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Biomedical subjects

B P Griffith

Publications and source records attributed to B P Griffith.

At least 271 records · Page 15Linked to original sources
PubMed1988

Role of the antibody to vascular endothelial cells in hyperacute rejection in patients undergoing cardiac transplantation.

Traditionally, the human lymphocyte antigens have been considered to be the major barrier to successful transplantation, and lymphocytes have been used as the target cell in evaluating histocompatibility. The presence in the serum of recipients of preformed antibodies, cytotoxic to donors lymphocytes, is associated with a high probability of hyperacute rejection. We identified 11 patients in whom, despite a compatible direct lymphocytotoxic cross-match, acute failure of the cardiac homograft was associated with histologic and immunologic findings consistent with hyperacute rejection. Direct immunofluorescence and immunohistochemical staining showed the presence of antibodies on the surface of vascular endothelial cells in each of these 11 patients. The serum of these recipients was found to contain antibodies against a panel of endothelial cells. In contrast, cytotoxic antibodies to vascular endothelial cells were not present in a control group of 18 heart transplant recipients who did not experience hyperacute rejection. Thus the presence of antibodies against vascular endothelial cells seems to be related to hyperacute rejection of the cardiac allograft.

Antibodies↗
PubMed1988

Extracorporeal membrane oxygenation in children. New trends.

At the Children's Hospital of Pittsburgh the extracorporeal membrane oxygenation program was started in 1980. The results of our experience from 1980 to 1985 were previously reported. In the past 2 years 39 additional newborn infants have been treated with this modality, with an overall survival rate of 79% (31/39). This survival rate is much better than that obtained in 33 neonates who had been treated in the previous 5 years (54%; p less than 0.05). A new aspect of our extracorporeal membrane oxygenation program is the use of total apneic lung rest for persisting pulmonary interstitial emphysema during support with the oxygenator. Six neonates were treated with this technique because of worsening pulmonary interstitial emphysema during extracorporeal circulation. Five of them survived. Another indication for extracorporeal membrane oxygenation in our pediatric population has been left ventricular or biventricular failure after cardiopulmonary bypass. Four of our seven patients treated for this indication are long-term survivors. At present, because of the impossibility of using other forms of left ventricular assist devices in the pediatric population, it seems that extracorporeal membrane oxygenation is the most effective treatment for left ventricular failure after cardiopulmonary bypass. From our experience, even in the absence of long-term follow-up of patients supported with extracorporeal membrane oxygenation, it appears that the benefits of this therapeutic modality far exceed the risks in the high-risk population for which it is being used.

Cardiopulmonary Bypass↗
PubMed1988

Upper gastrointestinal endoscopy after cardiac transplantation.

Three hundred four patients have undergone cardiac transplantation at the University of Pittsburgh since 1980. Twenty patients have required 27 upper gastrointestinal (GI) endoscopic procedures. After heart transplantation the primary indications for endoscopy were epigastric pain (six patients with gastritis, one with multiple shallow gastric ulcers, and one with normal test results), mild upper GI bleeding (four patients with esophagitis, two with gastritis, and two with multiple shallow gastric ulcers), dysphagia and odynophagia (two patients with esophagitis), persistent nausea and vomiting (one with normal test results), lower GI bleeding (one with normal test results), and routine follow-up (one with normal test results). After heart-lung transplantation the primary indications for the endoscopy were massive upper GI bleeding (three patients with actively bleeding duodenal ulcers), dysphagia and odynophagia (one patient with esophagitis), mild upper GI bleeding (one patient with gastritis), and routine follow-up (one patient with normal test results). No complications resulted from endoscopy. The procedures were performed in the GI suite without cardiac monitoring. Prophylactic antibiotics were not routinely administered. No patient had a fungal infection of the upper GI tract--a finding attributed to the prophylactic use of nystatin in all patients. Opportunistic viral infections were identified histologically in six patients, including two patients with actively bleeding duodenal ulcers. The possibility of opportunistic viral infections in this immunosuppressed group required aggressive diagnostic techniques, including endoscopy and biopsy, which can be safely performed after cardiac transplantation.

