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Biomedical subjects

C Barton

Publications and source records attributed to C Barton.

At least 91 records · Page 5Linked to original sources

Hepatic pharmacokinetics of glutaraldehyde-treated methotrexate-loaded carrier erythrocytes in dogs.

Methotrexate-loaded glutaraldehyde-treated canine carrier erythrocytes were used to deliver a 1.6-mg/kg dosage of drug. About 90% of the drug-loaded cells disappeared from circulation within 1 h. Approximately 11 mg of drug reached the liver, and a substantial portion of the methotrexate entered the enterohepatic bile salt circulation. Biochemical tests of liver function, such as alkaline phosphatase and serum glutamine pyruvate transaminase, indicated mild hepatocellular necrosis which was attributed to the action of methotrexate on the hepatocytes. Bilirubin levels were unchanged during and following drug treatment. The plasma half-life of the drug was extended 2.4-fold in the first 24 h following injection.

Aldehydes↗

Clinical features and molecular analysis of acquired hemoglobin H disease.

The presence of hemoglobin H (beta 4), resulting from a deficiency of alpha-globin chain synthesis, was observed as an acquired characteristic in the red cells of five elderly patients with myeloproliferative disorders or preleukemia. The variability in amount of hemoglobin H and in the alpha/beta globin synthesis ratios in these patients is most likely explained by the relative proportions of normal and abnormal cell populations in the peripheral blood, since some reticulocyte fractions with balanced alpha/beta globin synthesis ratios and others with almost no detectable alpha-chain production could be obtained from these patients. In one patient, the hemoglobin H virtually disappeared despite continuing disease. The amount of cytoplasmic alpha-mRNA matched the proportion of alpha-chain synthesis and, in one patient, this was also true for nuclear RNA. However, extensive analysis of the alpha-globin gene complex by restriction endonuclease mapping revealed no detectable rearrangements of the normal gene organization in any of these patients, suggesting that transcription of each pair of alpha-globin genes on each chromosome 16 is defective. These observations have important implications for both the normal regulation of alpha-globin gene expression and the molecular basis of the underlying defect that is associated with the neoplastic transformation of these cells.

Aged↗

Prediction of creatinine clearance from serum creatinine in spinal cord injury patients.

Measured endogenous creatinine clearance (Ccr) was compared with the predicted Ccr in 22 paraplegic, 36 tetraplegic and 11 ambulatory male individuals as well as 11 ambulatory females all of whom had normal renal function. While the predicted and measured values closely matched in the ambulatory patients the predicted values in the spinal cord injured patients consistently exceeded the measured values. It thus appears that the original Cockcroft and Gault formula; (formula; see text) when applied to SCI patients can be misleading. Modification of the original formula using a correction factor of 0.8 in paraplegics and 0.6 in tetraplegics was found to allow prediction of Ccr from age, sex, body weight, and serum creatinine in these patients with reasonable accuracy.

Adult↗

Perinephric and intranephric abscesses: a review of the literature.

Perinephric and intranephric (renal cortical and corticomedullary) abscesses, which may coexist, are associated with considerable mortality (21 percent to 56 percent) and are often difficult to diagnose. Most cases of renal cortical abscess are due to hematogenous seeding from distant foci of infection (often involving Staphylococcus aureus), while corticomedullary and perinephric abscesses are most often due to complications of urinary tract infections. Newer noninvasive studies such as ultrasonography, computerized tomography, gallium scanning and indium-labeled leukocyte scanning may facilitate determination of the diagnosis. While antibiotic therapy alone may suffice for the treatment of cortical abscesses, surgical drainage is an added requirement for the treatment of perinephric abscess.

Abscess↗

Circulating carrier erythrocytes: slow-release vehicle for an antileukemic drug, cytosine arabinoside.

The human anti-cancer drug Cytosine arabinoside (ana-C) was encapsulated in canine erythrocytes. When these autologous carrier cells were injected into dogs, the drug was slowly released into plasma. Erythrocyte encapsulation increased the plasma half-life of ara-C in dogs about 50-fold over that of the injected free drug. The whole blood half-life of encapsulated drug was 4.6 days and the elimination constant was 0.150 day-1. Erythrocyte encapsulation holds promise as a drug-delivering technique for treatment of some human and animal diseases, particularly with drugs that are highly toxic or have normally short biological half-life. It also could be used to sustain given concentrations of drugs.

