Search PubMed⌕ Search

Biomedical subjects

C Michel

Publications and source records attributed to C Michel.

At least 199 records · Page 11Linked to original sources
PubMed1993

Hemodynamic and mechanical determinants of myocardial O2 consumption in normal human heart: effects of dobutamine.

The relationship of myocardial O2 consumption (MVO2) to its potential hemodynamic and mechanical determinants was investigated in eight healthy normal volunteers at rest and during infusion of dobutamine (5-10 micrograms.kg-1.min-1). MVO2 was calculated from the monoexponential myocardial clearance of [1-11C]acetate with positron emission tomography, and left ventricular mechanical function was assessed by two-dimensional echocardiography. Infusion of dobutamine increased heart rate by 53%, the tension-time index by 31%, and the rate-pressure product by 116%. Cardiac output (+70%), left ventricular ejection fraction (+24%), total mechanical energy [systolic pressure-volume area, (PVA) +84%], and left ventricular pressure-work index (+100%) also increased during infusion of dobutamine. During infusion of dobutamine, MVO2 increased from 96 +/- 17 to 233 +/- 19 J.min-1.100 g left ventricle-1, while myocardial efficiency (the ratio of PVA to MVO2) decreased from 46 +/- 8 to 35 +/- 4% (P < 0.001 each). MVO2 was best correlated (P < 0.001) with the PVA (r = 0.92) and the pressure-work index (r = 0.92). Infusion of dobutamine also resulted in a significant parallel upward shift of the PVA-MVO2 relationship, indicative of an increase in PVA-independent MVO2. Our data indicate that, in human subjects, MVO2 is mainly related to systolic PVA and that inotropic stimulation with dobutamine results in decreased efficiency of contraction, such as that previously described in isolated hearts.

Acetates↗
PubMed1993

Direct comparison of [13N]ammonia and [15O]water estimates of perfusion with quantification of regional myocardial blood flow by microspheres.

BACKGROUND: Both [13N]ammonia and [15O]water have been used to quantify myocardial blood flow with positron emission tomography using appropriate tracer kinetic models. A direct comparison of the two tracers with radioactive microspheres has not been performed in the same experimental preparation. METHODS AND RESULTS: The two tracers have been tested for myocardial blood flow quantification in closed-chest dogs with circumflex coronary stenosis or permanent occlusion at rest and during adenosine-induced hyperemia. [13N]ammonia- and [15O]water-derived myocardial blood flow values have been compared with radiolabeled microspheres. Validation studies consisted of simultaneous measurements of blood flow with positron emission tomography and microspheres over a wide range of flow values. Blood pool and regional tissue activity curves were fitted with a three-compartment model for [13N]ammonia with and without arterial metabolite correction and with a single-tissue-compartment model for [15O]water. A correction for finite-resolution effect before the fit was also applied. In large regions of interest (5 cm3), a good correlation between the microsphere method and [13N]ammonia (with metabolite correction) was obtained (y = 3 + 0.78x, r = 0.94). The correlation with microspheres was slightly better with [15O]water (y = -3 + 0.89x, r = 0.97). Similar correlations were achieved in smaller regions of interest (1 cm3) as well as in akinetic segments and in central infarct regions. CONCLUSIONS: Positron emission tomography with appropriate tracer kinetic models using [13N]ammonia and [15O]water provides an accurate quantitative method for measuring regional myocardial blood flow over a wide range of flow values in normally contracting or akinetic canine myocardium in the absence and in the presence of infarction.

Ammonia↗
PubMed1993

Induction of oestrus in cats by photoperiodic manipulations and social stimuli.

The development of the nervous system can be studied only if the age of the embryo is exactly known. Since it is difficult to control reproduction in female cats, we tried to time fertilization very precisely to within one hour by using either artificial insemination, or by mating females in oestrus induced by light programming. In one trial, this programming was associated with male or female stimuli according to the work of McClintock (1971, 1978, 1984) and Preti et al. (1986).

Animals↗
PubMed1993

Worldwide demographics and future trends of the management of renal failure in the elderly.

