Biomedical subjects

R R Martin

Publications and source records attributed to R R Martin.

At least 55 records · Page 3Linked to original sources

PubMed1992

Pharmacokinetics of cefepime after single and multiple intravenous administrations in healthy subjects.

The pharmacokinetics of cefepime in 31 young, healthy volunteers were assessed after the administration of single and multiple 250-, 500-, 1,000-, or 2,000-mg intravenous doses. Each subject received a single dose of cefepime via a 30-min intravenous infusion on day 1 of the study. Starting from day 2, subjects received multiple doses of cefepime every 8 h for 9 days, and on the morning of day 11, they received the last dose. Serial blood and urine samples were collected after administration of the first dose and on days 1, 6, and 11. Cefepime concentrations in plasma and urine were assayed by using reverse-phase high-performance liquid chromatography with UV detection. Data were evaluated by noncompartmental methods to determine pharmacokinetic parameters. The mean half-life of cefepime was approximately 2 h and did not vary with the dose or duration of dosing. The regression analyses of peak levels (Cmax) in plasma at the end of the 30-min intravenous infusion and the area under the plasma concentration-versus-time curve (AUCo-infinity) showed a dose-proportional response. The steady-state volume of distribution (Vss) was approximately 18 liters and was independent of the administered dose. The multiple-dose pharmacokinetic data are suggestive of a lack of accumulation or change in clearance of cefepime on repeated dosing. Cefepime was excreted primarily unchanged in urine. The recovery of intact cefepime in urine was invariant with respect to the dose and accounted for over 80% of the dose. The values for renal clearance ranged from 99 to 132 ml/min and were suggestive of glomerular filtration as the primary excretion mechanism. It is concluded that cefepime linear pharmacokinetics in healthy subjects.

Adult↗

PubMed1991

Evolution of the treatment of the injured colon in the 1980s.

During the past 10 years, 1006 patients with colon injuries were treated in an urban trauma center. Primary repair, including suture repair and resection with anastomosis, was performed in 614 patients (61%), colostomy in 284 patients (28%), and exteriorized repairs in 83 patients (8.3%). In the remaining 25 patients (2.5%) who were exsanguinating, the colon injuries were ligated. Independent risk factors for adverse outcomes (defined as a fecal fistula, abdominal abscess, stomal complication, or death from multisystem failure) were identified using multiple logistic regression analysis. These factors were used to match patients at similar risk within different treatment groups, and odds ratios for each treatment were calculated. The odds ratios for primary repair, colostomy, and exteriorized repair were 1.0, 1.9, and 2.0, respectively. Therefore, the chance of an adverse outcome was twice as great for both exteriorized repair or colostomy as for primary repair. It is concluded that further increases in the use of primary repair are warranted.

Abscess↗

PubMed1991

Management of the difficult duodenal stump.

Leakage from the duodenal stump has been the most feared complication of the Billroth II reconstruction following gastric resection. The purpose of our study was to evaluate four methods of duodenal stump closure in 200 patients. One hundred and forty-seven (74%) patients had duodenal ulcers; 28 (14%) had gastric ulcers; and 25 (13%) had a variety of other inflammatory conditions. The most common indication for operation was acute hemorrhage (51%), followed by perforation (24%), intractability (15%), and obstruction (10%). Conventional duodenal closures were performed in 160 (80%) patients, Nissen's closure in 25 (13%), Bancroft's closure in 6 (3%), and tube duodenostomy in 9 (5%). Duodenal leaks occurred in four (2.5%) patients with conventional closures and in three (33%) patients with tube duodenostomies. No leaks occurred in patients with Nissen's or Bancroft's closures. The hospital mortality rate for the series was 9.5%; however, no patient who developed a duodenal leak died. We conclude that Nissen's and Bancroft's closures were safe and effective, but that tube duodenostomy did not reliably prevent uncontrolled leakage.

Adolescent↗

PubMed1991

Effects of challenge with trichostrongylid nematode larvae on immunologically resistant grazing yearling sheep in South Australia.

Paddocks near Gawler, South Australia, were grazed by newly weaned sheep which received either no anthelmintic treatment, regular 3-weekly treatment or a single treatment in February. A decline in the faecal egg count of untreated sheep in autumn associated with the ingestion of infective larvae indicated that the sheep had developed a resistance to reinfection. At the end of the experiment, 10 sheep were experimentally infected with Trichostrongylus vitrinus larvae to demonstrate this resistance. Untreated sheep grew less wool and had lower body weights when compared with treated animals and were extremely 'daggy'. A single treatment in February did not prevent production losses or scouring.

