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Biomedical subjects

J D Rogers

Publications and source records attributed to J D Rogers.

87 records · Page 5Linked to original sources
PubMed1983

Biopharmaceutical evaluation of 'Osmosin'.

'Osmosin' is an osmotically-controlled oral drug delivery system which presents a saturated solution of sodium indomethacin trihydrate (105.4 mg), equivalent to 85 mg indomethacin, to the gastro-intestinal tract at a constant rate of 7 mg per hour, with a release time of 10 to 12 hours. Drug delivery is not influenced by pH or gastro-intestinal motility. The bioavailability and functionality of 'Osmosin' have been studied after single-dose and after repeated administrations in man. Its performance was compared to that after intravenous administration and various capsule regimens of indomethacin. In both studies, comparable urinary excretion and renal clearance for all oral regimens indicated that like amounts of drug were available for absorption from 'Osmosin' and 'Indocid' capsules. This comparability was verified by the fact that indomethacin is 85% bioavailable from 'Osmosin' compared to intravenous or oral regimens (75 mg given as one dose of 3 X 25 mg capsules or 25 mg 3-times). Drug is absorbed at a constant rate for about 4 hours after 'Osmosin' administration. Indomethacin plasma profiles on an 'Osmosin' 12-hourly regimen were different from typical indomethacin capsule regimens (25 mg at 0, 4, 8 hours; 75 mg at 12 hours or 50 mg at 0, 4 and 14 hours daily). Indomethacin plasma levels from 'Osmosin' were more uniform and sustained, demonstrating more even distribution of drug with time. The constant-rate delivery of sodium indomethacin trihydrate to the gastro-intestinal tract from 'Osmosin' controls the rate of drug absorption, prolongs the effective half-life of drug in plasma, does not inhibit the efficiency of absorption, but does significantly decrease the extremes in plasma level fluctuation noted with conventional dosage forms.

Absorption↗
PubMed1982

Kinetics of osmotically controlled indomethacin delivery systems after repeated dosing.

Two osmotically driven, controlled-release dosage forms of indomethacin were evaluated in a multiple-dose crossover study in 12 healthy subjects. Following equivalent daily doses, less frequent dosing of both controlled-release forms resulted in plasma concentration profiles that are more uniform than those following capsule regimens. After the first day, morning predose plasma levels wer significantly higher for the controlled-release treatments. Renal clearances were similar between days and among treatments. Total urinary recoveries were comparable for all regimens.

Delayed-Action Preparations↗
PubMed1982

Carcinoma of the uterine cervix: results of radiation therapy at a regional community teaching hospital.

We analyzed the results of radiation therapy for carcinoma of the uterine cervix in 144 patients treated at a regional referral hospital. The local control was good in early stage disease, with only two pelvic failures in 92 stages I and II patients. Survival at 40 months was 86%, 83%, 48%, and 75% for stages I, IIa, IIb, and IIb (barrel-shaped lesions), respectively. Many IIb lesions could have been staged as IIb (barrel-shaped lesions). Control and survival in late disease was poor. The complications were minimal.

Adenocarcinoma↗
PubMed1980

Effect of orally administered probenecid on the pharmacokinetics of cefoxitin.

To characterize the effect of orally administered probenecid on the pharmacokinetics of cefoxitin in healthy male volunteers, we administered to one group of six subjects 2 g of cefoxitin by intravenous (i.v.) bolus either alone, with 1 g of probenecid concomitantly, or when 1 g of probenecid was administered 1 h previously by using a crossover design. Likewise, we administered to a second group of six subjects 2 g of cefoxitin intramuscularly (i.m.) together with 1 and 2 g of probenecid. Probenecid increased the mean terminal half-life and the area under the serum cefoxitin concentration-time curve (AUC0-24) and decreased renal clearance, but did not alter the volume of the central compartment or the total urinary recovery of i.v.-administered cefoxitin; pretreatment with probenecid produced a greater increase in cefoxitin AUC0-24 and a constant decrease in renal clearance compared to concomitant probenecid. The AUC0-24 after i.m.-administered cefoxitin was greater after 2 g than 1 g of probenecid; the AUC0-24 after i.v.-and i.m.-administered cefoxitin was similar after 1 g of probenecid was given concomitantly. Cefoxitin AUC0-24 was increased further when 1 g of probenecid was given before i.v.-administered cefoxitin or when 2 g of probenecid was given with i.m.-administered cefoxitin. The effect of probenecid was related to both timing and dose.

