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Biomedical subjects

C R Smith

Publications and source records attributed to C R Smith.

At least 145 records · Page 8Linked to original sources
PubMed1993

Cardiac performance preserved despite thiopental loading.

BACKGROUND: Some cerebral artery aneurysms require cardiopulmonary bypass and deep hypothermic circulatory arrest to be clipped safely. During bypass these neurosurgical patients often are given large doses of thiopental in the hope that additional cerebral protection will be provided. However, thiopental loading during bypass has been associated with subsequent cardiac dysfunction in patients with heart disease. This study was undertaken to determine how patients without concomitant heart disease would respond to thiopental loading. METHODS: Twenty-four neurosurgical patients with giant cerebral aneurysms and little or no cardiac disease were anesthetized with fentanyl, nitrous oxide, and isoflurane. Thiopental was titrated to achieve electroencephalographic burst-suppression before bypass, and the infusion was continued until after separation. Prebypass hemodynamic and echocardiographic measurements were obtained during a stable baseline and 15 min after thiopental loading began. They were repeated after bypass. RESULTS: Prebypass thiopental loading increased heart rate from 61 +/- 11 to 72 +/- 13 beats/min and decreased stroke volume from 43 +/- 10 to 38 +/- 8 ml.beat-1.m-2, but arterial and filling pressures, vascular resistance, cardiac index, and ejection fraction remained the same. Before bypass, thiopental plasma concentration measured 28 +/- 8 micrograms/ml. Loading continued for 2-3 h until after bypass was terminated, and the overall infusion rate was 18 +/- 5 mg.kg-1.h-1. All patients were easily separated from bypass without inotropic support. Following bypass, vascular resistance was decreased; heart rate, filling pressures, and cardiac index were increased; stroke volume had returned to its baseline; and ejection fraction was unchanged. CONCLUSIONS: It was concluded that if preoperative ventricular function is good, thiopental loading to electroencephalographic burst-suppression causes negligible cardiac impairment and does not impede separation from cardiopulmonary bypass.

Adult↗
PubMed1993

Supporting future surgical innovation. Lung transplantation as a case study.

OBJECTIVE: Using lung transplantation as a case study, this article addressed the problem of supporting innovative clinical surgery in an era of increasing pressures for cost containment. SUMMARY BACKGROUND DATA: After sporadic attempts at lung transplantation during the 1960s and 1970s, its clinical development began in earnest during the early 1980s. As a result of a wide range of incremental advances, the results have improved significantly. The Health Care Financing Administration, however, has not yet issued a national policy covering lung transplants and has left the coverage decision to the discretion of its regional contractors. METHODS: The authors surveyed the major commercial insurers, the Blue Cross Blue Shield Association, and a sample of Medicare intermediaries to evaluate the coverage of lung transplantation. They also interviewed the National Heart, Lung, and Blood Institute and industrial firms about their support for clinical research. RESULTS: Government and industry funding were limited, and the development and assessment of lung transplants have been financed predominantly by academic institutions through cross-subsidization from patient care and teaching funds. The major private payers and Blue Cross Blue Shield decided to cover this procedure in the early 1990s. Coverage decisions by Medicare intermediaries, however, revealed considerable variability. Moreover, the absence of a specific diagnosis-related group for lung transplants had considerable consequences for institutions in all-payer states, in which payments appeared to be considerably lower than the mean costs of a transplant procedure (about $110,000). CONCLUSIONS: This analysis indicated that there was a growing disparity between the increasing demand for outcomes data about new procedures and the limited resources available for supporting the development and assessment of new operations. It this disparity is not addressed, the rate of surgical innovation may be jeopardized, and timely outcomes data may not be acquired. It was concluded that provisional coverage within a predetermined research protocol may be a promising mechanism to remedy this situation, providing timely assessment of new procedures before widespread application.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1993

Light-cured dimethacrylate ocular prosthesis.

The use of a visible light-cure dental synthetic resin offers some advantages in the clinical delivery of an ocular prosthesis and a statistically significant reduction in the processing time.

Eye, Artificial↗
PubMed1993

Decreasing incidence of coronary disease in pediatric cardiac transplant recipients using increased immunosuppression.

