Search PubMed⌕ Search

Biomedical subjects

R R Martin

Publications and source records attributed to R R Martin.

At least 19 recordsLinked to original sources
PubMed2000

Trazodone-induced hepatotoxicity: a case report with comments on drug-induced hepatotoxicity.

Trazodone (Desyrel) is a second-generation, nontricyclic antidepressant that has been in use in North America since the early 1980s. It has the advantage of being more sedating and having less anticholinergic side effects than other secondary amines in the piperazine class, namely, desipramine and nortriptyline. Five previous cases of trazodone hepatotoxicity have been reported in the literature, one describing chronic damage and the others, more acute cellular and cholestatic injury. We describe a case of acute reversible liver injury with the use of trazodone. This case is unique in that injury occurred after protracted (18 months) drug use and while the patient was on corticosteroids. Moreover, the diagnosis was confirmed by an inadvertent challenge with trazodone. This case reports not only a well documented instance of trazodone-induced liver injury, but also serves as a basis for a brief discussion of mechanisms, clinical monitoring, and therapy in drug-induced hepatotoxicity.

Adult↗
PubMed1999

Pharmacokinetics and tolerability of intravenous trecovirsen (GEM 91), an antisense phosphorothioate oligonucleotide, in HIV-positive subjects.

Trecovirsen, a 25-mer antisense phosphorothioate oligonucleotide targeted at the gag site of the HIV gene, was administered to HIV-positive volunteers as an i.v. infusion. Single doses ranged from 0.1 to 2.5 mg/kg in an ascending escalation in cohorts of 6 to 12 subjects. Plasma trecovirsen concentrations and pharmacokinetic parameters could be assessed at doses > or = 0.3 mg/kg. Peak plasma concentrations and AUC values increased disproportionately with increasing dose while elimination half-life increased and plasma clearance decreased, indicating a saturable process over this dose range. The only significant adverse event observed was an isolated, transitory increase in activated partial thromboplastin time at doses > or = 2.0 mg/kg that was related to plasma trecovirsen concentrations and is attributed to the polyanionic character of the molecule. Thus, trecovirsen administration was well tolerated in single i.v. doses up to 2.5 mg/kg.

Adult↗
PubMed1998

Isolation and stability of histidine-tagged proteins produced in plants via potyvirus gene vectors.

A system for the expression and purification of histidine-tagged proteins from plants has been developed using a tobacco etch potyvirus (TEV)-derived gene vectors. The vectors offered a convenient polylinker and a choice of histidine tagging at the recombinant proteins' N or C termini. These vectors were utilized for expression of proteins encoded by beet yellows closterovirus (BYV). Approximately 4 micrograms/g of 20-kDa BYV protein was readily isolated from plants systemically infected by hybrid TEV. In contrast, only minute quantities of 22-kDa BYV capsid protein (CP) histidine-tagged at its N or C terminus could be purified. Rapid degradation of the recombinant CP has been implicated in its failure to accumulate in infected plants. Fusion with TEV HC-Pro stabilized the histidine-tagged BYV CP and facilitated purification of the fusion product from infected plants. This same fusion approach was successfully used with the 24-kDa minor BYV CP. The recombinant proteins were recognized by histidine-tag-specific monoclonal antibody in immunoblot analysis. These results demonstrate the utility of a designed series of TEV vectors for expression, detection, and purification of the recombinant proteins and suggest that intrinsic protein stability is a major factor in a recovery of recombinant proteins from plants.

Amino Acid Sequence↗
PubMed1998

Transfusion of phosphoenolpyruvate-treated blood increases oxygen consumption in acute hemorrhage.

BACKGROUND: Incubating blood with phosphoenolpyruvate decreases hemoglobin oxygen affinity (HOA). This study compared transfusion with phosphoenolpyruvate-treated blood and conventionally stored blood on oxygen consumption in acutely anemic dogs. METHODS: Dogs underwent isovolemic hemodilution (hematocrit = 10%). After 1 hour they were transfused to a hematocrit of 18% with control or phosphoenolpyruvate treated blood. Cardiac output, co-oxymetry, and hemoglobin P50 measurements allowed calculation of oxygen consumption during anemia, and posttransfusion. RESULTS: Hemodilution doubled cardiac output. Transfusion with phosphoenolpyruvate-treated blood allowed greater O2 consumption than control (8.31+/-2.1 and 3.73+/-0.11 cc/kg/mm). There were no differences in arterial or venous PO2 or pH; there were marked differences in HOA, measured by posttransfusion P50 (21+/-3 versus 47+/-4), and mixed venous O2 saturation. CONCLUSIONS: Decreased HOA results in increased O2 consumption in dogs subjected to anemic hypoxia. Phosphoenolpyruvate-treated blood provides increased oxygen consumption at a similar hematocrit when compared with untreated banked blood.

