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Biomedical subjects

A van Dijk

Publications and source records attributed to A van Dijk.

At least 37 records · Page 2Linked to original sources
PubMed1996

Absolute bioavailability of fluoride from disodium monofluorophosphate and enteric-coated sodium fluoride tablets.

OBJECTIVES: The absolute bioavailability and other pharmacokinetic parameters of two fluoride formulations were investigated in 13 healthy volunteers, aged 61-70 years. METHODS: The following formulations were administered, under fasting conditions, in a single-dose three-way cross-over design: tablets of 76 mg disodium monofluoro phosphate (MFP, equivalent to 10.0 mg F- ion), enteric-coated (e.c.) tablets of 25 mg sodium fluoride (NaFor, equivalent of 11.3 mg F- ion), and an isoosmotic aqueous injection solution (4 ml) of 22.1 mg sodium fluoride (NaFiv, equivalent of 10.0 mg F- ion). There was a wash-out period of at least one week between each administration. Blood was sampled before and during a 24-hour period after administration. For F- excretion urine was sampled 48 hours before (baseline) and over the 48 hours after the administration. RESULTS: The mean t1/2 values of the three formulations were 8.3, 8.7 and 8.3 h for MFP, NaFor and NaFiv respectively, and were not significant different. Mean Cmax after MFP was significantly higher than after NaFor [344 vs 142 micrograms.l-1]. Mean tmax for MFP was shorter than for NaFor [1.1 vs 4.6 h]. MFP had significantly higher bioavailability [102.8%] than NaFor [64.2%]. CONCLUSION: The MFP formulation showed higher bioavailability with smaller variation than the NaFor formulation. MFP is preferable, therefore, for fluoride therapy in clinical practice, and changing from NaFor to MFP will require adjustment of the dose.

Administration, Oral↗
PubMed1996

Bone marrow absorbed dose of rhenium-186-HEDP and the relationship with decreased platelet counts.

UNLABELLED: Rhenium-186(Sn)-1,1-hydroxyethylidene diphosphonate (186Re-HEDP) has been used for palliation of metastatic bone pain. The purpose of this study was to find a relationship between the bone marrow absorbed dose and the toxicity, expressed as the percentage decrease in the peripheral blood platelet count. METHODS: The bone marrow absorbed dose was calculated according to the MIRD model using data obtained from ten treatments of patients suffering from metastatic prostate cancer; noninvasive and pharmacokinetic methods were used. The bone marrow doses were related to toxicity using the pharmacodynamic sigmoid Emax model. RESULTS: The mean bone marrow absorbed doses using the noninvasive and pharmacokinetic methods were in a close range to each other (1.07 mGy/MBq and 1.02 mGy/MBq, respectively). There was a good relationship between the toxicity and the bone marrow absorbed dose (r = 0.80). Furthermore, the EDrm50 (i.e., the bone marrow absorbed dose producing a 50% platelet decrease) to bone marrow for 186Re-HEDP was on the order of 2 Gy. CONCLUSION: Although the function of normal bone marrow is affected by metastases in patients with metastatic bone disease, the MIRD model can be used to relate toxicity to the bone marrow absorbed dose after a therapeutic dosage of 186Re-HEDP.

Aged↗
PubMed1996

Phase 1 study of rhenium-186-HEDP in patients with bone metastases originating from breast cancer.

UNLABELLED: Rhenium-186-1,1-hydroxyethylidene diphosphonate (186Re-HEDP) has been used for the palliative treatment of metastatic bone pain. A Phase 1 dosage escalation study was performed using 186Re-HEDP in patients with metastatic breast cancer. METHODS: Twelve patients with metastatic breast cancer were studied. Each patient had at least four bone metastases and adequate hematological function. Groups of three consecutive patients were treated with dosages starting at 1295 MBq (35 mCi) and increasing to 2960 MBq (80 mCi) (escalated in increments of 555 MBq). RESULTS: A transient increase in pain ("flare" reaction) was observed in six patients. Two patients who received 2960 MBq 186Re-HEDP showed Grades 3 (platelets 25-50 x 10(9)/l) and 4 (platelets < 25 x 10(9)/l) platelet toxicity, which was defined as unacceptable. Prior to treatment, alkaline phosphatase levels were elevated in seven cases. These patients showed a transient decline in alkaline phosphatase levels during the first 4 wk. CONCLUSION: The maximum tolerated administered activity of 186Re-HEDP in patients with metastatic breast cancer is 2405 MBq (65 mCi). Thrombocytopenia proved to be the dose-limiting toxicity, which could not be predicted adequately by the administered activity. Changes of alkaline phosphatase levels suggest anti-tumor effects of 186Re-HEDP.

