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Biomedical subjects

T Wreghitt

Publications and source records attributed to T Wreghitt.

31 records · Page 2Linked to original sources

Bronchoalveolar lavage and transbronchial lung biopsy during acute rejection and infection in heart-lung transplant patients. Studies of cell counts, lymphocyte phenotypes, and expression of HLA-DR and interleukin-2 receptor.

The total and differential cell counts of 135 bronchoalveolar lavages (BAL) in 48 heart-lung transplant (HLT) patients were compared with the histologic findings in concurrent transbronchial lung biopsies (TBBs). Counts of CD3+, CD4+, and CD8+ lymphocytes were recorded, and a semiquantitative assessment of HLA-DR and interleukin-2 receptor (IL-2R) expression was made on 29 occasions. There were five diagnostic categories: normal (n = 8), acute rejection (ALR) (n = 57), treated rejection (TR) (n = 19), infection (INF) (n = 24), and chronic rejection (CR) (n = 24). Total cell counts in INF were significantly higher than counts in all the other diagnostic groups. The highest BAL lymphocyte counts, significantly higher than in INF, were found in ALR because of increased CD8+ cells, exceeding 15% in 13 of 57 BALs. TBBs in ALR by contrast showed significantly increased numbers of both CD8+ and CD4+ cells. High dose corticosteroid treatment of ALR caused a fall in cellularity of BAL and TBB specimens but not always to values seen when patients were well. During INF and CR, significantly increased numbers of PMNs were seen in the BAL. HLA-DR and IL-2R expression was enhanced in cells of BAL and TBB in all complications. BAL can only supplement at present histologic examination of TBB in the diagnosis of complications after HLT.

Acute Disease↗

Evaluation of the International Society for Heart Transplantation (ISHT) grading of pulmonary rejection in 100 consecutive biopsies.

Heart-lung and lung transplantation are accepted treatments for patients with end-stage pulmonary vascular disease or parenchymal lung disease. Survival rates for heart-lung and lung transplantation are lower than those for heart transplantation alone. The 5-year actuarial survival for heart-lung transplantation has been 41% largely due to rejection and infection remaining as the limiting factors for long-term survival. A standardized nomenclature for the histological grading of pulmonary rejection was formulated by the International Society for Heart Transplantation (ISHT) in July 1990. Infection, however, is a major problem in the histological assessment of lung recipient biopsies, potentially limiting the usefulness of such a classification. In this study, 100 consecutive transbronchial biopsies (TBBs) from lung transplant recipients were analysed, together with microbiological and serological data, in order to evaluate the proposed ISHT grading system for pulmonary rejection and the importance of concomitant infections in the histological interpretation of TBBs.

Adolescent↗

Diagnosis of toxoplasma infection in cardiac transplant recipients using the polymerase chain reaction.

Cardiac biopsy samples taken from transplant recipients around the time of primary toxoplasma infection were investigated by conventional histology and amplification of the P30 gene of Toxoplasma gondii by the polymerase chain reaction (PCR). Toxoplasma was detected more frequently by PCR than histology which may reflect the enhanced sensitivity of the former technique. Further studies are required to determine the optimal amount of tissue which should be examined by each technique and to develop a PCR assay capable of distinguishing between quiescent infection and active toxoplasmosis.

Animals↗

Early abdominal complications following heart and heart-lung transplantation.

In the first 11 years of the heart and heart-lung transplantation programme at Papworth Hospital, Cambridge, 356 patients underwent heart transplantation, and 73 patients received both heart and lungs. Out of 429 patients 41 (9.5 per cent) developed abdominal complications within the first 30 days, and 20 of the 41 required surgery. The complications included pancreatitis (10), peptic ulceration (8), and pseudo-obstruction (8), in addition to colonic perforation and small bowel obstruction. When laparotomy was performed it was well tolerated. This paper supports the view that successful management of abdominal complications following transplantation requires prompt diagnosis and treatment. Where doubt exists in the presence of an acute abdomen, laparotomy is the appropriate way to establish a definitive diagnosis.

Acute Disease↗

Cytomegalovirus infections in heart and heart-lung transplant recipients.

