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Biomedical subjects

H R Doyle

Publications and source records attributed to H R Doyle.

28 records · Page 2Linked to original sources
PubMed1994

Early death or retransplantation in adults after orthotopic liver transplantation. Can outcome be predicted?

Early, reliable outcome prediction after a liver transplant would help improve organ use by minimizing unnecessary retransplantations. At the same time, early intervention in those cases destined to fail may ameliorate the high morbidity and mortality associated with retransplantation. The purpose of this study was to analyze several parameters that have been identified in the past as being associated with patient and graft outcome, and to try to develop a model that would allow us to make predictions based on data available in the early postoperative period. A total of 148 patients were followed in a prospective, observational study. Graft failure was defined as patient death or retransplantation within 3 months of surgery. Preoperative variables studied included patient demographics, need for life support, presence of ascites, serum bilirubin, serum albumin, prothrombin time, serum creatinine, and the results of the cytotoxic crossmatch. During the first 5 postoperative days, standard measurements included serum transaminases, serum bilirubin, ketone body ratio, prothrombin time, factor V, and serum lactate. Oxygen consumption was measured shortly after surgery, once the patients had rewarmed to 36 degrees C. There were 131 successful transplants (88.5%) and 17 failures (11.5%). Most of the variables studied were found to be associated with outcome (by univariate analysis) at different points in the early postoperative period. However, receiver operating characteristic curve analysis showed that the predictive ability of even the best parameter was not adequate to make decisions on individual patients. Multivariate analysis, using stepwise logistic regression, yielded a model with an overall accuracy of 92.7%. Again, receiver operating characteristic curve analysis suggested that this model did not achieve the discriminating power needed for routine clinical use. We are still not able to accurately predict outcome in the early posttransplant period. We must be very careful when evaluating parameters, or scoring systems, that are said to accomplish this. It is especially important in this era of cost containment, with its renewed pressures to guide therapy based on our perceived understanding of a patient's future clinical course.

Bilirubin↗
PubMed1994

Liver transplantation without the use of blood products.

OBJECTIVES: To examine the techniques and the outcome of liver transplantation with maximal conservation of blood products and to analyze the potential benefits or drawbacks of blood conservation and salvage techniques. DESIGN: Case series survey. SETTING: Tertiary care, major university teaching hospital. PATIENTS AND METHODS: Four patients with religious objections to blood transfusions who were selected on the basis of restrictive criteria that would lower their risk for fatal hemorrhage, including coagulopathy, a thrombosed splanchnic venous system requiring extensive reconstruction, active bleeding and associated medical complications. All patients were pretreated with erythropoietin to increase production of red blood cells. All operations were performed at the same institution, with a 36-month follow-up. INTERVENTIONS: Orthotopic liver transplantation that used blood salvage, plateletpheresis, and autotransfusion and the withholding of the use of human blood products with the exception of albumin. MAIN OUTCOME MEASURES: Survival and postoperative complications, with the effectiveness of erythropoietin and plateletpheresis as secondary measures. RESULTS: All patients are alive at 36 months after orthotopic liver transplantation. One patient, a minor (13 years of age), was transfused per a state court ruling. Erythropoietin increased the production of red blood cells as shown by a mean increase in hematocrit levels of 0.08. Platelet-pheresis allowed autologous, platelet-rich plasma to be available for use after allograft reperfusion. Three major complications were resolved or corrected without sequelae. Only one patient developed postoperative hemorrhage, which was corrected surgically. The mean charge for bloodless surgery was $174,000 for the three patients with United Network for Organ Sharing (UNOS) status 3 priority for transplantation. This result was statistically significant when these patients were compared with all the patients with UNOS status 3 priority during the same period who met the same restrictive guidelines (P < .05). Only 19 of 1009 orthotopic liver transplantations performed at our institution were similar according to the UNOS status and the fulfillment of the guidelines. The mean charge for these comparison patients was $327,000, 3.8% of which was related to transfusions. CONCLUSIONS: Orthotopic liver transplantation without the use of blood products is possible. Blood conservation techniques do not increase morbidity or mortality and can result in fewer transfusion-related, in-hospital charges.

Adolescent↗
PubMed1994

Predicting outcomes after liver transplantation. A connectionist approach.

OBJECTIVE: The authors sought to train an artificial neural network to predict early outcomes after orthotopic liver transplantation. SUMMARY BACKGROUND DATA: Reliable prediction of outcomes early after liver transplantation would help improve organ use and could have an impact on patient survival, but remains an elusive goal. Traditional multivariate models have failed to attain the sensitivity and specificity required for practical clinical use. Alternate approaches that can help us model clinical phenomena must be explored. One such approach is the use of artificial neural networks, or connectionist models. These are computation systems that process information in parallel, using large numbers of simple units, and excel in tasks involving pattern recognition. They are capable of adaptive learning and self-organization, and exhibit a high degree of fault tolerance. METHODS: Ten feed-forward, back-propagation neural networks were trained to predict graft outcomes, using data from 155 adult liver transplants. The data included information that was available by the second postoperative day. Ten separate training and testing data subsets were prepared, using random sampling, and the ability of the different networks to predict outcomes successfully was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Four of the networks showed perfect discrimination, with an area under the ROC curve (Az) of 1.0. Two other networks also had excellent performance, with an Az of 0.95. The sensitivity and specificity of the combined networks was 60% and 100%, respectively, when using an output neuron activation of 0.6 as the cutoff point to decide class membership. Lowering the cutoff point to 0.14 increased the sensitivity to 77%, and lowered the specificity to 96%. CONCLUSIONS: These results are encouraging, especially when compared to the performance of more traditional multivariate models on the same data set. The robustness of neural networks, when confronted with noisy data generated by nonlinear processes, and their freedom from a priori assumptions regarding the data, make them promising tools with which to develop predictive clinical models.