Alkaline Phosphatase↗
PubMed1996

Transient cranial neuropathy in prostatic cancer with bone metastases after rhenium-186-HEDP treatment.

Rhenium-186 (tin) hydroxyethylidene diphosphonate (186Re-HEDP), a bone-seeking radiopharmaceutical, has been successfully used in the treatment of patients with painful bone metastases. Toxicity is usually limited to reversible thrombocytopenia. An infrequent but clinically significant side effect is the occurrence of transient cranial neuropathy. We report on two prostatic cancer patients with metastatic bone cancer. Both patients developed transient cranial neuropathy shortly after treatment with 186Re-HEDP. Transient neuropathy of cranial nerves needs to be distinguished from neurological abnormalities caused by disease progression.

Bone Neoplasms↗
PubMed1996

Efficacy of rhenium-186-etidronate in prostate cancer patients with metastatic bone pain.

UNLABELLED: Rhenium-186-etidronate has been developed for pain relief of bone metastases and has previously been studied with regard to toxicity, pharmacokinetics and dosimetry. Its palliating effect on bone pain has not been studied extensively. To justify further efficacy investigations, patients participating in two toxicity studies were studied using a strict pain assessment methodology. METHODS: Forty-three patients entered the study, 37 of whom were evaluable for pain assessment. Administered dosages ranged from 1295 MBq (35 mCi) to 3515 MBq (95 mCi) 186Re-etidronate. Pain relief was assessed using a handwritten diary containing questions reflecting the multidimensional character of chronic pain. The diary was marked twice daily for a maximum of 10 wk (2 wk prior to and 6/8 wk after the injection). A response was determined using a specific decision rule, in which pain intensity, medication index and daily activities were core determinants. RESULTS: A response was reached in 54% (20 of 37) of the patients and varied from 33% (n = 6) in the "35-mCi" group to 78% (n = 7) in the "50/65-mCi" group to 70% (n = 7) in the "80/95-mCi" group. CONCLUSION: Pain assessment using the multidimensional pain model showed that 186Re-etidronate is an effective agent in the treatment of metastatic bone pain in prostate cancer and warrants further placebo-controlled studies.

Bone Neoplasms↗
PubMed1995

The influence of extracorporeal clearance techniques on elimination of radiocesium after internal contamination.

Radiocesium, an isotope released after nuclear accidents such as Chernobyl, causes damage to the health of humans after internal contamination. As a result of an internal deposit of radiocesium these persons are continuously irradiated and noxious effects may occur. Removal of this internal radiation source will reduce immediate (short-term) and future damage (long-term). In order to obtain data with respect to cesium kinetics in vivo, data obtained in dogs by Nold et al. were fitted by a computer program. On the basis of these data, simulations were carried out to evaluate the influences of extracorporeal clearance on cesium kinetics. The influence of various treatments on the committed effective dose [E(50)] as a measure of radiation harm was simulated. For this purpose an equivalence between the committed effective dose and the area under the curve, a kinetic parameter, was derived. This equivalence only holds when comparisons are made for different treatments of one subject contaminated with one isotope. Treatment with orally administered Prussian Blue salts reduces the committed effective dose by 29% (50 y). This can be insufficient to prevent deterministic effects as a result of a severe internal contamination with radiocesium. For this purpose other methods are evaluated. In simulations, extracorporeal clearance (e.g. hemoperfusion or hemodialysis) proved to be more effective in reducing E(50) (> 50%, 50 y). Extracorporeal clearance also seems to be effective in the early dose reduction and its consequent deterministic effects. Simulations revealed that effectiveness is improved when the treatment is started earlier and continued for a longer period. Effective extracorporeal clearance may be considered to be a promising method to treat victims of nuclear accidents internally contaminated with radiocesium.

Animals↗
PubMed1995

Hemodialysis as a potential method for the decontamination of persons exposed to radiocesium.

