Search PubMed⌕ Search

Biomedical subjects

J Wallwork

Publications and source records attributed to J Wallwork.

At least 55 records · Page 3Linked to original sources
PubMed1999

The utility of pacemaker evoked T wave amplitude for the noninvasive diagnosis of cardiac allograft rejection.

Previous work suggested that pacemaker evoked T wave amplitude (ETWA) may be a sensitive noninvasive marker of cardiac allograft rejection. A Topaz QT sensing rate responsive pacemaker (Vitatron Medical) was implanted at transplantation using epicardial ventricular leads in 45 recipients (35 males; median age 51 years, range 20-63). The median duration of follow-up was 129 days (range 4-327). The ETWA at a paced rate of 100 beats/min was measured daily during hospitalization and at each outpatient attendance (900 readings). Endomyocardial biopsies were at routine intervals or when otherwise clinically indicated (257 biopsies with concurrent ETWA data). There were 58 episodes of rejection > or = grade 3a in 28 patients. The biopsies were classed as either no rejection (grade < 3a) or rejection requiring treatment (grade > or = 3a). The median normalized ETWA was 100.8% (range 24.6-239.7) without rejection and 89.9% (17.0-189.7) with rejection (Mann-Whitney U Test: P = 0.028). The performance of ETWA monitoring as a diagnostic test for the individual recipient was evaluated with exponentially weighted moving average quality control charts. For the diagnosis of all rejection episodes, ETWA monitoring had a sensitivity of 55%, a specificity of 62%, a positive predictive value of 30%, and negative predictive value of 83%. It is concluded that although analysis of pooled data showed a significant reduction in normalized ETWA with biopsy proven rejection, ETWA monitoring requires further refinement to improve sensitivity before it can be considered a clinically useful technique for the non-invasive diagnosis of cardiac allograft rejection in individual recipients.

Adult↗
PubMed1999

Prospective study of health related quality of life before and after coronary artery bypass grafting: outcome at five years.

OBJECTIVE: To determine the long term health related quality of life of coronary artery bypass graft patients, to look at changes between one and five years after surgery, and to examine the ability of preoperative variables to predict longer term outcome. DESIGN: Nottingham health profile (NHP) was used to assess patients at five years compared to results obtained at one year. PATIENTS: 100 male patients aged < 60 years at time of surgery; 77 had three vessel disease and 84 received three or more saphenous vein grafts. RESULTS: In comparing the five year results with those at one year, lower mean scores, indicating slight improvements, were seen in the NHP dimensions of pain, sleep, social isolation, and emotional reactions, whereas signs of deterioration were noted in the physical mobility and energy scores. Chest pain was experienced by 34 of 84 patients at five years compared with 17 of 89 patients at one year. The proportion of patients who were unrestricted in their activities ranged from 61-70% at five years compared with 82-88% at one year. Absence of dyspnoea before surgery, indicating relatively good left ventricular function, was a predictor of good outcome at both one and five years. CONCLUSIONS: Evidence of deterioration in physical function is compatible with expected decline in graft patency; specific rather than generic measures were most sensitive to this change.

Adult↗
PubMed1999

Metastatic endometrial stromal sarcoma masquerading as pulmonary lymphangioleiomyomatosis.

A 39 year old female presented with bilateral pneumothoraces and interstitial shadowing on chest x ray. A diagnosis of lymphangioleiomyomatosis was made following an open lung biopsy. Over the next eight years she developed respiratory failure leading to single lung transplantation but she died in the immediate postoperative period. Necropsy examination and review of the previous open lung biopsy revealed multiple pulmonary metastases from a low grade endometrial stromal sarcoma of the uterus. This case high-lights the importance of an accurate diagnosis before transplantation.

Adult↗
PubMed1999

[Xenotransplantation of hDAF-transgenic swine hearts].

Hearts of transgenic pigs expressing a human regulator of complement activation, decay accelerating factor (hDAF), were transplanted either heterotopically into the abdomen of cynomolgus monkeys or orthotopically into baboons. None of these transgenic hearts was hyperacutely rejected. Immunosuppression with a combination of cyclosporine A, cyclophosphamide and steroids produced a maximum survival of 62 days (median 40 days) in the heterotopic model. Transgenic hearts transplanted into the orthotopic position allowed a maximum survival of 9 days (median 2.5 days). A more effective and less toxic immunosuppressive protocol for the prevention of accelerated xenograft rejection is the subject of ongoing research. The use of organs from transgenic pigs may help to solve the problem of donor shortage in clinical allotransplantation.

