Early pulmonary endothelial enzyme dysfunction after phorbol ester in conscious rabbits.

We investigated changes in angiotensin converting-enzyme (ACE) activity before and at 5, 15, 60, and 240 min after 20 micrograms phorbol myristate acetate/kg body wt iv in conscious rabbits. ACE activity was estimated in vivo from the single-pass transpulmonary metabolism of the synthetic substrate [3H]benzoyl-Phe-Ala-Pro [( 3H]BPAP) under first-order reaction conditions. Within 5 min after PMA administration, all animals developed profound granulocytopenia (15% of control) and moderate thrombocytopenia (57% of control), both lasting for the duration of the experiment. Concomitantly, there was a significant decrease in the transpulmonary metabolism of [3H]BPAP and the calculated apparent first-order reaction constant Amax/Km of ACE for [3H]BPAP. No histological evidence of lung injury was observed at these times. Since a concomitant fall in the permeability surface area product for urea was also observed, we considered that the apparent decline in ACE activity might have resulted from a reduction in perfused endothelial surface area. To resolve this, we studied the effect of PMA on the Km (a measure of enzyme affinity for its substrate) and Amax (a derivative of Vmax that is dependent upon total enzyme present and thus capillary surface area) of ACE and 5'-nucleotidase for [3H]BPAP and [14C]AMP, respectively. A significant increase in Km for both enzymes was observed at 1 h after PMA, whereas Amax was unaffected, suggesting that low-dose PMA may indeed produce endothelial cell enzyme dysfunction independent of its effect on capillary surface area. These results provide evidence of pulmonary capillary functional injury before or in the absence of structural endothelial damage.

The assessment of medical technologist. Examples from Switzerland.

The need for assessment of new medical technologies has recently become evident in many countries, especially for the people responsible for health care policy. There are multiple reasons for making evaluation: rising costs in health care, medical efficacy, safety, as well as social and political issues. Each stage of life of a diagnostic, therapeutic or preventive technology, from its emergence to obsolescence, can be assessed by an appropriate procedure. In Switzerland, a country with decentralized health care as well as political systems, the assessment is made by various institutions. Evaluative aspects are included in some National Research Foundation programs. Most work, however, is done by the division of medical techniques at the Swiss Hospital Institute. The panel of experts has recently prepared a report on magnetic resonance imaging (MRI). As a result of the initial evaluation, the need for this new technology in this country, and the number and sites of MRI systems for the next few years were established. The capital, running and unitary costs of this diagnostic procedure were estimated. The report will be of aid to the people planning investments and dealing with questions of reimbursement and other issues of health care policy. The methods of epidemiology, biostatistics, sociology and health economics used by the institutes of social and preventive medicine are very helpful in the procedures of technology assessment.

Medical technology assessment: adequate questions, appropriate methods, valuable answers.

Medical Technology Assessment begins with carefully posing the appropriate questions to be examined. Specification of the critical assessment provides the framework for the design to provide the answers. This paper addresses the Technology Assessment process as a sequence of the above steps. The practical requisites of the diversity of questions, the economic, and study design considerations generated are addressed in a systems analysis model of input-process-outcome. Applications and the relative merits of such design consideration are discussed and illustrated. The questions related to medical technologies may come from different groups of people directly or indirectly interested, and having active or passive relationship to a given technology. There are 4 basic issues from which the detailed questions derive. These are the issues of need, effectiveness, safety and cost. The timing of asking questions in the life-cycle of a technology and the adequacy of the answers determines the choice of methods, the extent of an evaluation and the quality of the responses. The reliability, external validity, generalizability, and the clarity of conclusions are the characteristics of a practical and valuable assessment.

Study design for technology assessment: critical issues.

The epidemiological methods have become useful tools for the assessment of the effectiveness and safety of health care technologies. The experimental methods, namely the randomized controlled trials (RCT), give the best evidence of the effect of a technology. However, the ethical issues and the very nature of the intervention under study sometimes make it difficult to carry out an RCT. Therefore, quasi-experimental and non-experimental study designs are also applied. The critical issues concerning these designs are discussed. The results of evaluative studies are of importance for decision-makers in health policy. The measurements of the impact of a medical technology should go beyond a statement of its effectiveness, because the essential outcome of an intervention or programme is the health status and quality of life of the individuals and populations concerned.

Importance of databases for technology assessment.

The data indispensable for carrying out the comprehensive, multi-faceted process of medical technology assessment (MTA) should be collected from a variety of sources. The authors distinguish between type "A" general data, useful for assessment but collected without this specific aim, and type "B" data. Registries of health care procedures or of diseases, as well as clinical data bases are quoted as examples of type "B" data, specifically relating to MTA. Since demographic methods are of importance for the evaluation of long-term effects of medical technologies, examples of sources of type "A" data are presented. Their significance for health policy making is discussed.

The effect of alphanapthylthiourea (ANTU)-induced acute injury on lung binding of antibody to angiotensin converting enzyme (ACE).