Adult↗
PubMed1987

Temporary use of the Jarvik-7 total artificial heart before transplantation.

Between October 24, 1985, and July 31, 1986, the Jarvik-7 total artificial heart was implanted into six moribund patients in an attempt to test its potential as a bridge from almost certain death to cardiac transplantation. Four of these patients are now well and at home after implantation of the device and subsequent cardiac transplantation. Before transplantation, one patient died with sepsis and multiorgan failure that preceded implantation of the artificial heart. Another patient died with acute rejection 60 days after cardiac transplantation. Fifty-two days of total mechanical support with the artificial heart were accumulated in these six patients, and although the device worked flawlessly and no clinically apparent thromboembolic events occurred, each artificial heart contained areas of macroscopic aggregations of platelets and thrombi. The results of this trial indicate that in properly selected cases, direct benefit to the patient can be obtained when the Jarvik-7 artificial heart is used as a bridge to transplantation.

Adult↗
PubMed1987

Delayed amplification of cytomegalovirus infection in the placenta and maternal tissues during late gestation.

To stimulate first-trimester human cytomegalovirus infection, pregnant guinea pigs were inoculated with a low dose of guinea pig cytomegalovirus during the first trimester of pregnancy. Maternal viremia, which was cleared by 2 weeks after inoculation, was found to reappear near the time of delivery in one third of the animals tested. The virus, first detected in the placenta during initial maternal viremia, replicated after the time when maternal blood was cleared of virus, although high titers of maternal serum antibodies were present. In the last week of gestation (43 to 48 days after inoculation), the virus was detected in 95% of placentas and was present at high titers. Fetal infection first appeared on day 25 after inoculation and reached an incidence of 37% in the last week of gestation despite the presence of fetal antibody. These results suggest that the placenta may amplify cytomegalovirus infection late in human gestation, even after low-dose infection in the first trimester.

Animals↗
PubMed1987

Thymic hypoplasia, splenomegaly and immune depression in guinea pigs with neonatal cytomegalovirus infection.

The effects of cytomegalovirus (CMV) infection on the spleen and thymus of neonatal guinea pigs were assessed. Guinea pigs with neonatally acquired CMV infection developed growth retardation, thymic hypoplasia and splenomegaly. Significant depletion of the T lymphocyte population occurred in the thymuses of these animals whereas inflammatory and immune proliferative responses were clearly evident in their spleens. Higher titers of infectious virus were recovered from the spleen than from the thymus. In addition, spleen cells from neonatally infected animals had significantly reduced proliferative responses to both the T-cell mitogen, concanavalin A, and the B-cell mitogen, lipopolysaccharide. Responses to concanavalin A were most severely impaired. These results point to the significant immunodepressive effect of acute CMV infection and to the dissimilar alterations induced by CMV in the spleen and thymus of acutely infected neonates.

Animals↗
PubMed1987

Detection of guinea pig cytomegalovirus nucleic acids in cultured cells with biotin-labelled hybridization probes.

Biotin labelled hybridization probes prepared from recombinant plasmids containing segments of the guinea pig cytomegalovirus (GPCMV) genome were used to detect GPCMV nucleic acids in guinea pig cells by in situ hybridization. The time course of GPCMV infection was assessed in two cultured cell types, guinea pig embryo (GPE) cells and 104C1 cells, a transformed and cloned guinea pig cell line. Detection of GPCMV nucleic acids was accomplished in both cell types with individual GPCMV DNA fragments and with mixtures of GPCMV DNA fragments. When compared to other established methods of GPCMV detection, the method of in situ hybridization enabled the detection of a higher percentage of positive cells early during the course of the infection. In addition, differences in the replication cycle of GPCMV in the two cultured cell lines could be demonstrated. These findings will facilitate future studies of GPCMV tissue tropism in vivo.