Of the first 250 heart and 41 heart-lung transplant recipients in the Papworth series, 244 who survived for longer than one month after transplantation were studied for evidence of cytomegalovirus (CMV) infection by serological methods. Overall, 43 (17.6%) patients acquired primary CMV infection and 76 (31.1%) had evidence of CMV reactivation or reinfection. The source of CMV infection was found to be important. CMV infection was more severe when acquired from the donor organ than from blood or blood products and all seven fatal primary CMV infections were associated with CMV antibody-positive donors. Thus, we now have a CMV matching policy in our unit; whenever possible organs from CMV antibody-positive donors are not given to CMV antibody-negative recipients. Those CMV antibody-positive recipients who received organs from CMV antibody-positive donors had more severe CMV reactivation or reinfection than those who received organs from CMV antibody-negative donors. The severity of CMV disease was found to be dependent on the degree of immunosuppression patients received and heart-lung transplant recipients had more serious CMV infections than heart transplant patients. The severity of CMV infections in heart-lung transplant recipients was modified in the later part of the series by the use of prophylactic anti-CMV hyperimmune globulin and treatment of CMV infection with ganciclovir. While 75% of heart-lung transplant recipients who did not receive this treatment died of primary donor-acquired CMV infection, all three comparable patients given CMV hyperimmune globulin and ganciclovir survived. The outcome of CMV infections in the Papworth heart and heart-lung transplant recipients is compared with that in other comparable transplant centres.

Acyclovir↗

The importance of cytomegalovirus in heart-lung transplant recipients.

The first 33 heart-lung transplant recipients in our series were studied for evidence of CMV infection. CMV infection was diagnosed by a change in the serologic status, viral culture, or histology of lung tissue. Of 18 patients who were preoperatively negative for CMV antibody, eight received organs from CMV antibody-positive donors. Five developed pneumonitis (fatal in three)l; one survived primary CMV of the GI tract. Those who recovered from CMV pneumonitis received IV ganciclovir with CMV hyperimmune globulin given prophylactically from the time of transplantation. Only three of ten antibody-negative patients receiving organs from antibody-negative donors developed primary CMV, characterized by only fever in two but associated with rejection, and repeated infection was fatal in a third. CMV reactivation/reinfection occurred in seven of 15 (47 percent) without clinical disease in all but one case. Following heart-lung transplantation, CMV is the cause of considerable mortality and morbidity. We recommend that CMV antibody-negative recipients should receive organs only from antibody-negative donors. If a donor/recipient mismatch occurs, hyperimmune globulin and ganciclovir may improve survival.

Adult↗

Risk factors for the spread of AIDS in rural Africa: evidence from a comparative seroepidemiological survey of AIDS, hepatitis B and syphilis in southwestern Uganda.

Before commencing rational control programmes for AIDS in Africa it is desirable to determine the relative importance of heterosexual and various non-sexual modes of transmission. We investigated this by comparing the seroepidemiologies of AIDS, hepatitis B and syphilis at two rural hospitals in southwest Uganda. During August 1986, 3% of 357 outpatients, reflecting the age and sex composition of the general population, were anti-HIV positive. Anti-HIV seropositivity, both in the outpatients and among 36 suspected prostitutes and 14 suspected AIDS cases, was confined to individuals aged 20 or over. For men, seropositivity was associated with sexual contact with prostitutes (a risk factor for 61% of young men in the study). In the prostitute group, 25% were anti-HIV positive and 46% were positive on the Treponema pallidum haemagglutination (TPHA) test for syphilis. The risk factors for HIV, but not hepatitis B, were the same as for having a history of sexually transmitted disease (STD). However, there was, surprisingly, an association between a history of STD and seropositivity for hepatitis B virus but not for HIV infection. The geographical and age distributions of seropositivity for HIV and hepatitis B virus were also quite different. Finally, blood transfusions, scarification and exposure to mosquitoes (as assessed by a history of malaria) were not evident risk factors for either HIV or hepatitis B virus. AIDS in rural Africa seems to differ in its epidemiology from hepatitis B and appears to be spread predominantly by pre-existing patterns of heterosexual activity responsible for high rates of other sexually transmitted diseases.

AIDS Serodiagnosis↗

Heart-lung transplantation for end-stage respiratory disease in patients with cystic fibrosis at Papworth Hospital.

Between October 1985 and July 1992 we performed heart-lung transplantation in 42 patients with end-stage respiratory disease caused by cystic fibrosis. Twenty-eight of these patients are alive at 3 months to 7 years after heart-lung transplantation. Actuarial survival at 1 year and 3 years after transplantation was 78% and 65%, respectively, in this group, which compares favorably with 77% and 60%, respectively, in patients without cystic fibrosis undergoing heart-lung transplantation. Similarly no significant difference was found in the incidence of postoperative infections between patients with cystic fibrosis and patients without cystic fibrosis undergoing heart-lung transplantation. Quality of life indexes analyzed by the Nottingham Health Profile reveal significant improvements for patients surviving longer than 3 months from surgery. Long-term survival is determined by the development of obliterative bronchiolitis, which has occurred in 11 patients, six of whom have died. Early postoperative survival appears to be compromised by poor preoperative nutritional status. The study provides evidence that patients with end-stage respiratory disease caused by cystic fibrosis gain a survival advantage and improvement in quality of life after heart-lung transplantation when compared with patients who do not receive this form of therapy.

Actuarial Analysis↗