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Biomedical subjects

E Rondeau

Publications and source records attributed to E Rondeau.

At least 145 records · Page 8Linked to original sources

Unilateral lung transplantation in end-stage pulmonary emphysema.

Patients with end-stage pulmonary emphysema are usually proposed for either heart-lung or double-lung transplantation. The single-lung transplantation is reversed for patients with pulmonary fibrosis. Patients with emphysema are thought to be unsuitable for single-lung transplantation because of the ventilation-perfusion imbalance that is supposed to occur, the ventilation being preferentially distributed to the native lung when the perfusion is distributed to the transplanted lung. We now report a preliminary success with single-lung transplantation in two consecutive patients with end-stage pulmonary emphysema. Despite the persistence after transplantation of an obstructive syndrome, the clinical status was good, the blood gases were markedly improved, and ventilation-perfusion imbalance did not occur on lung scans. After discharge from the hospital, the patients could return to an almost normal life. Thus, our data support the feasibility of single-lung transplantation in patients with end-stage pulmonary emphysema, and we consider that single-lung transplantation could be the optimal form of lung transplantation in these patients.

Humans↗

Role of the renin-angiotensin system in the regulation of glomerular filtration.

Angiotensin II (Ang II) controls renal plasma flow, which depends on perfusion pressure and on renal vascular resistances; the glomerular filtration rate of single nephrons (SNGFR) also depends on these two parameters. The glomerulus can synthesize all components of the renin-angiotensin system. Renin is produced by mesangial cells and cells of afferent arterioles, angiotensinogen by mesangial cells, and angiotensin I-converting enzyme (ACE) by endothelial and mesangial cells. Ang II binds to afferent and efferent arterioles and to mesangial cells, which subsequently contract and enhance their production of vasodilator prostaglandins. Ang II participates in the regulation of the SNGFR by acting on arteriolar resistance, on the glomerular capillary surface area, and finally on the ultrafiltration coefficient. The synthesis of renin is initiated when the cAMP concentration increases under the influence of hormones (parathyroid hormone, catecholamines), of mediators (e.g., prostanoids), or of changes in composition of tubular fluid (in sodium, chlorine, or calcium) detected by the macula densa. Moreover, renin synthesis is stimulated by decreases in intracellular calcium concentration. The renin-angiotensin system plays an important role in the regulation of glomerular filtration. A decrease in renal plasma flow is followed by an increase in glomerular efferent arteriole resistance, so that perfusion pressure and glomerular filtration remain constant. Furthermore, if the decrease in renal plasma flow is more marked, vasodilator prostaglandins, whose synthesis is stimulated by Ang II, dilate afferent arterioles, which sustains glomerular filtration. Prostaglandins are also apt to bind to the juxtaglomerular apparatus and to increase the intracellular cAMP level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Aseptic necrosis of bone following renal transplantation: relation with hyperparathyroidism.

Bone status, calcium and phosphate metabolism were prospectively evaluated in 98 renal transplant recipients with stable renal function. Aseptic necrosis of bone was found in 30 patients, leading to arthroplasty in 12 patients. Plasma parathyroid hormone and nephrogenic cyclic adenosine monophosphate (cAMP) values were greater and the duration of pre-transplant chronic renal failure longer in patients with aseptic necrosis of bone than in those who were not affected. Cumulative oral corticosteroid doses and the number of acute rejection episodes treated by intravenous methylprednisolone pulses were similar in patients with or without aseptic necrosis of bone. Hyperparathyroidism was confirmed histologically in 14 patients, comprising 4 cases of adenoma and 10 of diffuse hyperplasia. Serum parathyroid hormone correlated positively with serum creatinine (r = 0.47; P less than 0.001) and with cumulative corticosteroid dose (r = 0.30; P less than 0.003). This study suggests that hyperparathyroidism is a factor in the pathogenesis of aseptic bone necrosis. The frequency and severity of bone necrosis may be decreased by early detection and treatment of post-transplant hyperparathyroidism.

Adult↗

Physiological significance of increased levels of endogenous atrial natriuretic factor in human acute renal failure.

