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Biomedical subjects

A van Dijk

Publications and source records attributed to A van Dijk.

At least 55 records · Page 3Linked to original sources

Pharmacokinetics of rhenium-186 after administration of rhenium-186-HEDP to patients with bone metastases.

The pharmacokinetics of 186Re-HEDP, a radiopharmaceutical for palliative treatment of metastatic bone pain, was investigated in 11 patients (17 studies) who suffered from metastatic breast or prostate cancer. Half-life times of 186Re in three blood fractions (whole blood, plasma and plasma water) were 40.1 +/- 5.0, 41.0 +/- 6.0 and 29.5 +/- 6.4 hr, respectively. Time-dependent increase in plasma-protein binding was observed, probably caused by in vivo decomposition of 186Re-HEDP. Total urinary 186Re excretion was 69% +/- 15%, of which 71% +/- 6% was excreted in the first 24 hr after injection. The BSI (i.e., fraction of the skeleton showing scintigraphic evidence of metastatic disease) closely correlated with the fraction of dose non-renally cleared (r = 0.98). This implies that the amount of radioactivity taken up by the skeleton and hence the bone marrow absorbed dose can be predicted from a diagnostic pre-therapy 99mTc-HDP scintigram. The pharmacokinetic behavior indicates that 186Re-HEDP has suitable properties to justify its application.

Aged↗

Mechanism of protection of alveolar type II cells against paraquat-induced cytotoxicity by deferoxamine.

Paraquat toxicity has been associated with the generation of free radicals in alveolar epithelial cells in which paraquat specifically accumulates via a polyamine uptake system. In the present study we investigated whether deferoxamine (DF), an iron chelator that has antioxidant capacity and that also has a polyamine-like structure, could protect alveolar type II cells (ATTC) against injury by paraquat. Radiolabeled [3H]adenine ATTC were incubated in a medium containing 75 microM paraquat in the absence or presence of DF (500 microM). After 3 hr of incubation paraquat-mediated cytotoxicity of ATTC, as measured by [3H]adenine release, was significantly (P less than 0.005) decreased by addition of DF (26.6 +/- 2.6% vs 7.4 +/- 1.7%). Accumulation of radiolabeled [14C]paraquat at a concentration of 75 microM was also decreased (70%) by 500 microM DF from 94.8 +/- 2.1 to 28.9 +/- 6.7 nmoles paraquat/2.5 x 10(5) ATTC. This effect of DF was dose dependent and comparable with the protective effect of equimolar concentrations of putrescine. However, per cent uptake of paraquat at a concentration of 500 microM was not significantly inhibited by DF (1 mM), whereas paraquat-induced injury was still markedly reduced (36.2 +/- 2.5% vs 2.6 +/- 4.2%). This indicated that the protective effect of DF could not be explained by its competition with paraquat on uptake alone. In the same series of experiments using another iron chelator, pyridoxal benzoyl hydrazone (PBH), which has antioxidant properties similar to DF but does not show its polyamine-like structure, ATTC lysis was also prevented although paraquat uptake was not reduced. These in vitro data indicate that the mechanism of protection by DF against paraquat toxicity in lung epithelial type II cells is two-fold: inhibition of paraquat uptake through its compliance with the structural requirements necessary for transport, and inhibition of paraquat-induced iron-catalysed free radical generation.

Animals↗

Comparative antidotal efficacy of activated charcoal tablets, capsules and suspension in healthy volunteers.

The efficacy of several formulations of activated charcoal (AC) was compared by measuring the intestinal absorption of a solution of 1 g paracetamol administered 2 min before administration of 5 g AC as suspension (200 ml), tablets (40 of 125 mg) or capsules (25 of 200 mg). The suspension medium without AC was used as the control treatment. Based on the results of a pilot experiment, an 8 subject panel was used in a two 4 x 4 Latin square design. All treatments with AC resulted in a statistically significant decrease in paracetamol absorption compared to the control treatment. The suspension was considerably and significantly more effective than the tablets or capsules. Treatment with tablets was slightly but significantly more effective than capsules. The intake of large numbers of tablets and capsules was difficult. In the hospital AC suspensions are available. For first aid elsewhere, at home, at the working place or in the general practitioner's surgery a preservable and easily redispersible AC formulation would be preferable to the present solid forms.

Acetaminophen↗

Once-daily dosing regimen for aminoglycoside plus beta-lactam combination therapy of serious bacterial infections: comparative trial with netilmicin plus ceftriaxone.