Acute Disease↗
PubMed1998

Potyvirus genome-linked protein (VPg) determines pea seed-borne mosaic virus pathotype-specific virulence in Pisum sativum.

The mechanism of Pisum sativum pathotype-specific resistance to pea seed-borne mosaic potyvirus (PSbMV) was investigated and the coding region determinant of PSbMV virulence was defined. Homozygous recessive sbm-1 peas are unable to support replication of PSbMV pathotype 1 (P-1), whereas biochemically and serologically related pathotype 4 (P-4) is fully infectious in the sbm-1/sbm-1 genotype. We were unable to detect viral coat protein or RNA with double antibody sandwich-enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction in sbm-1/sbm-1 P-1-inoculated protoplasts and plants. Lack of viral coat protein or RNA in P-1 transfected sbm-1/sbm-1 protoplasts suggests that sbm-1 resistance is occurring at the cellular level and that inhibition of cell-to-cell virus movement is not the operating form of resistance. In addition, because virus products were not detected at any time post-inoculation, resistance must either be constitutive or expressed very early in the virus infection process. P-1-resistant peas challenged with full-length, infectious P-1/P-4 recombinant clones demonstrated that a specific P-4 coding region, the 21-kDa, genome-linked protein (VPg), was capable of overcoming sbm-1 resistance, whereas clones containing the P-1 VPg coding region were noninfectious to sbm-1/sbm-1 peas. VPg is believed to be involved in potyvirus replication and its identification as the PSbMV determinant of infectivity in sbm-1/sbm-1 peas is consistent with disruption of an early P-1 replication event.

Amino Acid Sequence↗
PubMed1998

Isolation of tobacco necrosis virus from strawberry leaves in the Czech Republic.

Leaves of symptomless Fragaria ananassa Duch cv. Cacanská raná were grafted onto Fragaria vesca indicator clones. Thirty-five of 72 grafted indicator plants developed leaf mottle symptoms. Isometric virus-like particles were observed in purified preparations from symptomatic leaves of F. vesca. The latter were mechanically inoculated to herbaceous host plants. A virus was successfully purified from Nicotiana occidentalis 37 B symptomatic plants by differential and sucrose density gradient centrifugations and a polyclonal antiserum to the virus was prepared. On the basis of serological reactions, symptomatology on herbaceous hosts and electron microscopy studies the virus was identified as tobacco necrosis virus (TNV) D-strain. This is the first isolation of TNV from strawberry leaves and its first finding on strawberry in the Czech Republic. The new experimental hosts N. aucalis, N. bentamiana, N. occidentalis 37 B (systemic hosts), and Ammobium alatum, N. bigelovi, Petunia hybrida (local hosts) for TNV are reported. These results may not exclude the presence of strawberry mottle virus as a causal agent of mottle symptoms in the tested plant samples. Further research is necessary to clarify the aetiology of the strawberry mottle.

Animals↗
PubMed1998

[Quebec spirometry reference values].

Lung volumes forced expiratory flow rates and carbon monoxide diffusing capacity (apnea) were measured in 397 non-smoking, nonatopic, asymptomatic subjects (219 women, 178 men). The equipments and methods for measurements met the ATS criteria. The linear regression of the different variables according to age and height allowed the elaboration of a new set of predictive equations (Quebec). When comparing the different reference values used in North America and Europe, it is found that those of Miller and associates as well as those recommended by the CECA provide the best description of the Quebec situation. However, we would eventually prefer the reference values of Miller and associates over those of the CECA, because they better fit the current ATS criteria and also provide references for smokers. Lung volumes and forced expiratory flow rates of 97 non-smoking, nonatopic, asymptomatic manual workers were measured in the same conditions and submitted to the same comparisons. Quebec predictive values as well as those of Miller and associates isolated the same individuals in the so called abnormal zone. We therefore conclude that Quebec's standards should be preferred in the Province of Quebec pulmonary function laboratories.