In twelve patients with acute renal failure, mean plasma levels of atrial natriuretic factor (ANF) and of its second messenger cGMP were found elevated at the early phase of the disease, but tended to return towards normal values at recovery. Variations of plasma ANF and cGMP were correlated significantly (p less than 0.05) with those of total blood volume. At the early phase of the disease, plasma ANF was also correlated with the excreted fraction of filtered sodium (FENa) (r = 0.95). Moreover, plasma ANF and FENa peaked concomitantly at the onset of the diuretic phase in the five patients who were not treated by diuretics or dialysis and were studied sequentially during the course of the disease. It is suggested that enhanced plasma ANF levels might reflect one of the mechanisms of adaptation controlling body fluid balance in acute renal failure.

Acute Kidney Injury↗

[Renal disease associated with heroin abuse].

Thirteen patients developed a renal disease after using heroin alone or in combination with other drugs, for a period of 3 to 12 years. Eleven were IV drug addicts, 2 were sniffers. Six patients had acute tubular necrosis, due to rhabdomyolysis in 5 and to prolonged gentamicin therapy for bacterial endocarditis in 1. Five patients manifested a nephrotic syndrome, and renal biopsy showed various types of glomerulonephritis (GN) without glomerular sclerosis. The two last patients had hypertension with intrarenal vascular lesions and HBsAg was present in their serum. Chronic hemodialysis and/or renal transplantation were required in 2 cases with GN; all other patients recovered normal serum creatinine. There was no specific pathologic picture of heroin abuse in this series.

Adult↗

Multiple myeloma and severe renal failure: a clinicopathologic study of outcome and prognosis in 34 patients.

Renal failure (RF) occurring in the course of multiple myeloma is often judged irreversible and generally considered an ominous complication. The aim of the present study was to re-evaluate the outcome, triggering conditions and prognostic factors of severe RF in a series of 34 patients, 33 to 90 years old. RF was totally reversible in 7 patients and partially reversible in 9 although 6 of them had to be temporarily dialyzed. However, the improvement in renal function was often very slow as indicated by an average recovery time of 115 days. The high rate of RF reversibility was associated with markedly lengthened survival. Review of triggering events confirmed the leading role of dehydration and hypercalcemia, but further suggested that intake of nonsteroidal anti-inflammatory drugs and renal infection might play a part in the development of RF. Systematic statistical analysis of potential prognostic factors showed that the outcome was significantly more severe in females, but age, myeloma characteristics including tumor mass, calcemia, and triggering events had no predictive value. The most reliable prognostic indicators were provided by analysis of kidney biopsy performed in 30 patients. Complete recovery from RF was observed only in the absence of global tubular atrophy and interstitial damage. In contrast, cast-induced tubular obstruction detected by the presence of Tamm-Horsfall protein in urinary space of glomeruli did not seem to influence the outcome of RF. Finally, we analyzed the prognostic value of immunochemical properties of light chains (LC). Lambda LC were unexpectedly detected in 2 of 3 patients, as compared to a ratio of 1 to 3 in the population of normal and monoclonal Ig, but LC type did not correlate with the course of RF. Isoelectric points of LC measured in 32 patients were dispersed from 5.2 to 8.9 and bore only weak prognostic significance. These results underline the value of kidney biopsy and justify aggressive treatment including dialysis and chemotherapy.

Acute Kidney Injury↗

Production of 5-lipoxygenase pathway metabolites by peripheral leucocytes in capillary leak syndrome (Clarkson disease).

Periodic systemic capillary leak syndrome (Clarkson disease) is characterized by unexplained attacks of a marked increase in capillary permeability. As leukotrienes, derived from arachidonic acid via the 5-lipoxygenase pathway, enhance capillary permeability, we studied arachidonate metabolism in leucocytes of a patient with capillary leak syndrome. Leucocyte-platelet suspensions, prepared from blood collected from the patient during asymptomatic periods (n = 11) produced greater amounts of 5-hydroxyeicosatetraenoic acid (5-HETE) than control suspensions (P less than 0.05). Peripheral leucocytes, collected during attacks (n = 3) and studied without addition of A23187 released LTB4 in vitro but not sulphidopeptides leukotrienes. This result was never observed with leucocytes from control subjects or from the patient out of a crisis. These results suggest that in the patient, peripheral leucocytes could be stimulated by an unknown, as yet to be determined, endogenous factor to produce more 5-HETE and LTB4. Whether LTB4 plays a pathogenic role in the capillary leakage remains to be determined.

