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Biomedical subjects

G Dick

Publications and source records attributed to G Dick.

At least 19 recordsLinked to original sources
PubMed1999

Population pharmacokinetics of oral morphine and its glucuronides in children receiving morphine as immediate-release liquid or sustained-release tablets for cancer pain.

OBJECTIVES: (1) To determine the pharmacokinetics of morphine, morphine-6-glucuronide (M6G), and morphine-3-glucuronide (M3G) in children with cancer receiving morphine as immediate-release morphine liquid or sustained-release tablets. (2) To determine differences with age within the group and from adults. (3) To explore relationships between plasma concentration and pain measurements. STUDY DESIGN: Blood samples were collected and plasma analyzed by high-performance liquid chromatography with electrochemical and fluorescence detection. Population pharmacokinetic parameters were derived with the program P-PHARM. RESULTS: Forty children with a median age of 11.4 years (range 1.7 to 18.7 years) received a median dose of 1.4 mg/kg/d (range 0.4 to 24.6 mg/kg/d). A median of 4 blood samples per child was collected. Plasma clearance of morphine was 23.1 mL/min per kg body weight. The volume of distribution was 5.2 L/kg. Molar ratios of M3G/morphine, M6G/morphine, and M3G/M6G were 21.1, 4.7, and 4.2, respectively. Children <11 years had significantly higher clearance and larger volume of distribution for morphine and its glucuronides than older children and adults. Regression analysis indicated average plasma morphine concentration equal to dose (mg/kg/d) x 8.6 (95% confidence interval 7.4 to 9.9). Significant pain was present in 30% of the children. Higher pain scores were recorded in children with average morphine concentrations <12 ng/mL (P <.01 MW). CONCLUSION: Age differences in morphine pharmacokinetics exist within children and compared with adults. The study supports a starting dose of 1.5 to 2. 0 mg/kg/d to provide plasma morphine concentrations >12 ng/mL in children with cancer pain unrelieved by mild to moderate strength analgesia.

Adolescent↗
PubMed1999

Diastolic function and tachycardia in hypertensive children.

We investigated the prevalence and potential predictors of Doppler echocardiographic evidence of diastolic function in untreated hypertensive children. Doppler and M-mode echocardiographic values from 42 children (mean age 13, range 5-17 years) from a pediatric hypertension clinic were retrospectively reviewed and compared to data from 39 age and gender matched normotensive children in a control group. Compared to the participants in the control group, hypertensive patients had increased mean body mass index (29 v 19 kg/M2, P < .0001), peak mitral A velocity (57 v 42 cm/sec, P < .0001), isovolumic relaxation time (65 v 42 msec, P < .0001, resting heart rate (90 v 74 bpm, P < .0001), mitral E deceleration time (150 v 137 msec, P = .006), indexed left ventricular mass index (32 v 26 g/M2.7, P < .0001), relative left ventricular wall thickness (0.32 v 0.29, P = .02), and decreased ratio of peak mitral E velocity/peak mitral A velocity (1.7 v 2.1, P = .0001). Mean age, height, mitral E velocity, mitral A deceleration time, fractional shortening, and indexed left ventricular diastolic dimension were similar in patients and control group children. In the hypertensive patients, multivariate analysis demonstrated that heart rate (P = .0008) and systolic blood pressure (P = .03) were significant predictors of peak A velocity. In addition, heart rate (P = .0003), body mass index (P = .04), and indexed left ventricular diastolic dimension (P = .04) predicted the ratio of peak E/peak A velocity. None of the measures of diastolic function correlated with left ventricular mass index or relative wall thickness. Furthermore, none of the analyzed variables predicted isovolumic relaxation time or mitral E deceleration time. We conclude that untreated hypertensive children have Doppler indices suggestive of impaired left ventricular relaxation. Resting heart rate was the strongest predictor of abnormal diastolic indices.

Adolescent↗
PubMed1998

High-dose cyclosporin with etoposide--toxicity and pharmacokinetic interaction in children with solid tumours.