Age Factors↗

PubMed1991

Pharmacokinetics of didanosine in patients with acquired immunodeficiency syndrome or acquired immunodeficiency syndrome-related complex.

The pharmacokinetics of didanosine (2',3'-dideoxyinosine) after intravenous and oral administration were evaluated in an open, escalating-dose phase I study in patients with acquired immunodeficiency syndrome (AIDS) or severe AIDS-related complex. Didanosine was administered twice a day for 2 weeks as an intravenous infusion of 60 minutes duration at doses ranging from 0.4 to 16.5 mg/kg, followed by 4 weeks of oral treatment at twice the intravenous dose. Serial blood and urine samples were obtained on the first and final day of intravenous administration and after the first oral dose, as well as at steady state. Didanosine demonstrated linear pharmacokinetic behavior over the dose ranges of 0.4 to 16.5 mg/kg intravenously and 0.8 to 10.2 mg/kg orally. There was no indication of significant changes in pharmacokinetic parameters with repeated administration. The apparent elimination half-life after oral administration was approximately 1.4 hour. Renal clearance values exceeded the glomerular filtration rate, indicating that active tubular secretion of didanosine occurs. Bioavailability of didanosine when administered as a solution with an antacid was approximately 43% for doses from 0.8 to 10.2 mg/kg in patients with AIDS and advanced AIDS-related complex. Bioavailability of didanosine from the citrate-phosphate-buffered solution, the formulation currently used in phase II and expanded access studies, was comparable to the formulation used in the phase I trials.

AIDS-Related Complex↗

PubMed1991

Outcome for delayed operation of penetrating colon injuries.

It has been stated that delay in operative repair of penetrating injuries to the gastrointestinal tract will result in a high rate of complications related to infection. To test this assertion, a group of patients with penetrating injuries to the colon were analyzed who had operative repair delayed (usually because of triage considerations) more than 6 hours after admission to the hospital. Nine hundred six patients who survived at least 48 hours after injury were divided into two groups. The immediate group of 769 patients was treated within 6 hours of admission and the delayed group of 137 patients was treated more than 6 hours after admission. The mortality for the immediate group was 4.0% vs. 1.5% for the delayed group. Colon-related infectious complications, defined as abscess or colon suture-line failure, occurred in 10% of the immediate group and 4.4% of the delayed group. To eliminate the effect of associated injuries, the group of patients with colon injuries only was analyzed separately. There was no mortality for 128 patients with colon injuries only operated on within 12 hours of injury, and the colon-related infectious morbidity rate was 3%. Eleven patients with colon injuries only were treated after 12 hours with a mortality of 9% and colon-related infectious morbidity of 18%. These data demonstrate that even patients with fecal contamination can have operative repair delayed for up to 12 hours without undue morbidity related to infection.

Adult↗

PubMed1990

Safety, tolerance, and pharmacokinetics of cefepime administered intramuscularly to healthy subjects.

Steady state pharmacokinetics, absolute bioavailability, and dose proportionality of cefepime were evaluated in healthy male subjects after single (250, 500, 1000, or 2000 mg) and multiple (1000 mg every 12 hours for 10 days) intramuscular injections. Safety and tolerance were also monitored. High performance liquid chromatography/UV methodology was used to determine cefepime concentrations in plasma and urine. Key pharmacokinetic parameters were determined using noncompartmental methods. Cefepime was absorbed rapidly; mean peak times were 1.0-1.6 hours. Pharmacokinetics were linear over the 250-mg to 2000-mg dose range, with mean total body clearance ranging from 125 to 141 mL/min. The peak plasma concentration and area under the curve increased in a dose-proportional manner. The apparent elimination half-life (2 hours) did not appear to be influenced by dose or by duration of dosing. No accumulation of cefepime was observed during the multiple-dose study. More than 80% of the administered dose was excreted in the urine as unchanged cefepime, and absolute bioavailability after intramuscular dose was 100%. Cefepime was well tolerated. Most subjects experienced none to mild pain and only minimum discomfort at the site of injection.

Adult↗

PubMed1990

A modified technique for the estimation of the number of infective nematode larvae present on pasture, and its application in the field under South Australian conditions.

