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Biomedical subjects

R R Martin

Publications and source records attributed to R R Martin.

At least 19 recordsLinked to original sources
PubMed1992

Population pharmacokinetic analysis of didanosine (2',3'-dideoxyinosine) plasma concentrations obtained in phase I clinical trials in patients with AIDS or AIDS-related complex.

Plasma didanosine concentration data from 36 patients receiving once-a-day therapy and from 33 patients receiving twice-a-day therapy were subject to population pharmacokinetic analysis with the computer program NONMEM. Once- or twice-a-day regimens of didanosine were administered intravenously (i.v.) (dose: 0.8-33 mg/kg) during the first 2 weeks of therapy, and orally (dose: 1.6-66 mg/kg) for the remaining 4 weeks of therapy. Plasma pharmacokinetics were determined after the first and last (steady-state) i.v. and oral doses. Population pharmacokinetic parameters for the combined i.v. and oral steady-state data were (mean [%CV]): systemic clearance, CL, 0.70 (5.2) L/h/kg; central compartment volume, Vc, 0.18 (32) L/kg; steady-state distribution volume, Vdss, 0.84 (6.8) L/kg; first-order absorption rate constant, Ka, 1.3 (9.5) hr-1; and bioavailable fraction, F, 0.34 (8.5). Interindividual variability (omega) was (%CV) 22.3 and 71.0 for CL and Vc, respectively. Intraindividual (residual) variability (sigma) in plasma concentrations (%CV) was 50.2. Body weight, sex, and age did not account for the variability in either CL or Vc, and the use of alternate pharmacokinetic models did not reduce the value of intraindividual variability. Population parameters for the combined i.v. and oral first-dose data were generally similar to those for the steady-state data. The parameters can be used to design dosing regimens in patients using the Bayesian feedback approach.

AIDS-Related Complex↗
PubMed1992

Stuttering and speech naturalness: audio and audiovisual judgments.

Unsophisticated raters, using 9-point interval scales, judged speech naturalness and stuttering severity of recorded stutterer and nonstutterer speech samples. Raters judged separately the audio-only and audiovisual presentations of each sample. For speech naturalness judgments of stutterer samples, raters invariably judged the audiovisual presentation more unnatural than the audio presentation of the same sample; but for the nonstutterer samples, there was no difference between audio and audiovisual naturalness ratings. Stuttering severity ratings did not differ significantly between audio and audiovisual presentations of the same samples. Rater reliability, interrater agreement, and intrarater agreement for speech naturalness judgments were assessed.

Adult↗
PubMed1992

Abbreviated laparotomy and planned reoperation for critically injured patients.

The triad of hypothermia, acidosis, and coagulopathy in critically injured patients is a vicious cycle that, if uninterrupted, is rapidly fatal. During the past 7.5 years, 200 patients were treated with unorthodox techniques to abruptly terminate the laparotomy and break the cycle. One hundred seventy patients (85%) suffered penetrating injuries and 30 (15%) were victims of blunt trauma. The mean Revised Trauma Score, Injury Severity Score, and Trauma Index Severity Score age combination index predicted survival were 5.06%, 33.2%, and 57%, respectively. Resuscitative thoracotomies were performed in 60 (30%) patients. After major sources of hemorrhage were controlled, the following clinical and laboratory mean values were observed: red cell transfusions--22 units, core temperature--32.1 C, and pH--7.09. Techniques to abbreviate the operation included the ligation of enteric injuries in 34 patients, retained vascular clamps in 13, temporary intravascular shunts in four, packing of diffusely bleeding surfaces in 171, and the use of multiple towel clips to close only the skin of the abdominal wall in 178. Patients then were transported to the surgical intensive care unit for vigorous correction of metabolic derangements and coagulopathies. Ninety-eight patients (49%) survived to undergo planned reoperation (mean delay 48.1 hours), and 66 of 98 (67%) survived to leave the hospital. With the exception of intravascular shunts, there were survivors who were treated by each of the unorthodox techniques. Of 102 patients who died before reoperation 68 (67%) did so within 2 hours of the initial procedure. Logistic regression showed that red cell transfusion rate and pH may be helpful in determining when to consider abbreviated laparotomy. The authors conclude that patients with hypothermia, acidosis, and coagulopathy are at high risk for imminent death, and that prompt termination of laparotomy with the use of the above techniques is a rational approach to an apparently hopeless situation.