Animals↗
PubMed1987

Heart-lung transplantation: lessons learned and future hopes.

Since March, 1982, 33 patients have undergone cardiopulmonary transplantation. Nineteen were discharged from the hospital following the operation, and 16 continue to do well. Eight patients have survived 1 year, 5 patients 2 years, and 1 patient 3 years. Often survival has been influenced most by the selection of candidates, as no patient who had undergone a previous sternotomy survived (3 of 3). All 7 early (between 30 and 72 days) and 3 late (145 to 466 days) deaths were related to infection. Methods for ex vivo preservation of the heart-lung bloc have included storage at 4 degrees C, cardiopulmonary bypass and profound hypothermia, and autoperfusion of the heart-lung bloc. The last technique is original and currently is preferred for distant procurement. Because dehiscence of the tracheal anastomosis has occurred in 3 patients, a sutured line is now encircled with a wrap of omentum. Isolated rejection of the lung is frequent in the first three weeks following operation and has been controlled with methylprednisolone. Late survivors have shown a mild restrictive lung disorder that has not progressed between 6 and 24 months. Bronchoalveolar lavage has been useful for diagnosing infection and providing insight into the immunobiology of the transplanted lung. Although mortality and morbidity have been high, the experiences gained through this series will likely result in an improved outlook for future recipients.

Adolescent↗
PubMed1987

Early and late forms of cyclosporine nephrotoxicity: studies in cardiac transplant recipients.

To characterize the two forms of cyclosporine nephrotoxicity, we examined renal function in the immediate and late postoperative periods after cardiac transplantation. Moderate azotemia occurred during the first postoperative week in 58% of 43 cyclosporine-treated recipients, but in only 34% of 41 azathioprine-treated recipients, and 4% of 25 patients undergoing cardiopulmonary bypass for nontransplant surgery (both P less than .01 v cyclosporine). Acute renal failure developed in an additional 12% of the cyclosporine-treated group. Late postoperative renal dysfunction also occurred with a high prevalence. Life-table analysis indicated that at 6 months 55%, at 12 months 17%, at 24 months 4%, and at 36 months no cyclosporine-treated recipients retained normal renal function. Three renal biopsies performed in subjects with late nephrotoxicity demonstrated prominent interstitial fibrosis. Although one patient subsequently required chronic dialysis, reduction of cyclosporine dosage from a mean of 5.3 +/- 0.7 mg/kg/d to a mean of 2.3 +/- 0.3 mg/kg/d 9 to 21 months after transplantation with concurrent initiation of azathioprine therapy to prevent rejection led to an improvement of renal function in the five patients so treated. These data indicate that there are two distinct forms of cyclosporine nephrotoxicity. Although both occur with high prevalence, the early form does not appear to be a specific risk factor for the late form.

Acute Kidney Injury↗
PubMed1987

Heterotopic cardiac transplantation: current status.

Heterotopic cardiac transplantation first introduced by Bernard in 1974 currently is rarely used as the procedure of choice when orthotopic cardiac transplantation can be considered. Specific indications for heterotopic cardiac transplantation include elevation of pulmonary vascular resistance and availability of a small or poorly functioning donor organ for a mortally ill recipient. Most cardiac transplant centers have abandoned its routine use because the recipient's diseased and poorly functioning heart remains as a potential source for embolism, infection, and continued angina, because the operative procedure is more complicated. Pulmonary complications are common due to compressive atelectasis of the right lung. Experience indicates that the heterotopic procedure is useful for those selected individuals in whom the orthotopic procedure is not appropriate and that rates of survival are nearly equal.

Anastomosis, Surgical↗
PubMed1987

Monocyte-mediated immunosuppression in chronic multiple sclerosis: implications for therapy.

