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R S Smith

Publications and source records attributed to R S Smith.

At least 55 records · Page 3Linked to original sources
PubMed1999

Roles of Pseudomonas aeruginosa las and rhl quorum-sensing systems in control of twitching motility.

Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an important human pathogen. The production of several virulence factors by P. aeruginosa is controlled through two quorum-sensing systems, las and rhl. We have obtained evidence that both the las and rhl quorum-sensing systems are also required for type 4 pilus-dependent twitching motility and infection by the pilus-specific phage D3112cts. Mutants which lack the ability to synthesize PAI-1, PAI-2, or both autoinducers were significantly or greatly impaired in twitching motility and in susceptibility to D3112cts. Twitching motility and phage susceptibility in the autoinducer-deficient mutants were partially restored by exposure to exogenous PAI-1 and PAI-2. Both twitching motility and infection by pilus-specific phage are believed to be dependent on the extension and retraction of polar type 4 pili. Western blot analysis of whole-cell lysates and enzyme-linked immunosorbent assays of intact cells were used to measure the amounts of pilin on the cell surfaces of las and rhl mutants relative to that of the wild type. It appears that PAI-2 plays a crucial role in twitching motility and phage infection by affecting the export and assembly of surface type 4 pili. The ability of P. aeruginosa cells to adhere to human bronchial epithelial cells was also found to be dependent on the rhl quorum-sensing system. Microscopic analysis of twitching motility indicated that mutants which were unable to synthesize PAI-1 were defective in the maintenance of cellular monolayers and migrating packs of cells. Thus, PAI-1 appears to have an essential role in maintaining cell-cell spacing and associations required for effective twitching motility.

Bacterial Adhesion↗
PubMed1999

Severe ocular abnormalities in C57BL/6 but not in 129/Sv p53-deficient mice.

PURPOSE: To demonstrate the importance of genetic background interaction on the development of ocular phenotypes in p53-deficient mice. METHODS: Eyes of adult mice, homozygous and heterozygous for the p53 gene disruption in the 129/SvJ and C57BL/6J (B6) genetic backgrounds, and their F1 progeny were examined by indirect ophthalmoscopy and by light microscopy. RESULTS: Indirect ophthalmoscopy revealed unilateral or bilateral vitreal opacities, fibrous retrolental tissue, and retinal folds in adult B6 mice but not in 129/Sv mice homozygous for a p53 null mutation. In B6 p53-/- mice, blood vessels extended from the peripapillary inner retina through the posterior vitreous and into the retrolental membrane. Optic nerves were hypoplastic. CONCLUSIONS: These findings indicate that alleles from the B6 background contribute to the aberrant ocular phenotypes observed in p53 deficiency. They also suggest that p53 or the pathway in which it functions may be important for normal eye development.

Abnormalities, Multiple↗
PubMed1999

Serial pHi measurement as a predictor of mortality, organ failure, and hospital stay in surgical patients.

Intestinal ischemia is a common condition in critically ill patients and has been postulated to play a role in the development of organ failure and death. This has resulted in the recent interest in monitoring gastric intramucosal pH (pHi) in critically ill patients to provide earlier evidence of inadequate resuscitation, cardiogenic dysfunction, or sepsis. Several reports have indicated that low pHi values obtained during the initial 24 to 48 hours of intensive care unit (ICU) admission were associated with the development of organ failure and death. The purpose of this study was to assess the predictive value of serial pHi measurements obtained throughout the entire ICU admission. A retrospective analysis of critically ill trauma, burn, and surgical patients who had frequent pHi determinations during ICU treatment was performed. When stratified by pHi values, there were no significant differences in length of stay, organ dysfunction, or mortality. Our findings suggest that serial pHi determinations obtained beyond the early critical care period are less reliable predictors of poor outcome.

Adult↗
PubMed1999

Mouse genetics: a tool to help unlock the mechanisms of glaucoma.

