The medical hierarchy and perceived influence on technical and ethical decisions

Abstract. Objective. To investigate the influence of hierarchial position and perceived influence on ethical and technical decisions. Design. The study was conducted as a postal questionnaire survey. Subjects. A random sample of 329 Danish physicians working at departments of internal medicine and related subspecialties. Of these, 270 (82%) returned a completed questionnaire. Main outcome measure. Self-reported perceived influence in discussions about technical and ethical issues in connection with decisions to terminate treatment for patients with terminal malignant illness. Results. The odds ratio for perceived influence between consultants and house officers is 14.9 for ethical issues, 44.9 for technical issues, and 652.3 for questions concerning departmental policy. Gender plays no role, when one controls for hierarchial position. Conclusions. Hierarchial position is the major determinant of perceived influence on technical and ethical decisions. Position seem to play a larger role in technical than in ethical decisions.     

Insulin and glucose uptake and insulin sensitivity in patients with peripheral arterial insufficiency

Abstract. There have been previous reports of evidence for increased insulin sensitivity in patients with intermittent claudication as the only symptom of arterial insufficiency. This study was designed to evaluate the role of peripheral tissue with respect to insulin sensitivity in such patients. Intravenous glucose tolerance tests (IVGTT) and intravenous insulin tolerance tests (IVITT) were performed in patients with peripheral arterial insufficiency and in controls. During IVGTT the plasma insulin values were significantly lower in patients with arterial insufficiency. During IVITT the venous concentration of glucose decreased more and the area over the glucose curve was significantly larger, suggesting a higher insulin sensitivity in this group. The low insulin values could not be referred to a larger distribution volume or an increased degradation rate, suggesting decreased pancreatic insulin release in this group. At the time of surgery for arterial insufficiency and for varicose veins in controls, the uptake of insulin and glucose and the release of lactate were measured over the leg before and after a glucose load. The uptake of insulin over the leg correlated positively with the arterial insulin concentration and the uptake of glucose in both groups. The insulin uptake had a tendency to be increased in legs with arterial insufficiency during the glucose challenge. The glucose uptake in the leg did not differ in the basal state, but was 3 times higher in the legs of patients with arterial insufficiency during glucose challenge. The increased glucose uptake in this group could be ascribed to a high insulin sensitivity in the leg, as defined by glucose uptake per unit of insulin taken up.     

Relationship between muscle morphology and metabolism in obese women: the effects of long-term physical training

To evaluate the relationships between changes in muscle morphology and metabolic adaptation to physical training in obesity, twenty obese women were subjected to a physical training programme with three sessions a week for 3 months. Physical training resulted in lowering of plasma insulin and improved glucose tolerance. Neither body weight nor body fat changed. With physical training the percentage distribution of fast twitch oxidative (FTa) muscle fibres (m vastus lateralis) increased (from 30.3 +/- 5.1% to 35.2 +/- 4.8%, P less than 0.05) and that of fast twitch glycolytic fibres decreased (from 18.3 +/- 6.6 to 5.8 +/- 4.8%, P less than 0.05). The number of capillaries increased, mainly around slow twitch (ST) fibres (from 4.5 +/- 0.6 to 5.8 +/- 0.8, P less than 0.01) and fast twitch oxidative (FTa) fibres (from 3.9 +/- 0.7 to 4.7 +/- 0.8, P less than 0.01). The activities of oxidative enzymes (cytochrome-c-oxidase and citrate synthase) increased (P less than 0.05) while those of glycolytic enzymes (phosphofructokinase and hexokinase) decreased after physical training (P less than 0.01). Significant negative correlations between plasma insulin and number of capillaries in contact with ST fibres (r = 0.80, P less than 0.001) and FTa fibres (r = 0.62, P less than 0.001) were found before training. The capillary density around those fibres could predict 80% of the explained variance of plasma insulin levels (P less than 0.001). The changes of glucose concentration after training could be predicted by observed changes in enzyme activities. The strong associations between muscle morphology and capillarization and enzyme activities and glucose and insulin concentrations and their changes after training suggest an important regulatory role of muscle which warrants further studies.     

Capillary supply and muscle fibre types in patients with intermittent claudication: relationships between morphology and metabolism

Abstract There have been previous reports on an increased oxidative capacity in muscle tissue from the diseased legs of patients with intermittent claudication. The present study was designed to correlate metabolic and morphological data and to investigate whether the metabolic adaptive changes in muscle tissue of claudicating legs were also reflected in morphological variables such as capillary supply, fibre type distribution, and fibre area. The activity of cytochro-me-c-oxidase in gastrocnemius muscle was determined and the insulin and glucose uptakes were measured across the leg in the basal state and 10 min following intravenous administration of 25 g glucose. The finding of a reduced relative number of Type II B fibres and a reduced ratio Type II B/II A fibre area, as well as an increased capillary supply to Type II A, indicated that the most extensive morphologic changes in muscle tissue of claudicating legs had occurred in Type II fibres. The increased number of capillaries in contact with Type IIA fibres in muscle tissue from claudicating legs, compared with muscle tissue from control legs, suggested that the most apparent metabolic changes occurred in this fibre type in the adaptation process of these patients. The more pronounced morphologic and metabolic changes in Type II fibres suggest that these fibres are more intensely activated than Type I fibres during physical activity in claudicating legs. The insulin uptake correlated positively with the number of capillaries per fibre, suggesting that the endothelial surface area is one of the determining factors for insulin uptake. The percentage of Type II B fibres reflected to a certain extent the metabolic adaptation in muscle tissue.     