Animals↗
PubMed1999

Cytomegalovirus disease as a possible etiologic factor for early atherosclerosis.

A group of 284 patients who underwent orthotopic heart transplantation between April 1986 to June 1991 and who were followed up for at least five years was analyzed in this paper. Patients were divided into three groups according to the presence or absence of cytomegalovirus infection or disease: patients without infection, patients with serologycaly proven infection and patients with cytomegalovirus disease. The analysis of survival was performed with respect to all major factors that influence survival: age and sex of a donor and a recipient, number of rejection episodes, perioperative ischemic time and pulmonary vascular resistence. A recipient's age was shown to be a significant factor. Patients who experienced at least one episode of cytomegalovirus disease had significantly worse long-term survival compared to those with the infection only or without the infection. That difference was caused by the increased incidence of coronary atherosclerosis, which caused deaths in patients with a previous episode of cytomegalovirus disease. A possible mechanism responsible for this phenomenon is discussed.

Coronary Artery Disease↗
PubMed1999

Thoracic organ transplantation at Papworth Hospital.

More than 1,200 patients have now undergone thoracic transplantation at Papworth Hospital and about 90 transplants are performed annually. Papworth remains one of the largest transplant units in the UK. Unique activities include a very large heart-lung transplant program: 247 patients have now undergone heart-lung transplants and 73 domino heart transplants have been performed. The 5-year survival rates are 71% for heart transplants, 48% for heart-lung and 41% for lung transplants, respectively. Chronic obliterative bronchiolitis remains an important limitation for heart-lung and lung transplant survival.

Adolescent↗
PubMed1998

Cytochemical demonstration of sites of hydrogen peroxide generation and increased vascular permeability in isolated pig hearts after ischaemia and reperfusion.

Isolated pig hearts, subsequently perfused with pig or human blood, were prepared for the cytochemical demonstration of sites of hydrogen peroxide generation and increased vascular permeability. Oxidant stress was associated with ultrastructural changes commonly seen following myocardial reperfusion. In addition, the precipitation of cerium perhydroxide following perfusion with physiological saline containing cerium chloride suggested the vascular endothelium and leukocytes as sources of oxidants. This was associated with rapid penetration of horseradish peroxidase through the intercellular clefts of the vascular endothelium into the interstitial space, suggesting increased vascular leakiness at these sites. The rapid penetration of horseradish peroxidase was observed at all monitored periods of reperfusion with pig or human blood. This indicates that the increased permeability occurred during the ischaemic period and continued during reperfusion. Morphological damage was greatest in pig hearts reperfused with whole human blood and this was attenuated if the blood was preabsorbed to remove antibodies prior to reperfusion. We conclude that oxidant stress was initiated during ischaemia and continued during reperfusion in this model.

Animals↗
PubMed1998

Orthotopic heart transplantation in a transgenic pig-to-primate model.

BACKGROUND: Previous studies demonstrated that hearts from transgenic pigs expressing human decay-accelerating factor (hDAF) were not hyperacutely rejected when transplanted heterotopically into the abdomen of cynomolgus monkeys. This study examines orthotopic transplantation of hDAF transgenic pig hearts into baboon recipients. METHODS: Orthotopic xenogeneic heart transplantation was performed using piglets, transgenic for hDAF, as donors. Ten baboons were used as recipients and were immunosuppressed with a combination of cyclophosphamide, cyclosporine, and steroids. RESULTS: Five grafts failed within 18 hr without any histological signs of hyperacute rejection. Pulmonary artery thrombosis induced by a size mismatch was observed in two of these animals. The other three recipients died because of failure to produce even a low cardiac output and/or dysrhythmia. The remaining five animals survived between four and nine days. One animal died of bronchopneumonia on day 4. Three xenografts stopped beating on day 5 due to acute vascular rejection. The longest survivor was killed on day 9 with a beating, histologically normal xenograft, because of pancytopenia. CONCLUSIONS: The results reported here demonstrate that hDAF transgenic pig hearts are not hyperacutely rejected when transplanted into baboon recipients. Orthotopically transplanted transgenic pig hearts are capable of maintaining cardiac output in baboons. An optimum immunosuppressive regimen is the subject of ongoing research.

Animals↗
PubMed1998

Life-supporting pig-to-primate renal xenotransplantation using genetically modified donors.