Gene characterization holds great promise for understanding molecular mechanisms of disease. Although glaucoma gene identification is very valuable and allows assessment of an individual's genetic risk, it is not by itself sufficient to answer detailed questions about pathogenesis. Despite the recent identification of a number of glaucoma genes, there are still many questions regarding the ways in which mutations in these genes cause disease. The mouse system, including the ability to alter specific genes, provides a powerful experimental system for hypothesis testing and molecular dissection of pathogenesis subsequent to gene identification. The ability to control both genetic and environmental factors will allow the use of mice to identify modifier genes that alter complex glaucoma phenotypes and that are especially difficult to identify in human families. By providing a bridge between gene identification and tests of gene function, mouse studies will be an important complement to those in humans and other species. This article summarizes the recent use of mice and the future potential of applying approaches of mouse genetics to intraocular pressure and glaucoma research.

Animals↗
PubMed1998

Institutional learning curve of surgeon-performed trauma ultrasound.

BACKGROUND: Sonography has become the primary mode for the initial evaluation of abdominal injury in many trauma centers. However, the rate at which nonradiologists become proficient in this technique remains controversial. OBJECTIVE: To assess the learning curve for this technique in a single institution. DESIGN: Retrospective review of sonographic examinations for trauma performed by senior surgical residents during a 24-month period at an American College of Surgeons-verified level I trauma center. SETTING: University-affiliated private hospital. PATIENTS AND METHODS: Before the initiation of a program of surgeon-performed trauma ultrasound, senior surgical residents (postgraduate years 4 and 5) received 11.5 hours of hands-on and didactic instruction in the focused ultrasound examination for trauma. This examination then became a standard component of the evaluation of injured patients. Subsequent groups of senior residents received 8 hours of instruction at the onset of new academic years, 6 and 18 months, respectively, after the initial course. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were then calculated for each 6-month period after the introduction of trauma sonography. RESULTS: During the 24-month study period, 902 sonographic examinations were performed. No statistically significant differences were noted in sensitivity, specificity, accuracy, positive predictive value, or negative predictive value for any 6-month period of study when compared with the other 6-month periods or with the values calculated for the entire study period. CONCLUSIONS: Senior surgical residents are capable of performing the focused ultrasound examination for trauma with a high level of skill after a concise introductory course. A learning curve was not apparent in our series. Criteria for being permitted to perform trauma sonography that include the requirement of a large number of examinations or extensive proctoring should be reassessed.

Abdominal Injuries↗
PubMed1998

The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety.

There is some evidence that, in humans and experimental animals, psychological stress may suppress or enhance immune functions, depending on the nature of the stressor and the immune variables under consideration. The possibility that psychological stress may affect the production of pro-inflammatory and immunoregulatory cytokines was investigated in 38 medical students, who had blood samplings a few weeks before and after as well as one day before an academic examination. Psychological stress significantly increased the stimulated production of tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), IL-1 receptor antagonist (IL-1Ra), interferon gamma (IFN-gamma) and IL-10. Students with high stress perception during the stressful condition had a significantly higher production of TNF-alpha, IL-6, IL-1Ra and IFN-gamma than students with a low-stress perception. Students with a high anxiety response had a significantly higher production of IFN-gamma and a lower production of the negative immunoregulatory cytokines, IL-10 and IL-4, than students without anxiety. These findings suggest that, in humans, changes in the production of the pro-inflammatory cytokines, TNF-alpha, IL-6 and IFN-gamma, and negative immunoregulatory cytokines, IL-10 and IL-4, take part in the homeostatic responses to psychological stress and that stress-induced anxiety is related to a T-helper-1-like response.

Adult↗
PubMed1998

Magnesium reduces free radicals in an in vivo coronary occlusion-reperfusion model.

