Anti-endotoxin monoclonal antibodies.
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Antibodies, Monoclonal↗
Biomedical subjects
C R Smith
Publications and source records attributed to C R Smith.
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↗
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↗
Autologous fibrin glue from intraoperatively collected platelet-rich plasma.
A simple and inexpensive means of creating autologous fibrin glue is described that avoids the potential disadvantages of conventionally obtained material. This improvement may allow more widespread use of fibrin glue for operative bleeding.
Animals↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Recurrent encephalopathy and seizures in a US native with HTLV-I-associated myelopathy/tropical spastic paraparesis: a clinicopathologic study.
A patient with progressive spastic paraparesis originally ascribed to multiple sclerosis developed recurrent encephalopathy and seizures. A diagnosis of HTLV-I-associated myelopathy/tropical spastic paraparesis was established prior to death. Autopsy confirmed chronic inflammatory myelopathy and active inflammation in the white matter of the temporal lobes.
Aged↗
Reimbursement for the oral health care of cancer patients.
Oral conditions related to cancer therapy, which are largely preventable, continue to result in considerable morbidity, dysfunction and lost quality of life. Therefore, it is important for dentists to be knowledgeable about the problems of reimbursement for the oral health care of cancer patients and become involved in the issue of access to oral health care for cancer patients.
Dental Care for Persons with Disabilities↗
The implantable defibrillator: an electronic bridge to cardiac transplantation.
BACKGROUND: Sudden cardiac death (SCD) is common among patients awaiting heart transplantation. Medical management of SCD may fail due to lack of efficacy or adverse side effects. The implantable cardioverter-defibrillator (ICD) may extend patient survival until a donor heart is available. METHODS AND RESULTS: We reviewed 16 patients listed for transplantation between November 1988 and October 1991 who underwent ICD implantation for ventricular arrhythmias refractory to medical management. Mean age was 51.4 +/- 11.4 years (range, 19-66 years), mean ejection fraction was 15.4 +/- 3.0% (range, 10-21%), and underlying cardiomyopathy was ischemic (12 patients), valvular (one patient), or dilated (three patients). There was no mortality from ICD insertion. Fourteen patients were discharged before transplantation, and two patients remained in the hospital until transplantation. Twelve patients underwent transplantation after a mean of 155.7 +/- 113.7 days (range, 3-319) on the transplant list. The ICD delivered shocks for tachyarrhythmia associated with near syncope in 15 of 16 patients. ICD shocks numbered > 10 in five patients, 5-9 in three patients, and 1-4 in seven patients. There was no morbidity or mortality attributed to patch electrode removal. CONCLUSIONS: We conclude that the ICD can be implanted with minimal morbidity in transplant candidates, allowing the patients to be ambulatory and to leave the hospital while awaiting heart transplantation. In patients at risk of SCD, the ICD is an effective electronic bridge to transplantation.
Anti-Arrhythmia Agents↗
Evaluation of surgical procedures. Changing patterns of patient selection and costs in heart transplantation.
During the past 4 years we have observed a marked increase in costs of heart transplantation in our center. This trend coincides with a shift in our recipient population toward the more severely ill patients. The percentage of patients bound for the intensive care unit has doubled. In analyzing the components of cost, we find that the length of stay, both in special care and regular nursing units, accounts for most of the cost increase. In our study of outcomes we find no significant difference in survival, at 1 month and 1 year, between recipients operated on from the intensive care unit and those not in intensive care. We find that at 1 year after transplantation, approximately 80% of patients are rehabilitated, which we define as the ability to work or to go to school. Only 20% of patients are off disability rolls, however, primarily because of problems related to insurance and the cost of continuing care, including drugs. We conclude that the comprehensive evaluation of surgical procedures requires an approach that balances costs with results on a continuing and long-term basis.
Costs and Cost Analysis↗
Management of peripheral vascular problems in recipients of cardiac allografts.
