[Insulin resistance and arterial hypertension].
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Biomedical subjects
Publications and source records attributed to M Krempf.
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The effect of a subcutaneous injection of an intermediate-acting insulin at bedtime combined with glibenclamide has been evaluated in 16 non-insulin-diabetic patients with secondary failure to respond to oral agents. The patients showed poor metabolic control (HbA1 greater than 11%) after two months on diet and glibenclamide treatment (15 mg.day-1). For 3 months the glibenclamide was continued together with an injection of an intermediate-acting insulin at bedtime in order to maintain fasting blood glucose under 120 mg.dl-1. A significant reduction in fasting blood glucose and HbA1 (15.50 vs 10.35%) and fructosamine (2.03 vs 1.69 mmol.l-1) was observed (230 to 141 mg.dl-1) at a mean insulin dose of 0.28 U.kg-1. The peak blood glucose after a standard test meal was also significantly improved (290 vs 203 mg.dl-1). Two months after the bedtime insulin injection had been withdrawn, only one patient was still being treated with oral agents alone. Except for another patient who dropped out, all the others had to be treated again with insulin because their fasting blood glucose exceeded 180 mg.dl-1. It is concluded that a single subcutaneous injection of an intermediate-acting insulin at bedtime combined with glibenclamide improved fasting and post-meal blood glucose concentrations in non-insulin-dependent patients resistant to diet and oral hypoglycaemic treatment. Almost all of the patients relapsed after insulin was withdrawn.
Pulmonary surfactant is altered in experimental Pneumocystis carinii pneumonia. Although P carinii is a major causative agent of pneumonia in immunocompromised patients, the pathophysiology of lung injury caused by this organism is poorly understood. Therefore, we studied bronchoalveolar lavage specimens obtained from 19 HIV-infected subjects with PCP compared with specimens from ten healthy control subjects. As iterative BAL was performed, 37 BAL specimens were analyzed for protein and phospholipid. The BAL samples were divided into two groups as follows: 22 BAL samples with the presence of P carinii and 15 BAL samples without P carinii. Compared to control subjects, HIV+ BAL presented a significant increase of PR and a decrease of total PL in both P carinii+ and P carinii- BAL, but in P carinii+ BAL, the fall of PL/PR ratio was significantly more pronounced compared to P carinii- (0.09 +/- 0.02 vs 0.19 +/- 0.04, p less than 0.02). The BAL performed during the recovery of PCP showed an improvement of initial biochemical abnormalities. Surfactant composition was also altered, with a phosphatidylcholine and phosphatidylglycerol drop and a sphingomyelin and lysophosphatidylcholine increase. The presence, even in P carinii- BAL, of less polar compounds of undetermined nature, was revealed. We concluded that in HIV+ patients, abnormalities of pulmonary surfactant were present before PCP, and that the development of PCP enhances these abnormalities. These surfactant alterations may contribute to the saprophyte-pathogen transformation of P carinii, but this hypothesis requires further investigation that is presently in progress.
The authors demonstrate the value of thoracic HR-CT in a case of Wegener's granulomatosis with a typical presentation. This uncommon disease, often has a pseudo-infectious or pseudo-neoplastic appearance and the diagnosis can be difficult as indicated by a review of the literature.
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Both intravenous drug addiction (IVDA) and HIV infection can involve respiratory system. So, we have studied pulmonary function in 107 heroin abusers during deprivation to clarify the extent of these two factors respectively. Two groups were separated: 50 subjects without HIV infection (HIV-) and 57 seropositive subjects (HIV+) in early stage of the disease (mean CD4 lymphocytes: 457 +/- 61/mm3). 36 subjects have been investigated 6 months later to evaluate the reversibility of possible observed abnormalities. Altered pulmonary function was encountered similarly in HIV+ and HIV-. DLco was abnormal in 40% of cases both in HIV+ (mean DLco: 63.4 +/- 1.1% of predicted values) and HIV- (mean DLco: 65.4 +/- 1.5% pred); obstructive lung disease was present in 18% of HIV- (FEV1/VC: 63.8 +/- 2.5) and 9% of HIV+ (FEV1/VC: 61 +/- 3.6); restrictive lung disease was found more frequently (16% vs 10%) in HIV+ (FEV1/VC: 81.2 +/- 2.1, TLC: 72.4 +/- 3.6% pred) than in HIV- (FEV1/VC: 84.2 +/- 1.6, TLC: 71.2 +/- 0.9% pred). These abnormalities were not associated with significant arterial blood gas modifications. As a whole, DLco tend to improve in the two groups and this significantly for HIV+ (p less than 0.03). But for individuals initial DLco alteration was persistent in 68% of cases suggesting slow improvement. In conclusion, in this study HIV+ and HIV- IVDA were not different concerning pulmonary function. In this risk group, DLco itself had a poor specificity and only it follow-up may be of interest for pulmonary opportunistic infection screening.
