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Biomedical subjects

M Leeman

Publications and source records attributed to M Leeman.

At least 19 recordsLinked to original sources
PubMed1997

Erythropoietin response is blunted in critically ill patients.

OBJECTIVES: Critically ill patients often develop anaemia which can be related to a number of factors. However, the exact causes of anaemia in many patients remain unexplained. We hypothesized that the relationship between erythropoietin (EPO) and haematocrit may be altered in critically ill patients. DESIGN: Serum concentrations of EPO were serially determined by the ELISA method in 36 critically ill, non-hypoxaemic patients who stayed more than 7 days in the Intensive Care Unit, including 22 patients with sepsis and 14 without. Eighteen ambulatory patients with iron-deficiency anaemia served as a control group. SETTING: Two University Hospital Intensive Care Departments. RESULTS: A significant inverse correlation between serum EPO and haematocrit levels was found in the control patients (r = -0.81, p < 0.001), but not in the critically ill patients (r = -0.09, NS), except in a subgroup of non-septic patients without renal failure (r = -0.61, p < 0.01). CONCLUSIONS: EPO levels can be inappropriately low in critically ill patients, so that EPO deficiency may contribute to the development of anaemia in these patients. This phenomenon is observed not only in the presence of acute renal failure, but also in the presence of sepsis.

Acute Kidney Injury↗
PubMed1997

Detection of 16 p deletions by FISH in patients with inv(16) or t(16;16) and acute myeloid leukemia (AML).

Deletions of sequences centromeric to the p-arm breakpoint have been described in a subset of patients with inv(16) and acute myeloid leukemia (AML) and reported to be associated with a relatively good prognosis. We have investigated 16 p deletions in a cohort of 15 patients with AML and inv(16) or t(16;16) and compared non-deletion and deletion patients in terms of clinical course. Patients were studied by fluorescence in situ hybridization (FISH) using cosmid zit14 as a probe to detect the presence of 16 p deletions in metaphase chromosomes of leukemic cells. While seven patients (47%) revealed no evidence of a deletion, five patients (33%) presented 16 p deletions, thus bringing further support to the relatively frequent occurrence of this event in inv(16) patients. Remarkably, two patients with inv(16) and one patient with t(16;16) showed a mosaicism of deletion and non-deletion metaphases suggesting the presence of two distinct leukemic cell populations. Results let us assume that 16 p deletions are not restricted to inv(16) and may occur subsequently to inv(16) or t(16;16). The presence of a 16 p deletion in a case of inv(16) associated with CBFB-MYH11 transcript type E indicates that deletions are not limited to CBFB-MYH11 transcript type A rearrangements. Survival of deletion patients was compared with that of non-deletion and mosaic ones. No significant differences were observed. The advantage of FISH for enumerative and quantitative assessment of submicroscopic rearrangements of clinical significance is further emphasized.

Adolescent↗
PubMed1996

Effects of chronic dexfenfluramine treatment on pulmonary hemodynamics in dogs.

An epidemic of primary pulmonary hypertension occurred in Europe in the 1960s, after the introduction of the appetite suppressant aminorex. Recently, a cluster of cases of pulmonary hypertension was observed in France in relation to the intake of the appetite suppressant dexfenfluramine. We previously reported that intravenous dexfenfluramine enhances hypoxic pulmonary vasoconstriction in dogs. We therefore investigated the pulmonary hemodynamic effects of chronic oral intake of this drug. Twenty-four dogs with a strong (n = 12) and a weak hypoxic pulmonary vasoconstriction (n = 12) respectively were randomly allocated in a double blind manner to a twice daily oral intake of either a placebo or dexfenfluramine 1.5 mg/kg for 20 d. A strong hypoxic vasoconstriction was defined as a hypoxia-induced increase in pulmonary artery pressure by more than 3 mm Hg at a standardized cardiac output of 3 L/min/m2. Pulmonary hemodynamics were studied in hyperoxia (fraction of inspired O2 [F(I)O2] 0.4) and in hypoxia (F(I)O2 0.1) before and after treatment. Venous return was manipulated at post-treatment evaluation for isoflow comparisons of pulmonary vascular pressures. Dexfenfluramine had no effect on systemic hemodynamics or blood gases, but increased pulmonary vascular resistance from 155 +/- 17 to 192 +/- 14 dyne x s x cm(-5) in hyperoxia (mean +/- SE, p < 0.05) and from 237 +/- 27 to 293 +/- 47 dyne x s x cm(-5) in hypoxia (p < 0.01). Dexfenfluramine, and not placebo, increased the isoflow pulmonary vascular pressure gradient in hyperoxia and in hypoxia. This effect was unrelated to the magnitude of pretreatment hypoxic vasoconstriction. We conclude that the chronic intake of dexfenfluramine in dogs is associated with a moderate increase in pulmonary vascular resistance which is unrelated to pulmonary vasoreactivity to hypoxia.

