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Biomedical subjects

F Ducret

Publications and source records attributed to F Ducret.

At least 19 recordsLinked to original sources

[Recessive dystrophic epidermolysis bullosa (Hallopeau-Siemens) with IgA nephropathy: 4 cases].

BACKGROUND: The Hallopeau-Siemens type of recessive dystrophic epidermolysis bullosa (HS-RDEB) is a severe hereditary dermatosis, associated with a collagen VII deficiency. A chronic inflammatory syndrome, secondary to recurrent cutaneous infections, may be the cause of AA amyloidosis, with chronic renal failure, involving life prognosis. Less frequently, an IgA glomerulonephritis may occur and induce renal failure. Only two cases have been previously described. We report herein four new cases. CASE REPORT: We report four cases of HS-RDEB associated with IgA glomerulonephritis. A renal biopsy confirmed the diagnosis in all four cases. Later on, two patients had a second renal biopsy, indicated for deterioration of renal function. One of these patients showed AA type renal amyloidosis on the second biopsy. None of these six biopsies, conducted in our four patients led to local cutaneous complications. Subsequently three patients presented with terminal renal failure. Hemodialysis was set up, with good tolerance and improvement in quality of life. DISCUSSION: IgA glomerulonephritis should be suspected if a patient with HS-RDEB presents with hematuria. Renal biopsy is not contraindicated, confirms the diagnosis and helps to specify the prognosis. Hemodialysis is possible and well tolerated in the terminal stage of renal failure. There is not enough evidence for a genetic link between HS-RDEB and IgA glomerulonephritis, but repeated skin infections may be involved in the pathophysiology of the renal disease.

Adult↗

Pharmacodynamic study of low molecular weight dermatan sulphate (Desmin) after a single subcutaneous administration in patients with renal insufficiency.

The pharmacodynamic pattern of low molecular weight dermatan sulphate (CAS 24967-94-0, Desmin-LMWDS) was studied in patients presenting chronic renal insufficiency. Three groups of six patients were defined according to their creatinine clearance: group 1, more than 50 ml/min, group 2 between 10 and 50 ml/min and group 3 lower than 10 ml/min (haemodialized patients). Desmin-LMWDS concentrations were determined with the Heptest assay and the chromogenic specific heparin cofactor II dependent anti IIa assay. In patients of group 1 affected by moderate renal insufficiency, the pharmacodynamic profiles were roughly comparable to those obtained in normal subjects. In the two other groups, the profiles were markedly modified by the renal insufficiency. The maximal concentrations were doubled and the areas under the time-activity curve were 4-fold higher in haemodialyzed (group 3) and severe renal insufficient patients (group 2) than in patients of group 1. The clearance of the anti IIa activity were 13.98 +/- 6.25 l/h; 4.12 +/- 2.64 l/h and 2.94 +/- 1.53 l/h and the half-lives were 2.79 +/- 2.60 h, 6.15 +/- 4.02 h and 11.51 +/- 6.54 h in groups 1 to 3, respectively (p < 0.05). The Desmin-LMWDS clearance was directly correlated to the creatinine clearance (r = 0.8244, n = 18, p < 0.001). Thus, as for low molecular weight heparin, renal function plays a major role in the elimination of low molecular weight dermatan sulphate.

Adult↗

Pharmacokinetics of single-dose reboxetine in volunteers with renal insufficiency.

Reboxetine is a new selective norepinephrine reuptake inhibitor (selective NRI) for the short- and long-term treatment of depression that is effective and well tolerated at a dose of 8 to 10 mg/day. This study assessed the pharmacokinetics of reboxetine in volunteers with renal impairment. A single 4 mg dose of reboxetine was administered to a total of 18 volunteers with mild (n = 6), moderate (n = 6), or severe (n = 6) renal impairment (creatinine clearance: 56-64, 26-51, and 9-19 ml/min, respectively), and reboxetine concentrations were measured in plasma by HPLC. Mean AUC infinity increased by 43% (mild vs. severe; p < 0.01) as renal function declined, while renal clearance and total urinary excretion of unchanged reboxetine decreased by 67% and 62%, respectively (mild vs. severe; p < 0.01 for both parameters). tmax and t1/2 were not significantly different between groups. In comparison with historical data from young healthy volunteers, AUC infinity and t1/2 are at least doubled in volunteers with renal impairment, while CLr is halved. This pharmacokinetic study has shown that increasing renal dysfunction leads to increasing systemic exposure to reboxetine, particularly in severe renal insufficiency, although reboxetine was well tolerated by all volunteers. Thus, a reduction of the starting dose of reboxetine to 2 mg twice daily would be prudent in patients with renal dysfunction.

