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Biomedical subjects

D Baldwin

Publications and source records attributed to D Baldwin.

At least 127 records · Page 7Linked to original sources

Treatment of claudication with pentoxifylline: are benefits related to improvement in viscosity?

Forty-five patients with short-distance claudication were treated with pentoxifylline. The initial claudication distance increased significantly (32.5 m, p = 0.02) and the absolute claudication distance (ACD) increased significantly (49.5 m, p = 0.001) while the patients were receiving pentoxifylline. Patients with initial elevated viscosity levels were more likely to have decreased viscosity with pentoxifylline than were patients with normal viscosity levels (p = 0.01). No significant improvement in ACD or viscosity was noted in 51% of patients. Both ACD and viscosity improved in 15% of patients, viscosity improved without improvement in ACD in 9%, and ACD improved without improvement in viscosity in 25%.

Blood Viscosity↗

The effects of zero magnesium dialysate and magnesium supplements on ionised calcium concentration in patients on regular dialysis treatment.

The effect of oral magnesium carbonate or aluminium hydroxide on serum ionised calcium, total calcium, aluminium and magnesium, was assessed in 31 patients with chronic renal failure, during and after one haemodialysis. The behaviour of ionised calcium and total calcium was the same in both groups. Each showed a slight fall during dialysis, which was not significant. Serum total calcium was 0.2-0.3 mmol/l (0.8-1.2 mg/dl) greater throughout the period of dialysis in the group taking aluminium hydroxide. Serum magnesium and aluminium were both lower in the group treated with magnesium carbonate. In the group taking magnesium carbonate, serum magnesium concentrations fell markedly during dialysis, but otherwise were maintained within the reference range by the use of a magnesium-free dialysate. These results show the effectiveness of magnesium carbonate oral phosphate-binding agents and zero magnesium dialysate in reducing serum aluminium without affecting the behaviour of serum calcium fractions during dialysis.

Administration, Oral↗

Substitution of aluminium salts by magnesium salts in control of dialysis hyperphosphataemia.

For two years all 28 patients undergoing hospital haemodialysis were switched from a dialysate magnesium (Mg) of 0.85 mmol/l to one containing none. Oral aluminium hydroxide was discontinued, and magnesium carbonate was substituted as a phosphate binder. After 24 months on this regimen predialysis aluminium concentration had fallen significantly. There was no significant change in predialysis phosphate, which remained above the normal range; nor was there evidence of increased secondary hyperparathyroidism as judged by parathyroid hormone immunoassay and biochemical or clinical criteria. Predialysis Mg concentrations tended to fall towards the normal range. Aluminium-containing phosphate binders seem to be unnecessary for the control of dialysis hyperphosphataemia. Magnesium carbonate may be an alternative and less toxic compound.

Administration, Oral↗

Radioimmunoassay of buprenorphine with iodine label: analysis of buprenorphine and metabolites in human plasma.

Quantitative analysis of potent opiate drugs in plasma by radioimmunoassay is potentially inaccurate because of the occurrence of cross-reacting metabolites. This paper describes the chemical synthesis of buprenorphine-3-O-glucuronide, a metabolite of buprenorphine, and an extraction procedure coupled with radioimmunoassay which allows the sensitive and specific measurement of buprenorphine using an iodinated buprenorphine derivative. The measurement of extracted and unextracted samples using two different antisera allowed investigation of the metabolism of buprenorphine. In four patients who had taken sublingual buprenorphine for at least one month, N-dealkyl buprenorphine was present in similar concentrations to those of buprenorphine, while buprenorphine-3-O-glucuronide was present in two to three times those concentrations.

Administration, Oral↗

Sensitive and specific bromocriptine radioimmunoassay with iodine label: measurement of bromocriptine in human plasma.

Plasma bromocriptine assays must have high sensitivity because plasma concentrations are low, and high specificity because bromocriptine is extensively metabolised. This paper describes the simple preparation of a radioiodine-labelled derivative of dihydroergocriptine and its use in a radioimmunoassay employing an antiserum directed against the intact bromocriptine molecule. The method could measure plasma bromocriptine at concentrations of 0.05 nmol/L, had between-assay coefficients of variation of less than 10% and was more convenient than previous assays using tritium radiolabels.

Adenoma↗

Influence of meptazinol on metabolic and hormonal responses following major surgery. A comparison with morphine.

