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Biomedical subjects

M R Bending

Publications and source records attributed to M R Bending.

At least 37 records · Page 2Linked to original sources

Caecal perforation in a renal transplant patient with disseminated histoplasmosis.

A renal transplant patient developed a fatal caecal perforation after Histoplasma capsulatum infection acquired abroad. Disseminated histoplasmosis is an uncommon fungal infection, usually seen in patients with impaired immunity. The diagnosis should be considered in immunosuppressed patients who develop prolonged fever or whose health deteriorates unexpectedly after travelling overseas. The infection is endemic in parts of the United States of America but occurs all over the world. Rapid diagnosis is often possible by histological examination of infected tissues. Treatment if started early may lead to recovery, but if it is not treated it is usually fatal.

Cecal Diseases↗

Comparison of serum calcium fractions during haemodialysis and peritoneal dialysis.

Total, ultrafiltrable and ionised calcium concentrations were determined in anaerobic serum from healthy volunteers, patients immediately before and after haemodialysis and patients on continuous ambulatory peritoneal dialysis (CAPD). Protein-bound, complexed and albumin-corrected total calcium concentrations were calculated from the results. During haemodialysis, complexed calcium did not change, whereas the other fractions increased. For patients on CAPD, the total, ionised and protein-bound calcium results were frequently lower than the reference group, whereas the ultrafiltrable and albumin-corrected total calcium results were within or higher than the reference group. Albumin-corrected total calcium for all subjects correlated better with ultrafiltrable calcium than with ionised calcium. It was concluded that low ionised calcium concentrations found in CAPD patients may be related to low albumin concentrations, and the concentration of physiologically active calcium may be normal in these patients.

Adult↗

Pharmacokinetics of lidocaine and its deethylated metabolite: dose and time dependency studies in man.

The concentrations of lidocaine and of its deethylated metabolite, MEGX, were measured in blood following the intravenous administration of 50 and 100 mg lidocaine hydrochloride, the oral administration of 100, 300, and 500 mg lidocaine hydrochloride monohydrate, and the oral administration of 300 mg lidocaine hydrochloride monohydrate every 8 h for seven doses, to three healthy volunteers. The range of values for the parameters defining the disposition kinetics of lidocaine were: terminal half-life, 50-231 min; total clearance, 13-17 ml/min/kg; initial dilution space, 0.13-2.5 liters/kg; and volume of distribution at steady state, 0.6-4.5 liters/kg. Lidocaine absorption from solution was rapid, but due to presystemic hepatic metabolism, the availability was low, the range of average values lying between 0.19 and 0.38. No dose or time dependency in lidocaine and monoethylglycinexylidide pharmacokinetics following the single dose studies of lidocaine were noted. Effective hepatic blood flow, based on total clearance and availability measurements, was estimated to be 18-27 ml/min/kg. The concentrations of MEGX were approximately one-third of those of lidocaine following intravenous lidocaine and were comparable following oral lidocaine, but as predicted, the dose normalized area under the MEGX concentration-time curve was constant and independent of the route of administration of lidocaine. In two subjects, the blood concentrations of lidocaine and MEGX following multiple doses of oral lidocaine were those predicted from the single dose studies. In the third subject, the degree of accumulation of lidocaine was greater than predicted. The reasons and mechanism for this difference between subjects on multiple dosing remains unclear.

Administration, Oral↗

Malaria: a laboratory risk.

A case is described of malaria contracted in a clinical laboratory by accidental self-inoculation with infected blood.

Adult↗

Peptiduria in experimental Fanconi syndrome in rats.

1. The plasma concentrations and urinary output of proline and hydroxyproline contained in peptides were measured in normal rats and in rats with Fanconi syndrome produced by injection of sodium maleate. All animals received a prior injection of 10 mg of the dipeptide L-prolyl-L-hydroxy-proline to increase plasma and urinary peptide content. There was a significant increase of urinary output of the two imino acids contained in peptides and a fall in their plasma concentrations. 2. It is concluded that increased output of peptides derived from collagen degradation in the experimental Fanconi syndrome in rats is at least in part due to diminished tubular reabsorption of these compounds from the glomerular filtrate. The results are claimed to be relevant to the increased output of urinary peptides in the Fanconi syndrome in man.