BACKGROUND: Coronary artery disease (CAD) is a limiting factor to long-term survival in cardiac transplant recipients, affecting from 30% to 50% of patients by 4 years after surgery. Can the incidence of CAD be lowered with augmentation of immunosuppression? METHODS AND RESULTS: We compared the incidence of CAD in our pediatric transplant population with nine potential risk factors, including immunosuppressive regimen. The study group consisted of 55 patients who survived more than 1 year (or to first angiogram) or had autopsies. Coronary angiograms were performed yearly and compared sequentially. The mean follow-up of 55 patients was 36 months. Mean age was 10.3 +/- 6 years (range, 4 months to 18 years). Thirteen patients received double immunosuppression with cyclosporine and prednisone, and 42 received triple therapy with cyclosporine, prednisone, and azathioprine. Significant CAD occurred in 10 grafts (6 deaths and 3 retransplants). Cause for graft loss in 6 patients with CAD was acute rejection. CAD was detected by angiogram in only 2 patients. Nine of 10 patients received double therapy (P < .001). There was no difference in mean follow-up between immunosuppression groups. There was a higher rejection frequency for double therapy (0.19 +/- 0.16 rejections per patient month) compared with triple therapy (0.07 +/- 0.11). Ten patients were rejection free in the triple therapy group. CONCLUSIONS: We experienced a significant decrease in the incidence of CAD in our pediatric cardiac transplant recipients using increased immunosuppressive therapy. Type of immunosuppressive regimen (double) and rejection frequency were independent predictors for CAD by multivariate analysis.

Azathioprine↗
PubMed1993

Clinical experience with cardiac retransplantation.

Although more than 560 patients worldwide have undergone cardiac retransplantation, few studies of this population have been reported. To evaluate the risk of cardiac retransplantation and to better establish selection criteria, we reviewed the records of all patients who underwent retransplantation at the Columbia-Presbyterian Medical Center. Of 431 patients who underwent transplantation between February 1977 and March 1991, 408 underwent the procedure in the era of cyclosporine-based immunosuppression. Thirteen of these 408 patients underwent retransplantation (including one patient who received a third graft). Indications for the 14 retransplantations included transplant coronary artery disease (n = 8), rejection (n = 5), and intraoperative graft failure (n = 1). Immunosuppression and follow-up protocols used in this cohort were similar to those in the primary transplantation population. No significant differences were found in either actuarial survival between primary transplant recipients (75.1% +/- 2.2% at 1 year and 71.3% +/- 2.4% at 2 years) and patients who underwent retransplantation (71.4% +/- 12.1% at 1 year and 59.5% +/- 14.8% at 2 years) or in linearized rates of rejection and actuarial freedom from rejection between the two groups. No differences between these groups were found with regard to age, sex, race, origin of end-stage heart disease, or early (< 30 day) mortality. The origin of primary graft failure did not correlate with survival outcome in the retransplantation cohort. Follow-up time for patients having primary transplantation ranged from 0 to 8 years (mean 24 months) with a cumulative patient follow-up of 830 patient-years; follow-up time for patients who underwent retransplantation ranged from 0 to 3 years (mean 8.1 months) with a cumulative patient follow-up of 9.5 patient-years. Approximately 50% of patients in both groups had at least one rejection episode by 3 months. Within the limited time period studied after retransplantation, only one patient had transplant coronary artery disease, approximately 27 months after her first retransplantation procedure for acute rejection. These results indicate that the prognosis for patients undergoing cardiac retransplantation is good for patients for whom the indication for retransplantation is identified more than 30 days after initial transplantation.

Adolescent↗
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↗
PubMed1992

Normal bronchial healing without bronchial wrapping in canine lung transplantation.