OBJECTIVE: This study demonstrated that magnesium (Mg) reduces free radicals after a brief coronary occlusion-reperfusion sequence. BACKGROUND: Magnesium has been shown to reduce infarct size in patients with acute myocardial infarction. We hypothesized that this action of Mg occurs through its action on free radicals. METHODS: Eighteen mongrel dogs were studied (nine control, nine receiving Mg). Catheters were placed into the coronary sinus for continuous blood withdrawal. A Varian E-4 electron paramagnetic resonance spectrometer was used to monitor the ascorbate free radical (AFR) signal in the coronary sinus blood; AFR is a measure of total oxidative stress. Occlusion of the left anterior descending coronary artery for 20 min was followed by reperfusion. The study animals received 4 g Mg intravenously starting at 15 min of occlusion (5 min before reperfusion) and continuing during reperfusion. RESULTS: Results are presented as percent change from baseline +/- SEM. Magnesium blunted the peak AFR increase: at 4 min of reperfusion there was a 4.7 +/- 3.3% increase in AFR signal in the dogs receiving Mg versus an 18.2 +/- 3.3% increase in the control animals (p < 0.05). Total radical flux was reduced during reperfusion by 53% in the Mg dogs compared with controls (p < 0.05). CONCLUSIONS: Magnesium attenuates AFR increase after an occlusion-reperfusion sequence. To our knowledge this is the first in vivo real-time demonstration of Mg's impact on free radicals.

Animals↗
PubMed1998

Intracardiac echocardiographic imaging of the left ventricle from the right ventricle: quantitative experimental evaluation.

PURPOSE: Our purpose was to demonstrate that intracardiac ultrasound imaging from a transducer placed in the right ventricle can be used to quantitatively image the left ventricle in a swine model. BACKGROUND: The left ventricles and right ventricles of dogs and human beings have been studied with intracardiac echocardiography. Usually intracardiac echocardiography has been performed with the ultrasound catheter in the chamber being studied because of limited depth of field. Thus left ventricular imaging required that the ultrasound catheter be placed intra-arterially and manipulated into the left ventricle. The availability of lower frequency ultrasound catheters may allow left ventricular imaging from the right ventricle--a more clinically attractive approach. METHODS: In 10 closed chest swine, a 10F, 10-MHz ultrasound catheter was placed into the right ventricle through an introducer sheath placed in the right internal jugular vein. Two-dimensional transthoracic echo images were obtained for comparison. Two protocols were used to image global left ventricular function and regional wall motion during pharmacologic challenge. In protocol 1 (n = 4) we evaluated global left ventricular performance in response to interventions: dobutamine, halothane (a myocardial depressant), nitroprusside, and volume loading. In protocol 2 (n = 6) we evaluated regional contraction abnormalities induced by coronary arterial balloon inflation and deflation (reperfusion) and dobutamine. At baseline and after each intervention, global function of the right ventricle and left ventricle was measured as cross-sectional end-diastolic area and end-systolic area, and regional contraction was evaluated as the percentage of left ventricular circumference with a wall motion abnormality. Intracardiac pressures and cardiac output were also measured for comparison. Left ventricular cross-sectional area ejection fractions (area EF) were calculated for both intracardiac and transthoracic echo images as (end-diastolic cross-sectional area - end-systolic cross-sectional area)/end-diastolic cross-sectional area. RESULTS: The 10F, 10-MHz intracardiac ultrasound catheter successfully imaged the left ventricle from the right ventricle in all 10 swine. In protocol 1, dobutamine increased area EF from a baseline of 0.60 +/- 0.03 to 0.87 +/- 0.04 (P < .05). When dobutamine was added to the myocardial depressant halothane, left ventricular area EF increased from a baseline of 0.55 +/- 0.03 to 0.68 +/- 0.04. In protocol 2, coronary occlusion resulted in a detectable regional wall motion abnormality (circumferential percentage) of 23% +/- 3%. After reperfusion and during dobutamine stimulation, the wall abnormality decreased to 12% +/- 4%. Transthoracic echocardiography correlated well with these intracardiac findings. CONCLUSIONS: The left ventricle can be quantitatively imaged from the right ventricle with the use of a 10F, 10-MHz intracardiac catheter in swine. This system can detect changes in global and regional left ventricular systolic function. This technique warrants evaluation in clinical applications.