Animals↗

Glutaraldehyde-treated carrier erythrocytes for organ targeting of methotrexate in dogs.

Chemotherapeutic doses of methotrexate (MTX) were encapsulated in as little as 1 ml of canine carrier erythrocytes. Carrier erythrocytes prepared by a dialysis technique contained more than 3.0 mg of MTX/ml of cells. In vivo pharmacokinetic studies indicated that most of the drug leaked from the circulating MTX-loaded erythrocytes. In dogs, glutaraldehyde treatment of MTX-loaded erythrocytes prevented drug leakage and targeted more than 50% of the drug to the liver.

Animals↗

Preparation of resealed carrier erythrocytes and in vivo survival in dogs.

Canine carrier erythrocytes are prepared by dialysis to contain [14C]-sucrose. The procedure allows over 37% of the available sucrose to be encapsulated in the erythrocytes. Cell recovery from the dialysis procedure is greater than 80%. Carrier erythrocytes were prepared from 4 breeds of dogs in less than 2 hours. Although there were some animal-to-animal differences, breed differences were not noticeable in carrier cell preparation. The carrier or resealed erythrocytes contain ca 70% of their hemoglobin and when injected circulate with a half-life of 36 days. These carrier cells could thus serve as a drug delivery vehicle to provide circulating concentrations of encapsulated drug.

Animals↗

Dissociation of supraspinal and spinal actions of morphine: a quantitative evaluation.

Opiate suppression of spinal withdrawal reflexes was tested in rats with lesions of several spinal funiculi to determine the relative contribution of supraspinal descending systems. The latency of tail-flick to noxious heat was used to assess "analgesia". The effect of lesions of dorsolateral funiculus (DLF), dorsal columns (DC) and ventral quadrant (VQ) were compared to that of sham operations. None of the lesions produced a change in baseline latency. Each animal was tested with varying doses of morphine sulfate over several weeks. Only DLF lesions consistently antagonized tail-flick suppression by morphine across the dose range studied (5-15 mg/kg i.p.), although VQ lesions were somewhat effective. The reduction of morphine's action was proportionally greater for lower doses. The results indicate that both spinal and supraspinal sites contribute significantly to the analgesia produced by systemic administration of opiates.

Animals↗

Bicarbonate-buffered peritoneal dialysis. An effective adjunct in the treatment of lactic acidosis.

Severe lactic acidosis is associated with poor prognosis. Usually, the patient is treated with massive amounts of intravenous sodium bicarbonate, which in itself carries many undesirable consequences such as fluid overload and hypernatremia. We have successfully used peritoneal dialysis with a bicarbonate-buffered dialysate in the management of severe acidosis. Bicarbonate-buffered peritoneal dialysis provided an unlimited supply of physiologic buffer over a prolonged period without causing hypervolemia or hypernatremia. Furthermore, significant amounts of lactate were removed by dialysis. We, therefore, recommend the use of bicarbonate-buffered peritoneal dialysis as an adjunct in the treatment of severe lactic acidosis.

Acidosis↗

Control of bleeding from cannulation sites with topical thrombin in dialyzed patients.

Topical thrombin was applied to the cannulation sites during and after withdrawal of the needles. The duration of bleeding was reduced by 50% compared to the control period in patients with various internal arteriovenous communications undergoing maintenance hemodialysis treatment. Accordingly, use of topical thrombin appears effective in saving patients and staffs time, minimizing the blood loss in these anemic patients, and preventing the possible injurious effect of prolonged compression of vascular access to accomplish hemostasis.

Catheterization↗

The incidence of childhood leukaemia in West Berkshire.

This paper gives an overview of local work on the incidence of childhood leukaemia in West Berkshire since 1971. The most recently published figures show that between 1972-96, a total of 106 children contracted leukaemia when 81 cases would have been expected in the under 14s. Within ten kilometres of the nuclear establishments at Aldermaston and Burghfield, the risk of a child getting leukaemia, which is very small (400 children a year in the UK) is none the less doubled in under-fives meaning that one more child a year is affected. There is also an increased incidence of all cancers in this age group and geographical area. Theories as to why this should be abound, but until the cause of cancer is fully understood, and what the part of radiation in the process could be, no firm measures can be taken to redress the balance.

Adolescent↗