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Biomedical subjects

F Mignon

Publications and source records attributed to F Mignon.

At least 55 records · Page 3Linked to original sources

[Reflections apropos the stopping of dialysis treatments].

In North America, the withdrawal from dialysis is one of the major causes of death among patients treated for end-stage renal disease, especially when it comes to the elderly. The reasons for the decision to terminate treatment are either medical or can be seen in what we commonly call the "quality of life", even though the latter is difficult to define. Situations such as these are hardly ever referred to in European medical literature. They create difficult psychological, ethical and event legal problems that need to be anticipated and resolved for each individual case. According to the authors, the basis for this thinking and the debate surrounding the termination of treatment as well as the final decision to do so ultimately rest with the physician. The quality of the relationship established between patient, family and medical staff during the course of treatment is essential in situations like these.

Ethics, Medical

[Tubulo-interstitial renal complications of myeloma].

Tubulo-interstitial lesions are the main causes of renal failure in patients with myeloma, and they sometimes reveal this tumour. They are mainly found in large tumoral mass myelomas and are characterized by tubular lesions and specific casts of unexplained physiopathology. Symptomatic and aetiological treatments must be instituted at an early stage to obtain the recovery, at least partial, of renal function, as observed in more than 50% of the cases. The persistence of renal failure carries a sombre prognosis, which emphasizes the importance of a preventive treatment that is too often omitted. Functional tubular disorders are frequent but seldom result in Fanconi's syndrome. A better understanding of the mechanisms underlying the nephrotoxicity of monoclonal immunoglobulins should permit to reduce the incidence of tubular lesions in myelomas.

Fanconi Syndrome

[End-stage chronic renal failure in myeloma: results of dialysis].

Nowadays, maintenance dialysis can be proposed to patients suffering from myeloma with end-stage chronic renal failure. We report here data from eight patients dialysed either by hemo- (6) or peritoneal dialysis (2), together with chemotherapy in half of them. Six patients died; the longest survival has been about 6 years. The main cause of morbidity was sepsis, especially in peritoneal dialysis patients; therefore we now favour hemodialysis in patients exposed to aggressive chemotherapy. We think dialysis justified in all cases, including those with high tumor mass, in order to expect the effect of chemotherapy; then, provided good response to drugs, further survival can be consistently improved. Once on maintenance dialysis, main drawbacks for these patients are cardiovascular complications (AL amyloidosis) and above all anemia; the latter however can be markedly improved, thanks to erythropoietin therapy which provides these patients with much better quality of life.

Aged

Inhibition of neutral endopeptidase stimulates renal sodium excretion in patients with chronic renal failure.

1. The acute effects of a single oral dose of sinorphan (100 mg), an inhibitor of neutral endopeptidase, on the plasma atrial natriuretic factor level and the fractional excretion of sodium were examined in 12 patients with severe chronic renal failure who were not on maintenance haemodialysis and who ingested a normal sodium diet. The drug was administered against placebo by a double-blind cross-over protocol. 2. Basal plasma atrial natriuretic factor level and fractional excretion of sodium were high (23.2 +/- 3.7 pmol/l and 2.64 +/- 0.38%, respectively). Sinorphan inhibited plasma neutral endopeptidase activity by 68-75% 30 min after ingestion. This effect persisted for at least 4 h. There were simultaneously increases in plasma atrial natriuretic factor and cyclic GMP levels to 1.9 and 1.4 times the basal values, respectively. Fractional excretion of sodium increased during the second and third hour periods after ingestion of the drug with a peak of 1.9 times the basal value in the second period. Changes in fractional excretion of sodium were significantly correlated with those in plasma atrial natriuretic factor and cyclic GMP levels. Plasma aldosterone level, creatinine clearance and mean blood pressure were unchanged, whereas plasma renin activity increased slightly. An increase in urinary cyclic GMP excretion was observed in parallel with the increase in plasma cyclic GMP level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effects of clonidine on plasma catecholamines and neuropeptide Y in hypertensive patients at rest and during stress.