A modified technique for the recovery of larvae from pasture is described involving two centrifugations of pasture washings in a solution of potassium iodide. On average, the technique recovered 96% of larvae and was simple to perform. At three sites in South Australia (rainfall 550-330 mm year-1), the numbers of larvae present on pasture each month using this technique was compared with results obtained using one or four tracer sheep. The general pattern of larval availability was similar using the two methods, but discrepancies were noted. In some instances, particularly when numbers of larvae were low, pasture sampling underestimated the numbers of larvae available to sheep; in other situations, when the numbers of larvae were high, tracer sheep probably underestimated the number being ingested. Increasing the numbers of tracer sheep from one to four did not appreciably increase the correspondence between the two methods.

Animals↗

PubMed1990

Retroperitoneal vascular injury.

Retroperitoneal vascular injuries are among the greatest challenges that confront the surgeon. Problems in resuscitation, exposure, and repair are numerous. Techniques to improve such perioperative tactics result in improved survival.

Blood Vessels↗

PubMed1990

Nucleotide sequences of an Australian and a Canadian isolate of potato leafroll luteovirus and their relationships with two European isolates.

The genomes of an Australian and a Canadian isolate of potato leafroll virus have been cloned and sequenced. The sequences of both isolates are similar (about 93%), but the Canadian isolate (PLRV-C) is more closely related (about 98% identity) to a Scottish (PLRV-S) and a Dutch isolate (PLRV-N) than to the Australian isolate (PLRV-A). The 5'-terminal 18 nucleotide residues of PLRV-C, PLRV-A, PLRV-N and beet western yellows virus have 17 residues in common. In contrast, PLRV-S shows no obvious similarity in this region. PLRV-A and PLRV-C genomic sequences have localized regions of marked diversity, in particular a 600 nucleotide residue sequence in the polymerase gene. These data provide a world-wide perspective on the molecular biology of PLRV strains and their comparison with other luteoviruses and related RNA plant viruses suggests that there are two major subgroups in the plant luteoviruses.

Australia↗

PubMed1990

A new potexvirus associated with strawberry mild yellow edge disease.

A physical map of cDNA clones prepared from dsRNA associated with the MY-18 source of strawberry mild yellow edge (SMYE) was constructed and 854 nucleotides adjacent to the 3' poly(A) tail were sequenced. The larger open reading frame product of Mr 25714 showed considerable amino acid homology to the coat protein cistrons of six potexviruses and two carlaviruses. A second product of Mr 11216 encoded completely within the coat protein cistron, but in a different frame, has similarities to two potexvirus polypeptides. The Mr 25714 ORF was fused to the Protein A gene in an expression vector and the fusion protein was purified by affinity chromatography and used to immunize a rabbit. The resulting polyclonal antiserum reacted strongly in immunoelectron microscopical tests with filamentous particles resembling those of potexviruses. Such particles were detected in the following SMYE sources: D-74 from Germany, two from the United Kingdom in Fragaria vesca 'Alpine' indicator plants and Oregon MY-18 in Rubus rosifolius. Among 27 potexvirus antisera tested for serological reactions none yielded strong decoration. Examination of ultrathin sections of R. rosifolius and F. vesca tissue infected with SMYE revealed aggregates of filamentous particles in phloem parenchyma cells. dsRNA from nine sources of SMYE collected from around the world reacted with the cDNA clones of this potexvirus in Northern hybridizations. It is concluded that the potexvirus is hitherto undescribed and the name strawberry mild yellow edge-associated potexvirus is proposed.

Amino Acid Sequence↗

PubMed1990

A monoclonal antibody specific to zeatin o-glycosyltransferases of phaseolus.

Zeatin O-xylosyltransferase and zeatin O-glucosyltransferase occur in immature embryos of Phaseolus vulgaris and P. lunatus, respectively. Purified preparations of the xylosyltransferase were used as antigen to elicit the formation of antibodies in mice. Hybridoma clones were produced by fusion of mouse spleen cells with myeloma cell line Fox-NY. A clone secreting monoclonal antibody (MAb), XZT-1, capable of immunoprecipitating both enzymes was obtained. The MAb detected a unique protein band from crude embryo extracts of each species with the correct molecular mass (50 kilodaltons) and relative charge (R(F) = 0.5 and 0.3) of the respective enzymes. Competition experiments with substrates indicated that the glycosyl dinucleotide binding sites of the enzymes are probably not involved in MAb-enzyme recognition. Western blotting of samples from vegetative tissues of P. vulgaris detected a low level of O-glucosyltransferase but not O-xylosyltransferase, in leaves. These findings suggest the occurrence of two genes in P. vulgaris coding for O-glycosylation enzymes with tissue-specific expression. The MAb will be used to screen expression libraries and to obtain pure enzymes for amino acid sequencing and for the production of additional MAbs.