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The effect of 7-days of nifedipine treatment on insulin secretion has been analyzed in hypertensive patients with non-insulin-dependent mellitus (NIDDM). Pancreatic beta-cell function was assessed as insulin release following stimulation with arginine after potentiation by hyperglycaemia. Two groups of 5 patients with NIDDM (fasting blood glucose 139.2 mg.dl-1), on the same controlled diet, were compared; one was treated with nifedipine 30 mg per d and the other was the control. The mean blood pressure in the nifedipine group decreased (110 vs 102 mm Hg). Fasting blood glucose and basal plasma insulin were not affected by nifedipine. The acute insulin response (AIR) to 5 g arginine after potentiation by hyperglycaemia (clamped at 240 and 350 mg/dl for 30 min) was significantly (P less than 0.05) decreased, as well as the potentiation slope (line relating AIR and plasma glucose level) in those patients, and were unchanged in the control group. Thus, nifedipine may impair insulin secretion at high glucose levels in patients with NiDDM.
Six healthy young men were studied by indirect calorimetry for 6 h after eating a meal composed of glucose or manioc starch (equivalent to 50 g dextrose). Blood was drawn every 30 min for 6 h to measure plasma glucose, free fatty acid (FFA), and insulin concentrations. The glycemic index of the starch was 57%. Plasma insulin and glucose concentrations were significantly higher from 150 to 210 min and FFA concentrations remained significantly lower from 210 to 360 min after starch than after glucose. Carbohydrate oxidation rose from a similar initial concentration for glucose and starch, to a constant concentration until 200 min before becoming significantly higher for the starch load until the end of the test. Total glucose oxidation was significantly higher with starch. Total fat oxidation did not differ after the two loads. A negative correlation was found between glucose oxidation and plasma FFA concentrations. Use of low-glycemic-index carbohydrates increases carbohydrate oxidation because of lower plasma FFA concentrations and fat oxidation.
The efficacy and safety of m-[131I]iodobenzylguanidine ([131I]MIBG) were assessed in 15 patients with malignant pheochromocytomas in a nonrandomized, single arm trial, in which patients were treated with [131I]MIBG (SA, 740 megabequerel/mg) every 3 months. Seven of these patients had bone and soft tissue metastases, 4 had only soft metastases, and 4 had only bone metastases. The follow-up period ranged from 6-54 months; the number of doses ranged from 2-11, with 2.9 (78.4 mCi) to 9.25 gigabequerel (GBq) (250 mCi)/administration and a cumulative activity from 11.1-85.90 GBq (300-2322 mCi). The absorbed cumulative dose in tumors ranged from 12-155 Gy. A beneficial effect of the treatment was observed in 9 patients (60%). No complete remission of the disease was observed. Seven patients died during the study, among whom 4 never responded to the treatment. Seven had hormonal responses (4 complete and 3 partial), with a duration ranging from 5-48 months. Among these patients, 4 relapsed, and 3 died within 3 months. Five patients had partial tumoral responses mainly located in soft tissues and for a duration ranging from 29-54 months. All patients with a hormonal response had objective improvement in clinical status and blood pressure. There was no clear-cut relationship between the cumulative dose and the responses. The main side-effect observed in 1 patient with widespread bone metastases after three doses (12.9 GBq) was a pancytopenia, which resolved after treatment was discontinued. This study suggests that repeated [131I]MIBG treatment could be effective in patients with advanced malignant pheochromocytoma.
Although the main risk factors for atherosclerosis have been clearly identified and their correction has demonstrated its efficacy, many subjects do not receive the corrective measures appropriate for their case. The authors describe a hospital service for the prevention of atherosclerosis, which is intended for both primary and secondary prevention as well as for epidemiological monitoring and above all the evaluation of the preventive strategies employed. The results after the service has been running for one year are reported. They appear to confirm the initial options. Cooperation with other people involved in prevention both inside and outside the hospital, is also a fundamental aspect of this task.
Vitamin A and E status was studied in 35 type 1 (insulin-dependent) and 35 type 2 (non-insulin-dependent) diabetic patients and in 30 control subjects. Vitamin A blood concentration was significantly decreased in type 1 and increased in type 2 diabetic patients as compared to control subjects. No correlation was found between vitamin A blood concentration and blood glucose control as evaluated with HbA1c. Blood Vitamin E concentrations were significantly increased in both groups of diabetic patients and were statistically correlated with blood cholesterol, apoprotein B and triglycerides, but not with HbA1c.