Administration, Oral↗
PubMed1996

Determinants of right ventricular failure after heart transplantation.

Predictive factors of right ventricular failure after heart transplantation are not well identified. Clinical and hemodynamic data from 20 patients who developed right heart failure were compared to those of 20 matched patients who did not experience this complication after cardiac transplantation. Preoperative systemic and pulmonary hemodynamics were comparable in the two groups. Patients with posttransplant right ventricular failure had longer waiting time (27 +/- 6 vs 16 +/- 3 weeks, mean +/- SE, P < 0.05), no regression of pulmonary hypertension (0 +/- 0.1 vs 2.3 +/- 0.3 Wood units reduction in pulmonary vascular resistance after transplantation, P < 0.01), and had been ventilated with higher levels of positive end-expiratory pressure (5 +/- 1 vs 1.5 +/- 0.5 cm H2O, P < 0.05). One-month postoperative evolution (mortality, hospital stay, radionuclide ejection fractions) was similar in the two groups. These results suggest that a lesser reversibility of pulmonary hypertension (possibly due to a longer evolution of the cardiac disease, as indicated by the longer waiting time) is the main determinant of right ventricular failure after heart transplantation.

Heart Transplantation↗
PubMed1995

Methylene blue administration in septic shock: a clinical trial.

OBJECTIVE: A release of nitric oxide has been incriminated in the cardiovascular alterations of septic shock. Since guanylate cyclase is the target enzyme in the endothelium-dependent relaxation mediated by nitric oxide, we studied the acute effects of methylene blue, a potent inhibitor of guanylate cyclase in patients with septic shock. DESIGN: Prospective clinical trial. SETTING: Medical-surgical intensive care unit in a university hospital. PATIENTS: Fourteen patients with severe septic shock requiring adrenergic therapy. INTERVENTIONS: Short-term intravenous infusion of methylene blue. MEASUREMENTS AND MAIN RESULTS: Hemodynamic measurements were obtained at baseline, and 30, 60, and 90 mins after the infusion of 2 mg/kg of methylene blue. Methylene blue administration was followed by a progressive increase in mean arterial pressure (from 61.1 +/- 7.6 to 71.7 +/- 12.0 mm Hg at 60 mins, p < .01). Pulmonary arterial pressure, cardiac filling pressures, cardiac output oxygen delivery, and oxygen consumption were not significantly affected. Left ventricular stroke work increased from 42.5 +/- 17.9 to 48.9 +/- 14.5 g.m after 60 mins (p < .05). Arterial lactate concentration decreased from 3.4 +/- 1.4 to 2.7 +/- 1.3 mmol/L (p < .05). Since these effects were transient, a second dose of methylene blue was administered 90 mins later to six patients and was followed by a similar response. No adverse effect was observed. CONCLUSIONS: In septic shock patients, the administration of methylene blue results in a transient and reproducible increase in arterial pressure, associated with an improvement in cardiac function, but does not increase cellular oxygen availability. The significant reduction in blood lactate concentration is probably related to the reductor effect of methylene blue, rather than to an improvement in tissue oxygenation.

Adult↗
PubMed1995

Invasive hemodynamic evaluation of sublingual captopril and nifedipine in patients with arterial hypertension after abdominal aortic surgery.