Neuropeptide Y (NPY), a potent vasoconstrictor agent reported to be released, in addition to norepinephrine (NE), by sympathetic nerve endings during stress, may contribute to the pressor response to various stimuli. The objectives of this study were to determine (a) whether plasma NPY concentrations are altered during different types of stress (cold pressor test, mental stress, and active orthostatism) and (b) whether clonidine, via its central sympatholytic effect, affects the stress-induced blood pressure, NPY, and/or catecholamine changes. Eighteen untreated patients with mild essential or borderline hypertension participated in an acute randomized, double-blind, parallel study. The blood pressure and heart rate were recorded during three control periods, each followed by either a cold pressor test (CPT), a mental stress test (MS: mental arithmetic), or active orthostatism (AO), performed in a random order. Venous blood samples for catecholamines and NPY determination were taken at the end of each control and test period. This entire procedure was repeated after oral clonidine (150 micrograms) or placebo. Before treatment, a CPT, MS, or AO increased the blood pressure to the same extent. The stress-induced increase in plasma NE was greater during AO (+99 +/- 23%) than during CPT (+35 +/- 8%) and MS (+55 +/- 12%). The stress-induced increase in plasma epinephrine was only significant during MS (+142 +/- 69%). A small but significant increase in NPY (p < 0.05) was observed during AO only (+10 +/- 7%). Compared to placebo, clonidine significantly decreased the basal blood pressure and the pressor response to CPT, but did not change the pressor response to MS and AO.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Doppler echocardiographic evaluation of physical properties of the aorta and left ventricular geometry in normotensive hemodialyzed patients].

Twenty-five patients undergoing hemodialysis therapy with a normal blood pressure (16 men, 9 women, age = 54 +/- 14 years) and 25 sex and age-matched healthy normotensive subjects were examined by doppler-echocardiography. Pulse wave velocity (PWV) in the thoracic descending aorta, diameter of the ascending aorta (AD), left ventricular mass (m), thickness-radius ratio (th/r), shortening fraction (SF), end systolic pressure-diameter ratio (P/D) and the ratio of late and early mitral velocity (A/E) were obtained. Pulse wave velocity, SF, P/D, were not significantly different in the 2 groups whereas AD, m, th/r, and A/E were significantly larger in dialysis patients than in controls (both, p < 0.001). These results indicate that in patients treated by hemodialysis with a normal blood pressure, a concentric left ventricular hypertrophy is associated with a normal aortic stiffness, suggesting a depressed myocardial contractility.

Adult

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

["Idiopathic" extracapillary glomerulonephritides without immune deposits are vascularitides: clinical and serologic analysis].

To determine the spectrum of systemic diseases potentially associated with pauci-immune rapidly progressive glomerulonephritis (GN), most of which being considered as idiopathic, we have analyzed extra-renal manifestations, occurrence of extra-glomerular vasculitis and incidence and specificity of ANCAs in 40 patients selected only on histological criteria. Extra-renal symptoms were unexpectedly observed in all patients but one, and were suggestive of vasculitis in 24 of them. Extra-glomerular vasculitis was evidenced in 18 kidney biopsies and four biopsies from other organs. Among the 33 patients with suspected or established vasculitis, 13 had presumed or biopsy-proven Wegener's granulomatosis (WG), three had a macroscopic form of polyarteritis nodosa and 17 had a clinical presentation compatible with the so-called microscopic polyarteritis previously described in the british literature. An additional patient had clinical signs of WG without clinical and histological evidence of vasculitis. ANCAs were detected in 28/33 and 25/34 sera tested by IF and ELISA, respectively: 19 contained anti-myeloperoxidase (MPO) antibodies and 6 had anti-proteinase 3 (Pr3) activity. Anti-MPO and anti-Pr3 antibodies were present in all clinical subgroups but with various incidences: anti-MPO antibodies were surprisingly more often detected (6/12) than anti-Pr3 (4/12) in patients with suspected or histologically proven WG but anti-Pr3 antibodies were nonetheless 3- to 4-fold more frequent in WG than in non-WG systemic vasculitis (1/12) and necrotizing CGN without evidence of extra-renal vasculitis (1/10). These results strongly suggest that pauci-immune necrotizing CGNs belong to the broad spectrum of necrotizing vasculitides affecting glomerular capillaries. This hypothesis is also supported by the good response of patients to immunosuppressive treatments known for their efficacy in vasculitides, whereas these treatments are usually less successful in severe forms of extra-capillary GN with immune deposits.

Glomerulonephritis

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

Necrotizing crescentic glomerulonephritis without significant immune deposits: a clinical and serological study.

