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Biomedical subjects

J P Fillastre

Publications and source records attributed to J P Fillastre.

At least 19 recordsLinked to original sources
PubMed1992

[Drug-induced nephropathies].

Drug-induced nephropathies are frequent. Glomeruli, tubes, interstitium and arterioles may be altered. In this paper, we have tried to know if clinical, biological or histological signs of drug-induced nephropathies are similar or different from those observed in idiopathic nephropathies. We demonstrate that drug-induced nephropathies do not present any particular clinical or biological signs. We find that minimal changes and membranous glomerulopathies are the main lesions observed. In contrast, glomerular proliferations are very rare. Drug-induced tubulopathies are characterized by tubular necrosis with variable extension. Interstitial lesions are absolutely identical to those observed in immunologically mediated nephropathies. Vascular lesions are very rare. It should be noticed that evolution of drug-induced nephropathies differs completely from idiopathic nephropathies. Indeed, renal lesions are usually regressive when the drug administration is stopped. In conclusion, it appears that drug-induced nephropathies mimic other forms of nephropathies. It is important to know that some drugs are excellent experimental models to reproduce some aspects of human renal pathologies.

Animals↗
PubMed1992

[Renal aging in man].

Renal morphological and functional changes occur in the elderly. Between the ages of 50 and 80 years the renal mass diminishes by a mean of 20 percent, to the expense of the renal cortex. Glomerular sclerosis results in a gradual fall in the number of functioning glomeruli. Simultaneously, a decrease of about 7 percent in glomerular filtration rate per decade after the age of 40 years and a 10 percent decrease in renal plasma flow per decade, and therefore an increase in filtration fraction, are observed. These haemodynamic abnormalities are accompanied by changes in tubular function, including a delay in renal adjustment to sodium overload, and above all to sodium restriction, together with a decrease in concentrating and, to a lesser extent, diluting capacity. In actual fact, the intensity of glomerular sclerosis varies considerably from one subject to another, and the decrease in glomerular filtration rate is far from being constant. These changes are perhaps not ineluctably associated with aging; they might result from pathological processes that have gone unnoticed.

Adult↗
PubMed1992

Penetration of lomefloxacin into human prostatic tissue.

Serum and prostatic tissue concentrations of lomefloxacin were measured in 12 elderly patients who underwent transurethral resection of the prostate after receiving a single oral dose of 400 mg. The peak serum concentration of lomefloxacin was 2.5-10.0 micrograms/mL (mean, 5.2 +/- 1.9 micrograms/mL). During surgery, serum and tissue concentrations averaged 4.6 +/- 2.2 micrograms/mL and 6.5 +/- 2.7 micrograms/g, respectively. The ratio of tissue to serum concentrations was 1.53 +/- 0.54. The levels of lomefloxacin in serum and prostatic tissue were found to be higher than the minimum inhibitory concentration (MIC) values for most urinary tract pathogens.

Administration, Oral↗
PubMed1992

Pharmacokinetics of meropenem in subjects with renal insufficiency.

The pharmacokinetics of IV meropenem (500 mg over 30 min) has been studied in 6 healthy volunteers and 26 patients with various degrees of renal impairment. Blood samples were taken at different times over 24 h in healthy subjects and 36 to 48 h in uraemic patients, and four or five urine samples were collected over 24 or 48 h. Meropenem concentrations in plasma and urine were measured by a microbiological assay. The mean peak plasma concentration of meropenem ranged from 28 to 40 micrograms.ml-1 and was not affected by the degree of renal impairment. The terminal half-life of meropenem was approximately 1 h in subjects with normal kidney function and it was proportionately increased as renal function decreased. A significant linear relationship between total body clearance and creatinine clearance as well as between renal clearance and creatinine clearance was observed. The mean apparent volume of distribution at steady state was not significantly altered in uraemic patients. The mean cumulative urinary recovery of meropenem in healthy volunteers was 77% of the administered dose and it was significantly decreased in patients with renal impairment. Haemodialysis shortened the elimination half-life, from 9.7 h during the predialysis period to 1.4 h during the dialysis period. The dose of meropenem should be reduced in relation to the decrease in creatinine clearance.

