Growth hormone-induced insulin resistance in human subjects involves reduced pyruvate dehydrogenase activity.

AIM: Insulin resistance induced by growth hormone (GH) is linked to promotion of lipolysis by unknown mechanisms. We hypothesized that suppression of the activity of pyruvate dehydrogenase in the active form (PDHa) underlies GH-induced insulin resistance similar to what is observed during fasting. METHODS: Eight healthy male subjects were studied four times in a randomized, single-blinded parallel design: Control, GH, Fasting (36 h) and GH + Fasting. GH (30 ng × kg(-1) × min(-1)) or saline was infused throughout the metabolic study day. Substrate metabolism and insulin sensitivity were assessed by indirect calorimetry and isotopically determined rates of glucose turnover before and after a hyperinsulinemic euglycemic clamp. PDHa activity, PDH-E1α phosphorylation, PDK4 expression and activation of insulin signalling proteins were assessed in skeletal muscle. RESULTS: Both fasting and GH promoted lipolysis, which was associated with ≈50% reduction in insulin sensitivity compared with the control day. PDHa activity was significantly reduced by GH as well as fasting. This was associated with increased inhibitory PDH-E1α phosphorylation on site 1 (Ser(293)) and 2 (Ser(300)) and up-regulation of PDK4 mRNA, while canonical insulin signalling to glucose transport was unaffected. CONCLUSION: Competition between intermediates of glucose and fatty acids seems to play a causal role in insulin resistance induced by GH in human subjects.

[Counting of axillary lymph nodes during surgery of breast cancer. A comparison between radiographic examination and pathological assessment]. / Optaelling af lymfeknuder i aksilpraeparat ved operation for carcinoma mammae. En sammenligning mellem røntgenundersøgelse og patologisk vurdering.

Proper breast cancer surgery should include removal of at least ten axillary lymph nodes according to recommendations given by DBCG (The Danish Breast Cancer Group). The present study evaluated the results of counting the lymph nodes peroperatively on radiographs of the axillary tissue compared to the final pathological examination, the latter being considered the "gold standard". Since agreement between the two methods was found in only 66 out of 90 patients (Kappa value 0.279), we consider the peroperative radiological examination of the axillary fat to be of no practical value.

[Dobutamine stress echocardiography. Use of dobutamine stress echocardiography in diagnosis and assessment of ischemic heart disease]. / Dobutamin stress-ekkokardiografi. Anvendelse af dobutamin stress-ekkokardiografi til diagnosticering og kvantitering af iskoemisk hjertesygdom.

Dobutamine stress echocardiography (DSE) is a new diagnostic method for evaluation of patients with known or suspected coronary artery disease. We studied 30 consecutive patients referred for evaluation of chest pain. Coronary angiography was carried out in 28 patients. DSE was performed the following day. Readable echocardiographic recordings were obtained in all patients. Blinded wall motion analysis revealed a diagnostic sensitivity of 91% (95% confidence limits: 79-100%) for dobutamine stress echocardiography using coronary angiography as reference. No severe adverse events or arrhythmias occurred. It is concluded that DSE is well tolerated, feasible and has a high sensitivity for detecting coronary artery disease.

Effect of supine exercise on platelet aggregation and fibrinolytic activity.

In 12 healthy young men, strenuous cycling exercise in the supine position, caused platelet aggregability to decrease and the ADP threshold to rise from 7.0 microM resting, to 9.5 exercising (P < 0.01). At the same time, fibrinolytic activity increased markedly: euglobulin clot lysis time shortened from 178 to 68 min, PAI-1 fell from 8.91 to 5.16 IU ml-1, and t-PA rose from 0.56 to 3.95 IU ml-1, all three values were significant to P < 0.01. When the erect posture was assumed after lying at ease for 1 h after exercise, it did not increase platelet activity as expected, but caused a modest increase of fibrinolytic activity. These results suggest that supine exercise will not affect the haemostatic system adversely.

