Pharmacokinetics of intravenous and intraperitoneal cefotaxime in chronic ambulatory peritoneal dialysis.

We investigated the kinetics of cefotaxime in eight subjects undergoing continuous ambulatory peritoneal dialysis (CAPD). A single 1 gm iv dose was injected and a 1 gm dose was given intraperitoneally in the CAPD fluid during a 4-hour dwell time. Cefotaxime and desacetylcefotaxime were assayed by HPLC. After intravenous injection the cefotaxime serum kinetic parameters were as follows: plasma t 1/2, 2.31 +/- 0.20 hours; volume of distribution, 0.35 +/- 0.04 L/kg; total plasma clearance, 118.7 +/- 12.3 ml/min; and peritoneal clearance, 6.7 +/- 1.3 ml/min. Dialysate cefotaxime concentrations rose rapidly, but only 5% of the dose was eliminated by the peritoneal route. After intraperitoneal instillation, cefotaxime appeared in the serum rapidly and the peak serum concentrations ranged from 9 to 20 micrograms/ml between 1 and 3 hours. The absorption of cefotaxime from peritoneal space was 58.7% +/- 5.4%. Data suggest that cefotaxime has bidirectional exchange characteristics through the peritoneal membrane. Instillation of cefotaxime in CAPD fluid may permit rapid absorption to achieve therapeutic serum concentrations.

Low protein and low phosphorus diet in patients with chronic renal failure: influence on glucose tolerance and tissue insulin sensitivity.

Ten patients with advanced renal failure (glomerular filtration rate 25 mL/min) were treated with a low phosphorus and low protein diet supplemented with ketoacid analogues. Before starting the diet and four months afterwards, a 50 g oral glucose tolerance test with a three step euglycemic insulin clamp was carried out. A dose-response curve of total body insulin sensitivity was plotted. By the fourth month, glucose tolerance had improved with significantly lower T0, T30, and T60 insulin levels. These results are attributed to the improvement in insulin action as demonstrated by the clamp technique. The dose-response curve had a distinctly higher plateau after dietary treatment, and the tissue sensitivity index to insulin (M/l ratio) was significantly improved. It is suggested that treatment of uremic patients with a low protein diet may reduce levels of a putative insulin inhibitor.

Effect of a ketoacid diet on glucose tolerance and tissue insulin sensitivity.

Effects of a low protein (0.3 g/kg/day) diet on glucose tolerance and tissue insulin sensitivity were studied in 25 non-diabetic and eight insulin-dependent diabetic uremic patients before and three months after dietary treatment. Carbohydrates accounted for 65% of the caloric intake in the first group and 57% in the second. In the first group, a 50 g oral glucose tolerance test showed that after three months blood glucose was significantly reduced at T60 (P less than 0.05) and serum insulin at T0, T30 (P less than 0.05) and T60 (P less than 0.02). Ten patients of the first group underwent an euglycemic, hyperinsulinemic clamp study; the tissue sensitivity to insulin index of all three clamp periods improved (P less than 0.01 for the first and second, P less than 0.02 for the third). Five patients in the second group underwent a euglycemic clamp study; glucose metabolism increased with each clamp period. Concomitantly, their daily insulin requirements decreased from 37.2 +/- 3.1 to 24.8 +/- 2.7 U/day (P less than 0.05). This conspicuous improvement observed in both groups might be related to a decrease in uremic toxin(s) derived from protein intake. Beneficial results on atherosclerosis and cardiovascular pathology may occur from the reduction of hyperinsulinism.

Pharmacokinetics of fosfomycin in hemodialyzed patients.

The pharmacokinetics of fosfomycin, an original antimicrobial agent, were investigated in 11 voluntary hemodialyzed patients. Fosfomycin, 2 g, was administered intravenously, 15 minutes before hemodialysis began in group 1 (6 patients), and just after hemodialysis in group 2 (6 patients). Blood samples were collected during 8 hours (group 1) and during 44 hours (group 2). Antibiotic concentrations were determined microbiologically. In group 1, half-life was 4.2 +/- 0.27 hours, total clearance 65.1 +/- 7.1 ml/mn and clearance by hemodialyzer 103 +/- 10 ml/mn. In group 2 plasma levels were 60 mg/l at the 44th hour and half-life was 48.8 +/- 17.5 hours. These results suggest that fosfomycin is actively eliminated by the hemodialyzer in group 1, and largely retained between two dialysis sessions in group 2. As for therapy, intravenous administration of 2 g after dialysis and further administration after each succeeding session are proposed.

Pharmacokinetics of intravenous and intraperitoneal fosfomycin in continuous ambulatory peritoneal dialysis.