The tolerability, anti-tumour activity and pharmacokinetic interaction of high-dose intravenous cyclosporin combined with intravenous etoposide was evaluated in children. Eighteen patients with recurrent or refractory tumours, all of whom had previously received etoposide, were treated with a combination of high-dose cyclosporin and etoposide. In 13, cyclosporin was given as a continuous infusion (15 mg kg(-1) per 24 h for 60 h) and in five a short 3-hour infusion of 30 mg kg(-1) day(-1) on three consecutive days. Pharmacokinetic profiles of etoposide were determined with and without cyclosporin. Cyclosporin levels ranged from 1359 to 4835 ng ml(-1) and cyclosporin increased the median area under the concentration time for etoposide curve from 7.2 to 12.5 mg ml(-1) min. The major toxicity was acute with varying forms of hypersensitivity reactions. In four cases this was severe. Hyperbilirubinaemia was present in 25 of 32 courses but was of short duration. In 14 courses, creatinine and/or urea was elevated, but was also transient. Significant hypertension was seen in six courses. Four of 17 patients evaluable for response obtained a partial response and one showed stable disease. It is concluded that in children given the combination of high-dose cyclosporin and etoposide, the etoposide dose should be halved in order to achieve an area under the drug concentration-time curve similar to that with etoposide alone. A continuous infusion schedule of cyclosporin is better tolerated during the period of administration but is associated with similar hepatic and renal dysfunction to a short schedule. The 24% response rate in children who had previously received etoposide suggests that this may be an effective method of enhancing drug sensitivity and further phase II evaluation is justified.

Adolescent↗
PubMed1997

Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients.

PURPOSE: Infection in neutropenic patients is potentially life-threatening and carries important implications for hospital resource use. Prophylactic administration of cytokines may reduce the severity of neutropenia, but involves the treatment of all patients for the possible benefit of a minority. This study evaluates whether treatment with cytokines in the setting of established febrile neutropenia will influence outcome and be potentially more cost-effective. PATIENTS AND METHODS: In a double-blind study, pediatric patients with fever and severe neutropenia were randomized to receive granulocyte colony-stimulating factor ([G-CSF] filgrastim; 5 microg/kg/d) or placebo, in addition to antibiotics. The study protocol required a resolution of fever and a neutrophil count > or = 0.2 x 10(9)/L for hospital discharge. Patients could be randomized for up to four independent febrile episodes. A total of 186 episodes of febrile neutropenia were investigated. RESULTS: Patients randomized to G-CSF had a shorter hospital stay (median, 5 v 7 days; P = .04) and fewer days of antibiotic use (median, 5 v 6 days; P = .02). G-CSF-treated patients also had more rapid neutrophil recovery and higher neutrophil levels at discharge. The 2-day reduction in hospital stay reduced the median bed cost by 29% per patient admission (P = .04). CONCLUSION: Under the clinical guidelines of our institution, the use of G-CSF in the treatment of established febrile neutropenia produced a small but significant reduction in the time that children required antibiotics and hospital admission, with possible cost savings.

Anti-Bacterial Agents↗
PubMed1997

An economic evaluation of the use of granulocyte colony-stimulating factor after bone marrow transplantation in children.

Studies that have assessed the use of granulocyte colony-stimulating factor (G-CSF) following bone marrow transplantation have shown a significantly reduced time to neutrophil recovery with the use of this agent, which may translate into a reduced duration of antimicrobial therapy and hospitalisation. We performed a pharmacoeconomic study evaluating the elective use of G-CSF after bone marrow transplantation in children. 22 consecutive children who underwent bone marrow transplantation and received G-CSF 5 micrograms/kg/day were compared with 18 such children (control group) who did not receive G-CSF. Despite a significant reduction in time to recovery of the absolute neutrophil count (ANC) to > 0.5 x 10(9)/L in G-CSF recipients compared with the control group (14 days vs 20.9 days; p < 0.0001), there was only a trend towards a reduction in the duration of intravenous antimicrobial therapy (14.5 days vs 18.6 days; p = 0.15), and there was no significant difference in the duration of hospitalisation (25.3 days vs 29.8 days). Reasons for prolonged hospitalisation beyond ANC recovery included continued use of total parenteral nutrition, treatment of graft-versus-host disease and treatment of ongoing infection. Overall, the mean total cost for patients receiving G-CSF was Pounds 15001, compared with Pounds 15482 for the control group (1995 values). In conclusion, while there appears to be no benefit in financial terms, the release of a child from strict isolation as a result of early ANC recovery must be taken into consideration.

Bone Marrow Transplantation↗
PubMed1995

Continuous-infusion verapamil with etoposide in relapsed or resistant paediatric cancers.