Animals↗
PubMed1998

A comparison of sonographic examinations for trauma performed by surgeons and radiologists.

BACKGROUND: It has been demonstrated that surgeons and surgery residents, trained in the focused abdominal sonographic examination, are able to accurately and reliably evaluate trauma patients. Despite this, radiologists have objected to surgeon-performed sonography for several reasons. We set out to compare the accuracy of sonographic examinations performed by surgery residents and radiologists. METHODS: A retrospective review of medical records of all trauma patients who received focused ultrasound examinations from January 1, 1995, through June 30, 1996, at one of two American College of Surgeons-verified Level I trauma centers in the same city was undertaken. Ultrasound examinations were performed by surgery residents at trauma center A (TCA) and by radiologists or radiology residents at trauma center B (TCB). Findings for each patient were compared with the results of computed tomography, diagnostic peritoneal lavage, operative exploration, or observation. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated for each group of patients. Comparison of patient charges for the trauma ultrasound examinations at each of the trauma centers was also made. RESULTS: Patient populations at the two centers were similar except that the mean Injury Severity Score at TCB was higher than at TCA (11.74 vs. 9.6). Sensitivity, specificity, accuracy, or negative predictive value were not significantly different between the two cohorts. A significantly lower positive predictive value for examinations performed by surgery residents was noted and attributed to a lower threshold of the surgery residents to confirm their findings by computed tomography. Billing data revealed that the average charge for trauma sonography by radiologists (TCB) was $406.30. At TCA, trauma sonography did not generate a specific charge; however, a $20.00 sum was added to the trauma activation fee to cover ultrasound machine maintenance and supplies. CONCLUSION: Focused ultrasound examination in the trauma suite can be as safely and accurately performed by surgery residents as by radiologists and radiology residents and should be a routine part of the initial trauma evaluation process.

Adolescent↗
PubMed1998

Distribution of coronary arterial capacitance in a canine model.

The capacitative properties of the major left coronary arteries, left main (LM), left anterior descending (LAD), and left circumflex (LCX), were studied in 19 open-chest isolated dog hearts. Capacitance was determined by using ramp perfusion and a left ventricular-to-coronary shunt diastolic decay method; both methods gave similar results, indicating a minimal systolic capacitative component. Increased pericardial pressure (PCP), 25 mmHg, was used to experimentally alter transmural wall pressure. The response to increased PCP was different in the LAD vs. LCX; increasing PCP decreased capacitance in the LCX but increased capacitance in the LAD. This may have been due to the different intramural vs. epicardial volume distribution of these vessels and a decrease in intramural tension during increased PCP. Increased PCP decreased LCX capacitance by approximately 13%, but no changes in conductance or zero flow pressure intercept occurred in any of the three vessels, i. e., evidence against the waterfall theory of vascular collapse at these levels of PCP. Coronary arterial capacitance was also linearly related to perfusion pressure.

Animals↗
PubMed1998

Essential iris atrophy, pigment dispersion, and glaucoma in DBA/2J mice.

PURPOSE: To characterize ocular abnormalities associated with iris atrophy in DBA/2J mice and to determine whether mice of this strain develop elevated intraocular pressure (IOP) and glaucoma. METHODS: Different approaches, including slit-lamp biomicroscopy, ophthalmoscopic examination, ultrasound backscatter microscopy, and histology were used to examine the eyes of DBA/2J mice ranging from 2 to 30 months old. IOP was measured in DBA/2J mice of different ages. RESULTS: DBA/2J mice were found to develop pigment dispersion, iris transillumination, iris atrophy, anterior synechias, and elevated IOP. IOP was elevated in most mice by the age of 9 months. These changes were followed by the death of retinal ganglion cells, optic nerve atrophy, and optic nerve cupping. The prevalence and severity of these lesions increased with age. Optic nerve atrophy and optic nerve cupping was present in the majority of mice by the age of 22 months. CONCLUSIONS: DBA/2J mice develop a progressive form of secondary angle-closure glaucoma that appears to be initiated by iris atrophy and the associated formation of synechias. This mouse strain represents a useful model to evaluate mechanisms of pressure-related ganglion cell death and optic nerve atrophy, and to evaluate strategies for neuroprotection.