Opioid drugs in high doses can obtund the stress response to major surgery but only at the expense of marked cardiorespiratory depression. The postoperative hormonal response to surgical stress was measured in 20 patients undergoing hysterectomy who were given either meptazinol 100 mg or morphine 15 mg intramuscularly at the end of the surgery. Both drugs at the doses used failed to diminish the stress response. Those patients who received meptazinol showed elevated prolactin levels: this may be an indicator of agonist activity at the mu 1 opioid receptor.

Adult↗

Systemic availability of oral slow-release morphine in man.

In a within-patient crossover study on twelve patients we investigated plasma morphine concentrations for 48 hours after administration of intravenous morphine sulphate followed 24 hours later by oral MST Continus [MST]. Patients received either 10 mg i.v. morphine followed by 10 mg MST or 20 mg i.v. morphine followed by 2 X 10 mg MST tablets. Systemic clearance of morphine was low, being about 3 ml/min/kg after both intravenous and oral administration. The ratio of the areas under the concentration-time curve for MST relative to that for i.v. morphine was about 1:1 for 20 mg doses, but was significantly greater than 1:1 for 10 mg doses. The results suggest high oral systemic availability for morphine and low hepatic morphine metabolism.

Administration, Oral↗

Morphine kinetics and kidney transplantation: morphine removal is influenced by renal ischemia.

Morphine plasma concentrations were determined in six patients receiving kidney transplants from living-related donors, and nine patients receiving kidney transplants from cadavers. The total cold ischemic time was about 2 hr for kidneys from living-related donors and 14 hr for those from cadavers. After an intravenous bolus dose of morphine, plasma morphine concentrations decreased to a plateau that lasted for several hours; morphine elimination resumed when the transplanted kidney began to clear creatinine. The duration of the total cold ischemic time was significantly related to both the duration of the plateau in morphine concentration (P = 0.008) and the first postoperative day creatinine clearance (P = 0.021). Morphine elimination half-life after the plateau was related to first postoperative day creatinine clearance (P less than 0.001). It was concluded that morphine elimination depended upon intact renal function.

Adult↗

A novel form of dependency of hepatic extraction ratio of opioids in vivo upon the portal vein concentration of drug: comparison of morphine, diamorphine, fentanyl, methadone and buprenorphine in the chronically cannulated cow.

In the chronically cannulated cow, the hepatic extraction ratio for intravenous boluses of morphine, diamorphine, fentanyl, methadone and buprenorphine increased towards a plateau value as portal vein drug concentration increased. An extraction ratio close to zero for morphine was observed at a portal vein plasma drug concentration of about 200 nanomol per litre, which is within the range for significant pharmacodynamic effects. The similar concentrations extrapolated for the other narcotics would be of less pharmacodynamic importance. The phenomenon did not depend with morphine on the history of drug delivery to the liver; measurement of hepatic blood flow showed the effect was not an artifact of unrepresentative blood sampling, and was not related to any action of the narcotics on hepatic blood flow. The existence of this novel type of concentration dependent hepatic extraction ratio in vivo can explain a number of anomalous observations on narcotic pharmacokinetics, especially for morphine. Furthermore, similar behaviour may be expected for non-opioid drugs having similar pharmacokinetic properties.

Animals↗

An evaluation of the copulatory, endocrinologic, and spermatotoxic effects of carbon disulfide in the rat.

The present study was undertaken to evaluate the endocrinologic and spermatogenic effects of carbon disulfide (CS2) exposure in the rat. Adult, male rats were exposed to either 600 ppm CS2 or filtered air for 6 hr/day for 5 days/week for 10 weeks. One week prior to exposure and then at Weeks 1, 4, 7, and 10, males were placed with ovariectomized, hormonally primed females, and copulatory behaviors were scored. Fifteen minutes postcopulation, the female was killed and the ejaculate was recovered from the excised uterine tract along with the semen plug. Sperm counts, sperm motility, and morphology were determined. A blood sample was obtained for analyses of testosterone, follicle-stimulating (FSH), and luteinizing hormone (LH). At the end of the 10th week, five animals in each group were challenged with either human chorionic gonadotropin (HCG, 50 IU/animal, iv) or gonadotropin-releasing hormone (GnRH, 100 ng/animal, iv), and the testosterone or gonadotropin responses were monitored over time. Animals were subsequently killed with one epididymis and testis processed for histology and a sperm count determined from the other epididymis. Analysis revealed that CS2 exposure produced significant alterations in copulatory behavior and a decrease in ejaculated sperm counts by the fourth and seventh weeks of exposure, respectively. No endocrinologic alterations were observed. Moreover, caudal epididymal sperm counts were not depressed and the testes appeared histologically normal. These data suggest that CS2 does not exert a direct effect on the testes, but rather may interfere with the processes regulating sperm transport and ejaculation.