Adult↗

Renal response to volume expansion in heart-transplant and kidney-transplant recipients.

The renal excretion of an intravenous sodium load by ten heart-transplant recipients with (five patients) or without (five patients) moderate renal failure was compared with the results obtained in two matched control groups of ten kidney-transplant recipients with similar renal function. All patients were treated with prednisone and cyclosporine except, for the latter treatment, the kidney-transplant recipients without renal failure. A supplementary control group of five healthy subjects who did not receive any treatment was also included in the study. Fractional sodium and osmolal clearances were greater in heart-transplant than in kidney-transplant recipients for both the patients with and the patients without renal failure. These two parameters were also greater in heart-transplant recipients without renal failure than in healthy subjects. Free water clearance was smaller in the heart-transplant recipients than in the corresponding control patients. Fractional potassium clearance was not different from group to group. These results demonstrate that heart-transplant recipients excrete a greater fraction of the filtered sodium load than their controls. This increased fractional excretion of sodium cannot be attributed to the cyclosporine treatment or the moderate chronic renal failure which both have been taken into account in the comparisons. The unchanged blood pressure during the saline load and the high or normal plasma renin activity levels in the heart-transplant recipients make it also unlikely that the exaggerated natriuresis was the consequence of the higher blood pressure observed in these patients. The chronic cardiac denervation which is the consequence of surgery in these patients could play a role in the mechanism of the saline diuresis.

Adult↗

Polyunsaturated fatty acids increase fibrinolytic activity of human isolated glomeruli.

The release of plasminogen activators (PA) from human isolated glomeruli has been studied by a sensitive radioenzymatic assay using 125I-fibrin coated tubes and plasminogen. The glomerular fibrinolytic activity (GFA) was detectable after 15 minutes of incubation. Then it increased with time, the glomerular protein concentration, and with the plasminogen concentration (P less than 0.001 for all). CaCl2 (1 mM) increased the GFA (9.7 +/- 0.9 versus 4.9 +/- 0.4 micrograms fibrin/mg/30 min, P less than 0.05). The GFA was also enhanced when pH increased. Arachidonic acid (AA, 1 to 20 micrograms/ml) increased the GFA in a saturable manner. Inhibitors of cyclooxygenase (aspirin) or of lipoxygenase (nordihydroguaiaretic acid) did not modify the basal and AA-stimulated GFA. Other polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), eicosatrienoic acid (ETA), eicosatetraynoic acid (ETYA), or dihomo-gamma-linoleic acid (DHL), also stimulated the GFA whereas linoleic acid and oleic acid did not. Polyunsaturated fatty acids also stimulated the fibrinolytic activity of glomerular supernatants. Specific antibodies to t-PA, and to a lesser extent to u-PA, decreased this fibrinolytic activity whether or not AA was added. Furthermore, AA and EPA were found to increase the activity of purified u-PA and t-PA. We conclude that human glomeruli release both t-PA and u-PA, and that this release is increased by calcium and alkaline pH. The polyunsaturated fatty acids enhanced the GFA, mainly by a stimulatory effect of PA activity rather than an increased release of PA from glomerular cells.

Calcium↗

Identification and cellular localization of plasminogen activators from human glomeruli.

The plasminogen activators (PA) and cell types responsible for the fibrinolytic activity of isolated human glomeruli were studied by an indirect spectrophotometric method for plasminogen activation and immunohistological techniques with specific antibodies. Our results indicate that human glomeruli possess the ability to release both tissue-type PA (t-PA) and urokinase (UK). This has been shown for t-PA by quenching its fibrin-dependent activity with rabbit anti-t-PA antibodies and for UK by quenching its fibrin-independent activity with goat anti-UK antibodies. On the other hand, immunohistochemical analysis performed with a murine monoclonal antibody to plasma-t-PA and goat polyclonal antibodies to UK allowed the exclusive localization of t-PA in the endothelial cell lining of the glomerular flocculus and UK in the cytoplasma of glomerular epithelial cells. In addition, arachidonic acid and CaCl2 were shown to enhance glomerular fibrinolytic activity by stimulating the release of either UK or t-PA, respectively. This particular distribution and regulation of glomerular PA's may be important in the physiopathology of the intra and extracapillary fibrin deposits observed in several glomerulopathies.

Arachidonic Acid↗