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Biomedical subjects

J Boelaert

Publications and source records attributed to J Boelaert.

At least 19 recordsLinked to original sources

Effect of iron chelation on the in-vitro growth of Leishmania promastigotes.

The development of vaccines and drugs to control leishmaniasis is urgently needed. The presence of a leishmania transferrin receptor on the parasite suggests that an adequate supply of iron is needed for the life cycle of leishmania. We have investigated the effect of iron deprivation on the growth of leishmania promastigotes in vitro using an iron chelation approach. All chelators tested reduced the rate of promastigote multiplication in a dose-dependent fashion, whereas referrated ones did not. The hydroxypyridin-4-one chelators CP94 and L1 were found to be more efficient than desferrioxamine. We suggest that iron depletion may be an effective mechanism against leishmania infection.

Animals

The pharmacokinetics of remoxipride and metabolites in patients with various degrees of renal function.

1. The pharmacokinetics of remoxipride, a new neuroleptic, were investigated in an open study with three parallel groups. Twenty-one patients with severely impaired (ClCr < 25 ml min-1), moderately impaired (ClCr 25-50 ml min-1) and normal (ClCr > 65 ml min-1) renal function were evaluated. A single oral dose of remoxipride hydrochloride 100 mg was administered, and blood and urine were collected over 48 h. Concentrations of remoxipride and metabolites were measured by h.p.l.c. 2. In patients with severely decreased renal function, the AUC and Cmax of remoxipride were increased significantly, and t1/2 was prolonged, as compared with the control patients. The renal clearance and urinary recovery of the unchanged drug were significantly diminished. 3. The unbound fraction of remoxipride in plasma was decreased in patients with renal failure, in association with a disease-related increase in alpha 1-acid glycoprotein. In spite of a 25% recovery of unchanged drug in the urine in patients with normal renal function, the AUC of unbound drug was twice as high in patients with severely impaired renal function. 4. A strong correlation between creatinine clearance and renal drug clearance was observed indicating a direct relationship between kidney function and the renal clearance of remoxipride. 5. Remoxipride was the predominant compound in plasma as well as in urine in patients with severely decreased as well as normal renal function. In patients with severely decrease renal function, remoxipride and all five pharmacologically inactive metabolites showed increased peak plasma concentrations, delayed tmax, increased AUC, prolonged half-lives and decreased renal clearance.

Adult

Pharmacokinetics of nisoldipine in renal dysfunction.

The pharmacokinetics of nisoldipine have been studied after oral administration of one 10 mg tablet to 3 groups of patients: Group A (n = 8) with a mean creatinine of 90 ml/min, Group B (n = 8) with a mean creatinine clearance of 12 ml/min and Group C of 12 patients on maintenance haemodialysis. All of them were studied off-dialysis and 7 were also studied on a dialysis day. No significant differences were observed between Groups A, B and C (on an interdialysis day) in AUC (0-7h), tmax, Cmax and plasma protein binding. Unchanged nisoldipine could not be recovered from the urine in any patient. Haemodialysis did not significantly affect AUC, tmax and Cmax, and nisoldipine could not be detected in the dialysate. The results indicate that the dose of nisoldipine need not be changed in patients with renal dysfunction, and that a supplementary dose is not required after haemodialysis. Blood pressure in the uraemics fell more than in the patients with good renal function.

Adult

Itraconazole pharmacokinetics in patients with renal dysfunction.

The single-dose pharmacokinetics of 200 mg of oral itraconazole were studied in seven uremic patients, seven patients treated by hemodialysis, and five patients treated by continuous ambulatory peritoneal dialysis. Plasma concentration-versus-time profiles showed wide intersubject variation. This study could not demonstrate any significant effect of renal dysfunction and hemodialysis or continuous ambulatory peritoneal dialysis treatment upon the pharmacokinetics of itraconazole, and firm conclusions concerning dosing in such patients should await confirmation of our data in a larger patient population.

Administration, Oral

Impaired neutrophil defense against Yersinia enterocolitica in patients with iron overload who are undergoing dialysis.

Increased risk that patients with iron overload who are undergoing dialysis will have bacteremia caused by Yersinia enterocolitica has previously been shown. Iron overload is known to increase the virulence of Y. enterocolitica. Whether alterations of the phagocyte defense against this organism are also involved has not yet been determined. We compared neutrophil defense against a serum-resistant strain of Y. enterocolitica in three groups of individuals: nine patients receiving hemodialysis who had iron overload (group 1), nine patients receiving hemodialysis who did not have iron overload (group 2), and 10 healthy controls (group 3). Y. enterocolitica phagocytosis and killing were studied in the presence of autologous or pooled normal human serum. Phagocytosis was significantly decreased in group 1 compared with that in the other two groups. The use of normal serum for opsonization did not improve the phagocytosis function. Killing was moderately decreased in the group 1, but only in the presence of autologous serum. We conclude that in patients with iron overload who are undergoing dialysis, the high frequency of Yersinia bacteremia is attributable not only to increased virulence of this microorganism but also to disturbances of the mechanisms specifically involved in the neutrophil defense against Yersinia invasion.

Blood Bactericidal Activity

Multiple dose pharmacokinetics of intravenous acyclovir in patients on continuous ambulatory peritoneal dialysis.