OBJECTIVES: To examine the central hemodynamic and blood gas responses to sublingual captopril and nifedipine administration in patients with arterial hypertension after abdominal aortic surgery. DESIGN: Prospective, randomized, parallel-group clinical study. SETTING: Twenty-nine-bed medical-surgical intensive care unit in a university hospital. PATIENTS: Twenty patients with arterial hypertension (mean arterial pressure of > or = 115 mm Hg) the day after abdominal aortic surgery. Patients with bilateral renal artery stenoses, identified with the preoperative angiogram, were excluded. INTERVENTIONS: Pressures were measured using intravascular catheters and cardiac output was determined by thermodilution for 2 hrs after captopril 25 mg (n = 10) or nifedipine 10 mg (n = 10) was administered by the sublingual route. MEASUREMENTS AND MAIN RESULTS: Captopril administration and nifedipine administration decreased mean arterial pressure (from 121 +/- 1 to 94 +/- 4 mm Hg and from 121 +/- 2 to 94 +/- 2 [sem] mm Hg, respectively), pulmonary arterial pressure, pulmonary artery occlusion pressure, and right atrial pressure (p < .001 for all variables). Changes in heart rate and in cardiac output were not significant. PaO2 decreased after nifedipine, from 101 +/- 8 to 81 +/- 3 torr [13.5 +/- 1.1 to 10.8 +/- 0.4 kPa] (p < .01), but not after captopril (104 +/- 9 to 100 +/- 7 torr [13.9 +/- 1.2 to 13.3 +/- 0.9 kPa]). Excessive or symptomatic decreases in blood pressure were not observed, nor was deterioration in renal function observed. CONCLUSIONS: Sublingual captopril and nifedipine were equally effective for the treatment of arterial hypertension after abdominal aortic surgery. Nifedipine, but not captopril, caused a deterioration in pulmonary gas exchange.

Administration, Sublingual↗
PubMed1995

Starling resistor vs. distensible vessel models for embolic pulmonary hypertension.

We investigated whether the Starling resistor model (Mitzner et al. J. Appl. Physiol. 51: 1065-1071, 1981) or a distensible vessel model (Haworth et al. J. Appl. Physiol. 70: 15-26, 1991) best describes pulmonary vascular pressure-flow (Q) relationships in embolic pulmonary hypertension. Mean pulmonary arterial pressure (Ppa)-Q plots at constant left atrial pressure (Pla) and Ppa-Pla plots at constant Q were investigated in seven dogs before and after 500-micron glass bead pulmonary embolism. Embolization to a mean angiographic obstruction of 78% increased the slope and extrapolated pressure intercept (P(i)) of Ppa-Q plots and increased the inflection point of Ppa-Pla plots, above which an increase in Pla is transmitted to Ppa in a ratio of approximately 1:1. The Starling resistor and the distensible vessel model provided a reasonably good fit to the Ppa-Q and Ppa-Pla coordinates before and after embolism. However, contrary to the prediction of the Starling resistor model, no correlation was found between the inflection point of Ppa-Pla plots and P(i). We therefore conclude that an increased closing pressure is unlikely to contribute to embolic pulmonary hypertension.

Animals↗
PubMed1995

Effects of dexfenfluramine on hypoxic pulmonary vasoconstriction and embolic pulmonary hypertension in dogs.

There has been suggestion of a possible relationship between the intake of the appetite suppressant dexfenfluramine and the development of primary pulmonary hypertension. We investigated the pulmonary vascular effects of acute intravenous dexfenfluramine in pentobarbital-anesthetized dogs ventilated in hyperoxia (fraction of inspired oxygen, FIO2, 0.4) and either challenged with a FIO2 of 0.1 to induce hypoxic pulmonary hypertension (n = 20) or given autologous blood clots to induce embolic pulmonary hypertension (n = 6). Pulmonary vascular tone was evaluated by multipoint (mean pulmonary artery pressure [Ppa] - pulmonary artery occluded pressure [Ppao])/cardiac output (Q) plots. Hypoxia increased Ppa - Ppao over the entire range of Q studied, from 1.5 to 4.0 L/min/m2, in 12 dogs (responders) and had no significant effect on (Ppa - Ppao)/Q plots in 8 other dogs (nonresponders). Dexfenfluramine did not affect (Ppa - Ppao)/Q plots in 6 responders but shifted (Ppa - Ppao)/Q plots to higher pressures in hypoxia in 6 nonresponders (p < 0.001). Dexfenfluramine had no effect on (Ppa - Ppao)/Q plots in the 6 dogs with embolic pulmonary hypertension. Because dexfenfluramine has serotoninergic properties, we compared the effects of ketanserin, a serotonin (5-hydroxytryptamine, 5-HT) S2 receptor antagonist, on naturally present versus dexfenfluramine-restored hypoxic pulmonary vasoconstriction. Ketanserin did not affect hyperoxic or hypoxic pulmonary vascular tone, neither in 6 responders nor in 2 nonresponders with dexfenfluramine-restored hypoxic vasoconstriction. We conclude that dexfenfluramine restores hypoxic pulmonary vasoconstriction in dogs with weak or absent hypoxic pressor response and that this effect is unlikely to be mediated by activation of 5-HT S2 receptors.

