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Biomedical subjects

R S Smith

Publications and source records attributed to R S Smith.

At least 19 recordsLinked to original sources
PubMed1996

Direct current shocks to the heart generate free radicals: an electron paramagnetic resonance study.

OBJECTIVES: We sought to demonstrate that direct current (DC) shocks to the heart generate free radicals. BACKGROUND: Although it is a lifesaving maneuver, defibrillation is known to have myocardial toxicity. The mechanism of this toxicity is unknown. If DC shocks generate free radicals, free radicals could be a mechanism of myocardial injury. METHODS: In a canine model, DC shocks of 10 to 100 J were delivered to the epicardium of both beating and fibrillating hearts, and 200-J transthoracic shocks were administered in dogs with beating hearts. Ascorbate free radical (AFR) concentration was measured in arterial blood and blood continuously withdrawn from the coronary sinus. In some dogs, the antioxidant enzymes superoxide dismutase (15,000 U/kg) and catalase (55,000 U/kg) (SOD/Cat) were administered before shocks. RESULTS: Ascorbate free radicals were generated by DC shocks. A peak AFR increase of 14 +/- 2% (mean +/- SEM) was seen 5 to 6 min after 100-J epicardial shocks. A peak AFR increase of 7 +/- 5% occurred after transthoracic shocks. There was a significant linear relation between the shock energy and peak percent AFR increase: %AFR increase = 0.18 (Shock energy) + 2.9 (r = 0.73, p < 0.0001). Shocks delivered to hearts in ventricular fibrillation (30 s) resulted in generation of AFR equal to but not greater than that observed during similar shocks delivered to beating hearts in sinus rhythm. Multiple successive shocks (100 J delivered twice or five times) did not result in a greater AFR increase than single 100-J shocks, indicating that peak, not cumulative, energy is the principal determinant of AFR increase. Animals receiving SOD/Cat before shock administration showed significant attenuation of the AFR increase. CONCLUSIONS: Direct current epicardial and transthoracic shocks generate free radicals; antioxidant enzymes reduce the free radical generation by shocks.

Animals↗
PubMed1996

Chromosomal localization of a new mouse lens opacity gene (lop18)

Examination of mouse strains with a slit lamp and indirect ophthalmoscopy revealed that strain CBA/CaGnLe has a white cataract obvious at weaning age. It soon progresses to a large white nuclear cataract with mild cortical changes. Crosses with C57BL/6J showed that this is inherited as a single recessive fully penetrant gene, which we have designated lop18 (lens opacity 18). Linkage analysis using visible marker T (brachyury), histocompatibility marker H2, and microsatellite markers D17Mit21, D17Mit28, D17Mit38, and D17Mit46 shows that the lop18 gene is located, approximately 16 cM from the centromere on mouse Chromosome 17. It is a likely candidate mutation for the alpha-crystallin (Crya1) gene.

Animals↗
PubMed1996

Analysis of hypermutation in immunoglobulin heavy chain passenger transgenes.

Somatic hypermutation of immunoglobulin (Ig) genes plays a critical role in the maturation of the human antibody response. The molecular basis of this important process is, however, unknown. To identify cis-acting sequences that initiate and target hypermutation, we have made three minitransgenes containing different portions of an Ig heavy chain (IgH) locus. Each transgene is a passenger, bearing a nonsense mutation preventing its translation; thus, transgene mutations reflect the endogenous mutational process and are not subject to affinity selection. To study transgenes after their circulation through the compartment associated with hypermutation in vivo, we rescued B cells as hybridomas after hyperimmunizing mice with the hapten 4-hydroxy-3-nitrophenyl acetyl (NP). Hybridoma transgene and endogenous variable regions were amplified by polymerase chain reaction, subcloned, and sequenced. Endogenous anti-NP VDJ regions show the expected, at times extensive degree of base substitution. In mice bearing the smallest construct, which includes 2.4 kb of 5' IgH sequences, a rearranged VDJ region, the 5' matrix attachment region, and the intron enhancer, one of four evaluable hybridomas demonstrates two base substitutions in the V segment of one transgene copy. The two larger constructs include additional 3' IgH sequences (an alpha constant region and the 3' enhancer) and either the original VDJ segment or a substituted T cell receptor beta segment. Ten hybridomas derived from mice bearing these larger constructs demonstrate no evidence of targeted mutation, despite demonstrable transgene transcription in all hybridomas. In our system, mutation of a rearranged VDJ segment and surrounding promoter/enhancer regions is not increased by the juxtaposition of a constant region segment and the IgH 3' enhancer.