Aging↗
PubMed1997

Autoregulation of the human N-myc oncogene is disrupted in amplified but not single-copy neuroblastoma cell lines.

Amplification of the N-myc gene is a significant adverse prognostic factor in neuroblastoma, a common childhood tumor. In non-transformed cells, myc expression is controlled through an autoregulatory circuit, through which elevated Myc protein levels lead to down-regulation of myc transcription. The precise mechanism of myc gene autoregulation is unknown. Loss of c-myc autoregulation has been documented in transformed cells from a number of different lineages, but N-myc autoregulation has not yet been investigated. In neuroblastoma, the increased N-Myc protein produced by amplified tumors would be expected to silence N-myc transcription if the autoregulatory loop were intact. To determine whether N-myc autoregulation is operative in human neuroblastoma, and to localize cis-acting elements which mediate N-myc autosuppression, we transfected a series of N-myc 5' promoter constructs into a panel of human neuroblastoma cell lines carrying one or multiple copies of N-myc. The transfected promoter was equally active in single-copy and amplified lines. Significant promoter activity in the presence of abundant Myc protein in amplified neuroblastoma lines indicates that autoregulation is disabled in this subset of tumors. To investigate whether single-copy lines produce insufficient N-Myc protein to trigger autosuppression yet retain an intact autoregulatory circuit, we transfected neuroblastoma lines with 5' promoter constructs in the presence of a c- or N-myc expression vector. Overexpression of c- or N-Myc resulted in diminution of activity of both the transfected promoter and the endogenous N-myc gene in single-copy, but not amplified lines. Using a series of 5' promoter-deletion minigenes, we localized a cis-acting element required for autoregulation close to the transcription start sites. While the precise mechanism of autosuppression remains unknown, we demonstrated that Myc is incapable of silencing the adenovirus major late promoter (AdMLP) in neuroblastoma cells, indicating that Myc suppression of its own promoter and the AdMLP involve distinct components. These studies provide the first systematic investigation of autoregulation in neuroblastoma, and indicate that single-copy neuroblastoma lines produce insufficient N-Myc protein to activate downstream effector(s) of autosuppression; the autoregulatory circuit is otherwise intact. Amplified lines, in contrast, have lost autoregulation.

Adenoviridae↗
PubMed1997

In vivo immunomodulatory effects of clozapine in schizophrenia.

Recently, there have been some reports that schizophrenia is accompanied by an immune-inflammatory response, characterized by increased secretion of interleukin-6 (IL-6), soluble IL-2 receptor (sIL-2) and lower plasma levels of CC16 (Clara cell protein), an endogenous anti-cytokine. It was shown that clozapine, an atypical antipsychotic drug, may increase the plasma levels of sIL-2R and pro-inflammatory cytokines. This study was carried out in order to examine serum IL-6, IL-6R, CC16, IL-1R antagonist (IL-1RA), transferrin receptor (TfR) and sCD8 antigen, both before and after treatment with clozapine in schizophrenic subjects versus normal controls. Schizophrenic patients showed significantly higher plasma IL-6R and IL-1RA and lower plasma CC16 than normal controls. Treatment with clozapine significantly increased plasma sCD8, IL-6, CC16 and IL-1RA concentrations. The clozapine-induced increments in plasma IL-6 and CC16 appeared during the first 2 weeks of treatment, whereas the increases in plasma sCD8 and IL-1RA appeared after 5 weeks. Clozapine appears to have complex in vivo immunomodulatory effects.

Adult↗
PubMed1997

Sonographic screening to detect fetal cardiac anomalies: a 5-year experience with 111 abnormal cases.