Adult↗
PubMed1997

Suppression of potyvirus infection by coexpressed closterovirus protein.

A tobacco etch virus (TEV)-based expression vector has been used for insertion of several ORFs derived from the unrelated beet yellows virus (BYV). Hybrid TEV variants expressing the BYV capsid protein, 20-kDa protein, or HSP70 homolog systemically infected Nicotiana tabacum and stably retained BYV sequences. In contrast, insertion of the ORF encoding BYV leader proteinase (L-Pro) resulted in severely impaired systemic transport and accumulation of recombinant TEV. Progeny of this virus underwent various deletions affecting the L-Pro sequence and mitigating the defects in virus spread. Model experiments involving several spontaneous and engineered mutants indicated that the central domain of BYV L-Pro was responsible for the defect in hybrid virus accumulation, whereas full-size L-Pro was required for maximal debilitation of systemic transport. Strikingly, BYV L-Pro expression did not debilitate systemic infection of hybrid TEV in Nicotiana benthamiana plants. No major defects in replication or encapsidation of recombinant RNA were revealed in N. tabacum protoplasts. These results indicated that BYV L-Pro specifically interfered with TEV systemic transport and accumulation in a host-dependent manner and suggested a potential utility of closterovirus L-Pro as an inhibitor of potyvirus infection. In addition, it was demonstrated that the 107-amino-acid-residues-long N-terminal part of the TEV helper component proteinase is not essential for systemic infection.

Closterovirus↗
PubMed1997

Evaluation of diagnostic peritoneal lavage in stable patients with gunshot wounds to the abdomen.

BACKGROUND: Diagnostic peritoneal lavage (DPL) is used to diagnose intra-abdominal injury in patients with stab wounds and blunt trauma. Because exploratory celiotomy is routinely performed on patients with gunshot wounds to the abdomen, DPL is rarely employed. However, several studies have questioned routine exploration and have drawn attention to the associated morbidity of negative celiotomy. Diagnostic peritoneal lavage is an easily performed and inexpensive test that may be useful in this situation. OBJECTIVE: To evaluate the performance of DPL in the diagnosis of intra-abdominal injury in hemodynamically stable patients with gunshot wounds to the abdomen. DESIGN: A prospective clinical trial. SETTING: Two urban trauma centers. PATIENTS: Patients with gunshot wounds to the abdomen and a systolic blood pressure of at least 90 mm Hg. INTERVENTIONS: Clinical predication of intra-abdominal injury in the emergency department and DPL performed in the operating room before the initiation of celiotomy. Injuries found during the celiotomy were recorded. MAIN OUTCOME MEASURES: The results of the clinical evaluation and DPL were compared with the findings of the celiotomy. RESULTS: Forty-four patients were enrolled into the study. Intra-abdominal injury was present in 32 (73%) of these patients. The senior surgery resident correctly predicted the presence of intra-abdominal injury in 36 (82%) of the patients (sensitivity = 90.0%, specificity = 58.3%, positive predictive value = 85.3%, negative predictive value = 63.6%, phi = 0.52, P < .01) in the emergency department before DPL and celiotomy were performed. Diagnostic peritoneal lavage correctly identified the presence or absence of intra-abdominal injury in 40 (91%) of the patients (positive predictive value = 96.7%, negative predictive value = 78.6%, phi = 0.79, P < .01). CONCLUSIONS: Clinical judgment is highly accurate in separating patients with tangential gunshot wounds to the abdomen from those with intra-abdominal injury but may miss patients with intra-abdominal hemorrhage. Diagnostic peritoneal lavage is highly predictive of the presence of intra-abdominal injury. The return of gross blood on aspiration or a lavage red blood cell count greater than 10 x 10(9)/L should prompt an urgent celiotomy. Missed injuries are rare and most likely to be bowel perforations. Diagnostic peritoneal lavage is an objective test that may augment clinical judgment in selecting hemodynamically stable patients with potential tangential gunshot wounds for observation and is especially useful in identifying intra-abdominal hemorrhage.

Abdomen↗
PubMed1997

Comparison of preoperative endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy with operative management of gallstone pancreatitis.