Kinetics of fosfomycin were investigated in six patients undergoing continuous ambulatory peritoneal dialysis. Each subject received both an i.v. and an i.p. 1 g dose of fosfomycin with a one week washout between doses. Fosfomycin was assayed by a microbiological diffusion technique. After intravenous injection the fosfomycin serum kinetic parameters were as followed: elimination half-life (t1/2 beta) 38.4 +/- 8.7 h; volume of distribution 0.32 +/- 0.02 l/kg; total plasma clearance 7.0 +/- 1.4 ml/min and peritoneal clearance 3.2 +/- 0.2 ml/min. Dialyzate fosfomycin concentrations reached a maximum mean value of 32.2 +/- 2.8 micrograms/ml at 4 h post-injection and fosfomycin was detectable in dialyzate samples for up to 72 hours post-dosing. After intraperitoneal instillation, fosfomycin appeared in the serum rapidly and the mean peak plasma concentration was 36.2 +/- 2.8 micrograms/ml at the 4th h. The absorption rate (ka) was 0.580 +/- 0.039 h-1 and the absorption of fosfomycin from peritoneal space was 68.4 +/- 6.0%. These data suggest a bidirectional exchange through the peritoneal membrane. Intraperitoneal administration of 1 g either 48 h apart for anephric patients or 36 h apart for patients with residual renal function may achieve therapeutic serum concentrations.

[Assay of cefotaxime and desacetylcefotaxime in plasma and urine by high performance liquid chromatography]. / Dosage du céfotaxime et du désacétylcéfotaxime dans le plasma et l'urine par chromatographie liquide haute performance.

The authors propose an assay technique for cefotaxime and desacetylcefotaxime in the plasma and urine, using high performance liquid chromatography. The proteins are precipitated by adding propanol-2 to 100 microliter of plasma or urine. After centrifugation, the supernatant is extracted by a mixture of chloroform and isoamyl alcohol. The cephalosporins remain in the superior aqueous phase and a fraction of this phase is injected into the chromatograph. The cefotaxime, desacetylcefotaxime and cephaloridine (internal standard) are separated on a Radial Pak C 18 column by ion-binding chromatography. The mobile phase consists of a mixture of distilled water and acetonitrile (830/170, V/V) with the addition of an ampoule of Pic A (tetrabutylammonium phosphate). This rapid, specific and sensitive micro-method can be used for the assay of these antibiotics in adults and children, for therapeutic monitoring and for pharmacokinetic studies.

[Efficiency of antagonist IVF cycle programming by estrogens]. / Efficacité de la programmation des cycles FIV en antagonistes par les estrogènes.

OBJECTIVE: Assess the efficiency of estradiol programming in In Vitro Fertilization (IVF) with antagonists by comparing with classical long luteal agonist protocol. PATIENTS AND METHODS: It is a prospective randomized study, comparing 426 cycles in the arm estradiol antagonist with 412 cycles in the arm long agonist. Estradiol 4 mg/day begins on the 25th day of the previous cycle and continues during the menses until the first day of the stimulation which is from Thursday to Sunday whatever the beginning of the menses. The luteal protocol use Decapeptyl 0,1mg which begins on the 20th day of the previous cycle. RESULTS: Our two populations are similar. No pick-up has been done on Sunday. We have got significantly less oocytes and embryos in estradiol-antagonist (6,8+/-5,3 vs 7,6+/-5,7) and (3,7+/-3,2 vs 4,1+/-3,6) respectively. The ongoing pregnancy rate is comparable in the two groups: 28,6 % for estradiol antagonist 27,9 % for agonist for the whole population and 37 % vs 34,8 % respectively when at least one top embryo was transferred. DISCUSSION AND CONCLUSION: Programming antagonist cycles with estradiol allows the organization of the center; it is easy to implement and seems to give results as good as a long agonist protocol.

Short-term niflumic-acid-induced acute renal failure in children.

Several reports emphasize the adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) on renal function. We have observed over the last 10 years seven cases of acute renal failure (ARF) due to immune interstitial nephritis in children. A recommended oral or rectal dose of niflumic acid was prescribed for ear-nose-throat disorders. Length of exposure was 1-5 days. Clinical symptoms (oedema, oliguria or anuria) appeared between 3 and 6 days. Three patients had previously received the drug. Hypersensitivity signs (fever, skin rash, eosinophilia, and/or increased IgE) were present in all cases, leukocyturia in five cases, and haematuria in six cases. Renal biopsy showed interstitial lesions with lymphocyte, eosinophil, and plasma cell infiltrates without tubular cell necrosis. Glomeruli were normal on light-microscopy, except in one patient. Electron-microscopy showed extensive podocyte fusion in two patients, who had clinical and laboratory evidence of nephrotic syndrome (NS). ARF rapidly disappeared after NSAID withdrawal, except in two patients whose renal failure was irreversible despite methylprednisolone bolus. ARF is very rare in children treated with niflumic acid. When ARF occurs, different pathophysiological mechanisms are involved but the most common is immunological.