OBJECTIVE: To determine whether there is a difference between the types of cardiac lesions detected as abnormal prenatally and those that are not detected. METHODS: Consecutive fetuses at 14 weeks' gestation or more were scanned in our unit from February 1990 through July 1995 and later were delivered at our hospital. Outcome information was obtained from neonatal echocardiograms and autopsies. Our results were compared to sensitivities for individual cardiac lesions based on pooled data from studies published previously. RESULTS: There were 111 fetuses with cardiac anomalies, of which 73 (66%) were identified correctly as abnormal prenatally. Sensitivities for the most common cardiac lesions were as follows: 87% atrioventricular septal (endocardial cushion) defects, 65% tetralogy of Fallot, 63% transposition of the great arteries, 50% aortic coarctation, and 44% isolated ventricular septal defects. The lesions that went undetected most frequently were isolated septal defects (n = 17); most of these were ventricular and small or moderate in size. Based on our sensitivities and those calculated from previous studies, the fetal cardiac lesions with the highest detection rates involve hypoplastic ventricles and atrioventricular septal defects, followed by lesions of the great arteries and finally by isolated septal defects. CONCLUSIONS: The sensitivity of sonographic screening to defect fetal cardiac anomalies varies with the type of lesion. Isolated septal defects are the most difficult lesions to detect.

Female↗
PubMed1997

Maternal diabetes mellitus: which views are essential for fetal echocardiography?

OBJECTIVE: To determine which fetal echocardiography views are essential to detect the majority of cardiac defects in fetuses of women with diabetes mellitus. METHODS: Fetal echocardiograms performed from February 1990 through May 1996 on insulin-requiring women with diabetes were reviewed. Individual component views of the examination were analyzed for the detection of fetal congenital heart defects. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Multiple gestations and patients with additional risk factors for congenital heart defects were excluded. RESULTS: A total of 223 patients were included in the study. There were 11 (4.9%) congenital heart defects, eight of which were conotruncal. When the four-chamber view and outflow tracts appeared normal, additional views such as the ductal and aortic arches did not detect a cardiac defect. The sensitivity of the four-chamber view for detecting an abnormal heart increased from 73% to 82% with the addition of the aortic outflow tract. There were two false-negative and no false-positive diagnoses. CONCLUSION: The four-chamber and outflow tracts are the essential views that will detect most cardiac defects in fetuses of women with insulin-requiring diabetes mellitus.

Echocardiography↗
PubMed1997

Gestational diabetes mellitus in women receiving beta-adrenergics and corticosteroids for threatened preterm delivery.

OBJECTIVE: To determine whether the incidence of gestational diabetes mellitus (GDM) is increased in patients receiving corticosteroids with or without beta-adrenergic agents for threatened preterm delivery. METHODS: We reviewed the laboratory records of 3396 patients undergoing screening (1-hour glucose) and diagnostic testing (3-hour glucose tolerance test [GTT]) for GDM over 2 years. Patients with antepartum admissions during which they received corticosteroids with or without beta-adrenergic agents for threatened preterm delivery were compared with a control group during the same period. Differences between the study and control groups were analyzed using chi 2, Student t test, or Fisher exact test where appropriate. P < .05 was considered significant. RESULTS: Fifty patients in the study group were compared with 1985 control patients. The remaining 1361 patients failed to meet inclusion criteria. The overall incidence of diagnosed GDM was significantly greater in the corticosteroid-beta-adrenergic agents study group, in which five (23.8%) of 21 patients screened had abnormal 3-hour GTT results, compared with 79 (4.0%) of 1985 controls (P = .001). One-hour glucose screening test results were abnormal in 60% of the study group compared with 25% of the controls (P < .001). CONCLUSION: Patients treated with beta-adrenergic agents and corticosteroids for threatened preterm delivery are at a significantly increased risk for developing GDM. The high rate of abnormal results in response to the 1-hour glucose screen suggests that this test is of limited value in patients exposed to these medications.

Adrenergic beta-Agonists↗