Failure of donor-specific pretransplant blood transfusion to prolong heterotopic cardiac allograft survival in rats.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to C R Smith.
Explore the source record for details and available documents.
Cardiac xenotransplantation in nonprimates using traditional immunosuppression (azathioprine and prednisone) or cyclosporine has been unsuccessful or has required doses of immunosuppressants not tolerated by man. This study sought to determine if primate hearts could be transplanted successfully across genus boundaries using a dose of cyclosporine applicable to human transplantation. The hearts of outbred cynomolgus monkeys (Macaca fascicularis) were heterotopically transplanted into the necks of outbred baboons (Papio anubis). Hyperacute rejection did not occur and there were no cyclosporine-induced malignancies or nephrotoxicity. A 12-fold prolongation of mean cardiac xenograft survival to 77 days was accomplished using parenteral cyclosporine and steroids. The histology of rejection was notable for the appearance of reversible rejection on the 30-day biopsies. The histopathologic and immunologic data support the role of both cell-mediated and humoral mechanisms in primate cardiac xenograft rejection. Neither mixed lymphocyte cultures or cytotoxic antibody assays were predictive of graft loss, but there was a significant increase in their respective levels at the time of cessation of graft function. Thus, significant prolongation of primate cardiac graft survival across a genus boundary was accomplished using a dose of cyclosporine similar to that used in human transplantation.
One hundred and two cases of neonatal cancers, representing 2% of all paediatric malignancies, were seen during a 60 year period at The Hospital for Sick Children, Toronto, Canada. The neonatal cancers included neuroblastoma (47%), retinoblastoma (17%), soft tissue sarcoma (12%), central nervous system tumours (9%), leukaemia (8%), and a few cases of Wilms' tumour, liver tumour, and miscellaneous tumours. The overall mortality from disease was 41%. Patients with retinoblastoma, Wilms' tumour, and neuroblastoma had the best prognosis. Forty three patients (42%) survived their neonatal cancers; all were treated with surgery or radiochemotherapy, or both, but none suffered long term major handicaps as a result of treatment. There was one instance of second malignancy of the thyroid gland induced by radiation. We conclude that although neonatal cancers are difficult management problems, many patients can be cured. Physicians should discuss with parents the possible risks associated with treatment before treatment is begun.
A patient developed refractory hypoxemia and right-to-left shunt across a patent foramen ovale after orthotopic cardiac transplantation. The right-to-left shunt was produced by volume overload of the donor right ventricle during the period of early postoperative myocardial depression and resolved with preload reduction and diuresis. Increased preload of the right heart needs to be considered in the early postoperative management after cardiac transplantation. The foramen ovale of the donor and recipient should be evaluated at operation by visual and probe examination and securely closed if either is patent, since this pattern of hemodynamic changes is common following cardiac transplantation.
STUDY OBJECTIVE: To compare the effectiveness and adverse effects of air-fluidized beds and conventional therapy for patients with pressure sores. DESIGN: Randomized trial with both masked and unmasked comparisons of outcome after a median follow-up of 13 days (range, 4 to 77 days). SETTING: Urban, academic referral, and primary care medical center. PATIENTS: Of 140 potentially eligible hospitalized patients with pressure sores, 72 consented to randomization; 65 (90%) completed the study. INTERVENTIONS: Thirty-one patients on air-fluidized beds (Clinitron Therapy, Support Systems International, Inc., Charleston, South Carolina) repositioned every 4 hours from 0700h to 2300h without use of other antipressure devices. Thirty-four patients on conventional therapy used an alternating air-mattress covered by a foam pad (Lapidus Air Float System, American Pharmaceal Company, Cincinnati, Ohio) on a regular hospital bed; were repositioned every 2 hours; and had elbow or heel pads as needed. Topical therapy was standardized for both groups. MEASUREMENTS AND MAIN RESULTS: Pressure sores showed a median decrease in total surface area (-1.2 cm2) on air-fluidized beds, but showed a median increase (+ 0.5 cm2) on conventional therapy; 95% confidence interval (CI) for the difference between medians, -9.2 to -0.6 cm2 (p = 0.01). Improvement, as assessed from serial color photographs by investigators masked to treatment group, occurred in 71% and 47%, respectively; 95% CI for the difference, 1% to 47% (p = 0.05). For pressure sores 7.8 cm2 or greater, outcome differences between air-fluidized beds and conventional therapy were greater: median total surface area change was -5.3 and +4.0 cm2, respectively; 95% CI for the difference, -42.2 to -3.2 cm2 (p = 0.01). Improvement rates were 62% and 29% respectively; 95% CI for difference, 1% to 65% (p = 0.05). After adjusting for other factors associated with sore outcome, the estimated relative odds of showing improvement with air-fluidized beds were 5.6-fold (95% CI, 1.4 to 21.7) greater than with conventional therapy (p = 0.01). No significant increase in adverse effects was seen with air-fluidized beds. CONCLUSIONS: Our findings suggest that air-fluidized beds are more effective than conventional therapy, particularly for large pressure sores. Studies are needed to determine the effectiveness of air-fluidized beds in long-term care settings.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Severe elevation of pulmonary vascular resistance has been considered a contraindication to cardiac transplantation. Most centers exclude patients with pulmonary vascular resistance greater than 6 Wood units. Wood units, however, do not correct for variations in body size and therefore may not be the best measure for use in comparison of patients. We performed a retrospective analysis of 82 cardiac transplant recipients and compared preoperative pulmonary vascular resistance (PVR) calculated in two ways to the incidence of right ventricular failure and death. Our data show that the PVR index unit (PVRI) identifies those patients that are at risk for right heart failure better than the Wood unit, which does not correct for body size. Four patients died of right heart failure with resistance less than 6 Wood units, but had PVRI greater than 6 units. High resistance is not an absolute contraindication to cardiac transplantation; 28 of 33 patients operated on with a PVRI greater than 6 survived. The degree of elevation of PVR did not correlate with survival. Ten of 12 patients with a PVRI greater than 9 survived. Testing with nitroprusside at cardiac catheterization was helpful in determining reversibility of pulmonary vascular obstruction. No patients with a PVRI less than 6 developed right heart failure.