Adult↗
PubMed1993

Adult respiratory distress syndrome secondary to end-stage liver disease-successful outcome following liver transplantation.

The adult respiratory distress syndrome (ARDS) complicating liver failure carries a 100% mortality. Two cases of ARDS that resolved following liver transplantation have been reported, one associated with acute allograft rejection, and the second due to sepsis. There is, however, a great reluctance to transplant these very-high-risk patients. We report the first series of patients with ARDS secondary to liver failure who successfully underwent OLTX. No patient had sepsis or pneumonia. Posttransplant mechanical ventilation was required for a median of 14 days (range 6-37 days). All patients in this series are alive and well, with a follow-up of 6-15 months. This demonstrates that ARDS associated with liver failure, an otherwise uniformly lethal complication, can respond dramatically to OLTX.

Adolescent↗
PubMed1992

Antibody binding to endothelial and epithelial antigens triggers pig-to-rabbit xenograft rejection and its absence results in atypical complement deposition.

In pig-to-rabbit kidney xenograft (PRKX), endothelial antigen determinants (EAD) are immediately recognized by IgG and IgA, while IgM does not react with them. The purpose of this study was to investigate the different roles of IgG, IgA, IgM, and complement in the hyperacute rejection of a PRKX model. Nine isolated Landrace pig kidneys were each perfused with 10 ml normal New Zealand rabbit serum. Perfusates (serum A) were collected after discarding the first 0.5 ml. Serum A and rabbit complement were then incubated for 30 min with frozen sections of normal pig kidney. After washing with buffer solution all the specimens were treated for immunohistochemistry. Three frozen sections of normal Landrace pig kidney and three samples of normal New Zealand rabbit serum were used as controls. Immunohistochemical analysis of the nine perfused kidneys demonstrated IgG, IgA and C3 deposition on the peritubular and glomerular vascular endothelium. No IgM reactivity was shown. In the frozen sections exposed to serum A, immunofluorescence showed minimal IgG, IgA and C3 reactivity while IgM deposition was clearly evident on the tubular epithelium. Immunofluorescence of frozen sections exposed to rabbit complement, done by fluorescein-labeled goat anti-rabbit C3 antibodies were positive only in the glomerular endothelium. The same rabbit complement was active in antibody dependent cytotoxicity on human T cells. Our results indicated that in the PRKX model, IgG and IgA acted as preformed antibodies recognizing endothelial EAD. IgM did not bind to any endothelial molecules, but recognized antigens located on the brush border of the tubular epithelium. Furthermore, in this model, absence of antigen-antibody complexes resulted in atypical complement deposition.

Animals↗
PubMed1991

Orthotopic liver transplantation for life-threatening veno-occlusive disease of the liver after allogeneic bone marrow transplant.

Veno-occlusive disease (VOD) of the liver is a serious and often lethal sequela to bone marrow transplantation. Although a history of prior hepatitis moderately increases the risk of VOD, reliable screening methods for identifying high risk patients are not available. New approaches to managing patients who develop serious VOD are needed. One approach may be the use of orthotopic liver transplantation in selected patients who are likely to die of the disease. In this report we describe a patient who underwent liver transplantation for life-threatening VOD following allogeneic transplantation for CML. Although this patient died early from interstitial pneumonitis, the orthotopic liver functioned well up to her death. Other reports describing successful liver transplants in patients with advanced VOD or graft-versus-host disease of the liver are discussed and the possible indications for liver transplantation for VOD after marrow transplantation are considered. Taken together, these reports suggest that orthotopic liver transplantation may be a feasible and potentially effective approach to managing select patients with life-threatening liver dysfunction after marrow transplantation.

Adult↗
PubMed1988

The mechanism of the inhibitory action of neurotensin on pentagastrin-stimulated gastric secretion in dogs.

Neurotensin is a potent inhibitor of pentagastrin-stimulated gastric acid secretion. This study was done to investigate the possible role of vagal innervation and of prostaglandins on this inhibitory effect. Five dogs with gastric cannulas were infused with pentagastrin (1 microgram per kilogram of body weight each hour) for 210 minutes. In the 60 to 150 minute period, neurotensin (5.5 micrograms per kilogram of body weight each hour) was infused. Neurotensin significantly decreased pentagastrin-stimulated gastric acid output, while the simultaneous administration of indomethacin (bolus of 1 milligram per kilogram of body weight plus infusion of 0.5 milligrams per kilogram each hour) abolished the effect of neurotensin. After truncal vagotomy, the inhibitory effect of neurotensin was again studied. Since the sensitivity of the stomach to pentagastrin decreased after vagotomy, the dose of pentagastrin was doubled (2 micrograms per kilogram of body weight each hour) in order to achieve acid stimulation comparable with the levels before vagotomy. After vagotomy, neurotensin inhibited the effect of pentagastrin in a manner similar to that shown before vagotomy. The inhibitory potency of neurotensin on gastrin-stimulated gastric secretion is independent of the vagus, but requires intact synthesis for prostaglandins.

Animals↗
PubMedDate not supplied

Xenotransplantation rejection is antibody-mediated in both sensitized and nonsensitized recipients.

This study analyzes the mechanisms involved in xenotransplantation rejection between closely related species. Hamster hearts were transplanted heterotopically into both normal rats and rats previously sensitized by the transfusion of donor blood. Sequential ultrastructural and immunohistochemical analyses were performed on the grafts, spleens, and sera. The data obtained support the view that induced antibodies directed against the xenograft endothelium play a very important role in producing graft damage. Moreover, the demonstration of antibodies against myocyte determinants suggests that it is possible, in this particular model, that the antiendothelial antibodies are not the only ones involved in the injury process.

Animals↗