Once daily 60 min iv infusions of acyclovir at 2.5 mg/kg were administered to six uraemic patients (three male, three female of mean age 52 years and body weight 60 kg) treated by continuous ambulatory peritoneal dialysis (CAPD). Blood and dialysate samples were taken for analysis of acyclovir by radio-immunoassay. A three-compartment pharmacokinetic model was found necessary to explain the profiles obtained. Steady-state was reached by the third day, with little change in mean peak or trough plasma levels between day one (25 and 3 microM) and day five (29 and 4 microM). Mean total plasma clearance was 46 ml/h/kg, of which 12% was due to peritoneal dialysis. The model parameters predicted efficient transfer of acyclovir from the peritoneum to plasma, such that hypothetical peritoneal dosing might give 91% bioavailability. In patients treated by CAPD, iv acyclovir should be administered at 2.5 mg/kg/day.

Acyclovir

Surveillance of aminoglycoside resistance. European data.

The susceptibility patterns of gram-negative aerobic organisms to aminoglycosides differ widely from one European health care center to another and depend upon local antibiotic prescribing policies. Reports of the susceptibility of Pseudomonas aeruginosa to gentamicin and tobramycin have ranged from as low as 49.8 percent and 77.7 percent, respectively, in Greece, to as high as 96.6 percent and 99.2 percent, respectively, in the United Kingdom. The susceptibility of P. aeruginosa to gentamicin, tobramycin, and amikacin decreased in our hospital from 73.1 percent, 94.8 percent, and 95.6 percent, respectively, in 1982, to 43.1 percent, 70.6 percent, and 74.3 percent, respectively, in 1984. A prospective surveillance study of the susceptibility of gram-negative aerobic bacilli to four aminoglycosides (gentamicin, tobramycin, amikacin, and netilmicin) was performed over a period of 17 months. Gentamicin and tobramycin were freely used, while the use of amikacin was restricted throughout the hospital during a four-month baseline period (May through August 1984). Gentamicin and tobramycin accounted for 94 percent of the aminoglycoside use. During the following 13 months (September 1984 through September 1985), amikacin was used as the first-line aminoglycoside and accounted for more than 97 percent of the aminoglycoside usage. A total of 1,866 organisms were analyzed during the baseline period; 5,429 were analyzed during the amikacin-usage period. The overall susceptibility to gentamicin, tobramycin, amikacin, and netilmicin increased from 86.9 percent, 90.4 percent, 94.2 percent, and 88.3 percent, respectively, to 92.3 percent, 94.0 percent, 97.3 percent, and 92.3 percent, respectively. P. aeruginosa isolates had the most striking changes, with the susceptibility to gentamicin, tobramycin, amikacin, and netilmicin increasing from 43.1 percent, 70.6 percent, 74.3 percent, and 50.6 percent, respectively, during the baseline period, to 64.5 percent, 81.6 percent, 90.8 percent, and 65.1 percent, respectively, during the amikacin-usage period. The use of amikacin as a first-line aminoglycoside, while use of the other aminoglycosides was restricted, seemed to have a favorable influence on the susceptibility pattern of gram-negative aerobic isolates in our hospital.

Amikacin

Aztreonam treatment of gram-negative septicemia.

Seventy-five aztreonam treatment courses in 74 patients with gram-negative septicemia resulted in 56 clinical cures (75%), 12 partial clinical cures (16%), and 7 clinical failures (9%). Eradication of the original pathogen from the blood was obtained in all patients but two, who had relapses 1 and 4 days, respectively, after treatment. In nine patients (12%) a superinfection was reported. Significant adverse reactions were limited to one transient urticarial rash. Aztreonam may prove to be an effective alternative for the treatment of gram-negative septicemia, but superinfections should be carefully monitored.

Adolescent

In vitro activity of BRL 36650, a new penicillin.

Compared with four beta-lactam antibiotics and amikacin, BRL 36650 and BMY-28142 were the most active against 509 Enterobacteriaceae, including cefotaxime-resistant isolates and resistant laboratory mutants. BRL 36650 was more active than aztreonam, ceftazidime, and BMY-28142 against Acinetobacter spp., Pseudomonas aeruginosa, and other Pseudomonas spp.; all strains were inhibited by 2 micrograms/ml or less.

Acinetobacter

Lipoprotein distribution and composition in the human nephrotic syndrome.

Plasma lipoprotein profiles were quantitated in 9 patients with the nephrotic syndrome. Six subjects were studied both during an active proteinuric phase and during a remission phase without proteinuria. During the proteinuric phase, the plasma triglyceride, cholesterol and apo B levels were markedly increased, whereas the HDL cholesterol, apo A-I, and apo A-II concentrations were normal. Analysis of the distribution and composition of the lipoprotein subclasses, separated by isopycnic ultracentrifugation, showed typical patterns characterized by: (1) elevated apo B-rich VLDL and LDL fractions, (2) the presence of a denser LDL subfraction, floating at d 1.053 g/ml, which contained about 35% of LDL cholesterol and apo B and (3) a redistribution among HDL subclasses. The HDL2b (d 1.063-1.100 g/ml) fraction was markedly decreased, while the HDL2a + 3a (d 1.100-1.150 g/ml) and HDL3b + 3c (d 1.150-1.210 g/ml) subclasses were moderately elevated. The decreased cholesterol and apo A-I contents of HDL2b therefore counterbalanced their increase in HDL2a + 3a and HDL3b + 3c, resulting in normal plasma HDL cholesterol and apo A-I concentrations. When reinvestigated during a remission phase without proteinuria, the nephrotic patient's overall lipoprotein distribution and composition were similar to those in healthy controls. The combination of several factors such as the presence of elevated apo B-rich VLDL, IDL and LDL, together with decreased HDL2 cholesterol and HDL2 apo A-I suggests that nephrotic patients are at increased risk for atherosclerosis.

Adolescent