PURPOSE: Once-daily dosing of aminoglycosides has been suggested to improve their efficacy and reduce their toxicity. To test the clinical validity of this suggestion, we conducted a prospective, randomized trial comparing a conventional multiple-daily-dosing regimen of netilmicin with once-daily administration of the same total daily dose of this aminoglycoside. PATIENTS AND METHODS: We enrolled 141 predominantly elderly patients with severe bacterial infections. All patients received once-daily doses of 2 g ceftriaxone, in addition to netilmicin. RESULTS: Patients randomized to either of the two dosing strategies were comparable regarding age, APACHE II score, concomitant diseases, infection site, and rate of culture-proven bacteremia. Netilmicin treatment did not differ significantly in mean daily dose per kg body weight and days of therapy between the two treatment arms. Compared to patients receiving conventional doses, patients treated with a once-daily dose had higher serum peak netilmicin levels and lower trough levels. Outcome of infection and mortality were not influenced by dosing strategy. Although the overall incidence of nephrotoxicity was similar in both groups (16%), the occurrence of nephrotoxicity in patients treated with once-daily doses of netilmicin was significantly shifted to those given prolonged treatment, i.e., beyond 9 days. Auditory toxicity was documented in one patient treated with conventional doses and two patients treated with once-daily doses. CONCLUSION: Once-daily dosing of an aminoglycoside plus a long-acting cephalosporin in these patients constituted cost-effective and safe treatment for severe bacterial infections. Netilmicin-induced toxicity may be reduced by using once-daily dosing regimens and limiting the duration of treatment.

Adolescent↗

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 drowsy child: benzodiazepine poisoning?].

In The Netherlands accidental intoxications in children due to benzodiazepines are regularly encountered. In 1987 of 1630 requests for information at the National Poison Control Centre about probable benzodiazepine intoxications 144 (8.8%) concerned children 0-12 years of age. The symptoms of this type of intoxication are non-specific and if the physician does not think of benzodiazepine intoxication extensive diagnostic procedures may be performed. If children show symptoms e.g. unconsciousness, ataxia and hypotonia, the physician should always think of benzodiazepine intoxication and try to confirm or to exclude this possibility by toxicological analysis. We discuss ways and means of the diagnosis and how to avoid pitfalls on the way.

Anti-Anxiety Agents↗

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↗

A study of epidural morphine and sufentanil anesthesia for abdominal aortic surgery.

Thirty six comparable patients, ASA 2, without cardiac disease, underwent aortic disobliteration, 19 under epidural 100 micrograms/kg morphine (EM) and 17 under epidural 2 micrograms/kg sufentanil (ES), combined with general anesthesia. To compare the hemodynamics, measurements were taken pre-operatively, after induction of general anesthesia, during aortic dissection, aortic cross-clamping and 3-5 minutes after the first revascularisation. Plasma and CSF drug levels were measured at intervals in 6 patients in the EM end 5 patients in the ES group. Both drugs provided satisfactory analgesia which persisted for 10.4 hours in the EM and 6.3 hours in the ES group. The fall in systemic pressure and left ventricular work in both groups after induction of general anesthesia suggests that EM and ES must be used with caution in patients with hypovolemic or cardiovascular disease. There was a significant difference in SVR between the two groups during the aortic dissection, due to a rise in SBP in the ES group and a tendency for SVR to fall in the EM group. However significant differences in left ventricular work did not occur. Notable was the absence of significant changes in filling pressure, CI and left ventricular function during aortic cross-clamping. After revascularization a significant decrease in systolic blood pressure occurred in association with an increase in heart rate in the EM group. The influence of the plasma and CSF concentrations of morphine and sufentanil on the hemodynamic changes during surgery were evaluated.

Adjuvants, Anesthesia↗

Postoperative prophylaxis with norfloxacin in patients requiring bladder catheters.

The effect of once daily doses of 200 mg oral norfloxacin on the occurrence of catheter-associated bacteriuria (greater than 1000 CFU/ml) and pyuria was studied in 105 post-operative gynaecologic patients. Norfloxacin was given from the second day after surgery until catheter removal. Bacteriuria developed in 32 of 51 (63%) control patients compared to 8 of 54 (15%) patients receiving norfloxacin (p less than 0.001). Pyuria was present in 22 of 51 (43%) control subjects versus only 3 of 54 (5%) patients treated with norfloxacin (p less than 0.001). Bacteria isolated from control patients comprised species of Enterobacteriaceae (40%), Staphylococcus (35%), and Streptococcus (17%); seven isolates were resistant to multiple antibiotics reflecting their nosocomial origin. In contrast, strains isolated from norfloxacin-treated patients comprised non-fermenting gram-negative rods (79%, usually Alcaligenes or Acinetobacter spp.) and faecal streptococci (12%). It is concluded that once daily doses of 200 mg oral norfloxacin are effective in reducing the rate of catheter-associated bacteriuria and pyuria following reconstructive gynaecologic surgery.