Animals↗
PubMed1996

Videothoracoscopy an effective method for evaluating and managing thoracic trauma patients.

BACKGROUND: The objective of this study was to assess the diagnostic and therapeutic effectiveness of videothoracoscopy in thoracic trauma patients. METHODS: The design was a retrospective review. The setting was a major trauma center at an urban county hospital. Forty-one hemodynamically stable patients sustaining thoracic trauma were reviewed (34 penetrating and 7 blunt injuries). In the acute setting (< 24 h), videothoracoscopy was used for continued bleeding(6) and suspected diaphragmatic injury(17). Thoracoscopy was used in delayed settings (> 24 h) for treatment of thoracic trauma complications(18) including clotted hemothorax(14), persistent air leak(1), widened mediastinum(1), and suspected diaphragmatic injury(2). RESULTS: The average Injury Severity Score (ISS) of these patients was 18.9 +/- 10.0. Three of 6 patients (50%) with continued bleeding were successfully treated thoracoscopically. Nine of 10 (90%) diaphragmatic injuries were confirmed by thoracoscopy, and 7 of these 9 patients (77%) were repaired thoracoscopically. Thirteen of 14 patients (93%) with clotted hemothoraces and one with a persistent air leak were treated successfully using thoracoscopy. An aortic injury was ruled out in one patient. CONCLUSIONS: Videothoracoscopy is a safe, accurate, minimally invasive, and potentially cost-effective method for the diagnosis and therapeutic management of thoracic trauma patients.

Adolescent↗
PubMed1996

The significance of ultrasonographically diagnosed fetal wrist position anomalies.

OBJECTIVE: Our purpose was to determine the clinical significance of ultrasonographically diagnosed fetal wrist position anomalies. STUDY DESIGN: The relationship of the fetal hand to the forearm was prospectively evaluated in all second- and third-trimester scans over a 5-year period. If an abnormal wrist position was detected, a targeted scan, including echocardiography, was performed. The outcomes of abnormal pregnancies were obtained. RESULTS: An abnormal relationship of the hand to the forearm was found in 22 fetuses in 27,467 scans. Nine had a normal karyotype, and 13 had an abnormal karyotype. Among the nine with normal chromosomes, three had evidence of a movement disorder. Three with normal karyotypes are alive; two of these are the only normally functioning survivors. They had no other major anomalies and were shown prenatally to have normal movement of the limbs. CONCLUSIONS: An abnormal fetal wrist position is associated with a high incidence of karyotype and movement abnormalities.

Chromosome Aberrations↗
PubMed1996

Corn1: a mouse model for corneal surface disease and neovascularization.

PURPOSE: To describe a new mouse model of corneal surface disease and neovascularization. METHODS: Anatomic changes were demonstrated in corn1 and control A.By/SnJ mice from day 10 of gestation of 8 months of age by routine techniques of light microscopic and scanning electron microscopy. Corneal epithelial cell kinetics were evaluated by labeling cells in the "S" phase of the cell cycle by intraperitoneal injection of tritiated thymidine. Labeled cells were counted under 250X magnification, and the length of the corneal epithelial chord was measured by morphometric techniques. Results were expressed as labeled cells per linear millimeter of corneal epithelium. The corn1 locus was mapped using selected back-crosses. RESULTS: Corn1 is characterized by early, irregular thickening of the corneal epithelium, development of stromal neovascularization by 20 days of age, and cataract by 48 days of age. Corneal epithelial cell kinetics demonstrated prominent labelling of corn1 mice at 30 days of age compared to the control mice. Corn1 behaves as an autosomal recessive gene and is located on mouse chromosome 2, approximately 5.2 cM from the agouti locus. Heterozygotes have no corneal disease. CONCLUSIONS: Corn1 mice, with genetically determined corneal epithelial hyperplasia and stromal neovascularization, may be particularly useful in studies of neovascularization and corneal surface proliferative disease.

Animals↗
PubMed1996

Trauma experience of Navy surgeons: assessment and commentary.

Numerous reports have suggested that surgical readiness during Operation Desert Storm was poor. We surveyed active duty Navy surgeons to assess current trauma experience and capability. A survey concerning trauma and critical care experience, as well as self-rating of skills, was mailed to all active duty surgeons (n = 185) in 1993. The response rate was 79% (146/185). A high turnover rate of surgeons was indicated by: (1) 51% (75/146) of surgeons had less than 3 years of experience following residency; and (2) only 42% (61/146) had served in the Gulf War. Only 12% of active duty surgeons (18/146) were involved in trauma care. Only 10% (14/146) had performed more than 20 operations for trauma in the preceding 1 years, and 85% (124/146) had performed fewer than 10 operations. In the preceding 5 years, 84% (122/146) had performed fewer than 100 operations for trauma, and 42% (61/146) had performed none. Critical care experience ranged from 0 to 20 patients per month (mean = 3). Despite limited recent experience, 84% (123/146) of respondents rated their trauma skills as adequate (n = 43), good (n = 49), or excellent (n = 31). We conclude that most Navy surgeons have minimal recent experience in trauma care. A high rate of turnover mandates training strategies that provide an ongoing exposure to injured patients. This could be accomplished by designating military hospitals as trauma centers or by placing military surgeons in civilian trauma centers.