Aging will be a serious social problem in the future. The number of patients of 75 years and over with end-stage renal disease (ESRD) is bound to increase. The time has come to pay greater attention to their problems before and during dialysis treatment. Prevention of ESRD is an important challenge, especially in the field of vascular diseases which are the main cause of ESRD in the elderly. The exact number of elderly patients who will require dialysis in the next few years is difficult to foresee. It is only when the incidence of patients starting dialysis at 75 and over levels off that we may assume that elderly patients are no longer rejected from treatment; we could then assess the actual need in dialysis facilities. In elderly dialysis patients, mortality remains high. Improvements in geriatric medicine and dialysis techniques should contribute to better results in future years. As it is almost impossible to predict the survival and how an elderly patient will adapt to treatment, it appears more ethical to propose a trial of dialysis treatment, except in cases of severe dementia or malignancy. This large acceptance rate implies admitting that withdrawal from dialysis must sometimes be considered.

Age Factors↗
PubMed1993

Long-term effects of recombinant human erythropoietin on bone marrow progenitor cells.

Eleven uraemic patients were treated with recombinant human erythropoietin (rHuEpo). Seven haemodialysis patients and four peritoneal dialysis patients received a starting dose of 80 IU/kg i.v. and 40 IU/kg s.c. respectively, thrice weekly. The number of burst-forming-unit erythroid (BFU-E), colony-forming-unit erythroid (CFU-E), granulocyte-monocyte (CFU-GM) and megakaryocyte (CFU-Mk) were assayed 2 weeks before (D0), and 1 (M1) and 6 months (M6) after the initiation of rHuEpo treatment by means of a commonly applied in-vitro clonal assay. All the patients showed the same haematopoietic response. A significant increase of CFU-E and CFU-Mk could be observed within 1 month of treatment. At this time, no significant modification was observed in BFU-E and CFU-GM number. At the 6th month the increase of CFU-E was maintained, whereas a significant fall of BFU-E, CFU-GM and CFU-Mk was observed. These results suggest that in-vivo effects of rHuEpo are not restricted to the erythroid lineage but that erythropoietin might also act as a co-factor of megakaryopoiesis. In the long term erythropoietin might induce erythroid differentiation in multipotent progenitor cells at the expense of the non-erythroid progenitors.

Adult↗
PubMed1993

Daily subcutaneous administration of recombinant human erythropoietin (rhEPO) in peritoneal dialysis patients: a European dose-response study.

In a prospective randomized open multicenter study, 107 anemic (Hct < = 28%) peritoneal dialysis (PD) patients were treated with s.c. rhEPO daily. The mean observation period was 299 days (range 14-479 days). Patients were randomly assigned to 3 groups with different initial doses: 5 U/kg (G5), 10 U/kg (G10), 20 U/kg (G20). Initial doses were maintained for at least 8 weeks unless the target Hct (30-35%) was achieved earlier. The weekly increase of Hct was significantly (p < 0.05) dose-dependent: 0.19% in G5, 0.5% in G10 and 0.94% in G20. In case of insufficient response (< 0.5% per week), the dose was doubled every 4 weeks. Final doses on achieving the target Hct ranged from 5 to 40 U/kg (median 20 U/kg). The dose was then reduced to 50% and adjusted individually. The median maintenance dose was 9.9 U/kg/day. No tendency towards higher blood pressure or intensification of antihypertensive treatment was observed. When rhEPO is administered daily, 10 U/kg/day (70 U/kg weekly) is the recommended starting dose. The need for higher doses used in unsatisfactory response, should lead to further examination to rule out iron deficiency and other reasons for non-response. The median maintenance dose reported here is the lowest published in the literature for PD patients and seems to be linked to the daily injections.

Anemia↗
PubMed1993

Transcutaneous oxygen pressure. An effective measure for prosthesis fitting on below-knee amputations.

After amputation for arterial occlusive disease of the lower limbs, healing and local adaptation to a prosthesis depend on the oxygen ratio in the tissue. Transcutaneous oxygen tension (TcPO2) is a noninvasive microcirculatory exploration. Forty six below-knee stumps were selected without any prosthetic problem excepting vascular, with a follow-up mean duration of 23 months. They were classified into different prosthetic categories. The first was the worst because it required further amputation on the thigh and the fourth the best, which displayed complete adaptation to a socket contact. These groups were related to their TcPO2 values on the anterior and exterior face of the stumps in both reclined and seated positions. It seems that it is impossible to achieve healing when the TcPO2 value is lower than 15 mm Hg in lying position. However, healing is possible above 20 mm Hg but socket contact is not possible when TcPO2 values are under 40 mm Hg. When TcPO2 values are above 40 mm Hg, a good prosthesis fitting is possible when no problems are encountered other than vascular ones.