[Measurement of cholesterol in capillary blood using the Reflotron system. Results from approximately 1,000 comparisons with reference measurements of cholesterol in venous serum]. / Måling af kolesterol i kapillaerblod med Reflotron-systemet. Resultater fra ca. 1.000 sammenligninger med referencemålinger af kolesterol i venøst serum.

The results of 969 measurements of total cholesterol in capillary blood from fingerstick, performed with the Reflotron-system in the field, were compared with measurements of total cholesterol in venous serum. The comparison allows an evaluation of the combined effect of differences in sample material, working place, stability of methods and staff training. The mean values for all measurement were nearly identical with the two methods, and approximately 95% of the Reflotron-measurements were within an interval of +/- 0.7 mmol/l around the estimated true value. However, values below approximately 6 mmol/l were systematically underestimated, and values above approximately 7 mmol/l were overestimated with the Reflotron-system. The coefficient of variation of the system is below 5%, but both this precision and the accuracy appear to be unstable. Evaluated as a tool in screening for hypercholesterolemia, measurements with the system resulted in a modest extent of erroneous classification of subjects, but the positive diagnostic predictive value of the statement "cholesterol above 7 mmol/l" is only approximately 76%. Simulations of likely variations in the accuracy and precision of the method show a significant influence on the extent of errors. It is recommended that measurements with the system are routinely controlled by measuring an appropriate control material, at the start of each run and after every 30 samples.

[A comparison of results of simple evaluation of the risk of ischemic heart disease with calculations based on a multiplicative model]. / Sammenligning af resultater fra enkle vurderinger af risiko for iskaemisk hjertesygdom med beregninger baseret på en multiplikativ model.

A simple model for detection of subjects at risk of ischaemic heart disease, based on the addition of scores for different risk factors (Anggaard EE, Land JM, Lenihan J et al. Br Med J 1986; 293: 177-80), is at present widely applied in Denmark. The model could be tested in a prospective study, or a historical follow-up study, but we do not have the possibilities to do so. Instead we have compared the risk score of the model with the estimated five-year coronary mortality risk (ECR) in 742 men aged 40-44 years, calculated on the basis of data from the Seven Countries Study. There is a reasonable consistency in this comparison, in spite of the different principles of calculation, the consideration of different risk factors and/or weighting of risk factors. For example, the model has a sensitivity of 71%, a specificity of 89% and a positive predictive value of 68% in detecting 40-44 year old men in the upper quartile of ECR. The "false positives" are often men, who for other reasons may require preventive medical attention (obese heavy smokers), and the "false negatives" are often men with isolated hypertension.

[Occurrence of cardiovascular risk factors among working Danish men 20-59 years of age]. / Forekomst af kardiovaskulaere risikofaktorer blandt 20-59 årige erhvervsaktive danske maend.

The prevalence of risk factors for ischaemic heart disease (IHD) was recorded in 1,365 men aged 20-59 years in active employment. The purpose was to evaluate the implications of a high-risk strategy based on the rather conservative Danish guidelines for treatment of hypercholesterolemia. The prevalence of various risk factors depends on age, but in all, 1% had diabetes mellitus, 5% had a family history of premature IHD, 50% were smokers, 21% were obese, 12% had systolic blood pressure greater than or equal to 160 mmHg, 8% had diastolic blood pressure greater than or equal to 100 mmHg and 14% had serum cholesterol greater than 7 mmol/l. Only 24% had none of these risk factors and there was a considerable clustering of risk factors in certain subgroups. Approximately 34%, varying from 17% of the younger to 49% of the older, required medical follow-up as part of the high risk strategy. We have estimated the required number of visits to a general practitioner, if all Danish men aged 20-59 years were screened within three years and approximately 30% required follow-up for five years, with three visits in the first year and one thereafter. The number of visits peaks at 450 visits per year during the third year, and a number of circumstances could reduce this figure considerably. Multifactorial models to estimate risk in connection with screening should be adopted to the Danish guidelines for treatment of hypercholesterolemia and hypertension, and future guidelines for intervention should probably be integrated in such a multifactorial model. To practice preventive medicine, many physicians will need greater knowledge of dietary counselling.