Clinical Competence↗
PubMed1995

Predictive value of fetal serum beta 2-microglobulin for neonatal renal function.

When fetal urinary-tract malformations (UTM) are discovered, management is based on the prediction of postnatal renal function, currently made by fetal urinary biochemistry and sonography. Serum beta 2-microglobulin has been used postnatally to estimate renal function and does not cross the placenta. We investigated the relation between fetal serum beta 2-microglobulin and renal function by comparing 64 unaffected fetuses and 15 fetuses with UTM. A beta 2-microglobulin above a 5.6 mg/L cut-off gave cross-validated sensitivity of 80.0%, specificity of 98.6%, a positive predictive value of 88.9%, and a negative predictive value of 97.1% for our cohort study.

Cohort Studies↗
PubMed1995

Anterograde to retrograde reversal of fast axonal transport within cold blocked and rewarmed intact axons.

The possibility that anterograde to retrograde reversal of axonal transport might take place in mid axon at a site distant from any nerve termination was investigated in sciatic nerve preparations from Xenopus laevis. The nerve, containing a pulse of anterogradely transported protein labeled with [35S]methionine, was kept in a two-compartment temperature controlled chamber. One compartment containing the proximal nerve was maintained at room temperature throughout the duration of an experiment while the second compartment containing the distal nerve, and separated from the first by a thermal barrier, was initially cooled to 3-4 degrees C and later warmed to room temperature. Transport of labeled proteins in the nerve was detected with a position-sensitive detector of ionizing radiation. With the distal portion of the nerve cold, the pulse of labeled protein transported up to the thermal barrier and stopped. When the distal part of the nerve was warmed to room temperature, retrograde and anterograde pulses of label propagated away from the thermal barrier with no time delay. The retrograde pulse could be collected on the distal side of a proximally placed tie and could be eliminated by treatment of the proximal nerve with vinblastine or dinitrophenol. Functional and structural evidence indicated that the cold block and thermal barrier were not destructive to the axons. Electron microscopy showed that the numerical density of axonal microtubules distal to the cold block was decreased about seven fold during the cold treatment and that this decrease could be prevented by 10 mumol/l taxol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Ultrasonographic examination of wound tracts.

OBJECTIVE: To determine if ultrasonography is useful in evaluating penetrating injuries of the trunk to assess whether violation of the peritoneum or pleura has occurred. METHODS: The study group was 29 patients who suffered gunshot (n = 17), stab (n = 10), or shotgun (n = 2) wounds. The abdomen was at risk in 21 injuries, the thorax in eight. The results of physical examination and plain x-rays suggested the pleura and or peritoneum might be intact in all patients. Using a 7-MHz transducer, wound tract(s) were images, looking for the presence of soft-tissue air and/or echolucent areas consistent with soft-tissue blood. Injuries were deemed extraperitoneal or extrapleural if (1) the entire tract was visualized; (2) it appeared superficial to the deepest fascial structure in that area; and (3) in shotgun injuries, all visible pellets on x-ray films were identified by ultrasound in the abdominal wall. RESULTS: Evidence of penetration occurred in four abdominal wounds and one thoracic wound. These were confirmed by operation in the abdominal cases and by subsequent chest x-ray examination in the one thoracic wound. The diagnosis of nonpenetration was confirmed in all the remainder by serial benign abdominal examination (n = 15), chest x-ray examination (n = 8), and laparoscopy (n = 1). Positive and negative predictive accuracy were thus 100% in this pilot series. CONCLUSIONS: Ultrasonographic exploration of penetrating truncal injuries is feasible and accurate. Ultrasonographic wound exploration may serve as a noninvasive and safe replacement for diagnostic laparoscopy, conventional local wound exploration, peritoneal lavage, and 6-hour chest x-rays (repeated chest x-rays taken 6 hours after initial chest x-ray examination). If used as part of the initial physical examination, cost-effectiveness can also be realized.

Humans↗
PubMed1995

Ultrasonographic left cardiac axis deviation: a marker for fetal anomalies.