Aged↗
PubMed1992

Adenosylcobalamin and cob(II)alamin as prosthetic groups of 2-methyleneglutarate mutase from Clostridium barkeri.

The ultraviolet/visible spectrum of the pure pink-orange 2-methyleneglutarate mutase from Clostridium barkeri between 300-600 nm showed the presence of cobalamins; notably the peaks at 470 and 528 nm were indicative of oxygen-stable cob(II)alamin and adenosylcobalamin (coenzyme B12), respectively. Using the absorption coefficients of the isosbestic points at 340, 393 and 489 nm, the total cobalamin content was estimated as 3.7 +/- 0.3 mol/mol tetrameric enzyme (m = 300 kDa). Denaturation with 8 M urea in the presence of 2 mM dithiothreitol followed by gel chromatography and renaturation afforded an inactive enzyme which contained 40-50% of the initially bound cobalamin. This preparation could be reactivated to 95-100% by addition of adenosylcobalamin. The cobalamins were removed to 85% from the mutase by denaturation with 8 M urea in the presence of 1 M cyanide (pH 12) with irreversible loss of activity. 2-Methyleneglutarate mutase was inactivated by incubation with aquo-, cyano- or methylcobalamin; up to 50% of the activity was recovered by addition of adenosylcobalamin. Upon incubation of the mutase with [5'-3H]adenosylcobalamin about 30% of the total cobalamin was exchanged by the tritium-labelled cofactor without loss of activity. During aerobic catalysis the enzyme became sensitive towards oxygen which was accompanied by loss of activity and formation of aquocobalamin from adenosylcobalamin. EPR spectroscopy demonstrated the presence of 0.8 mol base-on cob(II)alamin/mol enzyme. Upon addition of 2-methyleneglutarate a second EPR signal of about equal intensity at g = 2.13 arose. The question of whether the oxygen-stable cob(II)alamin participates in catalysis or its complex with the enzyme represents an inactive form is currently under investigation.

Clostridium↗
PubMed1992

[Chronic kidney failure in the elderly].

Ageing does not spare the kidneys but, remarkably, renal impairment is virtually asymptomatic as homaeostasis remains ensured. Nevertheless, in routine practice physicians must take into account the "physiological" renal insufficiency of the elderly. In old people with chronic renal impairment the diagnostic and therapeutic approaches are special, owing to the age-related risks attached to both paraclinical examinations and treatments. Yet in certain subjects treatment can be remarkably effective and prevent the progression to terminal uraemia, and this justifies the detection and exploration of renal insufficiency in elderly patients. In the last few years, iterative dialysis programmes have been made available to third or even fourth age patients who had reached the so-called end-stage renal failure. The results are encouraging, but there are still purely medical questions concerning the measures to be taken in priority and the numerous organization problems to be solved for optimal management of these patients.

Aged↗
PubMed1992

Nephropathy associated with infection by human immunodeficiency virus: a report on 11 cases including 6 treated with zidovudine.

The human immunodeficiency virus (HIV) was recently suggested to be involved in generating kidney lesions in HIV-associated nephropathy (HIVN). The possibility that antiretroviral agents can slow down the usually explosive evolution of HIVN to end-stage renal failure (ESRF) has not been studied in many of the series of cases published. The present work is a retrospective analysis of 11 patients with histologically proven HIVN, 6 of whom were treated with zidovudine. Seven patients (group 1) either required dialysis at the outset, when HIVN was diagnosed, or progressed very fast to ESRF within 15-45 days. Two patients of this group were treated with zidovudine, but it had no effect on kidney function. In the remaining 4 patients (group 2), HIVN progressed more slowly than in group 1. All 4 patients were treated with zidovudine at an earlier stage of the disease than ESRF. Only 1 deteriorated to ESRF in 9 months. The 3 others, who did not have ESRF, were followed up for 13, 10 and 32 months, respectively. Although this is a preliminary study, its results do suggest that zidovudine can slow down the evolution of HIVN to ESRF. They highlight the need to screen HIV-positive patients regularly for proteinuria, in order to detect HIVN by renal biopsies at an early stage of renal lesion formation.

AIDS-Associated Nephropathy↗
PubMed1992

Regional oxidative metabolism in patients after recovery from reperfused anterior myocardial infarction. Relation to regional blood flow and glucose uptake.