Adrenergic Uptake Inhibitors↗

Effects of ribavirin on hepatitis C-associated nephrotic syndrome in four liver transplant recipients.

BACKGROUND: Hepatitis C virus infection (HCV) is associated with a variety of extrahepatic disorders such as membranoproliferative glomerulonephritis (MPGN), which is generally due to cryoglobulinemia. After liver transplantation for HCV cirrhosis, alpha-interferon treatment against the recurrence of HCV in the liver graft is poorly effective and may induce intractable graft rejection. METHODS: We describe the cases of four liver transplant recipients treated with ribavirin for HCV-related glomerulopathy and nephrotic syndrome. RESULTS: The nephrotic syndrome was attenuated or disappeared during ribavirin therapy, and patients showed a marked decrease in proteinuria and an increase in albuminemia. The syndrome relapsed in two patients when ribavirin therapy was stopped, and a favorable response was again obtained in both cases when the treatment was resumed. The main adverse effect of ribavirin was anemia in two patients with renal impairment. No graft rejection occurred. CONCLUSIONS: These findings suggest that continuous therapy with low doses of oral ribavirin may improve the proteinuria of hepatitis C-related glomerulonephritis, at least in liver transplant recipients.

Antiviral Agents↗

Pharmacokinetics of cadralazine in a large group of hypertensive patients chronically treated with cadralazine: advantage over a conventional study in a small group of patients.

The concentrations of cadralazine in plasma were studied in 101 hypertensive patients treated with oral doses of 10, 15, or 20 mg of cadralazine once daily. Most of the patients received additionally a beta-blocking drug (n = 87) and a diuretic (n = 52). Few blood samples were collected in each patient on several occasions during the treatment, which usually lasted for more than 6 months. No accumulation of cadralazine in plasma occurred in any of the patients and the maximum concentrations were similar to those recorded in a small sample of healthy volunteers. The terminal half-life of elimination (3.6 h) was longer than that observed in healthy subjects (approximately 2.5 h). Conversely, the total clearance (197 ml/min) was lower (285 ml/min in healthy). The half-life and the total clearance in plasma were not dose dependent. In the patients treated for more than 6 months, no change in the pharmacokinetics of cadralazine was detected. The description of the distribution of concentrations showed that one-half of the patients behaved similarly to healthy subjects concerning half-life and total clearance. The other half presented a slower elimination of the drug (t 1/2 = 4.4 h and ClT = 130 ml/min) and these patients were significantly older (p = 0.01) than the former. This suggests that special attention should be paid to old hypertensive patients when a dose higher than 15 mg once daily is prescribed. Though concentrations were proportional to the dose, the body weight was not found to be a determining factor for dose adjustment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Renin secreting tumor and severe hypertension. Apropos of a new case].

A renin-secreting tumour has been observed in a 32-year-old female with severe hypertension known for 17 years. The excision of the tumour lead to the complete normalisation of the blood pressure. Histological examination showed that the tumour was benign, contained secretion granules at different stages of maturation, and derived from the juxta-glomerular apparatus. After reviewing the 40 cases previously reported in the literature we discuss the clinical presentation of this type of tumour and the approach to their diagnosis.

Adult↗

The relevance of secondary radicals in the mode of action of anthralin.

The formation of free radicals during the reaction of anthralin analogues with peroxidizing polyunsaturated lipids was monitored by ESR spectroscopy. The biological effect of the different compounds was assessed by their ability to inhibit respiration of cultured human keratinocytes. C(10)-monosubstituted analogues of anthralin exhibited a strong antirespiratory effect and produced a cascade of radicals. Abstraction of the hydrogen atom at C(10) led to the generation of primary radicals which further decomposed into secondary radicals similar to those observed with anthralin itself. 10, 10'-disubstituted analogues of anthralin did not form any paramagnetic species during reaction with peroxidizing lipids while decomposition of a 2,7-disubstituted anthralin derivative under the same conditions resulted in primary, but not secondary radical species. Since both types of disubstituted analogues are devoid of antirespiratory activity we postulate that the antimitochondrial and thus antiproliferative activity of anthralin and its analogues is associated with their capacity to form secondary radicals during their decomposition.

Anthralin↗

Monensin and tunicamycin-induced inhibition of HT29 cell spreading and growth.

HT29 cells originating from a human colon adenocarcinoma, spread very rapidly after seeding on their own extracellular matrix (ECM). Preincubation of cells with the inhibitor of protein glycosylation tunicamycin (TM) or with the ionophore monensin substantially suppressed cell spreading in serum-free medium without affecting cell adhesion to ECM. Addition of the drugs after cell attachment and spreading inhibited cell growth. TM-treated cells remained viable after 6 days of exposure to 2 micrograms ml-1 of TM and resumed their normal growth rate and shape after removing the drug from the medium. On the contrary, monensin inhibition of cell growth was not reversible: after 3 days, cells detached from the ECM and were unable to exclude Trypan Blue. At the ultrastructural level, a swollen Golgi apparatus with numerous vacuoles was observed after treatment for 2 h in either TM or monensin-preincubated cells. These results suggest that TM and monensin interfere with the insertion and, or, function of one or more cell surface glycoproteins, possibly interacting with cytoskeleton and involved in cell spreading and growth.