This study evaluates the use of a multidrug resistance (MDR) modulator (verapamil) in combination with a standard dose of single-agent etoposide in relapsed or refractory paediatric malignancy. A total of 20 patients (median age 6.5 years) were treated with an infusion of verapamil (loading dose 0.1 mg kg-1, followed by continuous infusion 0.15 mg kg-1 h-1) for 72 h. Etoposide was given daily (150 mg m-2 day-1) for three doses (each over 1 h); the first dose was given 12 h into the verapamil infusion. Cardiovascular toxicity was monitored by ECG and 2 hourly blood pressure and pulse recordings. Verapamil and norverapamil plasma concentrations were measured daily. Disease response was assessed after two courses. A total of 29/35 treatment courses were given at the desired verapamil dose; five courses required a dose reduction owing to cardiovascular toxicity. No patient required intensive monitoring. All patients who developed cardiovascular toxicity were over 14 years old. There was no correlation between plasma verapamil or norverapamil concentrations and toxicity. There were six partial responses (three rhabdomyosarcoma, three neuroblastoma) after two courses, but because of variation in the dose and schedule of etoposide these cannot be unequivocally contributed to MDR reversal. In conclusion, a regimen using a continuous infusion of verapamil combined with divided-dose etoposide is tolerable in children, and this strategy may be effective in refractory neuroblastoma and rhabdomyosarcoma.

Adolescent↗
PubMed1993

24-hour plasma etoposide profile after oral and intravenous administration in children.

Pharmacokinetic profiles of oral and intravenous etoposide have been compared in 9 children receiving the drug either as a single agent or in combination chemotherapy. The plasma etoposide levels were estimated using a competitive coated antigen ELISA technique. The median bioavailability was 48% and beyond 30 min after either oral or intravenous injection there was little difference in the plasma profile. The duration of plasma concentrations above 1, 5 and 10 micrograms/ml following either route were compared. It is concluded that unless the height of initial peak concentration is of therapeutic value the oral route should be comparable in children provided that twice the intravenous dose is administered. The short elimination half-life results in low plasma levels beyond 12 h and suggests that a twice daily regimen may be preferable.

Administration, Oral↗
PubMed1986

Is multiple sclerosis caused by an oral spirochaete?

Evidence of a direct link between chronic sinusitis and multiple sclerosis (MS) prompted examination of the old "spirochaetal hypothesis". This hypothesis has not been shown to be erroneous and a spirochaetal infection of the central nervous system could explain the specific pathological, immunological, and epidemiological features of MS.

Acute Disease↗
PubMed1986

Multiple sclerosis associated with sinusitis: case-controlled study in general practice.

In an analysis of general practice records the rate of chronic sinusitis was significantly greater in 92 patients with multiple sclerosis (MS) than in matched controls (p less than 0.0001). MS and chronic sinus infection were also significantly associated in the timing of attacks, in the age at which patients suffered their attacks, and in the seasonal pattern of attacks.

Adolescent↗
PubMed1983

[Correlation of morphological criteria with the rate of growth in cancer of the breast].

Prognosis of carcinoma of the breast depends on a number of factors. Besides tumour staging, these parameters include the number of axillary lymph nodes with metastatic growths, the status of the hormonal receptors, and the histological type of the tumour, especially the tumour grading and the rate of growth correlated therewith. The first few of these criteria are relatively easy to determine. The tumour duplication time has so far been determined only by means of serial mammographies. Only few studies have been conducted on the correlation of the morphological parameters connected with the dynamics of growth of carcinomas of the breast. In a group of 61 patients with carcinoma of the breast and known tumour duplication time determined by serial mammography, it is shown that broadening of the conventional tumour grading by means of additional histopathological malignancy criteria (frequency of mitosis, incidence of nuclear hyperchromasias, formation of tubules and nuclear irregularities) correlates with the growth dynamics of the tumours. This makes it seem possible to draw prospective conclusions on the growth performance of carcinomas of the breast even without resorting to serial mammographies.

Axilla↗
PubMed1982

Computer-assisted sequencing, interval graphs, and molecular evolution.

In 1945, Fox developed the strategy for sequencing long proteins by using overlapping fragments. We show how the formal mathematical technique for the construction of interval graphs (Gilmore and Hoffman, 1964) is useful both pedagogically for understanding the underlying logic of sequencing linear molecules and is more amenable to automation because of its algorithmic nature. We also present a computer program, that employs the interval graph algorithm, which can be used to sequence proteins when given digest data. An example is given to illustrate all the steps involved in the algorithmic processing of the data. The need for such developments with respect to molecular evolution is discussed.

Amino Acid Sequence↗