Acidosis↗
PubMed1992

Emergency center arteriography.

From 1983 through 1989, 1,882 emergency center arteriograms were performed on 1,802 patients suspected of having peripheral vascular injuries. The most common indication for emergency center arteriography (ECA) was the proximity of an injury to a major vascular structure. This was the only indication in 1,712 injured extremities (91%). There were 1,510 true negative arteriograms, 294 true positives, 7 false negatives, and 14 false positives. Accordingly, the sensitivity was 95.5% and the specificity was 97.7%. The remaining 57 arteriograms were either equivocal or technically inadequate. Further evaluation of these patients uncovered an additional 11 vascular injuries. Operative intervention was required for 196 (64.3%) injuries detected by emergency arteriography. The remaining 109 injuries were considered minor and were not repaired. No complications developed in 91 patients (88%) with minor vascular injuries who were available for a mean follow-up duration of 12 months. One thousand forty-eight patients (69.4%) with negative arteriograms were followed for a mean of 18 months, and no vascular complications were noted. Emergency center arteriography is a rapid, accurate, and cost-effective technique. It is of particular value in detecting the presence of occult arterial injuries when proximity of a major vascular structure is the sole indication for arteriography. When formal arteriographic support is either unavailable or time consuming, ECA is recommended.

Adolescent↗
PubMed1992

Prospective evaluation of preoperative fluid resuscitation in hypotensive patients with penetrating truncal injury: a preliminary report.

Although intravenous (IV) fluid therapy is routinely prescribed for hypotensive injury victims, there are concerns that elevating the blood pressure before hemorrhage is controlled may be detrimental. This is a preliminary report of an ongoing randomized study designed to evaluate the effect fluid resuscitation, delayed until surgical intervention, has on the outcome for hypotensive victims of penetrating truncal injury. In the first year, 300 consecutive patients with gunshot or stab wounds to the trunk who had a systolic blood pressure of 90 mm Hg or less were entered into the study. Patients were excluded from the outcome analysis because of death at the scene or minor injury not requiring surgical intervention. The remaining study patients were randomized into (1) an immediate resuscitation group (n = 96) for whom IV fluid resuscitation was initiated in the ambulance and in the emergency center before surgical intervention, or (2) a delayed resuscitation group (n = 81) for whom IV fluid resuscitation was delayed until the time of surgical intervention. The two study groups were found to be well balanced with respect to anatomic injury severity, pretreatment vital signs, survival probability, and preoperative treatment times. There were no significant differences in the rate of survival to hospital discharge (immediate resuscitation group, 56%; delayed resuscitation group, 69%). There were no significant differences in the rate of postoperative complications. Further study is necessary to determine if it is advantageous to delay fluid resuscitation until surgical intervention.

Abdominal Injuries↗
PubMed1992

The nucleotide sequence and genome organization of strawberry mild yellow edge-associated potexvirus.

The nucleotide sequence (5966 nucleotides) of cDNA clones of strawberry mild yellow edge-associated potexvirus was determined. The genome contains six open reading frames (ORFs) encoding putative proteins with Mrs of 149,423, 25,344, 11,576, 8079, 25,714 and 11,216. In the first three putative proteins and the coat protein considerable similarity was found to comparable polypeptides of the potexviruses potato virus X, clover yellow mosaic virus, narcissus mosaic virus, papaya mosaic virus, white clover mosaic virus and lily virus X.

Amino Acid Sequence↗
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↗