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Biomedical subjects

R R Martin

Publications and source records attributed to R R Martin.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Nucleotide sequence of the carlavirus associated with blueberry scorch and similar diseases.

We have synthesized and mapped a library of cDNA clones representing the RNA genome of a strain of blueberry scorch carlavirus (BBScV) associated with a disease known locally, in New Jersey, U.S.A., as Sheep Pen Hill disease. The nucleotide sequence of that strain was determined to be 8514 residues, excluding the poly(A) tail. In addition, cDNA clones representing the 3' terminus of another strain of the virus from the same field were synthesized, mapped and sequenced. The overall identity between sequences of these two strains was approximately 90% spanning the 1634 residue overlap, confirming their identity as distinct strains and not simply different isolates of a single strain. Finally, the coat protein gene of a distinct strain of the virus, isolated from plants with blueberry scorch disease in the Puyallup Valley in Washington State, U.S.A., was cloned from total cDNA by PCR. Sequence analysis revealed that the strain from Washington was more divergent from the two New Jersey strains than they were from each other. Comparisons of these sequences with other carlavirus sequences indicated that BBScV is more closely related to lily symptomless virus and potato virus S than to potato virus M, Helenium virus S, carnation latent virus or poplar mosaic virus. BBScV and potato virus M shared approximately 54% nucleotide sequence identity overall.

Amino Acid Sequence↗

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↗

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↗

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↗

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↗

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↗

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↗