Adenocarcinoma↗

Internalization of the vasoactive intestinal peptide (VIP) in a human adenocarcinoma cell line (HT29).

The time course of internalization of radioiodinated vasoactive intestinal peptide (VIP) in HT29 cells was obtained using the technique of acetic acid removal of cell-surface-bound peptide. Even after 10 min incubation at 37 degrees C, 125I-VIP, initially bound on the HT29 cell surface, was compartmentalized within the cells. During the same time, degraded radioactive material was released by cells in the incubation medium. Localization of internalized 125I-VIP was investigated using two different subcellular fractionation techniques. 10 min after the onset of internalization, 125I-VIP labelling was found in intermediate structures and 10 min later the bulk of the radioactivity was detected in a low-density fraction containing very large lysosomes with a multivesicular aspect. The lysosomotropic agent NH4Cl appeared to inhibit 125I-VIP internalization, degradation and appearance of radiolabelled peptide in the large lysosomes in a time-dependent manner. Moreover, the effect of NH4Cl resulted in an accumulation of radioactive material in fractions containing microsomal structures. On the other hand, bacitracin, together with methylamine, highly enhanced 125I-VIP labelling in a membrane fraction, suggesting that these agents possibly act on a cell surface component of HT29 cells. These results support the conclusion that in HT29 cells, prelysosomal structures and large secondary lysosomes are probably part of the intracellular pathway of internalized VIP.

Adenocarcinoma↗

Antipsoriatic drug action of anthralin: oxidation reactions with peroxidizing lipids.

Reactions of anthralin with peroxidizing lipids were investigated. Using ESR spectroscopy and quantitative HPLC analysis radical species and decomposition products respectively were analysed in the reaction mixture as a function of time. Directly after mixing anthralin with peroxidized lipids, the 1,8-dihydroxy-9-anthron-10-yl radicals (primary radical) and small amounts of 1,8-dihydroxy-anthraquinone (AQ) were formed. After a few days of reaction, two secondary radicals were observed in addition to the primary radical. At the same time, 1,8,1'8'-tetrahydroxy-10,10'-bis-9(10H)-anthrone (DI) and an increasing amount of AQ and other nonidentified decomposition products were found. As the reaction proceeded further on the amount of AQ and the nonidentified decomposition products increased, the primary radical disappeared (within about 40 d) and the concentration of DI decreased to zero (within 1 yr). Nonidentified decomposition products are tentatively assigned to polymeric degradation products (anthralin brown) formed from DI via the observed secondary radical species. These radical reactions of anthralin with peroxidized lipids help to elucidate speculations on radical type reactions of anthralin in psoriasis indications, e.g., the role of peroxidized skin lipids as radical reaction initiators.

Animals↗

Vascularization and iodide transport down regulation in rat goitre.

This study was designed to investigate, in the rat, the regulation of the amount of thyroid iodide and of its organification during the involution of an experimentally induced goitre. The goitre was obtained by drastic iodine deficiency; male Wistar rats received an iodide deficient diet for 6 months, supplemented with PTU during the last 2 months. The study was followed for 16 days after the beginning of iodide refeeding (daily iodine intake = 50 micrograms). The thyroid iodide, total thyroid organic iodine and plasma iodide, PBI and TSH concentrations were determined from day 0 to 16 and compared to their control values (rats on a normal iodide diet for 6 months). In addition, a stereological study was carried out to determine if the extent of the gland vasculature might be implicated in the regulation of the thyroid iodide content. The plasma TSH concentration was very high and constant for 8 days (2.40 +/- 0.37 and 2.45 +/- 0.43 on day 0 and 8 respectively vs 0.25 +/- 0.12 microgram/ml in control rats), whereas iodination and secretion were blocked for 4 days (0.34 +/- 0.19 and 0.5 +/- 0.1 on day 0 and 4 respectively vs 14.4 +/- 2.0 micrograms 127I/gland in control rats) (Wolff-Chaikoff effect). Thyroid iodide amount increased enormously for 2 days (2.5 +/- 0.6 and 2.45 +/- 0.55 respectively on day 1 and 2 vs 0.09 +/- 0.01 micrograms 127I/gland on day 0), then strongly decreased between 2 and 4 days (1.15 +/- 0.27 127I/gland).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