[Intratubal transfer of an embryo or a zygote. (TET or GIFT) Past, present and future? Comparative study of tubal embryo transfer (TET) versus in vitro fertilization]. / Le transfert intratubaire d'embryon ou de zygote (TET ou ZIFT). Passé, présent et avenir? Etude comparative tubal embryotransfer (TET) versus FIVETE.

The pregnancy rate per transfer does not appear to be increased if the embryos are placed in the Fallopian tube rather than using in-vitro fertilization or inserting the gametes into the tubule ampulla. Consequently, the indications are specific to particular cases.

Low-protein, low-phosphorus diet and tissue insulin sensitivity in insulin-dependent diabetic patients with chronic renal failure.

Tissue insulin sensitivity was measured by the glucose clamp technique in 8 uremic insulin-dependent diabetic patients before and after 3 months on a low-protein diet (LPD) providing daily 35 kcal/kg body weight, 60% of the caloric supply being obtained from carbohydrates. An improvement in tissue insulin sensitivity was observed for each steady state of the clamp and daily insulin requirements decreased significantly from 38.3 +/- 3.2 to 28.2 +/- 2.5 units (p less than 0.01) in spite of an increased carbohydrate intake. It is suggested that LPD lowers the production and accumulation of uremic toxins interfering with insulin sensitivity.

Effect of a low-protein diet on urinary albumin excretion in uremic patients.

Fifteen patients with advanced renal failure (creatinine clearance less than 25 ml/mn) and with severe albuminuria (greater than 1.5 g/24 h) were put on a low-protein (0.3 g/kg body weight), low-phosphorus (5-7 mg/kg body weight) diet supplemented with essential amino acids and ketoanalogues. During the 6-month follow-up, urinary albumin excretion and fractional renal albumin clearance were reduced significantly while serum albumin concentration increased; no nutritional change occurred during the study.

[Castleman's disease and glomerular nephropathy (apropos of 1 case]. / Maladie de Castleman et néphropathie glomérulaire (à propos d'un cas).

We report a case of Castleman's disease of multifocal plasma-cell type revealed by a severe general weakness, associated to a nephrotic syndrome with renal failure. The characteristic aspects of lymphoid hyperplasia with hyalinization of follicles and interfollicular vascular proliferation were observed in mesenteric lymph nodes, the spleen was involved by an infarcted localisation of Castleman's disease. The glomerular lesions were consistent with a proliferative mesangial glomerulonephritis. The removal of the spleen and of the mesenteric nodes involved by the disease, associated with a steroid course was curative. The nephrotic syndrome appears to be etiologically related to the presence of the Castleman's tumor. The removal of the tumor relieves the proteinuria and the renal failure as in other cases reported in the literature.

Multiple myeloma and AL amyloidosis in a renal transplant recipient.

Seven years after a cadaver kidney transplantation a 33-year-old man presented with a monoclonal gammopathy secondarily complicated by AL amyloidosis mainly expressed as a sicca syndrome, gammopathy that ultimately developed into multiple myeloma. The mechanisms responsible for the occurrence of monoclonal gammopathy in renal transplant recipients are discussed.

Long-term control of hyperparathyroidism in advanced renal failure by low-phosphorus low-protein diet supplemented with calcium (without changes in plasma calcitriol).

Phosphorus (Pi) retention linked to chronic renal failure (CRF) favors secondary hyperparathyroidism (HPT). Reduction of Pi and protein intake has been shown to prevent the development of HPT in CRF. The aim of the present study was to assess in patients with advanced CRF the long-term effects on phosphate and calcium metabolism of a low-Pi (5-7 mg/kg/day), low-protein (0.4 g/kg/day) diet providing 300 mg/day calcium (Ca) and supplemented with amino acids and ketoacids, Ca carbonate (400-800 mg/day) and vitamin D2 (1,000 IU/day). Twenty-nine patients with advanced CRF (glomerular filtration rate (GFR) 13.7 +/- 4.5 ml/min) were selected for the study, on the basis of a follow-up of a least 2 years and a satisfactory compliance to the prescribed diet. At the start of the study, biological evidence of HPT was present with increased plasma PTH concentration (144 +/- 95 pg/ml), increased plasma Pi (1.57 +/- 0.33 mmol/l), an increase in alkaline phosphatase activity and plasma osteocalcin concentration. Plasma PTH concentration was positively correlated with plasma Pi and inversely with plasma Ca concentrations and GFR. Pi and protein restriction induced a significant correction of HPT within 3 months after starting the diet. After 2 years of diet, despite the diminution of GFR (11.1 +/- 3.7 ml/min, p < 0.0001), plasma PTH was still lower than at the start of the diet (88 +/- 57 pg/ml, p < 0.01), as was plasma Pi (1.32 +/- 0.24 mmol/l, p < 0.001), total plasma Ca being higher (p < 0.01). Plasma PTH levels were correlated only to plasma Ca concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)