Adult↗
PubMed1992

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↗
PubMed1992

Pharmacokinetics of meropenem (ICI 194,660) and its metabolite (ICI 213,689) in healthy subjects and in patients with renal impairment.

The pharmacokinetics of meropenem (ICI 194,660) and its open-ring metabolite (ICI 213,689) were studied in 6 healthy volunteers and 16 patients with moderate to severe renal impairment after a single intravenous dose of 500 mg given as a 30-min infusion. Concentrations of unchanged meropenem in plasma and urine were measured by both microbiological and high-pressure liquid chromatographic (HPLC) assays. A good correlation was found between the two techniques. Pharmacokinetic parameters of unchanged meropenem were determined by using the HPLC data. The terminal half-life of unchanged meropenem increased in relation to the degree of renal impairment, being 1.2 h in subjects with normal renal function and 10 h in patients with end-stage renal failure. Total body clearance and renal clearance of unchanged meropenem are linearly related to creatinine clearance. The concentrations of the metabolite in plasma, which are very low in healthy subjects, significantly increased in uremic patients. The apparent half-life of ICI 213,689 increased in uremic patients and was about 35 h in patients with severe renal insufficiency. Meropenem and its metabolite are effectively removed by hemodialysis. The dialysis clearance of the unchanged drug was 81 +/- 22 ml/min. Dosage adjustments of meropenem will be necessary in patients with severe renal impairment.

Adult↗
PubMed1992

Effects of ketoprofen (NSAID) on the pharmacokinetics of pefloxacin and ofloxacin in healthy volunteers.

The influence of ketoprofen (K), a non steroidal antiinflammatory drug (NSAID) on the pharmacokinetics of two fluoroquinolone derivatives: ofloxacin (O) and pefloxacin (P) was studied in ten healthy adult male volunteers. All subjects orally received every 12 h the fluoroquinolone derivative (either O or P) for three days and the combination of the quinolone and ketoprofen (once a day) during the three following days. Two pharmacokinetic studies were performed for each quinolone, on days four and eight of the treatment. Blood samples were taken at times 0, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h after dosing. Urine was collected during 4 time-periods: 0-4 h, 4-8 h, 8-12 h and 12-24 h. Plasma and urine concentrations of the active drug of O and P were measured by microbiological assay. Ketoprofen did not significantly modify the pharmacokinetic parameters of the two fluoroquinolones studied in terms of peak plasma levels, time to peak, area under the curve, elimination half-life, volume of distribution and total and renal clearances.

Administration, Oral↗
PubMed1992

[Should adult nephrotic syndrome secondary to idiopathic extramembranous glomerulonephritis be treated? An approach by decisional analysis].

Treatment of nephrotic syndrome (without renal insufficiency) due to idiopathic membranous glomerulonephritis in adults is not clearly defined. A decisional analysis was done from data published in literature in order to define the best therapeutic choice. Three therapeutic strategies were studied: corticosteroids (either 125 mg/48 h or 30 to 60 mg/24 h), alternate therapy according to Ponticelli protocol (corticosteroids and chlorambucil), abstention of therapy. The data were divided in two groups according to the time of follow-up. The first group allows a decisional analysis for a short period of time (16 to 37 months), the second group allows this analysis for a longer period of time (54 to 65 months). The results differed according to the length of post treatment follow-up. For the shorter follow-up, corticosteroids or the association corticosteroids and chlorambucil appeared to be better than no treatment. For longer follow-up, any treatment shows an advantage in comparison to abstention of therapy. Our tentative conclusion is to propose only symptomatic treatment for this disease.

Adrenal Cortex Hormones↗
PubMed1992

[Idiopathic hypercalciuria and bone density].