To determine the spectrum of systemic diseases associated with pauci-immune necrotizing crescentic glomerulonephritis, we have analysed extra-renal manifestations, occurrence of extra-glomerular vasculitis and incidence and specificity of antinuclear cytoplasmic antibodies (ANCA) in 40 patients selected only on renal histological criteria. Extra-renal symptoms were unexpectedly observed in all patients but one, and were suggestive of vasculitis in 24. Extra-glomerular vasculitis was seen in 18 kidney biopsies and four biopsies from other organs. Among the 33 patients with suspected or established vasculitis, 13 had presumed or biopsy-proven Wegener's granulomatosis, three had a macroscopic form of polyarteritis nodosa and 17 could not be adequately classified. An additional patient had clinical signs of Wegener's granulomatosis without clinical and histological evidence of vasculitis. ANCAs were detected in 28 of 33 and 25 of 34 sera tested by immunofluorescence and enzyme-linked immunoassay, respectively: 19 contained anti-myeloperoxidase antibodies and six had anti-proteinase 3 activity. Anti-myeloperoxidase and anti-proteinase 3 antibodies were present in all clinical subgroups but with various frequencies: anti-myeloperoxidase antibodies were more common (six of 12) than anti-proteinase 3 (four of 12) in patients with suspected or histologically proven Wegener's granulomatosis. Anti-proteinase 3 antibodies were 3- to 4-fold more common in patients with Wegener's granulomatosis than in those with systemic vasculitis of other causes (one of 12) or necrotizing crescentic glomerulonephritis without evidence of extra-renal vasculitis (one of 10). These results strongly suggest that pauci-immune necrotizing crescentic glomerulonephritis belongs to the broad spectrum of necrotizing vasculitides affecting glomerular capillaries. This study shows substantial improvement in renal prognosis and life expectancy with aggressive immunosuppressive therapy despite the older age of the patients, dissemination of the vasculitic process and often delayed diagnosis.

Adult

[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

Glomerulonephritis in chronic lymphocytic leukemia and related B-cell lymphomas.

We retrospectively analyzed clinical presentation, immunopathological data and renal outcome in 13 patients with glomerulonephritis (GN) and chronic lymphocytic leukemia (CLL) or related diffuse well-differentiated lymphocytic lymphoma (WDLL) of B-cell lineage. B-cell proliferation and glomerulopathy were simultaneously diagnosed in seven of the 13 patients. Nephrotic syndrome was observed in nine patients. Serum creatinine was elevated (greater than 120 mumol/liter) in 10 patients and exceeded 400 mumol/liter in three patients. A clear cut relationship between GN and hematologic disease could be established in nine cases: five patients had MPGN caused by type I or type II cryoglobulinemia; two had MPGN or mesangial hypertrophy with circulating and deposited noncryoprecipitating monoclonal IgG K and IgM K, respectively; in the two remaining patients, monotypic IgG K glomerular deposits exhibiting fibrillary organization were observed in association with MGN or MPGN, despite the absence of circulating M-component by immunofixation. The pathophysiologic link between glomerular lesions and B-cell proliferation was further evidenced by effectiveness of specific treatment of the malignancy by chlorambucil. This drug, used in the absence of steroids, induced complete remission of nephrotic syndrome in the five patients to whom it was given. Moreover, in the five patients with creatininemia greater than 200 mumol/liter who received chemotherapy, substantial improvement in renal function was observed. These overall data demonstrate that the occurrence of GN in B-CLL and related lymphoma is not fortuitous, and testify to the paraneoplastic nature of glomerular involvement mediated by deposition and possibly processing of cryoprecipitating or noncryoprecipitating M-components.

Adult

Didanosine pharmacokinetics in patients with normal and impaired renal function: influence of hemodialysis.

The pharmacokinetics of didanosine were investigated following oral administration of a single 375-mg dose to eight human immunodeficiency virus-seropositive patients with normal renal function and eight human immunodeficiency virus-seropositive uremic patients. In uremic patients, the plasma half-life was longer than that in control patients (respectively, 4.5 +/- 2.2 and 1.6 +/- 0.4 h). The ratio of total plasma clearance to absolute bioavailability was four- to fivefold lower in uremic patients than in patients with normal renal function (respectively, 491 +/- 181 and 2,277 +/- 738 ml/min). Because of the decrease in elimination, concentrations in plasma were higher for uremic patients than for control patients; the maximum concentrations of drug in plasma were, respectively, 3,978 +/- 1,607 and 1,948 +/- 994 ng/ml; the areas under the concentration-time curve were, respectively, 14,050 +/- 4,262 and 3,000 +/- 956 ng.h/ml. Didanosine was removed by hemodialysis with an extraction ratio of 53% +/- 8%, a hemodialysis clearance value of 107 +/- 21 ml/min, and a fractional drug removal during a 4-h dialysis of 20% +/- 8% of the dose. Dosage adjustments are necessary in uremic patients.

Administration, Oral