OBJECTIVE: To determine if a relation exists between left cardiac axis deviation and fetal anomalies. METHODS: Estimation of cardiac axis was attempted prospectively as part of the cardiac examination in approximately 41,500 second- and third-trimester fetuses scanned between 1987-1993. Those with heart axes greater than 75 degrees to the left were considered to have left axis deviation. Only cases with postnatal follow-up were included. RESULTS: Thirty-four fetuses with left cardiac axis deviation had postnatal follow-up; eight were normal and 26 abnormal (positive predictive value 76%). Twenty-one fetuses had cardiac abnormalities (ten of these had additional extracardiac findings), and five had extracardiac findings only. CONCLUSION: Although left cardiac axis deviation can occur as an isolated sonographic finding in an otherwise normal fetus, most cases will demonstrate abnormalities of cardiac and/or extracardiac anatomy. Left cardiac axis deviation is largely associated with cardiac abnormalities, especially conotruncal anomalies, which may not be detectable by a four-chamber view alone. Therefore, the cardiac axis should be examined routinely as part of the four-chamber view of the fetal heart.

Congenital Abnormalities↗
PubMed1995

Tetralogy of Fallot: prenatal diagnosis and postnatal survival.

OBJECTIVES: To correlate prenatal echocardiographic findings with infant outcome in a large screening population affected by tetralogy of Fallot. METHODS: Inclusion criteria required confirmed postnatal cardiac diagnosis, at least one fetal ultrasound examination with satisfactory heart visualization, and infant delivery at our institution. Aortic and pulmonary artery diameters were measured from real-time ultrasound or videotaped scans and compared against published nomograms. The pulmonary artery to aorta ratio was also evaluated in a similar manner. Infant survival was assessed 1 year after delivery. RESULTS: Seventeen fetuses were confirmed to have a ventricular septal defect and an overriding aorta with varying degrees of right ventricular outflow obstruction after delivery. All karyotypes were normal. Ultrasound screening identified 12 of 17 abnormal hearts at a mean gestational age of 22.9 +/- 5.1 weeks; two of these fetuses were thought to have only ventricular septal defect before delivery. Five fetuses had enlarged aortic roots during the initial scan. Only two of the ten fetuses with a measurable pulmonary artery had initial sonographic evidence for valve stenosis. Six other pulmonary arteries became abnormally small with advancing pregnancy. The pulmonary artery to aorta ratio was decreased in six of the ten fetuses with a measurable pulmonary artery. Sixteen infants survived at least 1 year after birth and successfully completed either corrective or palliative cardiac surgery. CONCLUSION: Fetuses with tetralogy of Fallot may present with only a ventricular septal defect and aortic septal override by prenatal ultrasound examination. Pulmonary artery stenosis is not always present at initial ultrasound examination, but this finding can develop or worsen during pregnancy. Furthermore, a normal aortic diameter does not exclude tetralogy of Fallot. Infant survival appears to be favorable in the absence of other major structural or chromosomal anomalies.

Female↗
PubMed1995

The macrophage-T-lymphocyte theory of schizophrenia: additional evidence.

Chronically activated macrophages and T-lymphocytes, along with excessive interleukin-2 and other cytokine secretions, were previously proposed as the fundamental mediators of schizophrenia. This paper provides further support for the immune model of schizophrenia, including evidence on neurotransmitter abnormalities, the low amplitude of the auditory P300 event-related potential, the neurodevelopmental model of schizophrenia and the possible involvement of the locus ceruleus in schizophrenia.

Acetylcholine↗
PubMed1995

Changes in fast axonal transport in sensory neurons during tadpole metamorphosis.

Fast axonal transport of radiolabeled protein was examined in lumbar and tail dorsal root ganglion (DRG) neurons at progressive stages of bullfrog tadpole metamorphosis. Accumulation of [35S]methionine-labeled protein proximal to a lumbar peripheral nerve ligature (at a fixed distance from the DRG) increased as tadpoles advanced from premetamorphosis through prometamorphosis to metamorphic climax. The rate of increase was steeper when expressed as a percentage of protein synthesized in the neurons of origin than when expressed as a percentage of total DRG protein synthesis. Further, the increase was not secondary to a rise in protein synthesis. In contrast, fast axonal transport decreased in DRG neurons of the tail at the onset of metamorphic climax, when tail resorption is initiated. The stage-related increase in protein transport in lumbar nerves is due, at least in part, to an increased rate of transport. As determined from optically detected anterograde organelles in individual lumbar nerve axons, an approximate doubling of the fast transport rate occurred between the premetamorphic stage and metamorphic climax. In addition, the rates of organelle transport in lumbar axons of adult bullfrogs were significantly greater than in corresponding axons of tadpoles at metamorphic climax, further suggesting that organelle velocity is a developmentally regulated parameter of fast axonal transport.