Journal Article↗

PubMed1990

Phase I study of single-dose BMY-28100, a new oral cephalosporin.

The objective of this Phase I study was to evaluate the safety, tolerance, and pharmacokinetics of BMY-28100 in 36 male subjects after the administration of single oral doses of 250, 500, and 1,000 mg. The subjects were divided into groups of 12 per dose group. All subjects completed the study, and BMY-28100 was well tolerated at all doses. The maximum concentration of the drug in plasma ranged from 6.2 to 17.7 micrograms/ml for the 250- and 1,000-mg doses, respectively, and the area under the curve increased in a dose-proportional manner. The elimination half-life and renal clearance averages were 1.2 h and 200 ml/min, respectively. The values for renal clearance suggest that BMY-28100 is excreted by glomerular filtration and tubular secretion. Mean concentrations of the drug in urine were highest during the first 4 h after the doses and ranged from 175 to 658 micrograms/ml following the 250- and 1,000-mg doses, respectively. The mean urinary recovery ranged from 57 to 70% of the dose. The results from this Phase I study indicate that BMY-28100 is well tolerated and exhibits linear pharmacokinetics.

Adult↗

PubMed1990

Safety, tolerance, and pharmacokinetic evaluation of cefepime after administration of single intravenous doses.

In this double-blind, single-dose phase I study, the safety and tolerance of cefepime were assessed in 24 healthy male subjects, with ceftazidime as the control drug. Four subjects in each of the six dose groups (62.5, 125, 250, 500, 1,000, or 2,000 mg as a 30-min intravenous infusion) received each antibiotic, according to a crossover design, with a 2-day washout period between treatments. Blood and urine samples were obtained to characterize the pharmacokinetics of cefepime. Plasma and urine samples were assayed for intact cefepime. Samples containing ceftazidime were discarded. The adverse effects observed in the study were mild and infrequent, with prompt recovery from adverse experiences and abnormal laboratory values. The cefepime pharmacokinetic parameters for the therapeutically significant doses of 250 to 2,000 mg appeared to be proportional to dose and similar to literature values for ceftazidime. The elimination half-life of about 2 h was independent of the dose. Urinary recovery of intact cefepime was invariant with respect to dose; an overall mean value of 82% of dose was obtained for the four highest levels. Mean renal clearance was 105 ml/min and suggestive of glomerular filtration as the primary excretion mechanism. In normal humans, the safety and pharmacokinetic profiles of cefepime are very similar to those of ceftazidime.

Adult↗

PubMed1990

Phase I study of multiple-dose cefprozil and comparison with cefaclor.

The objectives of this study were to assess the safety and tolerance of cefprozil, to characterize the pharmacokinetics of cefprozil after administration of multiple doses of the drug, and to compare these pharmacokinetic parameters with those obtained with cefaclor. The volunteers received 28 doses of 250, 500, or 1,000 mg of cefprozil or 500 mg of cefaclor every 8 h for 10 days. Serial blood samples and the total volume of urine voided by each individual were collected for pharmacokinetic evaluation on days 1, 5, and 10. Both cephalosporins were well tolerated after multiple oral dosing. The peak levels in plasma (Cmax) of cefprozil ranged from 5.7 to 18.3 micrograms/ml after oral administration of 250- to 1,000-mg doses. The regression analysis of Cmax on cefprozil dose showed a dose-linear response. The mean Cmax of cefaclor ranged from 15.2 to 16.7 micrograms/ml and did not change significantly on multiple dosing. The overall mean terminal half-life of cefprozil was 1.2 h and was invariant with respect to dose or duration of dosing. The area under the plasma-concentration-versus-time curve from 0 h to infinity (AUC0-infinity) of cefprozil increased in a dose-proportional manner with an increase in dose. The overall urinary recovery (61% of dose) and renal clearance values of cefprozil were generally invariant with respect to dose and duration of dosing. While cefprozil was apparently absorbed less rapidly and achieved lower Cmax values than cefaclor, the AUC0-infinity of cefprozil was nearly twofold greater than that of cefaclor. The half-life of cefprozil was also twofold longer than that observed for cefaclor. Although the urinary recovery of cefaclor (75% of dose) was significantly higher than that of cefprozil (61% of dose), the concentrations of cefprozil in urine remained significantly higher than those of cefaclor from 2 to 8 h postdosing. If the therapeutic concept is maintained that levels of beta-lactam antibiotics in plasma should exceed the MIC for the offending organisms over a period that approximates the dosing interval, then cefprozil would appear to be suitable for twice-daily administration, whereas cefaclor should probably be administered three or even four times a day.

