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Biomedical subjects

C M Rademaker

Publications and source records attributed to C M Rademaker.

At least 19 recordsLinked to original sources

Once-daily versus multiple-daily gentamicin in infants and children.

In this prospective randomized trial, the efficacy and safety of once-daily administration of gentamicin were compared with multiple-daily administration in infants and children. In addition, pharmacokinetic variables were calculated. Gentamicin therapy was started at a dose of 5 mg/kg per day under individual dose or dosage interval adjustments to achieve target levels. Fifty-two infants and children aged 1 month (postterm) to 16 years were enrolled. The duration of fever from the start of therapy, the percentage decline of C-reactive protein (CRP) on day 3 of treatment, and the clinical outcome were used as efficacy parameters. Nephrotoxicity was evaluated using creatinine serum levels. Basic characteristics in both groups were comparable. A good clinical response was observed in both groups. Fever may have resolved faster with multiple-daily administration, but this was not statistically significant. The percentage of decline of CRP was also comparable in both groups. Nephrotoxicity occurred in six patients, three per group. Many patients were too ill or too young to perform hearing tests, but no clinical signs of ototoxicity were observed. Mean doses of 6.8 mg/kg per day (multiple-daily administration) and 7.3 mg/kg per day (once-daily administration) were necessary to meet the target gentamicin levels. Triple-daily doses had to be reduced to a twice-daily regimen in 17 of 26 children. Dose and dosage interval adaptations can be performed by Bayesian forecasting using a one-compartment model with one set of K(e) and V(d) parameters. The authors consider both regimens equally effective, with a comparable incidence of nephrotoxicity. A starting dose of 6.5 mg/kg once daily is advised.

Adolescent↗

Population pharmacokinetics of gentamicin in preterm neonates: evaluation of a once-daily dosage regimen.

Population pharmacokinetic parameters of gentamicin in preterm neonates on a once-daily dosage regimen of 3.0 mg/kg given intravenously every 24 hours were established prospectively. In 34 preterm neonates with a mean gestational age of 32 +/- 4 (SD), 182 serum gentamicin levels (91 peak/trough pairs) were determined. Individual adjustments of dose or dosage interval were calculated by computer-aided Bayesian forecasting. The parameters Vd, ke, and CL for each patient were obtained by the nonparametric estimation of maximization method. The predictive power of the model was calculated and the pharmacokinetic estimates were statistically analyzed with SPSS/PC. Cluster analysis showed a division into 2 subpopulations (designated 1 and 2) on the basis of postnatal age. The mean +/- SD postnatal age of subpopulation 1 (n = 29) was 6 +/- 2 days (range 1-7) and of subpopulation 2 (n = 5) 15 +/- 4 days (range 12-24). The mean +/- SD gentamicin relative clearances of subpopulation 1 and subpopulation 2 were 0.0515 +/- 0.0128 and 0.1026 +/- 0.0102 L kg(-1) hr(-1), respectively (p < 0.05). The mean +/- SD values for Vd (Lkg(-1)) in both populations 1 and 2 were 0.6916 +/- 0.1670 and 0.7509 +/- 0.1961, respectively (not significantly different). For ke these data were 0.0744 +/- 0.0200 and 0.1366 +/- 0.0522 (p < 0.05). Statistics showed that the data for Vd and ke of subpopulation 1 were normally distributed (Vd and ke skewness 1.61 and 1.46; kurtosis 3.09 and 3.10 respectively). The model yielded a bias of -0.11 mg/L and a precision of 0.36 mg/L. It is recommended that gentamicin be started in a dosage of 3.5 mg/kg intravenously once-daily under close monitoring.

Age Factors↗

Cetrimide overdose.

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Anticestodal Agents↗

Detection of toxigenic Clostridium difficile in fecal samples by colony blot hybridization.

A hybridization assay for detection of toxigenic Clostridium difficile in fecal samples was developed and compared with the classical tissue culture cytotoxicity assay. A DNA fragment probe specific for the toxin B gene of Clostridium difficile was synthesized by the polymerase chain reaction and labelled with digoxigenin. Fecal samples were cultured for 24 hours, replica-plated and hybridized with the probe. The hybridization assay had a sensitivity of 100%, specificity of 96.7%, positive predictive value of 86.7% and negative predictive value of 100% compared with the cytotoxicity assay.