BACKGROUND: Enhanced uptake of the glucose analogue 18F-fluorodeoxyglucose (FDG) in relation to flow has been proposed as an accurate method of identifying viable myocardium. The evaluation of myocardial oxidative metabolism could be an alternate way to identify reversible injury. The aim of the present study was to investigate in patients with reperfused anterior infarction whether differences in regional oxidative metabolism exist among regions with and without flow-metabolism mismatch. METHODS AND RESULTS: Fifteen patients with reperfused anterior myocardial infarction were studied between 2 weeks and 3 months after the acute event. Regional myocardial blood flow (13N-ammonia; three-compartment model), oxidative metabolism (11C-acetate; monoexponential clearance), and glucose uptake (FDG, linear graphic analysis) were evaluated with dynamic positron emission tomography. Flow-metabolism patterns were used to differentiate reversibly (FDG/flow greater than 1.2) from irreversibly injured myocardium (FDG/flow less than 1.2) using circumferential profile technique. Relative 13N-ammonia uptake was reduced in 71 of 90 anterior and/or septal segments, including 24 with (seven patients) and 38 without (eight patients) flow-metabolism mismatch. Acetate clearance (k), reflecting oxidative metabolism, was reduced by 51% in the center of the infarct area versus remote segments (27 +/- 12 versus 55 +/- 13 min-1.10(-3), p less than 0.001). Compared with infarct segments without flow-metabolism mismatch, segments exhibiting increased glucose uptake relative to flow had faster acetate clearance (35 +/- 14 versus 23 +/- 9 min-1.10(-3), p less than 0.01). Similarly, myocardial blood flow was better preserved in segments with flow-metabolism mismatch (54 +/- 13 versus 45 +/- 8 ml/min/100 g, p less than 0.01) compared with segments without mismatch. However, at similar levels of hypoperfusion, there was no significant difference in acetate clearance among segments with and those without flow-metabolism mismatch: 37 +/- 14 versus 41 +/- 15 min-1.10(-3), respectively. A positive correlation (r = 0.89, p less than 0.001) was found between absolute myocardial blood flow and acetate clearance, regardless of the flow-metabolism pattern. CONCLUSIONS: In patients with reperfused myocardial infarction studied between 2 weeks and 3 months after the acute event, regional oxidative metabolism is reduced in proportion to residual myocardial blood flow and does not differ significantly among similarly hypoperfused segments with and without flow-metabolism mismatch.

Acetates↗
PubMed1992

Encapsulation of insulin for oral administration preserves interaction of the hormone with its receptor in vitro.

It has been shown that insulin associated with nanocapsules of isobutylcyanoacrylate retains biological activity after oral administration to diabetic rats from 6 to 21 days. Because part of this action is unexplained, we focused on the interaction of encapsulated insulin with the insulin receptor in vitro. We have shown that encapsulated insulin is able 1) to bind to insulin receptors both in rat liver plasma membranes and after solubilization from Chinese hamster ovary (CHO) cells transfected with the gene of human insulin receptor, 2) to accelerate 125I-labeled insulin dissociation from its receptor, and 3) to ensure transduction of a signal leading to stimulation of the beta-subunit phosphorylation, with parameters similar to those of native insulin. In addition, encapsulated 125I-insulin was rapidly internalized in transfected CHO cells. Analysis of cell-associated radioactivity showed that encapsulated insulin remained largely intact (greater than 80%) after 3 h, whereas native insulin was mostly degraded. These data indicate that encapsulated insulin fulfills all the earliest events at the receptor level leading to biological actions and suggests that encapsulation protects insulin against insulin degradation inside the cells.

Administration, Oral↗
PubMed1992

Urination frequency and cystic pressure resistance after fractionated whole or partial irradiation of the rabbit urinary bladder.

Urination frequency and cystic pressure resistance have been used as end-points to assess x-ray-induced changes of bladder function. Whole or half bladders of adult male rabbits were irradiated, caudally or cranially. The absorbed dose was 33 Gy, 36 Gy or 39 Gy, given in 5 daily fractions. Animals which received a whole bladder dose of 39 Gy or 36 Gy showed increased urination frequency and enhanced bladder pressure resistance during the whole follow-up time of 100 weeks, compared with the sham-irradiated controls. At half bladder irradiation, only the highest doses (39 Gy to the cranial part of the bladder and 39 Gy or 36 Gy to the caudal part) gave rise to a slight increase in frequency at about 20 weeks after exposure.

Animals↗