Animals↗
PubMed1995

Therapeutic laparoscopy in trauma.

PURPOSE: To assess the therapeutic potential of emergent laparoscopy in the trauma setting, a retrospective review was performed in a busy urban trauma center. PATIENTS AND METHODS: Between December 1991 and October 1993, 133 hemodynamically stable patients with suspected abdominal injury were evaluated laparoscopically. All laparoscopic procedures were performed in the operating room under general anesthesia. Mechanism of injury was stab wound (58), gunshot wound (57), and blunt trauma (18). No significant injuries were found in 72 patients (54%), and these patients received no further treatment. On the basis of laparoscopic findings, 52 patients underwent formal exploratory laparotomy. Surgical exploration confirmed the presence of significant injuries in 44 of the 52 patients (85%). Therapeutic laparoscopy was performed in 6 patients (5%) for diaphragm repair (4), gastrotomy repair (1), and splenorrhaphy (1). Additionally, 10 patients underwent laparoscopy-guided blood salvage for autotransfusion during laparoscopic evaluation of blunt trauma. Three small-bowel enterotomies were repaired during minilaparotomy. RESULTS: No significant injuries were missed as a result of our use of laparoscopy in trauma assessment. Complications--trocar enterotomy, trocar laceration of the inferior epigastric artery, and transient hypotension--occurred in 3 patients secondary to the use of laparoscopy. CONCLUSIONS: Trauma laparoscopy is a safe method for the evaluation of selected patients with abdominal trauma and can reduce the number of negative and nontherapeutic trauma laparotomies performed. Limited therapeutic intervention is possible in a small number of patients.

Abdominal Injuries↗
PubMed1995

Epstein-Barr virus-induced autoimmune responses. I. Immunoglobulin M autoantibodies to proteins mimicking and not mimicking Epstein-Barr virus nuclear antigen-1.

In previous studies of infectious mononucleosis, we found IgM autoantibodies which react with hematopoietic cell antigens. Many of these were inhibited by synthetic glycine/alanine peptides representing the glycine/alanine repeat of Epstein-Barr virus nuclear antigen-1. We have cloned and expressed fragments of genes encoding two of these autoantigens. One gene (p542) encodes a protein containing a glycine-rich 28-mer, which is its chief autoantigenic epitope and which represents a newly identified class of evolutionarily conserved autoepitopes. The other gene (p554) encodes a protein that is not demonstrably cross-reactive with Epstein-Barr virus nuclear antigen-1 or with any other EBV protein, but forms complexes with other proteins. Immunoaffinity-purified anti-p542 and anti-p554 have relatively high binding affinities, as evidenced by inhibition at 10(6)-10(8) M-1, and neither autoantibody showed polyreactivity with other common antigens. The data thus suggest that neither autoantibody is simply an expression of polyclonal B cell activation. We conclude that the two autoantigens stimulate autoantibody synthesis by different mechanisms. One autoantigen shares homology to a viral protein which generates cross-reacting antibodies to the autoantigenic epitope. The other has no recognizable cross-reaction with the infecting pathogen and may become immunogenic through complexing with other proteins.

Amino Acid Sequence↗
PubMed1995

Polysaccharide-mediated protection against abscess formation in experimental intra-abdominal sepsis.

Abscess formation is a major complication of intra-abdominal sepsis that causes significant morbidity and mortality. In such cases, Bacteroides fragilis is the predominant anaerobic isolate. In a rat model of intra-abdominal sepsis, the capsular polysaccharide complex (CPC) from B. fragilis promotes abscess formation and when administered sub-cutaneously, protects against this host response by a T cell-dependent immune mechanism. In the present study, the polysaccharide A (PS A) component of CPC protected animals against challenge with live heterologous bacterial species (mixtures of anaerobes and facultative organisms) that are most commonly isolated from intra-abdominal abscesses in humans. Protection against heterologous bacterial challenge was transferred by T cells. Administration of PS A shortly before or even after challenge with B. fragilis protected against this host response. In experiments designed to simulate fecal contamination of the human peritoneal cavity, PS A protected animals against abscess formation induced by a rat cecal contents inoculum. The surprisingly broad protective activity of PS A indicates that this molecule is likely suppressing a nonspecific host tissue reaction that forms in response to a variety of abscess-inducing organisms and that it might be useful in preventing abscess formation associated with intra-abdominal sepsis in the clinical setting.

Abdominal Abscess↗