Radiocesium may be deposited in the environment as a result of accidents in nuclear installations, for example, as in Chernobyl. Significant internal contamination with radiocesium poses a serious risk to human health, and, therefore, expedient removal is essential to reduce the radiation body burden. In vitro hemodialysis was tested as a potential method to remove radiocesium from a pasteurized plasma solution of bovine or human blood. Clearance values were calculated by a flow independent method. Hemodialysis appears to be a good method to remove radiocesium from blood: within 4 h more than 90% of the administered radiocesium is removed from blood or plasma. Radiocesium in dialysis fluid can be concentrated on Prussian Blue coated columns that were tested previously for hemoperfusion. Radioactive waste disposal problems can be solved by concentration of radiocesium on these columns. In vivo experiments are necessary to confirm these in vitro results.

Cesium Radioisotopes↗
PubMed1995

In vitro binding of radiocesium to Prussian Blue coated strips and Prussian Blue containing hemoperfusion columns as a potential tool for the treatment of persons internally contaminated with radiocesium.

Cellulose or nylon strips coated with three different Prussian Blue salts were prepared with cellulose nitrate as binding material. These strips were evaluated for their usefulness for the development of an extracorporal clearance device for radiocesium, a radionuclide often released after accidents in nuclear installations (for example in Chernobyl). Extracorporeal clearance can be used to enhance the elimination of radiocesium from internally contaminated persons. The stability of these strips and their binding characteristics for radiocesium were investigated. In all studies strips coated with Fe4[Fe(CN)6]3 proved to be the most suitable for further development of an extracorporeal clearance device: the strips are stable, have a high binding capacity for radiocesium, and can be sterilized. On the basis of these results, hemoperfusion colums containing Fe4[Fe(CN)6]3-coated strips were developed and tested. In in vitro experiments these columns proved to be successful in removing radiocesium from a pasteurized plasma solution (clearance was approximately 100 ml/min). The binding capacity of these columns is relatively high. In 4 h the columns are able to bind approximately 0.3 TBq of radiocesium. They are a promising development for the enhancement of the removal of radiocesium from the human body. They can also be used for the decontamination of other fluids of chemical or biological origin. Further research is, however, still necessary.

Cesium Radioisotopes↗
PubMed1994

Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer.

Rhenium-186 hydroxyethylidene diphosphonate (186Re-HEDP) has been used for the palliative treatment of metastatic bone pain. A phase 1 dose escalation study was performed using 186Re-HEDP. Twenty-four patients with hormone-resistant prostate cancer entered the study. Each patient had at least four bone metastases and adequate haematological function. Groups of at least three consecutive patients were treated with doses starting at 1295 MBq and increasing to 3515 MBq (escalated in increments of 555 MBq). Thrombocytopenia proved to be the dose-limiting toxicity, while leucopenia played a minor role. Early death occurred in one patient (10 days after administration) without clear relationship to the 186Re-HEDP therapy. Transient neurological dysfunction was seen in two cases. Two patients who received 3515 MBq 186Re-HEDP showed grade 3 toxicity (thrombocytes 25-50 x 10(9)/l), defined as unacceptable toxicity. After treatment alkaline phosphatase levels showed a transient decrease in all patients (mean: 26% +/- 10% IU/l; range: 11%-44%). Prostate-specific antigen values showed a decline in eight patients, preceded by a temporary increase in three patients. From this study we conclude that the maximally tolerated dose of 186Re-HEDP is 2960 MBq. A placebo-controlled comparative study on the efficacy of 186Re-HEDP has been initiated.

Aged↗
PubMed1994

Consumption of drinking water with high nitrate levels causes hypertrophy of the thyroid.

We studied the effect of nitrate contamination of drinking water on volume and function of the thyroid in human populations exposed to different nitrate levels in their drinking water. Two sets of low and medium (tap) water, respectively medium and high (well) water nitrate exposure groups were compared. Drinking of nitrate-contaminated water was dose-dependently related with 24-h urinary nitrate excretion and salivary nitrate levels. No iodine deficiency was observed in any of the nitrate exposure groups. A dose-dependent difference in the volume of the thyroid was observed between low and medium vs. high nitrate exposure groups, showing development of hypertrophy at nitrate levels exceeding 50 mg/l. An inverse relationship was established between the volume of the thyroid and serum thyroid stimulating hormone (TSH) levels.

Adult↗
PubMed1994

Melodic cues for metre.