The deleterious effect of steroids on bronchial healing in lung transplantation has led to the development of techniques to protect the anastomosis and to the exclusion of steroid-dependent patients from transplantation. The effect of steroids on bronchial healing was tested in a canine single-lung allotransplantation model. Twenty size-matched mongrel dogs (20 to 30 kg) underwent left lung transplantation without anastomotic wrap or direct revascularization. Postoperatively, all received daily doses of cyclosporine (15 mg/kg) and azathioprine (1 mg/kg) and were subdivided into three steroid dosage groups. Group A (n = 10) animals received 1.5 mg/kg of prednisone per day whereas groups B (n = 5) and C (n = 5) received 5.0 mg/kg of prednisone per day for 28 postoperative days. In addition, group C received prednisone (5.0 mg.kg-1.day-1) for 1 month preoperatively. In group A, 8 of 10 dogs survived 28 days without evidence of respiratory compromise, with anastomotic bursting pressure greater than 510 mm Hg. In group B, all 5 dogs survived to 28 days without evidence of respiratory compromise and with intact bronchial anastomoses (bursting pressures greater than 510 mm Hg). In group C, 3 of 5 animals survived to 28 days with intact anastomoses. Histological examination demonstrated normal bronchial healing in all anastomoses. These data suggest that preoperative steroid dependence should not be a contraindication to lung transplantation and that bronchial anastomotic wrapping with vascular tissue may not be essential.

Anastomosis, Surgical↗
PubMed1992

Juvenile hemangiomas involving the thoracic trachea in children: report of two cases.

Two 3-month-old girls presented with posterior mediastinal juvenile hemangioma (JH), a benign tumor rarely found in the mediastinum. Incomplete resections were performed. Over 4 and 7 months, respectively, the hemangiomas recurred and grew through the tracheal wall into the tracheal lumina, reducing the airway by 90% in one case and 70% in the other. The recurrences were resected, including five tracheal rings in the first case and four in the second. In case 1 the tumor recurred in the trachea 2 months later. A tracheostomy was performed, and corticosteroids were administered for 6 months. The tumor involuted and the patient was decannulated after 18 months; she is doing well 7 years later. The patient in case 2 has been well in the 18 months since her second operation. Airway obstructions can be treated by tracheal resection when conservative management fails.

Airway Obstruction↗
PubMed1992

Repair of long tracheal defects with cryopreserved cartilaginous allografts.

Tracheoplasties with various autografts (cartilage, periosteum, pericardium) have been used in the treatment of long-segment tracheal stenosis. Previous studies have shown that cartilage allografts survive transplantation on a long-term basis in various sites of the body. In this study we set out to determine if cryopreserved cartilage and cryopreserved tracheal allografts would survive when used to cover tracheal defects in animals. A rectangular defect (2.8 +/- 0.3 cm long and incorporating 50% of tracheal circumference) was created in the thoracic trachea of 18 piglets. The defect was covered with the excised tracheal segment in 6 (group A, control group), with a cryopreserved tracheal allograft in 6 (group B), and with a cryopreserved cartilage allograft harvested from the scapula in 6 (group C). The allografts were cryopreserved, by a standard slow-freezing technique, at -80 degrees C for more than 21 days. All animals survived the grafting procedure and were killed after 2 months. None had signs of airway obstruction. Using the trachea above the defect as the standard, the mean sagittal narrowing of the airway in the repaired trachea was 0.4 mm in group A, 0.7 mm in group B, and 0.6 mm in group C; the coronal diameter in normal and grafted trachea was similar. The lumen of all grafts was lined by regenerating respiratory epithelium, and cilia were seen in many. Some cartilage was reabsorbed in group A and B but cartilage islands were present in all. In group A, reabsorption of cartilage was minimal. These findings suggest that segments of trachea or cartilage allografts can be cryopreserved, stored, and, subsequently, used when necessary for tracheoplasty.

Animals↗
PubMed1992

Effect of complete cardiac denervation on atrial natriuretic factor release in baboons.

We investigated the influence of cardiac innervation on atrial natriuretic factor (ANF) release in baboons. For this purpose, plasma ANF levels were measured in control conditions and in response to head-down (-45 degrees) and head-up tilt (+45 degrees) in six anesthetized baboons before and after complete cardiac denervation obtained by orthotopic autotransplantation of the heart. Cardiac denervation did not modify baseline plasma ANF levels (60.4 +/- 17 pg/ml before and 63.1 +/- 16 pg/ml after heart autotransplantation). In contrast the significant ANF responses to changes in central venous pressure (CVP) induced by postural maneuvers (-45 degrees, + 16.2 +/- 4 pg/ml; +45 degrees, -18.5 +/- 4 pg/ml) were markedly altered after cardiac denervation (-45 degrees, +5.8 +/- 2 pg/ml; +45 degrees, -7.6 +/- 1 pg/ml). The changes in CVP and systemic blood pressure evoked by the postural challenges were comparable before and after cardiac denervation. These results demonstrate that cardiac nerves play a role in the control of ANF release.