Base Sequence↗

Frequency of enterovirulent Escherichia coli in diarrhoeal disease in The Netherlands.

To assess the role of enterovirulent Escherichia coli in The Netherlands, faecal samples of 279 patients (108 children, 171 adults) with diarrhoea and 100 healthy controls were investigated in a prospective study. Enterovirulent Escherichia coli were identified by hybridization with five different non-radioactively labelled DNA probes specific for enteropathogenic Escherichia coli (EPEC), verocytotoxin producing Escherichia coli (VTEC) and enterotoxigenic Escherichia coli (ETEC). The rate of isolation of EPEC was 6.5% in patients with diarrhoea and 2.0% in asymptomatic persons. During the study period, no VTEC were isolated from patients with diarrhoea. ETEC were isolated from two persons, both of whom had experienced diarrhoea and had returned from travel in (sub)tropical areas. Our results suggest that diarrhoea is sporadically caused by ETEC among the indigenous population of The Netherlands, and is mainly associated with travel in endemic areas. Furthermore, the presence of EPEC probe-positive strains in the stool need not always be accompanied by symptoms of diarrhoea.

Adult↗

Detection of enterovirulent Escherichia coli associated with diarrhoea in Seville, southern Spain, with non-radioactive DNA probes.

To assess the role of diarrhoeagenic Escherichia coli in Southern Spain, faecal samples from 135 patients with diarrhoea and 40 healthy subjects from Seville, Andalusia, were investigated. In this prospective study, enterovirulent E. coli were identified by hybridisation with five non-radioactive DNA probes specific for enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC) and verocytotoxin-producing E. coli (VTEC). Probe-positive strains were isolated from four patients (3%) with diarrhoea and from none of the healthy controls. Two patients harboured ETEC and two patients had EPEC probe-positive strains in their faeces. No VTEC were isolated during this study. Salmonella spp. were the most frequently identified enteric pathogens, accounting for 10% of the cases, followed by Campylobacter jejuni (3%) and diarrhoeagenic E. coli (3%). This study indicates that enterovirulent E. coli play a modest role in the aetiology of diarrhoea among the indigenous population of Southern Spain.

Adult↗

[Detection of diarrhea-causing Escherichia coli using DNA-probes].

To assess the role of enterovirulent Escherichia coli at home and abroad, faeces samples of patients with diarrhoea and of healthy controls in Tunisia, Seville (southern Spain) and the Netherlands were investigated. Enterovirulent E. coli were identified by hybridization with five different non-radioactively labelled DNA probes specific for enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC) and verocytotoxin producing E. coli (VTEC). ETEC was the main causative agent of travellers' diarrhoea in Tunisia. The isolation of ETEC in the Netherlands was shown to be related to travel in endemic areas. EPEC probe positive strains were isolated in children and in adults, but were not in all cases associated with intestinal disease. During this study no VTEC were detected. From an immunocompromised kidney transplantation patient with sepsis and diarrhoea ETEC were isolated from blood.

Adolescent↗

Comparison of the effect of midazolam or vecuronium on blood pressure and cerebral blood flow velocity in the premature newborn.

The effect of midazolam and vecuronium on mean arterial pressure (MAP) and mean cerebral blood flow velocity (MCBFV) was evaluated in premature infants (birthweight 550-2,560 g; gestational age 26-36 weeks) randomised to receive either 0.1 mg/kg midazolam (n = 7) or 0.05 mg/kg vecuronium (n = 8) intravenously. MAP, by means of an indwelling arterial catheter, and MCBFV, by means of non-invasive pulsed-Doppler of the middle cerebral artery, were measured every 5 min, starting at 10 min prior to until 1 h after drug administration. A transient 25-43% decrease in MCBFV (mean 0.06 m/s) dependent on a 8-23% decrease in blood pressure (mean 9 mm Hg) was noted in all patients within 15 min following administration of midazolam, which returned to baseline values within 1 h. In 2 out of 7 infants, a plasma expander was required. In contrast, vecuronium only decreased the MCBFV in 3 of 8 infants. Thus, a bolus of midazolam transiently decreased blood pressure and MCBFV, and should be used cautiously in sick preterm infants.