The effects of ANTU-induced acute pulmonary capillary injury on lung and serum ACE functional activity and the specific accumulation of radio-labelled anti-ACE in lung were explored. Rats were injected either with ANTU or the solvent and sacrificed at various intervals up to one week after injection. All ANTU-injected animals developed pulmonary edema and bilateral pleural effusions which resolved by the one week time point. At no time was there any significant change in serum ACE levels. The specific activity of total lung ACE however rose from 11.0 +/- .95 (mean +/- SEM) to 18.4 +/- 1.1 by two hours after ANTU; by 24 hours, however, solubilized lung ACE had fallen significantly to 6.9 +/- .79 (p less than .01). Total lung ACE had returned to control values by one week. In parallel groups of animals the accumulation of 125I-labelled anti-ACE (AA) or normal sheep immunoglobulin (NSG) was compared in control and ANTU-treated rats. The ratio of the radioactivity in the lungs of AA--injected animals to that in NSG--injected animals fell significantly after ANTU administration (5.0 +/- .88 to 1.2 +/- .28 at 2 hours) suggesting that immunoreactive ACE had fallen despite an increase in ACE functional activity. The decreased binding of AA at the early time points perhaps reflects internalization of endothelial cell ACE in response to injury and an inability of the antibody to interact with the enzyme. The reduction in binding at 24 hours (1.38 +/- .47) correlates with a reduction in total lung ACE. ANTI-ACE may be a useful reagent for quantitating endothelial cell damage following lung injury.

[Impact of hormonal prevention on fractures of the proximal femur in postmenopausal women: a simulation study]. / Impact de la prophylaxie hormonale sur les fractures du fémur proximal des femmes postménopausiques: une étude de simulation.

A simulation model of the effects of hormone replacement therapy (HRT) on hip fractures and their consequences is based on a population of 100,000 post-menopausal women. This cohort is confronted with literature derived probabilities of cancers (endometrium or breast, which are contra-indications to HRT), hip fracture, disability requiring nursing home or home care, and death. Administration of HRT for life prevents 55.5% of hip fractures, 22.6% of years with home care and 4.4% of years in nursing homes. If HRT is administered for 15 years, these results are 15.5%, 10% and 2.2%, respectively. A slight gain in life expectancy is observed for both durations of HRT. The net financial loss in the simulated population is 222 million Swiss Francs (cost/benefit ratio 1.25) for lifelong administration of HRT, and 153 million Swiss Francs (cost/benefit ratio 1.42) if HRT is administered during 15 years.

The contrast media used for myelography.

A review of the contrast media used for myelography and radiculography is presented. Water-soluble, nonionic medium like metrizamide enables the examination of the entire CSF space. The relation of the diagnostic benefit to complications when using this contrast medium is favorable. Attention must be paid in using the correct myelographic technique and in controlling the possible severe adverse reactions which appear in 1.5% of the cases during 24 h after the examination.

Swiss Hospital Institute's approach to the problems of magnetic resonance imaging.

The Swiss Hospital Institute, a nonprofit institution that provides guidance on hospital planning and operation to Switzerland's health care community, conducted in 1984 a comprehensive study of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy via a 17-member commission that examined all aspects of these emerging technologies. Future MRI utilization was estimated by developing five clinical categories of possible MRI use, based on ICD codes, and a probability of MRI utilization was developed for each category. By applying these probabilities to the number of inpatient admissions in each category, an annual nationwide volume of 20,000 scans was estimated. Ten MRI systems were considered adequate for a period of up to five years after the report's promulgation, based on a per-system annual throughput of 1,900-2,000 patients. A superconducting-magnet system with an 0.5-T field strength was deemed the most suitable, with units to be located in university hospitals. [Spectroscopy was considered best left to separate research installations.] The cost of equipment and construction for the 0.5-T superconducting magnet system were calculated as high as 3.6 million Swiss francs (Sfr) (approximately $1.65 million at fall 1985 exchange rates). the annual operating cost was estimated as Sfr 1.3 million ($600,000). On this basis a per-study fee of Sfr 690 ($315) was projected. The study recommended health insurance coverage of MRi use, only in patients with well-proven clinical indications for an MRI scan. The report is expected to aid in the orderly introduction of MRI into Switzerland's health care system.

Data bases for the assessment of medical technologies. Examples from Europe.

The assessment of medical technologies has to answer several questions ranging from safety and effectiveness to complex economical, social, and health policy issues. The type of data needed to carry out such evaluation depends on the specific questions to be answered, as well as on the stage of development of a technology. Basically two types of data may be distinguished: (a) general demographic, administrative, or financial data which has been collected not specifically for technology assessment; (b) the data collected with respect either to a specific technology or to a disease or medical problem. On the basis of a pilot inquiry in Europe and bibliographic research, the following categories of type (b) data bases have been identified: registries, clinical data bases, banks of factual and bibliographic knowledge, and expert systems. Examples of each category are discussed briefly. The following aims for further research and practical goals are proposed: criteria for the minimal data set required, improvement to the registries and clinical data banks, and development of an international clearinghouse to enhance information diffusion on both existing data bases and available reports on medical technology assessments.

Congenital hemiparesis: the spectrum of lesions. A clinical and computerized tomographic study of 37 cases.

Cerebral computerized tomography (CT) was obtained in 37 children with congenital hemiparesis to document the type of cerebral anomalies found in this group, correlate them with various features of the neurological handicap and clinical history and determine the prognostic and practical value of this examination in a newly diagnosed case. The CT-findings were: 1. normal CT: 4 children (11%); 2. unilateral ventricular enlargement: 9 children (24%); 3. others (cortical and subcortical lesions): 24 children (63%). In this latter group, special patterns were found: a) focal ischemic lesions: 7 cases; b) cystic porencephaly: 2 cases; c) ventricular deformities with hydrocephalus: 7 cases; d) varia: 8 cases. The children with normal CT or unilateral ventricular enlargement had mild or moderate hemiparesis without epilepsy or mental retardation. The third group comprised the more severe cases but the prognosis was very variable. The different types of CT-lesions, their possible origin and neuropathological correlates are described and compared with two previous studies. The variety of lesions found in this series and the relative prognostic value of the CT-Scan justify this examination in a newly diagnosed case.