The goal of immunotherapy in multiple sclerosis (MS) is to halt disease progression by correcting an immunologic abnormality. The experiments described here sought an abnormality of immunoregulation. Specifically, the immunosuppressive activity of adherent monocytes in an in vitro assay of immunoglobulin-secreting cells was tested. Although the peak response was slightly lower, the induction, development and shutdown of the response by MS cells reproduced that of control cells. Most importantly, adherent monocytes from patients with MS exerted the same maximal suppression as did monocytes from controls. Further experiments are required to determine if the adherent monocyte is an appropriate target for immunotherapy in MS.

Adult↗
PubMed1987

Effects of cyclosporine on chronic cytomegalovirus infection in the guinea pig.

Following establishment of chronic guinea pig cytomegalovirus (GPCMV) infection, animals received by gavage either cyclosporine (CS), 20-33 mg/kg, or drug vehicle daily for 28 days. At sacrifice the frequency of CMV isolation from tissues of GPCMV-infected animals was 20% for the immunosuppressed group versus 12% for controls (difference, NS). GPCMV isolation rates from lymphoid tissues (thymus, spleen, cervical lymph nodes) of experimental animals was 7 of 69 (10%) vs. 0 of 42 (0%) from controls (p less than 0.05). Although CS immunosuppression was associated with increased rates of GPCMV isolation from lymphoid tissues of chronically infected animals, it was not accompanied by detectable systemic disease.

Animals↗
PubMed1987

Development of coronary artery disease in cardiac transplant patients receiving immunosuppressive therapy with cyclosporine and prednisone.

Coronary artery disease (CAD) has been shown in previous uncontrolled studies to be a limiting factor to long-term survival in patients undergoing cardiac transplantation and who were taking conventional immunosuppressive agents. To study the development of CAD after cardiac transplantation in patients taking the newer immunosuppressive agent cyclosporine, we prospectively performed yearly coronary arteriography on all eligible transplantation patients (first year, 57 patients; second year, 30 patients; third year, 14 patients). The prevalence of CAD by life table analysis was 18% at 1 year, 27% at 2 years, and 44% at 3 years. The occurrence of two or more major rejection episodes was associated (p less than .005) with the development of CAD. In two patients who died of CAD, coronary artery histology revealed subintimal inflammatory cellular infiltration in some lesions. These data demonstrate that the prevalence of CAD rises progressively over time and immunologic factors may be important in its development.

Adult↗
PubMed1987

Sternotomy infections with Mycoplasma hominis.

Mycoplasma hominis caused sternal wound infections with mediastinitis in three patients. One infection occurred in a nonimmunocompromised man after coronary artery bypass grafting. The wound did not heal after repeated debridement, closed irrigation of the mediastinum with povidone-iodine solution, and antimycoplasmal chemotherapy; muscle flap grafting was eventually required. Two infections occurred in recipients of heart-lung transplants after the isolation of mycoplasma from bronchial secretions. Although no Mycoplasma species were isolated after specific antimycoplasmal therapy was begun, the wounds still did not heal. Both patients died of other complications. Infection of wounds after sternotomy is another of an increasing number of infections caused by M. hominis in the normal and immunocompromised host. Familiarity with the morphologic characteristics of M. hominis on bacteriologic culture media may increase the recognition of this pathogen in atypical clinical settings.

Adult↗
PubMed1987

Heart-lung transplantation.

The survival rate (average, 50%) of patients undergoing cardiopulmonary transplantation falls well below that expected for cardiac transplantation alone. We give a broad overview of the various grounds upon which this difference is likely based and discuss recent advances in each area: 1) criteria for the selection of candidates and donors, 2) methods for ex-vivo preservation of donor organs, 3) technical execution of the operative procedure, and 4) prevention of postoperative infection. In connection with the prevention of postoperative infection, we discuss the potential for the development of a chronic obliterative disease that, once established, has proved inexorable. Current efforts are focused on detection when the process is in an early, reversible stage, and on research into causation.

Journal Article↗