Blood Flow Velocity↗

[Magnesium poisoning in an infant].

We present the case of a girl aged 3 weeks with extreme hypermagnesaemia (7.94 mmol/l) due to an overdose of magnesium oxide, prescribed as a laxative. We treated her successfully with a combination of hyperhydration, forced diuresis and natriuresis, and additional intravenous calcium and insulin. We also performed an exchange transfusion which, however, had a questionable effect on the final outcome.

Combined Modality Therapy↗

Analysis of Escherichia coli isolates from subjects with travellers' diarrhoea using DNA probes and serotyping.

Escherichia coli isolated from faeces of 54 healthy volunteers who visited Tunisia for eight days were examined. These volunteers participated in a randomized double-blind placebo-controlled study to establish whether ciprofloxacin could prevent travellers' diarrhoea. Escherichia coli strains isolated before travel, during episodes of travellers' diarrhoea, immediately after return and five weeks after return were serotyped and tested for the presence of virulence genes indicating diarrheogenic properties by hybridization with a set of four non-radioactively labelled DNA probes. Subjects receiving ciprofloxacin prophylactically to prevent travellers' diarrhoea were asymptomatic and no Escherichia coli could be cultured shortly after return home. Sixty-four percent of subjects (18/28) who did not receive antibiotic prophylaxis suffered from travellers' diarrhoea. Hybridization tests detected 8 enterotoxigenic Escherichia coli strains producing heat stable toxin, 13 enterotoxigenic strains producing heat labile toxin and 10 strains which produced both heat labile and stable toxin. Of the 31 probe positive strains, 29 (94%) were cultured from 11 volunteers with travellers' diarrhoea. A bacterial cause was thus determined in 61% of the volunteers who experienced travellers' diarrhoea.

Adult↗

A double-blind comparison of low-dose ofloxacin and amoxycillin/clavulanic acid in acute exacerbations of chronic bronchitis.

The efficacy and safety of ofloxacin 400 mg once daily and amoxycillin/clavulanic acid 500/125 mg three times daily were compared in a double-blind manner in patients with an acute exacerbation of chronic bronchitis. Of 102 patients enrolled, 95 (93%) could be assessed for effectiveness. Treatment success was achieved in 41 (84%) of 49 patients in the ofloxacin group compared with 41 (89%) of 46 patients in the amoxycillin/clavulanic acid group. One patient who received ofloxacin and four patients in the amoxycillin/clavulanic acid group stopped medication because of unacceptable side effects. Microbiological results were evaluable in 47% of the patients. Predominant initial pathogens were Haemophilus influenzae, Streptococcus pneumoniae, sometimes in combination, and less frequently Branhamella catarrhalis. In two patients with clinical failure, randomized to ofloxacin, the initial pneumococcal strains persisted in the sputum after treatment.

Amoxicillin↗

Pharmacokinetics of cefepime in patients with respiratory tract infections.