Administration, Oral↗
PubMed1980

Processing haematological data on a dedicated computer.

A system of processing the laboratory data of a busy haematology department serving a teaching group of hospitals and the general practitioners of the district is described. The system, which has been in routine use for over two years, is based on a dedicated CTL8030 computer sited in the laboratory utilising Lynwood visual display units (VDUs) for both input and access to the data files. Data from the Coulter 'S' is fed by an interface to the computer and to other data handling modules. Manual test results are entered via VDUs, mainly by laboratory staff who also validate all data. Access is available to all data for answering telephone requests. Data are retained on the disc file for 48 hours only, and cumulative reporting was not planned into the system as deliberate policy. Quality control of the Coulter 'S' output is maintained both throughout the day and retrospectively at the end of each working day using both whole blood patient blood transfusion profiles, a record of blood and product usage, worksheets, quality control information, end-of-day listing in alphabetical order plus statistical information for administrative purposes. Since its introduction the system has been remarkably free from breakdown as a result of hardware failure. A number of fail safe/fallbacks have been included in the system.

Blood Cell Count↗
PubMed1978

Direct modification of the glycocalyx of a cultured muscle cell line by incorporation of foreign gangliosides and an integral membrane glycoprotein.

As part of a program to better understand the cause-or-effect nature of the relationship between cell surface carbohydrate and cell properties and behaviour, experiments have been carried out on direct modification of the glycocalyx of cultured cells. Modification was by incorporation of gangliosides and an integral membrane glycoprotein chosen to be dissimilar to species occurring naturally in the cell line. Two methods of incorporation were investigated: simple addition of the new components to the culture medium for various times, or assembly of the components into the walls of lipid vesicles which were subsequently fused with cells. Gangliosides from beef brain and glycophorin, the major human erythrocyte sialoglycoprotein, were successfully added to the surface of myoblasts in quantities sufficient to represent a significant perturbation. Changes in cell adhesion, morphology, and viability were observed which seem to be a direct result of glycocalyx modification.

Animals↗
PubMedDate not supplied

Pharmacokinetics and comparative pharmacology of cefoxitin and cephalosporins.

Features of the distribution, metabolism, elimination, and pharmacokinetics of the cephalosporins and cefoxitin must be considered when concentrations of these drugs in biological fluids are interpreted. The extensive (approximately 86%) binding of cefazolin to plasma protein may account for the smaller volume of distribution and slower rate of renal clearance than are observed for cefoxitin, which is less extensively (73%) bound to protein. Results of microbiological assays of drug in urine may be influenced by the extent of metabolism of the drugs, which is 33% for cephalothin but less than 2% for cefoxitin. Elimination of cephalosporins and cefoxitin occurs by both glomerular filtration and tubular secretion and can be inhibited by the concurrent administration of probenecid. The pharmacokinetics of cefoxitin may be described by a linear, two-compartment, open model that has been used to predict levels of drug achieved in serum and urine after various dose regimens, including administration by intravenous bolus or infusion. The bioavailability of intramuscularly administered cefoxitin is equivalent to that of intravenously administered cefoxitin and is 90% complete within 3-4 hr after the dose is given.

Biological Availability↗
PubMedDate not supplied

Pharmacokinetics of imipenem and cilastatin in volunteers.

Imipenem/cilastatin sodium consists of imipenem, a broad-spectrum carbapenem antimicrobial agent, and cilastatin sodium, an inhibitor of dehydropeptidase I, the renal enzyme that catalyzes the metabolism of imipenem. When imipenem is administered alone by the intravenous route, the levels excreted in the urine are low and variable (6%-38% of the dose) between subjects. Kinetics of imipenem in plasma are less variable, and the half-life of imipenem in plasma is 1 hr. When imipenem is coadministered with an equal amount of cilastatin, the amount of imipenem excreted in the urine represents 70% of the plasma clearance and the plasma half-life remains at 1 hr. Whether administered alone or with imipenem, the urinary excretion of cilastatin is 70%-80% of the dose administered, and its plasma half-life is also 1 hr. Thus, the pharmacokinetics of both agents are linear across the therapeutic dose range, and no accumulation of these agents occurs for therapeutic regimens. Decreases in renal function slow the elimination of both compounds and require a reduction in dosage when the glomerular filtration rate is less than 30 ml/min per 1.73 m2.

Bacterial Infections↗
PubMedDate not supplied

Influence of culture media and environmental factors on mycelial growth and pycnidial production of Sphaeropsis pyriputrescens.