BACKGROUND: Preoperative endoscopic retrograde cholangiopancreatography (ERCP) with laparoscopic cholecystectomy (ERCP/LC) should reduce hospital stay when compared with laparoscopic cholecystectomy/intraoperative cholangiogram (LC/IOC) and selective common bile duct exploration (CBDE). METHOD: Retrospective review of 82 patients with gallstone pancreatitis. RESULTS: Thirty-one patients had preoperative ERCP/LC and 51 patients underwent LC/IOC. Nineteen percent in the ERCP/LC group developed postprocedure pancreatitis. The presence of choledocholithiasis was associated with an increased incidence of post-ERCP pancreatitis (38%) and an increased length of stay ([LOS] 24 versus 10 days). The development of post-ERCP pancreatitis markedly increased LOS to 30 days. Six percent in the LC/IOC group developed postoperative pancreatitis. The mean LOS was 10.1 days. Open CBDE increased the LOS to 14.5 days. Postoperative pancreatitis increased the LOS to 23 days. The LOS of patients with choledocholithiasis who underwent uncomplicated ERCP/ES or LC/IOC with open CBDE was similar. CONCLUSIONS: The development of postprocedure pancreatitis is a more important determinant of hospital stay than an open operative procedure. LC/IOC with its lower incidence of postprocedure pancreatitis resulted in a shorter hospital LOS even when open CBDE was performed.

Cholangiography↗
PubMed1997

Postoperative care and complications of damage control surgery.

Damage control procedures are being used with increasing frequency as the physiologic limits of the surgical patient are approached and recognized. These patients are returned to the SICU, where rapid restoration of circulating volume, normothermia, maintenance of oxygen delivery, and correction of transfusion-associated coagulopathy are essential to the success of the technique, which requires expeditious reoperation and completion of definitive surgical management. The potential need for early return to the operating room to control surgical bleeding must be recognized, as well as the difficulty in distinguishing between surgical bleeding and ongoing hemorrhage due to hypothermia and coagulopathy. Because the damage control technique is resource intensive and involves numerous personnel, organization and leadership are important to success.

Hemostatic Techniques↗
PubMed1995

Pharmacokinetics of an anti-human immunodeficiency virus antisense oligodeoxynucleotide phosphorothioate (GEM 91) in HIV-infected subjects.

Human pharmacokinetics of an antisense oligodeoxynucleotide phosphorothioate (GEM 91) developed as an anti-human immunodeficiency virus (HIV) agent was carried out in this study. 35S-Labeled GEM 91 was administered to six HIV-infected individuals by means of 2-hour intravenous infusions at a dose of 0.1 mg/kg. Plasma disappearance curves for GEM 91-derived radioactivity could be described by the sum of two exponentials, with half-life values of 0.18 +/- 0.04 and 26.71 +/- 1.67 hours. The radioactivity in plasma was further evaluated by polyacrylamide gel electrophoresis, showing the presence of both intact GEM 91 and lower molecular weight metabolites. Urinary excretion represented the major pathway of elimination, with 49.15% +/- 6.80% of the administered dose excreted within 24 hours and 70.37% +/- 6.72% over 96 hours after dosing. The radioactivity in urine was associated with lower molecular weight metabolites. No drug-related toxicity was observed.

Adult↗
PubMed1995

Design and implementation of the stavudine parallel-track program.

In a randomized, double-blind, large, simple trial, the safety and efficacy of two weight-adjusted dose levels of stavudine were evaluated in patients with advanced human immunodeficiency virus (HIV) infection. All patients were refractory to or intolerant of both zidovudine and didanosine. Patients weighing > or = 60 kg received 20 or 40 mg of stavudine twice daily. The dose was reduced to 15 or 30 mg for patients weighing 40-59 kg and to 10 or 20 mg for those weighing < 40 kg. The primary efficacy end points were survival and time to clinical progression of HIV disease. The primary safety end point was time to dose-limiting neuropathy. A total of 8127 patients were enrolled as of 31 July 1993. Although many patients who might have benefitted from stavudine were reached by the parallel-track program, a review of demographic data revealed disproportionate representation by white men from large metropolitan areas on both coasts.

Adult↗
PubMed1994

Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries.

