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C R Smith

Publications and source records attributed to C R Smith.

At least 19 recordsLinked to original sources
PubMed1995

Ischemia-induced interleukin-8 release after human heart transplantation. A potential role for endothelial cells.

BACKGROUND: Interleukin-8 (IL-8) secreted from endothelial cells is a powerful neutrophil chemoattractant and activator. We hypothesized that human endothelial cells deprived of oxygen would secrete IL-8, which might translate into elevated IL-8 production after cardiac ischemia. Furthermore, we hypothesized that coronary sinus (CS) IL-8 levels would be particularly high after cardiac preservation for transplantation, due to extended ischemic times. METHODS AND RESULTS: Human saphenous vein endothelial cells exposed to a hypoxic environment (PO2 < 20 mm Hg) demonstrated a time-dependent release of IL-8 (measured by ELISA) into the culture supernatant as early as 4 hours after exposure. To determine whether cardiac preservation in humans was associated with IL-8 production, we obtained CS blood samples 5 minutes after reperfusion in a consecutive series of patients after they underwent cardiac transplantation (CTX, n = 20) or elective cardiac surgery (non-CTX, n = 21). CTX patients demonstrated significantly higher CS IL-8 levels than non-CTX patients (325 +/- 123 versus 50 +/- 17 ng/mL, respectively, P < .05). Further analysis of the CS samples revealed that a biochemical marker of myocyte injury (myoglobin) was similarly elevated in the CTX patients compared with the non-CTX patients (3340 +/- 625 versus 1151 +/- 525 ng/mL, respectively, P < .05). CONCLUSIONS: These differences may reflect the longer ischemic times of CTX compared with non-CTX hearts (161 +/- 10 versus 80 +/- 6 minutes, P < .0001) and suggest that the neutrophil chemoattractant/activator IL-8 may contribute to myocyte injury after prolonged hypothermic cardiac ischemia, as occurs during human cardiac transplantation.

Aged↗
PubMed1995

Vesamicol analogues as sigma ligands. Molecular determinants of selectivity at the vesamicol receptor.

The present study compares the affinities of 2-(4-phenylpiperidino)cyclohexanol (vesamicol, 1) and selected analogues of the latter at the vesamicol receptor (VR) with the corresponding affinities at sigma 1 and sigma 2 binding sites. For this study, the parent structure 1 was divided into three fragments: A (cyclohexyl), B (piperidyl) and C (phenyl). Vesamicol analogues were then selected to reflect structural modifications in these fragments. Consistent with earlier reports, vesamicol was found to exhibit nanomolar affinities at the VR and sigma 1 and sigma 2 sites, resulting in poor selectivity for the VR over the sigma sites. Vesamicol analogues characterized by an acyclic A-fragment showed moderate to low affinities at the VR and moderate to high affinities at sigma 1 and sigma 2 sites. As a result, many of these analogues showed poor selectivity for the VR. Replacement of the C4 carbon of 1 with a halobenzyl amine resulted in higher affinities at the VR coupled with moderate to low affinities at sigma 1 and sigma 2 sites. The introduction of a benzofused substituent at the C4 and C5 positions of 1 (compound 2) resulted in a 200-fold increase in affinity at the VR accompanied by a 5- to 6-fold decrease in affinity at sigma 1 and sigma 2 sites relative to the parent structure. Consequently, compound 2 showed 12,000-fold higher affinity at the VR than at sigma sites. Restricting the rotation of fragment C relative to B (by means of alkyl and alkenyl bridges) generally yielded analogues with subnanomolar affinities at the VR. The corresponding affinities of these spirofused conformationally restricted analogues were moderate to poor at sigma 1 and sigma 2 sites when fragment A was preserved. In contrast, the affinities at sigma 1 and sigma 2 sites were decreased 3- to 11-fold when fragment A was modified at position C4 and decreased up to 100-fold with benzofusion at the C4 and C5 positions of fragment A. Consequently, the spirofused analogues 15-19 were among the most selective VR ligands examined. Thus, the effect of conformational restriction in fragments A and B-C is to increase affinity at the VR while decreasing affinity at sigma 1 and sigma 2 sites, and thereby increasing selectivity for the VR over the sigma sites.

Animals↗
PubMed1995

Classmode: a new data format for real-time multiparameter data analysis and data compression.