Sphaeropsis pyriputrescens, the causal agent of Sphaeropsis rot of pears and apples, is a recently described species. In this study the effects of culture media, temperature, water potential, pH and light on mycelial growth and pycnidial production of S. pyriputrescens were evaluated. Apple juice agar and pear juice agar were most suitable for mycelial growth of all six isolates tested. Cornmeal agar was not suitable for either mycelial growth or pycnidial production. The fungus grew from -3 to 25 C, with optimum growth at 20 C and no growth at 30 C. The fungus grew at water potential as low as -5.6 MPa on potassium chloride-amended potato-dextrose agar (PDA). Hyphal extension was not observed at -7.3 MPa after 10 d incubation, but growth resumed when the inoculum plugs were placed on PDA. The fungus grew at pH 3.3-6.3 and optimum growth was at pH 3.3-4.2. No mycelial growth was observed at pH above 7.2 after 10 d incubation, but growth resumed when the inoculum plugs were transferred onto PDA. Regardless of medium tested, few pycnidia formed at 20 C in the dark. Pycnidial production was enhanced significantly by fluorescent light, but continuous light appeared to reduce pycnidial production, depending on the medium. Oatmeal agar (OMA) was most suitable for production of pycnidia and conidia. Pycnidia that formed on 3 wk old OMA cultures at 20 C under 12 h light/12 h dark produced abundant conidia, and the technique is recommended for inoculum production.

Agar↗
PubMedDate not supplied

Phacidiopycnis washingtonensis--a new species associated with pome fruits from Washington State.

A new species of Phacidiopycnis associated with pome fruits is described. The fungus causes fruit rot on apples during storage and is associated with a twig dieback and canker disease of crabapple trees and dead twigs of pear trees. To characterize the biology of the fungus and compare it with Ph. piri, the type species of the genus, effects of nine media and light on mycelial growth and pycnidial production, mycelial growth in response to temperature and mode of conidial germination in response to nutrient were determined. Apple-juice agar, pear-juice agar, prune-juice agar, potato-dextrose agar (PDA) and malt-extract agar, Czapek-Dox agar and oatmeal agar (OMA) favored mycelial growth. Cornmeal agar (CMA) did not favor mycelial growth. Light effect on pycnidial formation was medium dependent. Abundant pycnidia with mature conidia formed in 14 d old PDA and OMA cultures at 20 C, regardless of light, whereas none or very few pycnidia formed on other media in the dark. Fluorescent light stimulated formation of pycnidia except on CMA. The fungus grew at -3-25 C, with optimum growth at 15-20 C. Conidia germinated either by forming germ tubes or less often by budding. Budding of conidia occurred in 1 and 10% pear-juice solutions but not in 100% pear-juice solution. Six isolates of Ph. washingtonensis from different species of pome fruits had identical ITS sequences. The sizes of the ITS region were the same for both Ph. washingtonensis and Ph. piri, and four polymorphic nucleotide sites were found in the ITS region between Ph. washingtonensis and Ph. piri. The similarity in ITS sequences between these two taxa is confirmatory evidence for the erection of the new species of Phacidiopycnis associated with pome fruits we describe here.

Ascomycota↗
PubMedDate not supplied

Metabolic disposition of simvastatin in patients with T-tube drainage.

A study to investigate the disposition and biliary excretion of simvastatin (SV) was conducted in four cholecystectomy patients with T-tube drainage. Each patient received a single oral dose of 100 mg of [14C]SV (20 microCi). Of the 14C-labeled dose, approximately 35% was excreted in urine, 25% in bile, and 20% in feces. Thus, at least 60% of the oral dose was absorbed from the gastrointestinal tract. Of the AUC for radioactivity in plasma, 13% was contributed by the HMG-CoA reductase inhibitors. In addition, only 2% of the 14C-dose was eliminated in urine as HMG-CoA reductase inhibitors. Thus, most of the SV-related compounds in plasma and urine have little or no HMG-CoA reductase inhibitory activity. The same is probably true for these compounds in bile. Two major active metabolites were present in the bile. Based on HPLC and MS/MS data, they were identified as 6' beta-COOH-SVA and 6'-OH-SVA. In general, the majority of the radioactivity in the bile and urine was excreted within 24 hr postdose. Of the radioactivity excreted in the 0- to 24-hr bile, on average, approximately 30% was contributed by 6' beta-COOH-SVA and 6'-OH-SVA. These two metabolites accounted for the majority of HMG-CoA reductase inhibitory activity in the bile. Little or SV or no SVA was present in the bile.

Adult↗