A decrease in bone density of the spine has been reported in individuals with hypercalciuria and the finding of the latter in osteoporosis patients is not uncommon. We studied 21 men and 8 women (mean age 47 +/- 13) with idiopathic hypercalciuria (IHCU) defined by an urinary calcium of more than 7.5 mmol/24 h in men and 6.25 mmol/24 h in women. The duration of IHCU was 10 (+/-) 8 years. Among the 29 patients, 24 had one or more renal calculi. Twenty one had been treated, by low calcium diet only (and diuresis), combined with a thiazide diuretic, or sodium phytate, or phosphorus. Bone mineral content (BMC) was measured in the lumbar spine and the upper end of the femur using an ORIS ODC 200 densitometer and compared with 29 control subjects paired for age and sex. No difference was found between the two groups concerning BMC values in either the spine or the 3 femoral sites (neck, Ward, trochanter). BMC was not correlated with urinary calcium. Thus individuals with IHCU showed no decrease in their bone mass, among this group seen in a department of nephrology. The influence of the treatment of IHCU remains to be defined.

Adult↗
PubMed1991

[Value of renal biopsy in the elderly. 32 cases].

Between November 1985 and November 1989, percutaneous renal biopsy was performed in 32 patients aged 75 or more (mean age 78). The major clinical presentations were nephrotic syndrome in 22 patients, variable amounts of proteinuria in 6 patients and unexplained severe renal insufficiency in 4 patients. In 27 cases the histological study revealed a glomerular disease. Minimal change disease (7 cases), membranous nephropathy (6 cases), amyloidosis (5 cases) and crescentic glomerulonephritis were the most frequent types. The rate of complications after biopsy was low (3 percent) with only one retroperitoneal hematoma. Owing to the atypical renal presentation of some glomerulopathies in the elderly, renal biopsy was useful to differentiate between minimal change disease, membranous nephropathy and amyloidosis. In 4 patients with minimal change disease, remission of nephrotic syndrome was obtained with corticosteroids. Moreover renal biopsy allowed to detect underlying diseases and gave indications to initiate specific therapy particularly in crescentic glomerulonephritis the outcome of which remained unfavourable. It is concluded that, even in elderly, renal biopsy is a valuable and safe diagnostic tool to obtain a rapid diagnosis, particularly in glomerular diseases, leading to a biopsy-guided therapy. It must therefore have the same indications as in younger adults with glomerular syndrome or rapidly progressive renal insufficiency.

Acute Kidney Injury↗
PubMed1991

Relationship between renal function and disposition of oral cefixime.

The pharmacokinetics of cefixime following a single oral dose of 200 mg have been investigated in 6 normal subjects and in 22 patients with various degrees of renal insufficiency. Serum and urine samples were collected between 0 and 72 h and were subjected to two methods of analysis: bioassay and HPLC. There was a linear relationship between the two sets of results from 228 samples. This result suggests that none of the metabolites, which may accumulate in uraemic patients, has antibacterial activity. In normal subjects, the peak serum level (Cmax) was 2.50 micrograms.ml-1 at 2.83 h (tmax); the apparent elimination half-life (t1/2) was 3.73 h; the apparent total body clearance (CL.f-1) was 154 ml.min-1, the mean renal clearance (CLR) was 39.1 ml.min-1 and the apparent fraction of the dose recovered in 24 h urine was 0.22. In uraemic patients, Cmax and tmax were slightly increased and t1/2 was increased to 12-14 h in patients with an endogenous creatinine clearance below 20 ml.min-1. The apparent volume of distribution was decreased. Apparent total and renal clearances were lower in proportion to the degree of renal insufficiency. Linear relationships were found between CL/f, CLR and creatinine clearance (CLCR). The findings suggest that the dose of cefixime needs to be reduced only in patients with severe renal failure.

Administration, Oral↗
PubMed1991

Subcellular localization of celiptium-induced peroxidative damage in rat renal cortex.

Celiptium (N2-methyl-9-hydroxyellipticinium) is an antitumor agent of the ellipticine series. We have shown a dose-dependent nephrotoxicity in rats and demonstrated a lipid overload in proximal tubular cells (unsaturated free fatty acid accumulation). We have also shown an increase in thiobarbituric acid reactive substances (TBARS), namely the 4-hydroxyalkenals, that is paralleled by a decrease in phosphatidylethanolamine in rat kidney cortex. In the present study, peroxidative damage was localized in mitochondria, microsomal and brush-border membranes of kidney cortex. Female Wistar rats were injected with a single i.v. dose of 20 mg/kg celiptium and sacrificed on day 8. Subcellular fractionation studies showed that celiptium induced alterations: 1) in mitochondria (slight increase in aldehydes), 2) in microsomal membranes (increase in free fatty acids (FFA) with in particular rises in oleic (18:1) and linoleic (18:2) acids), 3) in brush-border membranes or BBM (decrease in protein and phospholipid contents); residual membranes showed an increase in oleic and linoleic acids and a decrease in the polyunsaturated fatty acids, arachidonic (20:4) and docosahexaenoic (22:6) acids, 4) in cytosol (increase in FFA and TBARS content). Thus, celiptium induces peroxidative damage in kidneys through lipid abnormalities which predominantly occur in brush-border membranes and consist of an increase in free fatty acids and aldehydes in cytosol.