Adult↗

PubMed1990

Tracheal dead space influences regional ventilation measurement in dogs.

The lung volume at which airway closure begins during expiration (closing volume, CV) can be measured 1) with a radioactive bolus inspired at residual volume (RV) and 2) with the single-breath N2 elimination test. In previous studies in dogs, we observed that N2 CV was systematically larger than 133Xe bolus CV (Xe CV) [N2 CV %vital capacity (VC) = 35 +/- 2.3 (SE) vs. Xe CV %VC = 24 +/- 2.2, P less than 0.01]. Because the regional RV in the dog is evenly distributed throughout the lung and all airways closed at RV, N2 CV is related to the regional distribution of the tracheal N2; differences between N2 and Xe CV could then be related to the size of the inhaled dead space. Simultaneous measurements of Xe and N2 CV were performed at various sites of Xe bolus injection while the regional distribution of the bolus was measured. Injections at the level of the carina increased Xe CV to a value (30 +/- 1.4%VC) near simultaneous N2 CV (32 +/- 1.5%VC) and increased the unevenness of regional distribution of the Xe bolus. The difference between N2 and Xe CV is then the result of the size of the inspired tracheal dead space. Moreover, comparisons between different values of Xe CV require injections of the boluses at the same distance from the carina.

Animals↗

PubMed1990

Relationships among luteoviruses based on nucleic acid hybridization and serological studies.

The luteoviruses barley yellow dwarf virus (BYDV-PAV and BYDV-RPV), bean leaf roll virus (BLRV) beet western yellows virus (BWYV), carrot red leaf virus, potato leaf roll virus, and soybean dwarf virus (SDV) were compared by hybridization with random cDNA probes and serologically with polyclonal antisera. For hybridizations, filters had each RNA blotted in duplicate dots at 10 ng/dot. Random-primed cDNA probes were prepared from 300 ng of each RNA and used to probe filters at three levels of stringency. Homologies were observed between BLRV and SDV and between BWYV and BYDV-RPV at the lowest level of stringency (Tm-38). In double-antibody sandwich enzyme-linked immunosorbent assay using polyclonal antisera, two-way relationships were observed between BWYV and BYDV-RPV. In indirect enzyme-linked immunosorbent assay, where purified virus denatured in pH 9.6 carbonate buffer was coated directly onto microtiter plates, relationships between members of the luteoviruses were much more extensive. BLRV, BWYV, BYDV-PAV, carrot red leaf virus, potato leaf roll virus, and SDV antisera reacted with each of the six luteoviruses tested in the indirect test, while the BYDV-RPV antiserum reacted only with BYDV-RPV, BWYV, and BLRV. BWYV and BYDV-RPV are closely related in both tests and should be considered strains of one virus.

Antibodies, Viral↗

PubMed1990

Penetrating iliac vascular injuries: recent experience with 233 consecutive patients.

During a recent 11-year period, 233 consecutive patients with 358 penetrating iliac vascular injuries were treated at our institution. Injuries of the common and external iliac arteries were most often repaired with lateral suture (31%) although several other techniques were also employed. Lateral suture and ligation were used with nearly equal frequency in the management of venous injuries. The hospital mortality rate for the series was 28%, and 56/66 deaths (85%) were due to exsanguination or shock. One patient, initially treated with an end-to-end anastomosis of the iliac artery, died a year after discharge from a ruptured false aneurysm. Two patients treated with lateral suture of venous injuries died of pulmonary embolism. Arterial complications occurred in 15% of patients with arterial injuries and three patients required amputation. No graft infections occurred in 16 patients treated with PTFE interpositions, including four with associated colorectal injuries. Venous complications occurred in 12% of patients with venous injuries, and most were noted in those treated with ligation. Four patients treated by venous ligation developed chronic venous insufficiency. The prevention of death from exsanguination is the greatest problem in the management of patients with iliac vascular injuries. Although some late deaths and many complications may be related to the technique of vascular repair, circumstances often prohibit alternative methods. Despite two deaths from pulmonary embolism, insufficient data exist to condemn lateral suture of venous injuries.

Adult↗