Multiple sclerosis (MS) is one of the most common diseases capable of producing severe disability in the young adult population. In fact, only rheumatic disorders and trauma exceed MS in this respect. Because the total population of patients in the United States is probably 250,000 to 500,000 and as a substantial number suffer severe disability, MS is a disease of considerable social and economic impact. The authors discuss the treatment of many of the most troubling symptoms of MS, including disorders of gait, bladder and bowel, upper extremities, speech, and deglutition. Such treatment entails careful assessment of the patient's neurologic and other symptoms; knowledge of his or her intellectual, emotional, and social skills and demands; and an understanding of the patient's support network.
Explore the source record for details and available documents.
Successful cardiac xenotransplantation would alleviate the severe shortage of donor organs that presently limits the availability of cardiac transplantation. Early attempts at human xenotransplantation achieved minimal success. However, the effectiveness of cyclosporine in nonhuman xenotransplant models has received little experimental investigation. We have therefore studied the effect of cyclosporine-based immunosuppression in primate cardiac xenograft models using cynomolgus monkey donors and baboon recipients. Donor hearts were transplanted heterotopically into the necks of recipients or in the orthotopic position. Recipients were treated with no immunosuppression (controls), cyclosporine and steroids, or cyclosporine, steroids, azathioprine, and antithymocyte globulin. Statistically significant prolongation of graft survival compared to the control group was observed in the heterotopic groups. Mean survival time of the cyclosporine-treated and steroid-treated heterotopic grafts was 61 days compared to 6 days for grafts in the control group (p = 0.01); the addition of azathioprine and antithymocyte globulin yielded a mean survival of 84 days (p less than 0.01). No significant increase in graft survival was noted in the orthotopic groups treated with either immunosuppressive regimen. Although long-term use of human xenografts as an alternative for heart replacement is not supported by these data, further investigation of the orthotopic model is clearly justified.
Explore the source record for details and available documents.
We assessed the value of 41 skin biopsy specimens obtained from 32 immunocompromised patients with fever and neutropenia. Fifty-six percent (23/41) of these biopsy specimens resulted in a specific diagnosis. These diagnoses included infection in 12 cases, graft-vs-host disease in nine, leukemic infiltrate in one, and drug reaction in one. The remaining 18 biopsy specimens showed either nonspecific changes or normal tissue. The infectious agents identified included Aspergillus in nine patients, Candida in three patients, and Staphylococcus aureus in one patient. As a result of the biopsy findings, therapy was altered in 49% (20/41) of the cases. The most frequent therapeutic change was initiation of amphotericin B for a demonstrated fungal infection. We found skin biopsies to be a valuable diagnostic tool in the assessment of the febrile, neutropenic, immunocompromised patient with skin lesions.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
To further define the nature of Lyme carditis, electrophysiologic study and endomyocardial biopsy were performed in a patient with Lyme disease, whose principal cardiac manifestation was high-degree atrioventricular block. Intracardiac recording demonstrated supra-Hisian block and complete absence of an escape mechanism. Gallium 67 scanning demonstrated myocardial uptake, and right ventricular endomyocardial biopsy revealed active lymphocytic myocarditis. A structure compatible with a spirochetal organism was demonstrated in one biopsy specimen. It is concluded that Lyme disease can produce active myocarditis, as suggested by gallium 67 imaging and confirmed by endomyocardial biopsy. Furthermore, the presence of high-grade atrioventricular block in this disease requires aggressive management with temporary pacemaker and corticosteroid therapy.
To determine if aminoglycoside use and liver disease interact to cause an increased risk for renal dysfunction, data from 179 hospitalized patients who had been enrolled in a prospective, randomized trial of nafcillin/tobramycin versus cefotaxime were analyzed. The cefotaxime-treated patients served as a control group not receiving an aminoglycoside. Renal dysfunction occurred in seven of 88 (8 percent) given cefotaxime and 37 of 91 (41 percent) given tobramycin (p less than 0.001), in 11 of 29 (38 percent) with liver disease and 33 of 150 (22 percent) without liver disease (p less than 0.08), and occurred in 11 of 15 (73 percent) with both liver disease and tobramycin use and in 0 of 14 (0 percent) with liver disease and cefotaxime use (p less than 0.001). By logistic regression analysis, the relative odds of renal dysfunction developing during tobramycin treatment in a patient were 6.0 (95 percent confidence interval: 3.8 to 9.5). The relative odds of renal dysfunction developing in a patient receiving tobramycin and having liver disease were 31.8 (95 percent confidence interval: 19.7 to 51.4). This analysis demonstrates an interaction between tobramycin use and liver disease for increasing the risk of renal dysfunction.
The method of caval occlusion during cardiopulmonary bypass using snares is at times cumbersome. An alternative technique of caval occlusion around venous cannulas using elastomer tape is described.