A new data acquisition and analysis format (classmode) was developed that allows real-time data classification in a flow cytometer. In our cytometer, detected events were classified in real time by their presence or absence in a set of look-up tables (LUT). A modification of the cytometer hardware allows the exclusive transfer of the LUT data to the acquisition/storage computer. Using a combination of 8 LUTs, the analyzed events can be classified into 256 subpopulations. Real-time data classification results in an increased data transfer rate and a significant compression of the data.

Cells, Cultured↗
PubMed1995

Rapid optimization of electroporation conditions for plant cells, protoplasts, and pollen.

The optimization of electroporation conditions for maximal uptake of DNA during direct gene transfer experiments is critical to achieve high levels of gene expression in transformed plant cells. Two stains, trypan blue and fluorescein diacetate, have been applied to optimize electroporation conditions for three plant cell types, using different square wave and exponential wave electroporation devices. The different cell types included protoplasts from tobacco, a stable mixotrophic suspension cell culture from soybean with intact cell walls, and germinating pollen from alfalfa and tobacco. Successful electroporation of each of these cell types was obtained, even in the presence of an intact cell wall when conditions were optimized for the electroporation pulse. The optimal field strength for each of these cells differs, protoplasts having the lowest optimal pulse field strength, followed by suspension cells and finally germinating pollen requiring the strongest electroporation pulse. A rapid procedure is described for optimizing electroporation parameters using different types of cells from different plant sources.

Electroporation↗
PubMed1995

Use of aprotinin in LVAD recipients reduces blood loss, blood use, and perioperative mortality.

Aprotinin, a bovine protease inhibitor, has been used extensively in patients undergoing cardiac surgical procedures in an effort to minimize blood loss and prevent the complications associated with blood replacement. We sought to evaluate the effect of aprotinin on postoperative blood loss, renal function, and the incidence of right ventricular failure in patients undergoing placement of a TCI Heartmate left ventricular assist device as a bridge to cardiac transplantation. Retrospective data analysis in 142 patients (42 receiving aprotinin and 100 untreated) demonstrated that the use of aprotinin was associated with a significant decrease in postoperative blood loss (p = 0.019) and in the intraoperative packed red blood cell transfusion (p = 0.019) and total blood product (p = 0.016) requirements. A transient, yet significant, increase in the postoperative creatinine level in the aprotinin group (p = 0.0006), but not in blood urea nitrogen level (p = 0.22), was noted. Interestingly, we noted an association between blood loss and the subsequent development of right ventricular failure; patients who required a right ventricular assist device bled significantly more than did those who did not suffer right ventricular failure (p = 0.02). Additionally, aprotinin recipients benefited by a reduction of nearly one half in the incidence of the need for a right ventricular assist device. The incidence of perioperative mortality was reduced in those receiving aprotinin compared with that in untreated patients, (p = 0.05). We conclude that aprotinin is safe and effective in decreasing postoperative blood loss and intraoperative blood product requirements, and in reducing perioperative mortality in patients undergoing left ventricular assist device placement as a bridge to cardiac transplantation.

Adult↗
PubMed1995

Ibogaine possesses a selective affinity for sigma 2 receptors.

The alkaloid ibogaine is potentially useful to reduce craving for several drugs of abuse, but its mechanism of action is not known. In the current study, in vitro studies were conducted in order to determine the affinity of ibogaine for sigma receptors. Our results indicate that ibogaine has a relatively high affinity for sigma 2 receptors (Ki = 90.4 and 250 nM) and a significantly lower affinity for sigma 1 receptors (Ki = 9310 nM). These data suggest that ibogaine may have a higher affinity at sigma 2 receptors than any other known CNS receptor. Its low affinity for sigma 1 receptors also suggests that ibogaine may be a suitable lead compound for structure-activity relationship studies aimed at developing sigma 2-selective ligands.

Animals↗
PubMed1995

Heart transplantation in children with congenital heart disease.