Animals↗
PubMed1991

Biochemical, functional, and morphological characterization of a primary culture of rabbit proximal tubule cells.

Primary cultures of renal rabbit proximal tubule cells were initiated from a pure suspension of proximal tubule fragments. Proximal tubule cells were grown in a hormone-supplemented, serum-free medium containing low concentrations of antibiotics. Confluent monolayers exhibited multicellular dome formation, indicating the presence of transepithelial solute and water transport. Ultrastructural examination revealed a monolayer of polarized epithelial cells with tight junctions and sparse membraneous microvilli facing the culture medium. Time course biochemical characterization was performed using a palette of 12 enzymes, representative of important metabolic functions or pathways. Brush-border-associated enzymes (gamma-glutamyl transpeptidase and alanine aminopeptidase) were moderately reduced throughout the culture whereas alkaline phosphatase was markedly decreased at confluency. Mitochondrial and lysosomal marker enzymes were well preserved over the culture period. Glutathione-S-transferase activity remained stable during the 16-day culture period investigated. Glycolysis enzyme activities (lactate dehydrogenase and hexokinase) were enhanced, as a function of culture age. Na(+)-K(+)-ATPase activity rise was concomitant with the increase of glycolysis marker enzymes. In contrast, the gluconeogenesis marker enzyme, glucose-6-phosphatase, fell dramatically to reach a low level equivalent to 4% of the activity measured in isolated proximal tubules. Primary cultures exhibited several differentiated functions of the proximal tubule cell: (a) PTH alone was able to induce a significant stimulation of adenylate cyclase activity, unlike isoproterenol, thyrocalcitonin, and arginine vasopressin, and (b) sodium-dependent alpha-methylglucoside (AMG) transport was detected. This AMG uptake was selectively inhibited by phlorizin (5 X 10(-3) M), which is a competitive inhibitor of glucose uptake at the apical membrane. Complete characterization made it possible to investigate hitherto unexplored aspects of in vitro cultured proximal tubule cells. This primary culture model could provide a useful and reliable tool to investigate in vitro renal proximal tubule function, under normal conditions or after a drug-induced toxicity.

Adenylyl Cyclases↗
PubMed1991

Nitrosoureas lomustine, carmustine and fotemustine induced hepatotoxic perturbations in rats: biochemical, morphological and flow cytometry studies.

Chloroethylnitrosoureas are reactive compounds that are highly effective against malignant neoplasms in humans and animals. The most widely used nitrosoureas, lomustine and carmustine, are known to be hepatotoxic and to induce pericholangitis and intrahepatic cholestasis, which in the long term lead to cholangiolysis and biliary cirrhosis. However, the nitrosourea fotemustine has proved to be non-hepatotoxic at 20 mg/kg and 50 mg/kg. We have studied the effect of these three nitrosoureas on the cytotoxicity and cellular kinetics of rat liver cells. Lomustine and carmustine modify the proliferation index of liver cells in vivo: flow cytofluorometry showed that DNA cell distribution is quite similar for lomustine and carmustine, with subsequent accumulation of cells in G2 + M phase. 3 months later regressive morphological and cell cycle perturbations are noted for the lower dose of lomustine and carmustine. The most severe lesions are noted with lomustine (50 mg/kg). Fotemustine is not hepatotoxic and preferentially induces S phase perturbations. The more toxic nitrosoureas, lomustine and carmustine, induce comparable hepatocyte cell cycle alterations which differ from those induced by the less hepatotoxic nitrosourea fotemustine.

Alkaline Phosphatase↗