Animals↗
PubMed1994

Effects of endogenous nitric oxide on pulmonary vascular tone in intact dogs.

The interaction between inspiratory fraction of O2 (FIO2) and endogenous nitric oxide (NO) regulation of pulmonary vascular tone was examined in intact anesthetized dogs. Stimulus (FIO2 of 1, 0.4, 0.21, 0.12, and 0.1)-response (changes in pulmonary artery pressure minus pulmonary artery occlusion pressure) curves were constructed with cardiac output kept constant (by opening a femoral arteriovenous bypass or inflating an inferior vena cava balloon catheter), before and after administration of compounds acting at different levels of the L-arginine-NO pathway, NG-nitro-L-arginine (L-NNA, 10 mg/kg iv, n = 16), a NO synthase inhibitor, and methylene blue (8 mg/kg iv, n = 16), a guanylate cyclase inhibitor. L-NNA and methylene blue did not influence pulmonary vascular tone in hyperoxic and in normoxic conditions, but they increased it during hypoxia, thus enhancing the vasopressor response to hypoxia (from 4.5 +/- 0.9 to 10.4 +/- 1.2 mmHg and from 4.2 +/- 0.8 to 9 +/- 1.5 mmHg, respectively, both P < 0.01). Hypoxic pulmonary vasoconstriction was augmented in dogs with a baseline hypoxic response ("responders") and restored in dogs without hypoxic response ("nonresponders"). These results suggest that endogenous NO does not influence hyperoxic and normoxic pulmonary vascular tone, but that it inhibits hypoxic pulmonary vasoconstriction in intact anesthetized dogs.

Animals↗
PubMed1994

Stimulus-response curve of hypoxic pulmonary vasoconstriction in intact dogs: effects of ASA.

Hypoxic pulmonary vasoconstriction (HPV) has been reported to decrease during severe hypoxia in isolated lungs, but it remains unknown whether this decrease occurs in the intact animal and how it is affected by cyclooxygenase inhibition. We investigated the HPV stimulus-response relationship in eight pentobarbital sodium-anesthetized intact dogs with a naturally occurring response to hypoxia ("responders"). The pulmonary arterial minus wedge pressure difference (Ppa-Ppw) was measured at 11 inspired O2 fraction (FIO2) values between 0.40 and 0.04 while ventilation, cardiac output, and acid-base status were kept constant. Ppa-Ppw increased by 8 +/- 1 mmHg between FIO2 of 0.40 and 0.10 (alveolar PO2 of approximately 40 Torr) and decreased by 3 +/- 1 mmHg between FIO2 of 0.10 and 0.04. To assess the effects of cyclooxygenase inhibition, similar stimulus-response curves were obtained after administration of 20 mg/kg of acetylsalicylic acid (ASA) in 16 more dogs selected as either nonresponders or responders to hypoxia. ASA restored HPV in nonresponders and enhanced HPV in responders, with the difference between Ppa-Ppw at FIO2 of 0.10 and 0.40 increasing from 1 +/- 1 to 8 +/- 1 mmHg (P < 0.001) and from 7 +/- 1 to 10 +/- 1 mmHg (P < 0.05), respectively. In both groups, the shape of the stimulus-response curve after ASA was comparable to that of spontaneous HPV, with a maximum at FIO2 of 0.10 and a significant decrease at lower FIO2. We conclude that severe hypoxia attenuates HPV in the intact animal and that ASA restores or enhances HPV by affecting the magnitude of the hypoxic response and not the sensitivity to hypoxia.