Adult↗

Responders and non-responders after fluoride therapy in osteoporosis.

Patients with osteoporosis were treated for two years with sodium fluoride. Fifteen received sodium fluoride in capsules, 56 in enteric coated slow release tablets (Ossin) and 20 in enteric coated tablets (Procal). Seven women treated with Procal were also treated with oestrogens. All patients had a calcium intake between 1000 and 2000 mg/day, used dihydrotachysterol for vitamin suppletion and were advised to exercise. Non-responders were arbitrarily defined as those who had an increase in serum alkaline phosphatase less than 10 U/l, those who had no increase in bone mineral content measured with CT in L4 and those who got a femoral neck fracture during the period of therapy. In the overall group of 91 patients 20% were non-responders based on a serum alkaline phosphatase increase less than 10 U/l. Based on the changes in bone mineral content 40% were non-responders during the first year of treatment, 45% during the second year and 23% over the first plus second year. The impression is that patients with a femoral neck fracture have a higher increase in serum parathyroid hormone concentration than patients without fractures. The urinary excretion of fluoride has a better predictive value than the change in serum alkaline phosphatase concentration for the prediction of an increase in bone mineral content.

Aged↗

Therapeutic problems in cyanide poisoning.

In three patients with severe acute cyanide poisoning, a cyanosis was observed instead of the bright pink skin coloration often mentioned as a sign in textbooks. Treatment of cardiopulmonary insufficiency is as essential as antidotal therapy and the use of sodium nitrite and 4-DMAP is not without risk as, in practice, the methemoglobin-level induced is difficult to control.

Adult↗

Massive theophylline intoxication: effects of charcoal haemoperfusion on plasma and erythrocyte theophylline concentrations.

The results of a charcoal haemoperfusion on plasma and erythrocyte theophylline concentrations are described in a patient, intentionally intoxicated with a sustained-release theophylline formulation. It is demonstrated that the charcoal-filled Gambro Adsorba 300-C column is effective in removing theophylline. This effectiveness is based on pharmacokinetic parameters, which are presented. The necessity of measuring plasma and erythrocyte theophylline concentrations is outlined. Calculations based on plasma theophylline concentrations only can lead to an underestimation of the effectiveness.

Charcoal↗

Additive and heterosis effects on preweaning traits, maternal ability and reproduction from crossing of the Angus and brown Swiss breeds in Florida.

Angus (A), Brown Swiss (S) and A X S reciprocal F1 (AS) dams were mated to A, S and AS (also reciprocal F1) sires resulting in nine breed groups of progeny with varying proportions of Angus and Brown Swiss breeding. Breed group of dam and of sire significantly influenced birth weight, preweaning daily gain, weaning weight, 205-d weight, condition score and frame size. The means for birth weight and weaning weight were 33 and 213 kg, respectively. Brown Swiss bulls sired calves with the heaviest birth and weaning weights. Calves produced by S dams likewise were heavier at birth and weaning. Pregnancy rates were influenced significantly by year, age and breed of dam and averaged 79, 95 and 92% for S, AS and A cows, respectively. Survival rate averaged 97% and was not influenced significantly by any of the effects examined. Because survival rates were similar for all breed groups, the results for weaning rate paralleled those for pregnancy rate. Genetic influences on preweaning growth traits and survival rate were partitioned into additive breed differences (B) and heterosis (H) effects for direct (d) and maternal (m) components. Pregnancy and weaning rates were examined using similar analyses except that genotype of service sire of dam replaced that of the offspring for the direct additive breed and direct heterosis components. The Bd values indicated that the Angus breed was inferior (P less than .01) to the Brown Swiss breed for all preweaning growth traits except for condition score, in which the Angus breed surpassed (P less than .01) the Brown Swiss. The Bm values also showed an advantage for the Brown Swiss breed for all preweaning growth traits. The additive maternal effect (the genotype of the females exposed), Bm, was important for pregnancy rate and weaning rate (P less than .001 and P less than .05) but not for survival rate (P greater than .10). The direct additive breed effect was not important for any reproductive trait. Direct heterosis did not affect any of the preweaning or reproduction traits; however, maternal heterosis (Hm) significantly affected all traits except birth weight, frame score and survival rate. The Hm estimates were 12.0 and 8.4 kg for weaning weight and 205-d weight, respectively. The Hm estimates for pregnancy rate, survival rate and weaning rate were 10, 2 and 13%, respectively.

Animals↗