OBJECTIVES: The aim of this study was to describe heart transplantation in children with congenital heart disease and to compare the results with those in children undergoing transplantation for other cardiac diseases. BACKGROUND: Reports describe decreased survival after heart transplantation in children with congenital heart disease compared with those with cardiomyopathy. However, transplantation is increasingly being considered in the surgical management of children with complex congenital heart disease. Present-day results from this group require reassessment. METHODS: The diagnoses, previous operations and indications for transplantation were characterized in children with congenital heart disease. Pretransplant course, graft ischemia time, post-transplant survival and outcome (rejection frequency, infection rate, length of hospital stay) were compared with those in children undergoing transplantation for other reasons (n = 47). RESULTS: Thirty-seven children (mean [+/- SD] age 9 +/- 6 years) with congenital heart disease underwent transplantation; 86% had undergone one or more previous operations. Repair of extracardiac defects at transplantation was necessary in 23 patients. Causes of death after transplantation were donor failure in two patients, surgical bleeding in two, pulmonary hemorrhage in one, infection in four, rejection in three and graft atherosclerosis in one. No difference in 1- and 5-year survival rates (70% vs. 77% and 64% vs. 65%, respectively), rejection frequency or length of hospital stay was seen between children with and without congenital heart disease. Cardiopulmonary bypass and donor ischemia time were significantly longer in patients with congenital heart disease. Serious infections were more common in children with than without congenital heart disease (13 of 37 vs. 6 of 47, respectively, p = 0.01). CONCLUSIONS: Despite the more complex cardiac surgery required at implantation and longer donor ischemic time, heart transplantation can be performed in children with complex congenital heart disease with success similar to that in patients with other cardiac diseases.

Adolescent↗
PubMed1995

Single-stage treatment of sternal wound complications in heart transplant recipients in whom pectoralis major myocutaneous advancement flaps were used.

Treatment of sternal wound complications is controversial, particularly in immunosuppressed heart transplant recipients. Regardless of the severity of infection, we combine immediate, aggressive débridement with bilateral pectoralis major myocutaneous advancement flaps in a single procedure. Compared with management with pectoralis major turnover flaps or distant pedicled muscle flaps, treatment of these sternal wounds with pectoralis major myocutaneous advancement flaps is simpler and quicker and provides better aesthetic results. Furthermore, because pectoralis major myocutaneous flaps are based on the thoracoacromial arteries, whether or not the internal mammary arteries have previously been harvested for coronary grafts is irrelevant. Twenty consecutive heart transplant recipients with sternal wound complications were treated with this technique. No intraoperative or perioperative deaths occurred. The morbidity rate was 30%, with seroma treated by needle aspiration in four patients (20%) being the most common complication. Only one patient had a postoperative wound infection. All patients had excellent functional and aesthetic results.

Debridement↗
PubMed1995

Inhaled nitric oxide fails to confer the pulmonary protection provided by distal stimulation of the nitric oxide pathway at the level of cyclic guanosine monophosphate.

It has been suggested that inhaled nitric oxide gas may be beneficial after lung transplantation, because endogenous levels of pulmonary nitric oxide decline rapidly after reperfusion. However theoretical concerns remain about the formation of highly toxic oxidants during the quenching of nitric oxide by superoxide. To determine whether distal stimulation of the nitric oxide-cyclic guanosine monophosphate pathway at the level of cyclic guanosine monophosphate might confer the beneficial vascular effects of nitric oxide without its potential toxicities, we studied an orthotopic rat left lung transplant model. In this model, hemodynamic and survival measurements can be obtained independent of the native right lung. Lungs were preserved for 6 hours at 4 degrees C in Euro-Collins solution alone (control, n = 6) or supplemented with the cyclic guanosine monophosphate analog, 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic guanosine monophosphate (cGMP, n = 4). In additional experiments in which lungs were preserved with Euro-Collins solution alone, inhaled nitric oxide was administered during reperfusion (NO, n = 12). Thirty minutes after transplantation and ligation of the native right pulmonary artery, pulmonary vascular resistance, arterial oxygenation, graft neutrophil infiltration (myeloperoxidase activity), and recipient survival were evaluated. Cyclic guanosine monophosphate decreased pulmonary vascular resistance (1.1 +/- 0.2 vs 12.1 +/- 6.3 mm Hg/ml/min, p < 0.05), improved oxygen tension (369 +/- 56 vs 82.8 +/- 48 mm Hg, p < 0.05), reduced myeloperoxidase activity (1.7 +/- 0.3 vs 3.1 +/- 0.9 delta Abs 460 nm/min, p < 0.05), and improved recipient survival (100% vs 0%, p < 0.005) compared with Euro-Collins solution alone (control group). Animals receiving inhaled nitric oxide during reperfusion did not differ from control animals with respect to any of these parameters. These data suggest that distal stimulation of the nitric oxide-cyclic guanosine monophosphate pathway at the level of cyclic guanosine monophosphate has a protective effect that is not seen with inhaled nitric oxide in the immediate pulmonary reperfusion period.