Animals↗
PubMed1992

Diaphragmatic contraction band necrosis in a perinatal and infantile autopsy population.

A morphologic study of the anterolateral costal diaphragm in 125 newborns and infants who died suddenly showed that contraction band necrosis is a common finding. In cases that showed the most extensive lesions, acute asphyxia was the usual mode of death; within eight diagnostic categories birth asphyxia (11 of 26 cases) and sudden infant death syndrome (19 of 30 cases) had the highest frequency of lesions. It was more frequent than myocardial contraction band necrosis and myocardial coagulation necrosis among the cases studied. The morphologic age and, if present, the stage of healing in each case suggested that the diaphragmatic lesion commenced at or shortly before death or at the time of the cardiac arrest that led to death. Thus, the lesion appeared to represent a very early event after a lethal injury, but it had no specificity for the nature of the injury. Because skeletal muscle of the respiratory diaphragm structurally and functionally resembles myocardium, the pathogenesis of contraction band necrosis may be similar in the two muscle types.

Autopsy↗
PubMed1992

Effectiveness of a human monoclonal anti-endotoxin antibody (HA-1A) in gram-negative sepsis: relationship to endotoxin and cytokine levels.

Gram-negative sepsis is caused by endotoxin-induced release of tumor necrosis factor (TNF) and other cytokines. HA-1A is a human monoclonal antibody that binds specifically to endotoxin. HA-1A should prevent death in endotoxemic patients and reduce serum levels of TNF and interleukin-6 (IL-6). This hypothesis was tested in 82 septic patients who were randomly allocated to receive a single intravenous 100-mg dose of HA-1A or placebo. Pretreatment endotoxemia was detected in 27 patients (33%). Death occurred within 28 days of treatment in 8 (73%) of 11 placebo recipients and in 5 (31%) of 16 HA-1A recipients (P = .02). The median decrease in serum TNF level 24 h after treatment was 12 ng/L in patients given HA-1A and 0 ng/L in placebo recipients (n = 65; P = .04). For IL-6, this was 204 ng/L in patients given HA-1A and 44 ng/L in placebo recipients (n = 67; P = .4). Thus, HA-1A reduces mortality in septic patients with endotoxemia and lowers serum TNF levels.

Adult↗
PubMed1992

Experimental verocytotoxemia in rabbits.

The clinicopathologic effects of intravenously administered purified verocytotoxin 1 (VT1; Shiga-like toxin 1) in 2-kg male rabbits was studied. The 50% lethal dose was 0.2 micrograms of protein per kg of body weight (2 x 10(4) 50% cytotoxic doses per kg). The clinical features included nonbloody diarrhea and a progressive flaccid paresis, usually culminating in death. The histopathology was characterized by edema and hemorrhage in the mucosa and submucosa of the cecum and edema, hemorrhage, and neuronal necrosis in the brain and gray matter of the spinal cord. Thrombotic microangiopathy, the characteristic histopathologic renal lesion in the hemolytic-uremic syndrome, was also found to be the underlying lesion in verocytotoxemic rabbits. To determine the specific distribution of VT1 in rabbit tissues, purified 125I-labelled VT1 was administered intravenously to 20 rabbits (both immunologically naive and VT1-immune rabbits). The highest specific uptake of 125I-VT1 was in the spinal cord, brain, cecum, colon, and small bowel in unimmunized animals but in the liver, spleen, and lungs in immune animals. Immunofluorescent staining of cecal and spinal cord tissues after intravenous administration of VT1 showed evidence of specific vascular endothelial cell binding of the toxin. The striking correlation of the central nervous system and gastrointestinal localization of 125I-VT1 with the sites of known histopathology is consistent with direct toxin-mediated injury to these tissues, initiated by the specific binding of VT1 to the vascular endothelium. We conclude that the vascular damage induced by VT1 in affected rabbit tissues is similar to that seen in the kidneys and other tissues in patients with verocytotoxin-producing Escherichia coli-associated hemolytic-uremic syndrome. This suggests that although the rabbit model fails to replicate human hemolytic-uremic syndrome, it is useful for studying the pathogenesis of the vascular lesions in verocytotoxin-producing E. coli-associated diseases.

Animals↗