BACKGROUND: In order to circumvent the complement-mediated hyperacute rejection of discordant xenografts, a colony of pigs transgenic for the human regulator of complement activity, human decay-accelerating factor (hDAF), has been produced. METHODS: Seven kidneys from hDAF transgenic pigs and six kidneys from nontransgenic control pigs were transplanted into cynomolgus monkeys; both native kidneys were removed during the same operation. The recipient animals were immunosuppressed with cyclosporine, steroids, and cyclophosphamide. RESULTS: In the transgenic group, the median survival time was 13 days (range, 6-35 days); the median survival time in the control group was 6.5 days (range, 0.3-30 days). There were no cases of hyperacute rejection in the transgenic group, and the two longest-surviving kidneys in this group showed no evidence of rejection on histological examination. In contrast, all control kidneys underwent antibody-mediated rejection, one demonstrating hyperacute rejection and the others acute vascular rejection. CONCLUSION: This study demonstrates that (i) a kidney from an hDAF transgenic pig can support the life of a primate for up to 35 days (and also shows the basic physiological compatibility between the pig and nonhuman primate); (ii) nontransgenic kidneys are not routinely hyperacutely rejected; and (iii) the presence of hDAF on the kidney confers some protection against acute vascular rejection. Improved immunosuppression and immunological monitoring may enable extended survival.

Animals↗
PubMed1998

Evaluating the donor pool: impact of using hearts from donors over the age of 49 years.

The shortage of hearts for transplantation has led to the use of organs from older donors in many centres. Despite the lack of coronary angiography on potential organ donors, hearts from carefully selected donors over 49 years of age have been used at this centre since 1988. In the study reported here looked at the impact of this strategy on morbidity and mortality. Between May 1988 and August 1996, 400 first heart transplants were performed, 35 recipients (31 male, 4 female; age 51 +/- 5.9 years) received hearts from donors over 49 years of age (group 1) while 365 (310 male, 55 female; age 49 +/- 9.7 years) had younger donors (group 2). The mean ischaemic time was 189 min (+/- 63.1) in group 1 and 180 min (+/- 59.2) in group 2 (n.s.). The main aetiology of heart failure in groups 1 and 2 was coronary artery disease in 46% and 51%, and dilated cardiomyopathy in 40% and 45% respectively (n.s.). There were no differences in the duration of stay on the intensive care unit or in hospital between the groups. One-year survival was 79% in group 1 and 82% in group 2 (n.s.) and actuarial 5-year survival 69% and 67%, respectively. Six patients in group 1 (17%) and 45 patients in group 2 (12%) died in the first 3 months; of these primary donor organ failure accounted for 50% in group 1 and 13.3% in group 2 (n.s.). Episodes of acute rejection (in the first 3 months) were similar in the two groups: 1.4 and 1.6 per 100 patient days, respectively. Infection rates were also similar: 0.5 and 0.6 per 100 patient days, respectively. The prevalence of coronary artery disease on surveillance coronary angiography at 2 years was 23% in group 1 and 9% in group 2 (P < 0.005). There was a greater proportion of CMV antibody donors in the older donor group, but the association between donor age and coronary artery disease persisted after adjusting for CMV status in multivariate analysis. Too few patients underwent angiography thereafter for valid comparisons. In summary, recipients of organs from donors aged 49 years and over can expect comparable survival rates and morbidity levels to recipients of organs from younger donors, at least in the first 2 years postoperation. There is evidence that older donors confer a significantly higher risk of cardiac allograft vasculopathy which may result in a greater attrition rate thereafter. Careful follow-up of these patients after 2 years is required.

Age Factors↗
PubMed1998

Association between blood eosinophil counts and acute cardiac and pulmonary allograft rejection.

BACKGROUND: Peripheral blood eosinophilia is a particularly early and specific marker of both renal and hepatic allograft rejection. Therefore we evaluated the relationship between blood eosinophil counts and cardiac and pulmonary allograft rejection. METHODS: Differential blood counts were available within 3 days before 383 endomyocardial biopsy specimens in 56 heart transplant recipients. Blood counts were also available before 84 treated rejection episodes and 28 transbronchial biopsy specimens showing no rejection in 58 lung transplant recipients. RESULTS: Cardiac allograft rejection: There was a significant association between the mean maximum blood eosinophil count and treated acute rejection (p < 0.01) and a linear relationship between this eosinophil count and the histologic grade of rejection (p < 0.01). The first increase in eosinophils occurred at a median of 4 days before treated rejection. Pulmonary allograft rejection: The mean maximum blood eosinophil count was 0.14 x 10(9)/L (95% confidence interval = 0.10, 0.18) preceding treated rejection, and this was significantly greater than the mean maximum blood eosinophil count of 0.07 x 10(9)/L (confidence interval = 0.05, 0.09) measured when there was no rejection or during infection (p = 0.01). The first increase in eosinophil occurred at a median of 5 days before treated rejection. There was no relationship between blood neutrophil counts and either cardiac or pulmonary allograft rejection. CONCLUSIONS: An increase in peripheral blood eosinophils but not neutrophils is a specific and early marker of clinically significant rejection of both cardiac and pulmonary allografts. Furthermore, the maximum blood eosinophil count measured in the 3 days before rejection is linearly related to the severity of cardiac allograft rejection.