Animals↗

Plasma levels of 5-fluorouracil after oral and intravenous administration in cancer patients.

1. Plasma levels of 5-fluorouracil (5FU) have been determined in eleven cancer patients after 0.5 g and 1.0 g intravenous doses, and in one patient after paired 1.0 g oral and intravenous doses. 2. The plasma half-life after the 0.5 g intravenous dose was relatively constant, irrespective of the stage and spread of the disease. 3. Plasma kinetics of the drug were dose dependent. Doubling of the intravenous dose produced a 1.5-fold increase in plasma half life, a two-fold increase in initial plasma drug concentration, and a three-fold increase in area under the concentration/time curve. 4. In one patient receiving paired 1.0 g intravenous and oral doses nine weeks apart, an increase in the bioavailability of the drug coincided with a marked clinical regression in palpable intra-abdominal metastases. 5. The significance of measuring plasma drug kinetics and their relationship to drug efficacy and toxicity are discussed.

Administration, Oral↗

Drug concentration in saliva.

It is possible to predict plasma concentrations of drugs by measurement in saliva, obviating the need for venipuncture. Using a selection of weakly acidic and basic drugs, we have found this prediction reliable for drugs largely nonionized at normal plasma pH (phenytoin, phenobarbital, antipyrine) but unreliable for ionized drugs (chlorpropramide, tolbutamide, propranolol, meperidine). Deliberate alteration of saliva flow rate and pH using different stimuli have produced twofold changes in saliva drug concentrations. Wide interindividual variability of saliva pH is the likely explanation for the inconstancy of saliva to plasma concentration ratios for ionized drugs.

Adolescent↗

Use of a nitrogen detector for GLC determination of fluorouracil in plasma during single- and combined-agent chemotherapy.

A GLC assay for fluorouracil was developed and used to monitor plasma drug levels in patients on both single- and combined-agent chemotherapy. Fluorouracil is extracted from plasma, derivatized by flash methylation, and estimated using a thermionic nitrogen-phosphorus detector. The GLC determination was accurate at concentrations as low as Q.1 microgram/ml of human plasma. Other drugs commonly used in combination with fluorouracil did not interfere with the assay.

Antineoplastic Agents↗

Peptide excretion in experimental Fanconi syndrome in the rat.

A study has been made of urinary peptide output in rats before and after production of a Fanconi syndrome induced by a single injection of sodium maleate. There was an unequivocal increase of urinary peptides on the first and second days after the injection, without any detectable change in the concentration of plasma peptides. 2. Similar results were obtained in osteolathyritic rats in which skeletal lesions had been produced by ingestion of beta-aminopropionitrile. 3. The fractional amino acid content of urinary peptides after maleate and beta-aminopropionitrile is shown to be significantly different from that in control animals. 4. Evidence is presented that the increased output of peptides is mainly due to increased renal clearance similar to that previously described for amino acids, glucose and several electrolytes in this type of experimental Fanconi syndrome.

Aminopropionitrile↗

Trial of combination of guanethidine and oxprenolol in hypertension.

Thirteen hypertensive patients entered a double-blind crossover trial of guanethidine and oxprenolol in combination. In nine patients who completed the trial there was an additive effect on blood pressure, but the combination had a smaller effect on heart rate than was expected from the individual effects, and side effects were not increased. During treatment with oxprenolol the plasma potassium concentration rose from 3.6 mmol (mEq)/1 to 3.9 mmol (mEq)/1. No correlation was found between the plasma oxprenolol concentration and changes in blood pressure or response to injected isoprenaline, but measurements of plasma oxprenolol concentrations were of value in determining compliance with the protocol.

Blood Pressure↗