Animals↗

Spinal fluid kinetics of morphine and heroin.

Nine patients undergoing cardiopulmonary bypass surgery were given either 2 mg diamorphine or 2.5 mg morphine by intrathecal injection. Spinal fluid (sf) samples were collected over 25 min and drug concentrations measured by HPLC. Concentrations in sf were about 4000 times as great as after 1 mg/kg IV morphine. The kinetic properties of morphine and heroin in sf differed; diamorphine was removed from sf much more rapidly than morphine. Lipophilic opiates may be safer for intrathecal use because of the shorter life of substantial drug concentrations in the mobile sf phase.

Chromatography, High Pressure Liquid↗

Morphine kinetics during and after renal transplantation.

Plasma concentrations after intravenous morphine were measured by a specific radioimmunoassay method in patients undergoing renal transplantation and in control subjects. In both transplant patients and controls, plasma morphine fell in the first 10 min, but there was no significant further fall in the transplant patients until between 3 and 5 hr, when there was an abrupt reversion to the same elimination t1/2 as the controls. This coincided with recovery of renal function after the period of cold ischemia. In the transplant patients the AUC over 24 hr was higher and the plasma clearance was lower than in controls. The role of the kidney in morphine elimination is discussed.

Adult↗

Plasma morphine concentrations and clinical effects after thoracic extradural morphine or diamorphine.

Twenty-seven patients undergoing thoracotomy received either morphine sulphate 2 mg or diamorphine hydrochloride 2 mg by thoracic extradural injection for postoperative analgesia. Arterial plasma morphine concentrations were measured by specific radioimmunoassay, and the analgesic, respiratory and biochemical effects noted. The plasma morphine concentrations were significantly greater after extradural diamorphine than after extradural morphine in the first 30 min after injection. The maximum increase in plasma morphine concentration was significantly (P less than 0.02) greater after extradural diamorphine, and mean peak values occurred at 5 and 10 min for diamorphine and morphine, respectively. There were significant decreases in respiratory rate and plasma cortisol concentration with maximum effects between 90 and 180 min after the extradural injection. The analgesia produced by these doses was inadequate. The role of lipophilicity is discussed.

Adult↗

Controlled comparison of intrathecal cinchocaine with intrathecal cinchocaine and morphine. Clinical effects and plasma morphine concentrations.

Twenty patients scheduled for elective total hip replacement were given either intrathecal cinchocaine with morphine hydrochloride 2.5 mg or intrathecal cinchocaine alone before general anaesthesia. Arterial plasma morphine concentrations were measured and analgesic, respiratory and biochemical effects compared. Plasma morphine concentrations increased to 19.3 nmol litre-1 at 210 min. PaCO2 concentrations increased significantly only in those patients who received morphine as well as cinchocaine. Patients receiving cinchocaine alone, but not those given cinchocaine and morphine, had significant (P less than 0.01) increases in plasma cortisol concentrations' in the period after operation. Median time to next analgesic in patients receiving cinchocaine with intrathecal morphine was 22 h, significantly (P less than 0.01) longer than in patients receiving intrathecal cinchocaine alone (7.8 h).

Aged↗

HPLC of morphine with electrochemical detection: analysis in human plasma.

A method is described for the measurement of morphine in human plasma by ion-paired reverse-phase liquid chromatography. It includes a novel solid-phase extraction of morphine from plasma which is simple, rapid and complete. No known morphine metabolites could be shown to interfere with the measurements. Determination of morphine pharmacokinetics in patients undergoing heart surgery with 1 mg/kg intervenous morphine produced plasma morphine clearances which agreed with established estimates.

Cardiac Surgical Procedures↗

Sensitive and specific morphine radioimmunoassay with iodine label: pharmacokinetics of morphine in man after intravenous administration.

Analysis of morphine in plasma by radioimmunoassay is complicated by interference from morphine metabolites, particularly morphine-3-glucuronide. This interference makes radioimmunoassay a poor technique to study the pharmacokinetics of morphine in man. The method described here is one which uses commercially available anti-morphine antiserum and separating reagent with a simply prepared iodinated morphine derivative. Cross-reactivity to morphine metabolites is negligible and the method correlates well with HPLC. Results obtained for pharmacokinetic parameters after intravenous administration in man are in agreement with published data using GLC or HPLC. The method is inexpensive, simple and rapid; choice of a different antiserum could allow the method to be used for screening for drugs of abuse such as morphine, diamorphine, codeine and dihydrocodeine.

Chromatography, High Pressure Liquid↗