Adolescent↗
PubMed1998

Life-supporting pig-to-baboon heart xenotransplantation.

BACKGROUND: The aim of this study was to investigate the effect of the expression of human decay-accelerating factor in transgenic pigs on hyperacute rejection in a pig-to-baboon heterotopic heart transplantation model and to assess the ability of such transgenic pig hearts in supporting the life of a primate when transplanted orthotopically. METHODS: Hearts from pigs transgenic for human decay-accelerating factor were transplanted heterotopically (n = 3) and orthotopically (n = 5) into the baboon. All animals received cyclosporine, steroids, and cyclophosphamide. Blood was sampled regularly for total antipig antibody titers, trough cyclosporine levels, full blood count, electrolytes, and creatinine. Rejection of the heterotopic hearts was defined as the absence of palpable cardiac pulsation. Explanted hearts were examined histologically with hematoxylin and eosin and with immunochemistry for complement components C3, C4, C9, and immunoglobulin M. RESULTS: None of the hearts were hyperacutely rejected. In the heterotopic group one heart underwent acute vascular rejection on day 13, and the remaining two recipients with beating xenografts were killed on days 2 and 21. In the orthotopic group, one recipient with a life-supporting xenograft was killed on day 9 because of poor general condition. Histologic examination demonstrated no evidence of rejection. Two xenografts stopped beating on day 5, and histologic study showed acute vascular rejection in both. There were also two graft failures for technical reasons in this group. CONCLUSIONS: Hyperacute rejection is abrogated in pig-to-baboon heart xenotransplantation with the expression of the human decay-accelerating factor transgene. The human decay-accelerating factor transgenic pig heart is able to support primate life for a prolonged period.

Animals↗
PubMed1998

Bronchiolitis obliterans syndrome: incidence, natural history, prognosis, and risk factors.

BACKGROUND: In lung transplantation, obliterative bronchiolitis is the major factor limiting long-term survival. Bronchiolitis obliterans syndrome (BOS), defined as staged decline in pulmonary function has proved a reproducible and sensitive marker of obliterative bronchiolitis. METHODS: The incidence of, and risk factors for, BOS were investigated in 230 lung transplant recipients who underwent transplantation from April 1984 to December 1995 and who survived at least 3 months after operation. Progression and prognosis was investigated in the 109 cases with development of BOS. RESULTS: Actuarial BOS-free probability at 5 years was 36%. Post-BOS onset survival was 51% at 3 years. BOS onset conferred increased risk of death (hazard ratio [HR], 5.96; 95% confidence interval [CI], 3.61, 9.83). Donor and recipient characteristics such as sex, age, underlying disease, type of transplant, and graft ischemic time did not affect BOS onset, progression, or prognosis. Cytomegalovirus serologic status and early acute rejection were risk factors for BOS onset in multivariate modeling. In univariate analysis, other risk factors were lung infection, cytomegalovirus episodes, organizing pneumonia, and human leukocyte antigen mismatch. Later transplantation era (1991 to 1995) was associated with decreased risk of BOS (HR, 0.64; 95% CI, 0.44, 0.92). Acute rejection affected post-BOS progression (HR, 1.28/episode; 95% CI, 1.12, 1.45) and survival (HR, 1.20/episode; 95% CI, 1.05, 1.37). Post-BOS lung infection was an independent prognostic factor (HR, 1.12/episode; 95% CI, 1.01, 1.24). BOS onset in the later half of the series (1992 to 1997) was associated with decreased risk of progression (HR, 0.52; 95% CI, 0.33, 0.82). CONCLUSIONS: This study confirms that BOS is a major problem in lung transplantation, with a high incidence, rapid progression, and poor survival. It affects all modes of lung transplantation, regardless of sex, age, or underlying diagnosis. Acute rejection is a major prognostic factor. Lung infections after BOS onset worsen survival rates.

Actuarial Analysis↗