Complications with the MICRA TPS Pacemaker System: Persistent Complete Heart Block and Late Capture Failure

A Medtronic MICRA transcatheter pacing system (Medtronic, Minneapolis, MN, USA) was implanted in an 86‐year‐old patient with sick sinus syndrome and left bundle branch block after transfemoral aortic valve implantation. During implantation she developed a persistent complete heart block due to manipulation with the large‐bore delivery catheter. Two weeks later, acute pacemaker dysfunction occurred due to massive increase of pacing threshold and impedance without obvious pacemaker dislocation or myocardial perforation. Recurrent capture failure was seen with pacing output set at 5 V/1.0 ms. Hence, microdislocation or fixation of the tines in the right ventricular trabeculae has to be assumed.     

Effect of captopril on the cerebral circulation in chronic heart failure

Cerebral blood flow (CBF) was investigated in 8 patients with chronic heart failure (CHF) (functional class III) and in twelve controls before and after administration of 6.25 mg and 25 mg captopril, respectively. In four controls, CBF was measured by the intracarotid xenon-133 (133Xe) injection technique using stationary external detectors, while inhalation of 133Xe and single photon emission computer tomography was used in the remaining cases. In the control group, the cerebral metabolic rate for oxygen was calculated from measurements of the arterio-venous oxygen difference as well. Mean CBF was significantly (P less than 0.01) lower in the patients with CHF as compared to our controls. Following captopril administration the mean arterial blood pressure decreased in the CHF patients, ranging from 5 to 40%. Three patients showed decreases of blood pressure to values of 56, 65, and 76 mm Hg, but no symptoms of cerebral hypoperfusion were elicited. CBF was unchanged after captopril administration, even in the patients showing a marked reduction in blood pressure. In the control group, the blood pressure, CBF and the cerebral metabolic rate for oxygen remained essentially constant following captopril administration. It is concluded that the cerebral circulation is well preserved during captopril treatment of chronic heart failure. This might be explained by a shift of the lower limit of CBF autoregulation towards lower blood pressure levels.     

Cellular Production of Antibodies Related to the Acetylcholine Receptor in Myasthenia Gravis: Correlation with Clinical Stage

Spontaneous and pokeweed mitogen-induced production of specific autoantibodies were studied in cultures of peripheral blood mononuclear cells from patients with different clinical stages of myasthenia gravis. Receptor antibody-related idiotypes and anti-idiotypic antibodies were defined by binding to mouse monoclonal anti-idiotypic and anti-receptor antibodies, respectively. Patients with severe disease had a more complete spectrum of idiotypes in serum, and cells from such patients spontaneously produced more antibody species and higher concentration of both idiotypes and anti-idiotypes than patients with mild disease. The frequencies of antibody specificities in tissue culture supernatants more closely reflected disease activity than those in serum. Tissue culture for the study of different species of autoantibodies has proved to be a useful tool for monitoring the disease and the effects of treatment.     

Acid-induced duodenal mucosal nitric oxide output parallels bicarbonate secretion in the anaesthetized pig

We recently showed the involvement of the L -arginine/nitric oxide (NO) pathway in acid-induced duodenal mucosal bicarbonate secretion in rats. The aim of the present study was to confirm this observation in pigs by direct measurements of NO production. Experiments were performed on 16 anaesthetized pigs of both sexes treated with guanethidine (6 mg kg^?1, intravenously). A duodenal segment, devoid of pancreaticobiliary influxes, was perfused with saline and the duodenal mucosal bicarbonate secretion was calculated from continuous measurements of pH and Pco₂. The perfusate contents of NO and its oxidative product nitrite were determined by chemiluminescence, after reduction of nitrite to NO. Luminal acidification with 30 mM hydrochloric acid increased the output of bicarbonate as well as NO to the perfusate, by 195 ± 45% and 106 ± 10%, respectively. These responses to acid were markedly inhibited by adding the NO synthase inhibitor N^G-monomethyl- L -arginine (L-NMMA, 0.3 mM) to the perfusate. The inhibitory effect of L-NMMA could be reversed by administration of L-arginine (3 mM). The study presents simultaneous measurements of bicarbonate and NO outputs to a duodenal luminal perfusate. The results strongly support the view that the L -arginine/NO pathway is involved in the acid-induced duodenal mucosal bicarbonate secretory response.     

Native Human Serum Amyloid P Component is a Single Pentamer

Serum amyloid P component (SAP) and C-reactive protein (CRP) are members of the pentraxin protein family. SAP is the precursor protein to amyloid P component present in all forms of amyloidosis. The prevailing notion is that SAP in circulation has the form of a double pentameric molecule (decamer) whereas CRP is a single pentameric molecule.
We have investigated by gel permeation chromatography the M_r of SAP in freshly collected human serum and of SAP purified by carbohydrate affinity chromatography and anion exchange chromatography. SAP was monitored by quantitative immunoelectrophoresis and ELISA. and SAP peak fractions were analysed by use of SDS-PAGE, Western blotting, and electron microscopy. The results indicate that native SAP circulates as a single pentamer, a part of which forms complexes with C4b-binding protein. The properties of SAP changed during purification as indicated by rocket immuno-electrophoresis and electron microscopy. Thus, electron micrographs of purified SAP showed a predominance of decamers. However, the decamer form of SAP reversed to single pentamers when purified SAP was incorporated into SAP-depleted serum.