculitis may occasionally be encountered in nondiabetic breast biopsies, EFBs appear to be unique to the diabetic condition. Control cases of chronic mastitis in nondiabetic or short-duration diabetes patients failed to show the complete constellation of lymphocytic lobulitis and ductitis, vasculitis, keloidal fibrosis, and EFBs. Diabetic mastopathy may represent an immune reaction to abnormal matrix accumulation. A hypothesis is presented.     

POSSIBLE INVOLVEMENT OF INOSITOL-LIPID METABOLISM IN MALIGNANT HYPERTHERMIA

-Adrenoceptor stimulation may induce malignant hyperthermia(MH) in vivo. Consequently, we have investigated the effectsof the -adrenoceptor agonist phenylephrine and, for comparison,the effects of the ß-adrenoceptor agonist isoproterenolon inositol-lipid metabolism of malignant hyperthermia susceptible(MHS) and healthy control (MHN) swine. The experiments wereperformed on electrically stimulated (frequency 0.2 Hz) trabeculaeisolated from the right ventricles of the hearts of MHS andMHN animals. After labelling with [³H] inositol for 6 h, differentinositol phosphates were measured by high pressure liquid chromatography,including inositol 1 - phosphate, inositol 1,4-bisphosphate,inositol 1,3,4-trisphosphate, inositol 1,4,5-trisphosphate (1,4,5-IP₃)and inositol 1,3,4,5 - tetrakisphosphate. After stimulationwith isoproterenol, the inositol phosphate content did not increaseor vary between muscle from MHS and MHN animals. In contrast,all inositol phosphates increased after stimulation with phenylephrinein both muscle types, the effects being greater in MHS thanin MHN, especially as regards 1,4,5-IP₃ content. As 1,4,5-IP₃,a presumed second messenger, has been shown to mobilize intracellularcalcium, it is concluded that an enhanced -adrenergic responseis involved in the development of MH. ^*Address for correspondence: Abteilung für Anästhesiologie,Universitäts-Krankenhaus Eppendorf, Martinistrasse52, D-2000Hamburg 20, Germany. Presented in part at the 1989 Meeting of the European Academyof Anaesthesiology in Bonn.     

Using neural networks to diagnose cancer

While artificial brains are in the realm of science fiction, artificial neural networks (ANNs) are scientific facts. An artificial neural network is a computational structure modeled somewhat on the neural structure of the brain; both have many highly interconnected processing elements. These biologically inspired processing elements are taught by feeding examples until the results are acceptable. In the past 5 years, neural networks have become successful in providing meaningful second opinions in clinical diagnosis. In our research, a prototype artificial neural network was trained on numeral ultrasound data of 52 actual cases and then correctly identified renal cell carcinoma from renal cysts and other conditions without diagnostic errors. Our nonlinear artificial neural network was trained on software using the standard backpropagation paradigm on a 80386 microcomputer. Our ANN learned from ultrasound data in 52 cases (17 malignant, 30 cysts, and 5 other) at a Memphis hospital. The trained prototype performed without error on 47 cases which were not in the data used for training. This prototype must be validated by extending this study to more cases.