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Biomedical subjects

M Bolt

Publications and source records attributed to M Bolt.

At least 19 recordsLinked to original sources

Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain.

OBJECTIVES: To compare patients' preference for transdermal fentanyl or sustained release oral morphine, their level of pain control, and their quality of life after treatment. DESIGN: Randomised, multicentre, international, open label, crossover trial. SETTING: 35 centres in Belgium, Canada, Denmark, Finland, the United Kingdom, the Netherlands, and South Africa. PARTICIPANTS: 256 patients (aged 26-82 years) with chronic non-cancer pain who had been treated with opioids. MAIN OUTCOME MEASURES: Patients' preference for transdermal fentanyl or sustained release oral morphine, pain control, quality of life, and safety assessments. RESULTS: Of 212 patients, 138 (65%) preferred transdermal fentanyl, whereas 59 (28%) preferred sustained release oral morphine and 15 (7%) expressed no preference. Better pain relief was the main reason for preference for fentanyl given by 35% of patients. More patients considered pain control as being "good" or "very good" with fentanyl than with morphine (35% v 23%, P=0.002). These results were reflected in both patients' and investigators' opinions on the global efficacy of transdermal fentanyl. Patients receiving fentanyl had on average higher quality of life scores than those receiving morphine. The incidence of adverse events was similar in both treatment groups; however, more patients experienced constipation with morphine than with fentanyl (48% v 29%, P<0.001). Overall, 41% of patients experienced mild or moderate cutaneous problems associated with wearing the transdermal fentanyl patch, and more patients withdrew because of adverse events during treatment with fentanyl than with morphine (10% v 5%). However, within the subgroup of patients naive to both fentanyl and morphine, similar numbers of patients withdrew owing to adverse effects (11% v 10%, respectively). CONCLUSION: Transdermal fentanyl was preferred to sustained release oral morphine by patients with chronic non-cancer pain previously treated with opioids. The main reason for preference was better pain relief, achieved with less constipation and an enhanced quality of life.

Administration, Cutaneous↗

Interaction of acrylonitrile with hepatic microsomes of rats and men.

Acrylonitrile (AN) showed spectral interaction with hepatic microsomes from mouse, rat and man. Whereas human and rat liver microsomes resulted in ligand AN-binding spectra, mouse liver microsomes behaved differently. Hepatic microsomes from phenobarbital-treated mice with AN showed a type I substrate binding; ligand spectra are recorded with microsomes from benzo[a]pyrene-treated mice. Microsomes from untreated control mice showed a mixed type behaviour.

Acrylonitrile↗

Some biochemical indices of nutrition in treated cystic fibrosis patients.

Postprandial levels of copper, ceruloplasmin, iron, total iron binding capacity, cholesterol, vitamin A, carotene, folic acid, vitamin C, albumin, and total globulins in plasma, of 25-OH-vitamin D in serum, and of glutathione reductase activity, an index of riboflavin status, in erythrocytes were determined in a group of 18 juvenile cystic fibrosis patients receiving specialized outpatient care with attention to diet, vitamin supplementation, and pancreatic enzyme replacement. Bone mineralization was assessed by radiographic and photon beam technique. In the plasma of cystic fibrosis patients, levels were elevated for copper, ceruloplasmin, total globins, and total proteins and were depressed for iron, vitamin D, vitamin A, carotene, and albumin. Cortical thickness was diminished in the patients, but bone density was not. For patients with cystic fibrosis, a relation was established between forced vital capacity and certain biochemical indices in plasma. As forced vital capacity decreased, plasma levels increased for copper, total globulins and total proteins and decreased for albumin.

Adolescent↗

The maternal pheromone and bile acids in the lactating rat.

Bile was drawn from virgin rats and from postpartum rats that were with young for 5, 12, 21, and 30 days, respectively. The bile thus drawn was analyzed enzymatically after chromatographic separation to test an hypothesis relating cholic acid and one of its metabolites, deoxycholic acid, to the appearance of the maternal pheromone. Our finding that cholic acid, but not deoxycholic acid, reached a peak that was tied specifically to the period of pheromonal emission led us to advance a revised hypothesis. We now think that cholic acid alone, or more likely a cholic metabolite other than deoxycholic acid, underlies the appearance of the pheromone.

Animals↗

Interaction of rifampicin treatment with pharmacokinetics and metabolism of ethinyloestradiol in man.

[6,7-3H]Ethinyloestradiol (50 microng) was administered intravenously to volunteers and the free extractable ethinyloestradiol in the plasma was measured. The compound showed a biphasic plasma decline. The half-life of the second phase was 7.5+/-1.7 (SD) hours. Administration of rifampicin (600 mg for 6 days) shifted the half-life of ethinyloestradiol to 3.3+/-0.9 h while the apparent volume of distribution for the second phase of elimination was not changed. When [2,4,6,7-3H]ethinyloestradiol (100 microng) was administered orally, some of the tritium was released by oxidative metabolism from the steroid and transformed to tritiated water (HTO) which equilibrated with whole body water. This portion, normally 7.17+/-1.66% of the tritium dose, was increased by previous administration of rifampicin to 10.62+/-2.27%. The initial rate of oxication of [2,4,6,7-3H]ethinyloestradiol was increased more than twofold by rifampicin treatment. The results are consistent with previous findings that rifampicin induces the oestrogen-2-hydroxylase in the endoplasmic reticulum of human liver, and explain the reduced effectiveness of ethinyloestradiol in oral contraceptives, if the patients are treated with rifampicin.

Administration, Oral↗

Comparison of vitamin D and 25-hydroxy-vitamin-D in the therapy of primary biliary cirrhosis.

Skeletal demineralisation and low serum concentrations of 25-hydroxy-vitamin-D were observed in patients with primary biliary cirrhosis. Neither oral nor parenteral vitamin-D increased 25-hydroxy-vitamin-D in serum or prevented further skeletal demineralisation. In contrast, oral 25-hydroxy-vitamin-D increased serum-25-hydroxy-vitamin D concentrations in all patients, and bone mineral content either improved or stabilised in all but one, 25-hydroxy-vitamin-D may be the preferred form of vitamin-D therapy in primary biliary cirrhosis.

Administration, Oral↗

Effect of rifampicin treatment on the metabolism of oestradiol and 17alpha-ethinyloestradiol by human liver microsomes.

Liver biopsies were obtained from four patients treated with rifampicin 600 mg for 6-10 days. Hepatic microsomes were incubated with an NADPH-regenerating system and the substrates [2,4,6,7-3H] oestradiol, [6,7-3H] oestradiol, [2,4,6,7-3H] ethinyloestradiol and [6,7-3H] ethinyloestradiol. The hydroxylation rates of these steroids at the labelled positions of rings A and B were determined by measuring the transformation of tritium into HTO by the microsomal enzymes. Comparison with previously published data showed that treatment with rifampicin caused a fourfold increase in the rate of hydroxylation of oestradiol and ethinyloestradiol at positions C-2/C-4 of ring A and C-6/C-7 of ring B. The acceleration of oestrogen hydroxylation by rifampicin was paralleled by an increase in microsomal cytochrome P-450, and also by microsomal reduction of rifampicin-quinone, a reactive metabolite of rifampicin. The increased aromatic hydroxylation of oestradiol and ethinyloestradiol leads to enhancement of their irreversible binding to microsomal protein. The data provide an explanation for the diminished efficacy of oestrogens in contraceptive formulations given to patients under treatment with rifampicin.

Adult↗