Five hundred and twenty consecutive heart transplant cases (458 adult, 62 pediatric) were reviewed to assess the impact of peripheral vascular problems. Peritransplant interventions requiring vascular cannulation (e.g., intraaortic balloon pump procedures, catheterization of the right and left sides of the heart, femoral bypass) resulted in 10 complications that necessitated nine surgical procedures. Five aortic aneurysms (three infrarenal and two suprarenal) were resected. There was one death unrelated to the aneurysm resection. Sixteen patients had evidence of peripheral vascular disease (PVD). There were three deaths in this group, none directly related to the PVD. Three patients required vascular reconstruction (axillobifemoral, bilateral femoral distal and popliteal endarterectomy) in the posttransplant period, all for advanced ischemic symptoms. Except for one patient in whom ischemia-related ulcers developed on the heels, all patients had improved or stable symptoms that did not require intervention. There were no limb losses or vascular infections. We conclude that despite the rigors of posttransplant immunosuppression, patients with stable manifestations of PVD may successfully undergo heart transplantation and subsequent vascular reconstruction, when indicated, without prohibitive risk.
Adolescent↗
Cardiac transplantation after prolonged graft preservation with the University of Wisconsin solution.
We tested the ability of University of Wisconsin solution to extend hypothermic preservation of the nonperfused heart during orthotopic baboon allotransplantation. Seven baboons received hearts after cardioplegia and storage (4 degrees C) with University of Wisconsin solution, with a preservation time of 14.2 +/- 1.6 hours. One animal died as a result of a technical error. Six survivors were immunosuppressed for 45 days and then put to death. Preservation did not alter heart weight or histologic features according to light and electron microscopy. Animals were weaned from bypass and returned to their cages without intravenous support within 3.9 +/- 0.8 hours. Weekly biopsies, electrocardiograms, enzyme analyses, echocardiograms, and right heart catheterizations demonstrated excellent cardiac function. University of Wisconsin solution can extend hypothermic cardiac preservation and has no deleterious effects on long-term myocardial function (up to 45 days). This study validates the rationale for human trials with preservation and storage in University of Wisconsin solution toward the goal of improving and prolonging donor heart preservation.
Adenosine↗
Permanent pacing following cardiac transplantation.
Permanent pacemakers were inserted in 20 of 439 patients who had received 453 orthotopic cardiac allografts since 1980 at the Columbia-Presbyterian Medical Center. Mean age at transplantation was 45 +/- 4 (SEM) years (range 10 to 64). Pacemakers were inserted an average of 2.4 +/- 1 months after transplantation (range 0.4 to 29), 16 of 20 (80%) within the first month. Indications included sinus bradycardia or sinus arrest in 15 (75%), third-degree heart block in 2 (10%), and both sinus node and atrioventricular node dysfunction in 3 (15%). Rejection episodes and pacemaker insertion were associated in 8 patients (40%). Pacing modes included DDD (7 patients, 35%), AAI,R (7 patients, 35%), VVI,R (3 patients, 15%), DDD,R (2 patients, 10%), and VVI (1 patient, 5%). There was no pacing-related morbidity or mortality. Fourteen of 20 patients (70%) are alive and well 3 to 48 months (mean 24 +/- 4) after transplantation. Late follow-up indicated that atrioventricular node dysfunction resolved in one of two patients, sinoatrial node dysfunction improved or resolved in 7/13 patients, and no atrioventricular block developed in 11 (8 to 37 months, mean 22 +/- 3). Permanent pacing can be safely performed following orthotopic cardiac transplantation, predominantly for sinus node dysfunction. The requirement for pacing may reflect ongoing or new onset rejection and patients should therefore be evaluated accordingly. Dual-chamber pacing is probably not necessary unless atrioventricular node dysfunction is coexistent. Further, as most transplant recipients return to an active life-style, AAI,R may be the preferred mode of pacing.
Adolescent↗