BACKGROUND: Fluid resuscitation may be detrimental when given before bleeding is controlled in patients with trauma. The purpose of this study was to determine the effects of delaying fluid resuscitation until the time of operative intervention in hypotensive patients with penetrating injuries to the torso. METHODS: We conducted a prospective trial comparing immediate and delayed fluid resuscitation in 598 adults with penetrating torso injuries who presented with a pre-hospital systolic blood pressure of < or = 90 mm Hg. The study setting was a city with a single centralized system of pre-hospital emergency care and a single receiving facility for patients with major trauma. Patients assigned to the immediate-resuscitation group received standard fluid resuscitation before they reached the hospital and in the trauma center, and those assigned to the delayed-resuscitation group received intravenous cannulation but no fluid resuscitation until they reached the operating room. RESULTS: Among the 289 patients who received delayed fluid resuscitation, 203 (70 percent) survived and were discharged from the hospital, as compared with 193 of the 309 patients (62 percent) who received immediate fluid resuscitation (P = 0.04). The mean estimated intraoperative blood loss was similar in the two groups. Among the 238 patients in the delayed-resuscitation group who survived to the postoperative period, 55 (23 percent) had one or more complications (adult respiratory distress syndrome, sepsis syndrome, acute renal failure, coagulopathy, wound infection, and pneumonia), as compared with 69 of the 227 patients (30 percent) in the immediate-resuscitation group (P = 0.08). The duration of hospitalization was shorter in the delayed-resuscitation group. CONCLUSIONS: For hypotensive patients with penetrating torso injuries, delay of aggressive fluid resuscitation until operative intervention improves the outcome.

Abdominal Injuries↗
PubMed1994

Roentgenographic evaluation of the cervical spine. A selective approach.

BACKGROUND: To determine if routine radiographic evaluation of the cervical spine could be eliminated in the alert, sober trauma patient who has no neck pain, tenderness, or other major injuries without a significant increase in missed occult injury. DESIGN: Prospective cohort study. SETTING: Emergency department and general surgery service at a military tertiary medical center. MAIN OUTCOME MEASURE: Those patients with cervical spine injuries. RESULTS: Sixteen patients (2%) had cervical spine injuries, all had signs and/or symptoms of their injury on presentation. Ninety-six patients (14%) who were not intoxicated and had no neck pain, tenderness, or other major injuries were evaluated. None of these patients had abnormal cervical spine studies. Two hundred ninety patients (43%) were followed up between 30 to 150 days. No missed injuries were noted. CONCLUSIONS: These results indicate that blunt trauma patients may not require cervical spine roentgenography if they meet the following criteria: absence of mental status changes, intoxication, neck pain or tenderness, neurologic signs or symptoms, or simultaneous major distracting injury. Because of the small incidence of cervical spine injuries, further studies are necessary to evaluate the positive predictive value of history and physical examination of the cervical spine in a trauma patient.

Alcoholic Intoxication↗
PubMed1994

Psychophysical analysis of audiovisual judgments of speech naturalness of nonstutterers and stutterers.

The purpose of this study was to determine through psychophysical comparison of scaling data whether speech naturalness judgments of stutterers and nonstutterers from audiovisual recordings form a prothetic or a metathetic continuum. Comparison of direct magnitude estimation and equal-appearing interval scale data indicated that speech naturalness forms a metathetic continuum when observers judge audiovisual recordings, suggesting that either scaling procedure is valid for the quantification of this dimension. Ease of use, an existing body of comparative data from different clinics, and somewhat better reliability favor the interval scaling procedure.

Humans↗
PubMed1994

Analysis of potential risk factors associated with the development of pancreatitis in phase I patients with AIDS or AIDS-related complex receiving didanosine.

Phase I dose-escalating trials of didanosine revealed dose-limiting toxicities, including pancreatitis, and established a total daily dose of 12.5 mg/kg/day as the maximum tolerated dose. Clinical and pharmacokinetic data of 61 patients from two trials were analyzed to further evaluate the risk of pancreatitis: 1 (6.3%) of 16 patients who received < 500 mg/day didanosine, 2 (13.3%) of 15 who received 500-750 mg/day, and 15 (50%) of 30 who received > 750 mg/day developed pancreatitis (P < .001). A relationship between risk of pancreatitis and steady-state plasma concentrations of didanosine and age was also observed, suggesting that knowledge of didanosine pharmacokinetics provided additional information regarding risk of toxicity. Further confirmation of these findings will be necessary to determine if the risk factors for pancreatitis remain the same at lower doses currently used.

AIDS-Related Complex↗