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Biomedical subjects

W A Craig

Publications and source records attributed to W A Craig.

At least 145 records · Page 8Linked to original sources
PubMed1976

Correction of protein binding defect in uremic sera by charcoal treatment.

Protein binding of numerous drugs, primarily organic acids, is decreased in sera from uremic patients. The defect in binding is (1) greater than can be accounted for by hypoalbuminemia alone; (2) unchanged by prolonged in vitro dialysis; (3) transferred in the protein but not the ultrafiltrate fraction of uremic serum; and (4) not reproduced by addition of low and middle molecular weight compounds known to accumulate in uremia. However, treatment with activated charcoal at pH3 was found to significantly increase drug protein binding in uremic sera. This effect was studied with six different drugs in sera from groups of 6 normal subjects and 8 patients on chronic hemodialysis. The percentage of sulfamethoxazole, dicloxacillin, diphenylhydantoin, salicylate, and digitoxin bound to protein in normal sera (65.9, 97.1, 93.1, 96.7, and 92.7, respectively) was unchanged by charcoal treatment. In contrast, charcoal treatment significantly (p less than 0.01) increased the percentage of drug bound to protein in uremic sera from 41.7 to 59.0 for sulfamethoxazole, 90.7 to 96.3 for dicloxacillin, 84.3 to 90.8 for diphenyhydantoin, 86.4 to 93.8 for salicylate, and 89.5 to 90.9 for digitoxin. Charcoal treatment significantly (p less than 0.05) reduced penicillin protein binding in normal sera and failed to correct the binding defect for penicillin in uremic sera. The effect of charcoal can be explained by removal of an inhibitor which accumulates in uremia and (1) occupies the binding site of certain drugs, (2) changes the configuration of the albumin molecule, or (3) both. Free fatty acid (FFA) concentrations in uremic patients were similar to those in normal subjects and were not the cause of the binding defect.

Blood Proteins↗
PubMed1976

Compensating osteotomy at the base of the femoral neck for slipped capital femoral epiphysis.

A compensating osteotomy for correction of the varus and retroversion components of severe slipped capital femoral epiphysis is presented. It is safer than a cuneiform osteotomy done through the callus of the slipped epiphysis because the line of osteotomy is distal to the major blood supply of the posterior retinaculum. The threaded Steinmann pins used for fixation sross both the osteotomy site and the epiphyseal plate, and therefore not only are the mechanical relationships restored, but further slipping is prevented also.

Adolescent↗
PubMed1975

Influence of diet and fluid on bioavailability of theophylline.

The influence of various test meals, and of fluid volumes, on the bioavailability of theophylline from a solid dosage form has been studied in healthy male volunteers. Absorption of a drug was faster after dosing immediately following a high protein meal than after a high fat or a high carbohydrate meal. Absorption from a solution was faster than from a solid dosage form in all treatments; areas under serum level time curves after dosing were also significantly higher up to 12 hr. Areas up to 12 hr after dosing also tended to be higher after the high protein meal and after dosing with 500 ml water on an empty stomach than after other solid dose treatments.

Adult↗
PubMed1975

Prediction of drug dosage in patients with renal failure using data derived from normal subjects.

A one-compartment model designed to predict alterations in persistence of drugs in uremic patients was constructed using information obtained from normal subjects. Data obtained from the literature in which the fraction of absorbed drug eliminated unchanged in the urine and the apparent elimination rate constants were compared in both normal control subjects and in severely uremic patients. Twenty-two drugs were examined. Despite changes in apparent volume of distribution and metabolism reported in uremia, the model was able to predict overall elimination rate constants in severe uremia with an error under 10% for 12 and under 20% for 7 additional drugs. The method appears to be most informative for drugs that tend to be retained in the presence of renal failure. Great error was observed with doxycycline and erythromycin. Studies with erythromycin lactobionate and a cupplate assay reduced the error for this drug from 56% for the glucoheptonate to 18%. Doxycycline is known to have a complex enterohepatic circulation. The model is offered as a useful approach to predict dosage adjustment in uremic patients with drugs for which data are not available.

Cephalosporins↗
PubMed1975

Pharmacokinetics of minocycline in renal failure.

The pharmacokinetics of minocycline have been studied after single intravenous infusions and repeated oral doses to human subjects with varying degrees of renal impairment. There was no evidence of reduced drug clearance with reduced renal function after intravenous doses although there appeared to be an increase in the tissue distribution of antibiotic in the body in uremia. After identical multiple oral dosage regimens serum levels of antibiotic were comparable in normal and mildly uremic subjects. There was no evidence of renal toxicity in normal or uremic subjects with the repeated dosage regimen used.

Administration, Oral↗
PubMed1974

Prevention of the generalized Shwartzman reaction and endotoxin lethality by polymyxin B localized in tissues.

Pretreatment with multiple doses of polymyxin B and colistimethate was evaluated as to its ability to sequester sufficient antibiotic in tissues to neutralize the effects of endotoxin in three animal models. Animals were challenged with endotoxin 24, 48, or 72 h after the last dose of antibiotic when there was minimal or not detectable drug in serum. Pretreatment with polymyxin B was successful in preventing the generalized Shwartzman reaction in rabbits and reducing endotoxin lethality in mice; however, large doses (20 mg per kg per day for 2 or 4 days) were required. Prolongation by more than 24 h of the interval between the last dose of polymyxin B and endotoxin challenge resulted in reduction or loss of protection. Dogs were unable to tolerate the high polymyxin B dosage which was protective in the mouse and rabbit. Lower, nontoxic doses of polymyxin B in dogs did not prevent endotoxin shock and lethality, even when challenged as soon as 1 h after the last dose. Pretreatment with colistimethate was ineffective in all three animal models.

Animals↗
PubMed1973

Evaluation of new urinary tract infection screening devices.

Several new methods for detection of bacteriuria were studied to evaluate their usefulness as screening procedures. A new filter paper device incorporating dehydrated media and tetrazolium was found to be reliable when compared with the standard pour plate method in the laboratory and with the dip-slide method in a field test. It failed to detect yeasts and slowly growing streptococci. Antibiotics blocked the test when susceptible organisms were present. An agar-cup method was found to be quite reliable, but could be improved by use of differential media. The Griess test was confirmed in a small trial to be highly specific when used in conjunction with a first morning specimen, but of little value with random specimens. Phenzopyridine was found to give false positive reactions. The subnormal glucose test, although highly sensitive and specific, gave too many false positive tests to be useful other than as a screening method.

Agar↗
PubMed1972

Quantitative urine culture method using a plastic "paddle" containing dual media.

A new dip-inoculum method for quantitative urine culture is described which utilizes a dual-chambered plastic "paddle" housing both a general purpose and differential medium. Comparative bacterial counts of 1,000 clinical specimens using the pour plate and this device were identical in 82.9% and within a factor of five in 95.6%. The "paddle" detected all but 19 of 258 specimens (92.6%) with 100,000 or greater colonies per ml. This simple, convenient method should allow more extensive use of quantitative urine culture in the diagnosis and follow-up of patients with urinary tract infections in office practice. It should not be considered as a substitute for the more definitive pour plate method or for standard methods for characterization of bacteriological species when more exact information is required.

Bacteriological Techniques↗