Administration, Inhalation↗
PubMed1995

Nitroglycerin maintains graft vascular homeostasis and enhances preservation in an orthotopic rat lung transplant model.

Transplanted lungs often fail during the peritransplantation period for poorly understood reasons. Because the nitric oxide pathway regulates pulmonary vascular tone, helps to maintain the integrity of the endothelial barrier, and modulates neutrophil adhesivity and activation, we hypothesized that perturbation of this pathway during the preservation and reperfusion of transplanted lungs might play a critical role in mediating early graft failure. To evaluate whether supplementing the preservation solution with the nitric oxide donor nitroglycerin enhances lung preservation for transplantation, we obtained hemodynamic measurements in a model of orthotopic left lung transplantation in the rat after ligation of the native right pulmonary artery. In these experiments, recipient survival and hemodynamics depended solely on the transplanted lung. The left lung was harvested from 22 rats, flushed with either lactated Ringer's solution alone (control, n = 11) or Ringer's solution supplemented with nitroglycerin (0.1 mg/ml, n = 11), preserved for 4 hours at 4 degrees C, and then transplanted using a rapid cuff technique for bronchial and vascular anastomoses. Nitroglycerin significantly improved arterial blood oxygenation (339 +/- 66 versus 130 +/- 12 mm Hg, p < 0.05), increased pulmonary arterial flow (7.6 +/- 1.9 versus 0.9 +/- 0.2 ml/min, p < 0.005), decreased pulmonary vascular resistance (1.7 +/- 0.4 versus 6.6 +/- 1.9 x 10(3) Wood units, p < 0.05), and enhanced recipient survival (64% versus 0%, p < 0.05). Control grafts had significantly greater neutrophil accumulation (50% greater as quantified by myeloperoxidase activity, p < 0.05) than grafts preserved in the presence of nitroglycerin. These studies show that supplementation of the preservation solution with the nitric oxide donor nitroglycerin maintains graft vascular homeostasis and significantly improves pulmonary function and recipient survival after transplantation.

Animals↗
PubMed1995

Do standard monitoring sites reflect true brain temperature when profound hypothermia is rapidly induced and reversed?

BACKGROUND: Brain temperature is closely approximated by most body temperature measurements under normal anesthetic conditions. However, when thermal autoregulation is overridden, large temperature gradients may prevail. This study sought to determine which of the standard temperature monitoring sites best approximates brain temperature when deep hypothermia is rapidly induced and reversed during cardiopulmonary bypass. METHODS: Twenty-seven patients underwent cardiopulmonary bypass and deep hypothermic circulatory arrest in order for each to have a giant cerebral aneurysm surgically clipped. Brain temperatures were measured directly with a thermocouple embedded in the cerebral cortex. Eight other body temperatures were monitored simultaneously with less invasive sensors at standard sites. RESULTS: Brain temperature decreased from 32.6 +/- 1.4 degrees C (mean +/- SD) to 16.7 +/- 1.7 degrees C in 28 +/- 7 min, for an average cerebral cooling rate of 0.59 +/- 0.15 degrees C/min. Circulatory arrest lasted 24 +/- 15 min and was followed by 63 +/- 17 min of rewarming at 0.31 +/- 0.09 degrees C/min. None of the monitored sites tracked cerebral temperature well throughout the entire hypothermic period. During rapid temperature change, nasopharyngeal, esophageal, and pulmonary artery temperatures corresponded to brain temperature with smaller mean differences than did those of the tympanic membrane, bladder, rectum, axilla, and sole of the foot. At circulatory arrest, nasopharyngeal, esophageal, and pulmonary artery mean temperatures were within 1 degree C of brain temperature, even though individual patients frequently exhibited disparate values at those sites. CONCLUSIONS: When profound hypothermia is rapidly induced and reversed, temperature measurements made at standard monitoring sites may not reflect cerebral temperature. Measurements from the nasopharynx, esophagus, and pulmonary artery tend to match brain temperature best but only with an array of data can one feel comfortable disregarding discordant readings.

Adult↗
PubMed1995

Metabolic and hemodynamic responses to walking with shoulder-worn exercise weights: a brief report.