A method of time-series analysis and a time-beating experiment were used to test the structural and perceptual validity of notated metre. Autocorrelation applied to the flow of melodic intervals between notes from thirty fragments of compositions for solo instruments by J S Bach strongly supported the validity of bar length specifications. Time-beating data, obtained with four stimuli from the same set, played in an expressionless mode, and presented under categorically distinct tempos to different subgroups of musically trained subjects, were rather inconsistent with respect to tapped bar lengths. However, taps were most frequently given to the events in the stimuli that corresponded with the first beats according to the score notations. No significant effects of tempo on tapping patterns were observed. The findings are discussed in comparison with other examinations of metre inference from musical compositions.

Fingers↗
PubMed1994

Mercury kinetics in a case of severe mercuric chloride poisoning treated with dimercapto-1-propane sulphonate (DMPS).

A case of severe mercuric chloride poisoning with clinical signs of mucosal damage of the gastrointestinal tract and anuric renal failure, is presented. The initial whole blood mercury concentration was 14,300 micrograms l-1. This concentration is supposed to be associated with fatal outcome due to multiple organ failure. Because of anuric renal failure, haemodialysis was necessary. Kidney function returned to normal within 10 days. Haemodialysis proved to be ineffective with regard to total mercury elimination. Treatment with DMPS was started because of very severe poisoning, anuric renal failure and optimistic reports on the "new" chelating agent 2,3-dimercapto-1 propanesulphonic acid (DMPS) in mercury poisoning. DMPS was administered by parenteral route initially and was continued thereafter by oral route, until whole blood and urine mercury concentrations had decreased below a level considered as toxic. Except for a temporary pruritic erythema of the skin, no side effects of DMPS treatment were observed. The clinical course was mild, despite continuing high whole blood mercury concentrations. Recovery was uneventful and complete. DMPS treatment, administered by intravenous and oral route, was shown to be an effective alternative for BAL in life-threatening mercuric chloride intoxication. The pharmacokinetic data presented in this case report suggest that non-renal mercury clearance may considerably exceed renal mercury clearance.

Adult↗
PubMed1994

Evaluation of thrombocytopenia in patients treated with rhenium-186-HEDP: guidelines for individual dosage recommendations.

UNLABELLED: A potential limitation of rhenium-186-1,1-hydroxyethylidene diphosphonate (186Re-HEDP) therapy in patients with painful bone metastases is thrombocytopenia. Given the palliative character of this therapy, it is essential to be able to predict the degree of thrombocytopenia before therapy. METHODS: Thus far, 39 prostatic cancer patients with multiple painful bone metastases were treated. Twenty-one patients underwent the therapy twice, resulting in 60 therapies. From the pre-therapy 99mTc-HDP scintigram, the bone scan index (BSI) was determined as an index of the extent of bone involvement. RESULTS: The administered activity ranged from 1104 to 3479 MBq 186Re-HEDP. The platelet count was lowest 4 wk following therapy. From this value and the pretreatment level, the percentage decrease in the platelet count was determined (47% +/- 19%, range 14%-89%). The BSI ranged from 8 to 93. Regression analysis showed a functional relation (R = 0.78; p < 0.001) of the percentage of platelet decrease with BSI and administered activity normalized to standard body surface area. CONCLUSION: Using this relation, it is possible to predict thrombocytopenia by pretreatment bone scintigraphy and to adjust the dosage to each patient to avoid unacceptable toxicity.

Aged↗
PubMed1993

Pharmacokinetics of cefepime in patients with the sepsis syndrome.

We investigated the pharmacokinetics of cefepime after administration of multiple doses to seven patients with the sepsis syndrome. Patients ranged in age from 66 to 78 years (mean +/- S.D.: 74 +/- 5 years); all fulfilled the criteria of the sepsis syndrome and had APACHE-II scores between 14 and 21 (mean +/- S.D.: 17 +/- 2). Serial blood and urine samples were collected after a minimum of 3 days (steady state) of treatment with cefepime 2.0 g bd i.v. Cefepime was assayed by HPLC. Data were analysed using non-compartmental methods. The mean +/- S.D. creatinine clearance (Clcr) was 55 +/- 8 mL/min. Mean +/- S.D. values for selected pharmacokinetic parameters on day 5 were Cmax (94.2 +/- 23.9 mg/L), T1/2 (3.4 +/- 1.1 h), Vdss (32.6 +/- 17.5 L), and the total clearance Cl(total) (125 +/- 51 mL/min). Time to peak plasma concentration (Tmax) and area under curve (AUC) averaged 0.7 +/- 0.2 h and 305 +/- 115 mg.h/L, respectively. Cefepime plasma concentrations were above the MIC90 for Pseudomonas aeruginosa (7 mg/L) for approximately 80% of the time and in the case of Enterobacteriaceae (0.5 mg/L) for 100% of the time. The more prolonged T1/2 in comparison with young healthy volunteers (T1/2 = 2.1 h) is consistent with the changes in renal function associated with increased age, and is comparable to data obtained in healthy elderly subjects (T1/2 = 3.7 h). Cmax, AUC and Cl(tot) were more variable than those observed in previous studies and are probably a reflection of the clinical conditions under which dosing and sampling occurred.