The transmucosal passage of alpha-lactalbumin (alpha-La), phytohemagglutinin (PHA), and concanavalin A (Con A) (1 mg/ml) was measured in the rabbit ileum mounted in the Ussing chamber, with and without 10(-2) M glucose or galactose. The transport of the radiolabelled proteins was assessed by radioisotopic determination, high pressure liquid chromatography (HPLC) and enzyme linked immunosorbent assay (ELISA). In the absence of galactose, the transmucosal transport was significantly higher for PHA (4.1 +/- 1.8 micrograms/h.cm2 mean +/- SE) than for alpha-La (2.9 +/- 1.2) and very low for Con A (0.6 +/- 0.5). HPLC analysis of the transported material revealed differential processing of the proteins. ELISA indicated that 3 percent of radiolabelled alpha-La that crossed the epithelium was in an immunoreactive form, whereas no immunoreactive forms of PHA and Con A were detected. The uptake or binding by the tissue was identical for PHA and Con A (7.8 +/- 2.9 and 5.8 +/- 2.8 micrograms/cm2, respectively), and significantly lower for alpha-La (1.5 +/- 0.31). 10(-2) M galactose did not modify the uptake or binding of alpha-La and Con A, but significantly decreased that of PHA to a level that was not significantly different from that of alpha-La. The present results indicate that the initial uptake of the proteins is most likely dependent upon their interactions with the luminal side of the epithelium. After uptake, the proteins are subjected to intracellular processing which also appeared differential. Thus, protein transport depends on the properties both of the compartment crossed (Glycocalyx, brush-border membrane, cytoplasm, basolateral membrane), and of the protein.
The kinetics of three different tracers of phenylalanine were studied when continuously infused together either by an intravenous (IV) or intragastric (IG) route in six young healthy men during a fasting state. During IV infusion, mean flux values were 39.2 +/- 1.8, 40 +/- 3, 41.8 +/- 3.6 mumol.kg-1.h-1 for L-[ring-2H5], [15N], and L-[1-13C]phenylalanine, respectively (differences not significant). Fluxes were higher (P less than .001) during IG than IV infusion, indicating a disappearance of tracer during the first pass through the splanchnic area. Also, higher fluxes were found for [ring-2H5]phenylalanine (74 +/- 6.23 mumol.kg-1.h-1) compared with [15N] and L-[1-13C]phenylalanine (54.24 +/- 4.7 and 61.15 +/- 5.3 mumol.kg-1.h-1) during IG infusion. Proton exchange might explain this difference, possibly limiting in vivo use of this label when the tracer is to be administered by the IG route.
We used pulsed Doppler echocardiography to examine the systolic ejection flow from the right ventricle in 66 patients with chronic obstructive pulmonary disease. Adequate recordings were obtained in 60 patients, in conjunction with right heart catheterization. Patients without pulmonary artery hypertension at rest (mean pulmonary artery pressure less than 20 mm Hg) underwent an exercise test which identified a group with PAH during exercise (MPAP greater than 30 mm Hg). The patients were divided into four groups: group 1, or control group: 17 healthy nonsmokers without normal respiratory function data; group 2: COPD without PAH (n = 12); group 3: PAH during exercise (n = 26); group 4: PAH at rest (n = 22). Analysis of Doppler data included time to peak velocity, right ventricular pre-ejection period, and ejection period. Pulsed Doppler echocardiography was a simple and reliable method of detecting PAH. Latent PAH, revealed by the exercise test, was accompanied by significant changes in Doppler findings, confirming the sensitivity of the method.
Vitamin E (alpha-tocopherol) concentrations of plasma, platelets and erythrocytes were determined by HPLC in insulin-dependent (type I) and age-matched non-insulin-dependent (type II) diabetic patients and in two control groups. Plasma alpha-tocopherol levels were significantly increased in diabetic patients compared to control groups. Platelet and erythrocyte alpha-tocopherol levels were not significantly different in type I and type II diabetics as compared to their respective control groups, but differed from one another. Plasma vitamin E concentrations showed a significant correlation with plasma cholesterol and apoprotein B concentrations in different groups. The alpha-tocopherol/cholesterol and alpha-tocopherol/apoprotein B ratios in plasma were higher in diabetic patients, as were triglyceride contents. Platelet vitamin E levels were not significantly correlated with plasma concentrations. These findings suggest that vitamin E activity is altered in diabetic patients but that no diet supplementation seems necessary.