This study examined the acute physiological responses to steady-rate walking with additional weight carried at shoulder level. Sixteen healthy subjects completed two treadmill walking bouts with and without a 4.54-kg shoulder-worn load carriage system in place. Addition of the external shoulder weights resulted in small increases in level walking oxygen uptake (+0.44 ml.kg-1.min-1; +0.03 L.min-1) and minute ventilation volumes (+0.81 L.min-1) (p < 0.05). RER values, heart rate (+3 beats.min-1), and blood pressure responses [systolic blood pressure (SBP) + 4.5 mm Hg, diastolic blood pressure (DBP) + 1.3 mm Hg] were not significantly changed (p > 0.05). These findings indicate that the efficacy of shoulder-worn exercise weights to augment the physiological demand of walking exercise is marginal at best.

Adolescent↗
PubMed1995

Management strategies for pulmonary vein thrombosis following single lung transplantation.

Pulmonary vein thrombosis following lung transplantation is an infrequently reported and often fatal vascular complication. Two cases of early pulmonary vein thrombosis following single lung transplantation are described. Both patients underwent surgical thrombectomy and anastomotic reconstruction following institution of cardiopulmonary bypass, but died of multiorgan failure within 5 days of diagnosis. The efficacy of transesophageal echocardiography as a diagnostic modality, as well as medical and surgical management strategies for thrombectomy, are discussed.

Adult↗
PubMed1994

A review of laboratory techniques and their use in the diagnosis of Leptospira interrogans serovar hardjo infection in cattle.

This paper reviews the laboratory diagnosis of Leptospira hardjo infection in cattle. Two genotypes of L hardjo, Hardjoprajitno and Hardjobovis, have been identified in cattle, but only Hardjobovis has been isolated in Australia. There are problems with diagnosis and control of bovine leptospirosis. Infection is usually subclinical and the serological titres vary greatly in peak and duration. Leptospires may be excreted in urine for up to 18 months. Low microscopic agglutination test titres may be significant in unvaccinated herds as indicators of endemic infection. Vaccines differ in their composition, and their efficacy is difficult to evaluate. The serological response after vaccination is difficult to differentiate from the response after infection. Pregnant cows that become infected may abort, but this is usually after the serological response has peaked. Therefore, paired serum samples are of little use in diagnosing abortion caused by L hardjo. Fluorescent antibody techniques are more sensitive than dark field microscopy for detection of leptospires in urine and tissue samples. Techniques for culture have improved but are still difficult to perform and take 3 months or longer for results to be known. DNA probes and polymerase chain reaction tests are very sensitive and specific, quick to perform, and can be used on fluid and tissue samples.

Agglutination Tests↗
PubMed1992

Replication footprint analysis of cucumber mosaic virus electroporated into tomato protoplasts.

Total RNA extracted from cucumber mosaic virus (CMV) strains WT, with its associated satellite CARNA 5 (CMV-associated RNA 5), was successfully electroporated into isolated tomato protoplasts. At various time intervals samples were extracted for total nucleic acids and analyzed by semidenaturing polyacrylamide gel electrophoresis (PAGE). Sequence-specific hybridization probes were used for the detection of viral and satellite RNAs following Northern transfer. The resulting PAGE patterns and/or autoradiographs depict the proportional presence of viral and satellite RNAs in the extracts over time and have been referred to as "replication footprint profiles" (RFPs) of specific CMV/CARNA 5 combinations. The effective isolation and infection of tomato protoplasts, combined with the ability to follow virus/satellite titers during the infection by RFP analysis, yield results similar to those of infected plants and reduces experiments of 21 or more days in whole plants to less than 72 h in protoplasts.

Autoradiography↗
PubMed1992

A prospective study of depression and immune dysregulation in multiple sclerosis.

This study examined psychologic distress and immune function in patients with chronic-progressive multiple sclerosis participating in a placebo-control trial of cyclosporine. Immune measures included percentages and absolute numbers of CD2+, CD4+, CD8+, Leu-11-b+, HLA-DR (IA+), and transferrin-receptor-positive cells, which were evaluated by immunofluorescence using monoclonal antibodies. Distress was measured with self-report scales. The Expanded Disability Status Scale assessed neurologic disability. Subjects were followed up for 2 years, and their high-depressed and low-depressed times were compared. Times of greater depression were associated with lower CD8+ cell numbers and CD8+%, and a higher CD4/CD8 ratio. CD4+ cell numbers and percent were also higher when subjects were depressed, but only in the placebo group. There were no differences in Expanded Disability Status Scale when subjects were more depressed. Evaluation of a single subject revealed that Ia+ and transferrin-receptor-positive lymphocytes increased 3 months before distress increased. It was concluded that distress is associated with immune dysregulation in multiple sclerosis, although the mechanisms of this association have yet to be delineated.

Adult↗