The steady-state pharmacokinetics of cefepime were evaluated in 10 middle-aged and elderly patients with acute lower respiratory tract infections who were receiving 1 g intravenously every 12 h. One preinfusion and 15 postinfusion serum samples and total urine output were collected over one dosing interval between days 3 and 8 of therapy. Cefepime concentrations in serum over time exhibited a multicompartmental profile. Peak and trough concentrations in serum determined by a validated high-performance liquid chromatography method were 71.2 +/- 17.2 (mean +/- standard deviation) and 6.0 +/- 4.9 mg/liter, respectively. The steady-state volume of distribution was 0.22 +/- 0.05 liter/kg. Elimination half-lives ranged from 1.93 to 6.04 h (3.92 +/- 1.28 h), and total body clearances ranged from 36.9 to 102 ml/min per 1.73 m2 (73.0 +/- 19.7 ml/min per 1.73 m2). The disposition of cefepime at steady state in patients was comparable to previous observations in healthy elderly volunteers. The predictive performance of regression equations derived from single-dose studies in volunteers relating creatinine clearance with total body and renal clearances of cefepime exhibited slight biases (mean predictive errors, -9.7 and 2.1 ml/min per 1.73 m2, respectively) and similar precisions. Predicted and observed total body clearances (63.3 +/- 25.1 versus 73.0 +/- 19.7 ml/min per 1.73 m2, respectively) and renal clearances (51.3 +/- 24.4 versus 49.3 +/- 19.6 ml/min per 1.73 m2, respectively) were not significantly different. The pharmacokinetics of cefepime in infected patients appeared to be unaltered by illness, and the steady-state disposition of cefepime was predictable from data derived from single-dose studies in volunteers.

Aged↗

Pharmacokinetics of a single dose of ofloxacin in healthy elderly subjects using noncompartmental and compartmental models.

The pharmacokinetics of ofloxacin following a single 200 mg oral dose were studied in twelve healthy elderly volunteers. Relevant pharmacokinetic parameters were analysed by both noncompartmental and compartmental models. In compartmental analysis, the data on plasma concentrations was best described by an open two-compartment model. A zero-order absorption behaviour was found in some volunteers. The terminal half-lives were slightly prolonged and ranged from 6.2-11.6 h. A linear relationship was found between the renal clearance of the drug and the estimated creatinine clearance. Computer predictions of a multiple 200 mg dose regimen showed no important accumulation of ofloxacin. The recommendation of some authors that, in general, ofloxacin dosage may be halved in the elderly could not be confirmed. This has to be determined through further clinical experience in elderly ill subjects.

Aged↗

A ready-to-use activated charcoal mixture. Adsorption studies in vitro and in dogs: its influence on the intestinal secretion of theophylline in a rat model.

A practical, ready-to-use preparation of activated charcoal (AZU mixture) for application in toxicology has been formulated. To establish its efficacy, the formulation was tested in vitro and in dogs. The in vitro adsorption capacity was compared to that of freshly prepared charcoal suspension in water (CW) and to Carbomix. Langmuir adsorption coefficients demonstrated small but clinically insignificant differences in adsorption capacity between the preparations. The laxative sodium sulfate did not reduce the adsorption capacity of charcoal in vitro. Dogs were given 60 mg of paracetamol per kg as an oral solution followed by 5 g of activated charcoal preparation. The area under the plasma concentration versus time curve (control 2955 +/- 353 mg.min-1.l-1) was significantly reduced following CW (921 +/- 453) and AZU (786 +/- 270). The premixed AZU charcoal formulation is efficacious, inexpensive and overcomes the problems of bed-side preparation. An isolated vascularly perfused rat small intestine can be used to describe the effect of activated charcoal on the intestinal secretion of theophylline.

Acetaminophen↗

Results of a double-blind placebo-controlled study using ciprofloxacin for prevention of travelers' diarrhea.

To determine the efficacy, safety and effect on fecal flora of ciprofloxacin in the prevention of travelers' diarrhea, 54 volunteers traveling to Tunisia were randomized in a double-blind manner to receive either 500 mg ciprofloxacin or a placebo once daily for one week. Results of 53 volunteers were available for evaluation of efficacy. One of 25 subjects (4%) receiving ciprofloxacin versus 18 of 28 subjects (64%) in the placebo group experienced travelers' diarrhea (p less than 0.0001). The protection offered by ciprofloxacin was 94%. In one volunteer taking ciprofloxacin, prophylaxis was terminated due to sunburn with blistering. Among 41 subjects reporting sunburn, no statistical difference was observed between the two treatment groups in the percentage of body surface area of sunburn. Quantitative feces cultures revealed a marked decrease in the number of gram-negative organisms in volunteers receiving ciprofloxacin and a significant increase in the number of Escherichia coli in the placebo group. Five weeks after return, the aerobic bacterial flora of both treatment groups showed the pre-travel pattern.

Adult↗