Acid-Base Equilibrium↗
PubMed1993

Systemic and renal haemodynamic effects of angiotensin converting enzyme inhibition by zabicipril in young and in old normal men.

Zabicipril is a recently introduced angiotensin converting enzyme (ACE) inhibitor, which has been observed in experimental animals to increase diuresis, natriuresis, glomerular filtration rate (GFR) and renal plasma flow (RPF). We have investigated the acute effects of zabicipril on systemic and renal haemodynamics in two groups of 8 sodium-replete normal men, aged 23 to 30 y and 65 to 74 y. Zabicipril 0.5 mg, 1 mg or 2.5 mg and a placebo were administered orally, at one week intervals, in a random order and in a double blind fashion. Haemodynamic measurements were performed at base line and every hour for 4 hours after intake of drug or placebo. Cardiac output (Q) was measured by Doppler echography, and RPF and GFR by the constant infusion technique using I123 iodohippurate and Cr51 EDTA, respectively. In the young men zabicipril did not affect Q, heart rate (HR), systemic arterial pressure (AP) or GFR, but it did increase RPF at the 4th hour after the highest dose (from 540 to 653 ml.min-1.m-2). In the old men zabicipril had similar actions, but the effect of the highest dose on RPF (from 355 to 415 ml.min-1.m-2) was less marked than in the young men. In the young and old men the inhibition of ACE peaked at about of 90% or more from the 2th to the 4th hour after the highest dose of zabicipril. We conclude that, in normal men, zabicipril increases the renal fraction of cardiac output in the absence of a concomitant change in systemic haemodynamics. This specific effect of zabicipril on the kidney may be less important with advancing age.

Adult↗
PubMed1993

Sotalol poisoning associated with asystole.

Sotalol overdose has special features because this beta-blocker has the potential to lengthen the Q-T interval and to initiate severe arrhythmias such as ventricular tachycardia or fibrillation. We describe the case of a 70-year-old woman who ingested 6.72 g sotalol with suicide attempt. Despite administration of activated charcoal, glucagon, atropine and isoprenaline, two episodes of asystole occurred, requiring cardiopulmonary resuscitation. Further treatment included ventricular pacing and dopamine. The patient recovered without neurologic nor cardiac sequelae.

Aged↗
PubMed1993

Systemic and renal hemodynamic responses to carvedilol and metoprolol in hypertensive renal transplant patients.

According to a randomized double-blind cross-over design, the short-term (8 weeks, n = 12) and acute (2 h, n = 6) systemic and renal hemodynamic effects of carvedilol (25-50 mg o.d.) and metoprolol (100-200 mg o.d.) were compared in kidney allograft recipients with mild transplant dysfunction and arterial hypertension chronically treated with metoprolol. Cardiac output (Q) was measured by Doppler echography and renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by constant infusion techniques using [123I]iodohippurate and [51Cr]EDTA, respectively. After 8 weeks, mean blood pressure (101 +/- 3 vs. 103 +/- mm Hg) and RBF (318 +/- 14 vs. 316 +/- 14 ml/min) were comparable for the two drugs, whereas heart rate (HR), Q, and GFR (39 +/- 2 vs. 42 +/- 2 ml/min, p < 0.05) were slightly lower and the RBF/Q ratio (6.4 +/- 0.4 vs. 5.8 +/- 0.4%, p < 0.05) was higher with carvedilol than with metoprolol. During short-term treatment, a single dose of metoprolol acutely decreased HR and Q, carvedilol increased RBF, and both carvedilol and metoprolol enhanced the RBF/Q ratio and decreased renal vascular resistance (by 23 and 7%, p < 0.01 carvedilol vs. metoprolol). These data suggest that carvedilol has beneficial acute renal hemodynamic effects in hypertensive kidney allograft recipients with mild transplant dysfunction.

Adrenergic beta-Antagonists↗