Adult↗
PubMed1993

In vitro cyanide release of four prussian blue salts used for the treatment of cesium contaminated persons.

Prussian blue salts are used in clinical practice as an antidote for the treatment of humans contaminated with radioactive cesium. A decomposition product of these Prussian blue salts may be the highly toxic cyanide. A method to simulate gastrointestinal cyanide-release was applied to four different Prussian blue salts: K3Fe[Fe(CN)6], Fe4[Fe(CN)6]3, NH4Fe[Fe(CN)6] (pur. and unpur.). Cyanide-release was higher in artificial gastric juice than in water and artificial intestinal juice. Under all conditions cyanide-release from Fe4[Fe(CN)6]3 was the lowest. Since Fe4[Fe(CN)6]3 also binds more cesium, it appears to be the most suitable Prussian blue salt for use as an antidote after radiocesium contamination in humans.

Antidotes↗
PubMed1992

Prophylactic ciprofloxacin for catheter-associated urinary-tract infection.

Patients receiving antibiotics during bladder drainage have a lower incidence of urinary-tract infections compared with similar patients not on antibiotics. However, antibiotic prophylaxis in patients with a urinary catheter is opposed because of the fear of inducing resistant bacterial strains. We have done a double-blind, placebo-controlled trial of prophylactic ciprofloxacin in selected groups of surgical patients who had postoperative bladder drainage scheduled to last for 3 to 14 days. Patients were randomly assigned to receive placebo (n = 61), 250 mg ciprofloxacin per day (n = 59), or 500 mg ciprofloxacin twice daily (n = 64) from postoperative day 2 until catheter removal. 75% of placebo patients were bacteriuric at catheter removal compared with 16% of ciprofloxacin-treated patients (relative risk [RR] [95% CI] 4.7 [3.0-7.4]). The prevalence of pyuria among placebo patients increased from 11% to 42% while the catheter was in place; by contrast, the rate of pyuria was 11% or less in patients receiving ciprofloxacin (RR 4.0 [2.1-7.3]). 20% of placebo patients had symptomatic urinary-tract infections, including 3 with septicaemia, compared with 5% of the ciprofloxacin groups (RR 4.0 [1.6-10.2]). Bacteria isolated from urines of placebo patients at catheter removal were mostly species of enterobacteriaceae (37%), staphylococci (26%), and Enterococcus faecalis (20%), whereas species isolated from urines of ciprofloxacin patients were virtually all gram-positive. Ciprofloxacin-resistant mutants of normally sensitive gram-negative bacteria were not observed. Ciprofloxacin prophylaxis is effective and safe in the prevention of catheter-associated urinary tract infection and related morbidity in selected groups of patients requiring 3 to 14 days of bladder drainage.

Adult↗
PubMed1992

In vitro binding characteristics for cesium of two qualities of prussian blue, activated charcoal and Resonium-A.

The in vitro binding characteristics of radioactive 137Cs to two forms of Prussian blue [colloidally (soluble) K3Fe[Fe(CN)6] and insoluble Fe4[Fe(CN)6]3] and to activated charcoal and sodium polystyrene sulfonate (Resonium-A) were investigated by constructing Langmuir isotherms at pH = 1.0, 6.5 and 7.5 at 37 degrees C. At the three pHs investigated, 137Cs binding to activated charcoal and sodium polystyrene sulfonate was negligible. Binding of 137Cs to insoluble Prussian blue exceeded that for the soluble form and was pH dependent for both formulations. Maximum binding capacities were 87 mg/g (pH = 1.0), 194 mg/g (pH = 6.5) and 238 mg/g (pH = 7.5) for the insoluble form and 48 (pH = 1.0), 73 (pH = 6.5) and 78 (pH = 7.5) for the soluble form. As activated charcoal did not bind 137Cs, charcoal hemoperfusion is of no value. This has been confirmed by an in vitro experiment, using a Gambro Adsorbs 300 C cartridge.

Cesium Radioisotopes↗