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Biomedical subjects

T Wreghitt

Publications and source records attributed to T Wreghitt.

At least 19 recordsLinked to original sources
PubMed2005

Extended ganciclovir prophylaxis in lung transplantation.

BACKGROUND: Positive cytomegaloviral status of the donor or of the recipient adversely affects survival and enhances the development of bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. The role of ganciclovir prophylaxis in cytomegalovirus infection in respect to obliterative bronchiolitis or to BOS development is not known. METHODS: From the Papworth transplant database, we identified 146 patients who received organs from cytomegalovirus-positive donors. We classified patients into 3 groups as follows: Group 1 consisted of 42 patients who underwent transplantation between 1990 and 1992 when no prophylaxis was given; Group 2 consisted of 49 patients who underwent transplantation between 1992 and 1995 when 4 weeks of IV ganciclovir was given as prophylaxis; and Group 3 consisted of 55 patients who underwent transplantation between 1995 and 1998 when cytomegalovirus prophylaxis consisted of IV (1 week) followed by oral ganciclovir for a total of 3 months. Donor management, recipient management during and after surgery, and pharmacotherapy were uniform during the study period. We used survival and regression methods to compare these groups, adjusting for the transplantation type (single lung, double lung, or heart-lung) and for HLA typing. RESULTS: We found a significant difference among all 3 groups in numbers of cytomegaloviral disease episodes in the 1st year after transplantation. The number of rejection episodes in the 3 groups during the 1st post-transplant year gradually decreased from Group 1 to Group 3. We identified no statistically significant benefit in the time to BOS occurrence or in actuarial survival. CONCLUSION: Extended prophylaxis with IV and oral ganciclovir practically abolishes cytomegaloviral disease and is related to a decreased incidence of rejection episodes. However, ganciclovir prophylaxis is not related to a decreased incidence or progression of BOS or survival.

Adult↗
PubMed2003

Prevalence of measles susceptibility among health care workers in a UK hospital. Does the UK need to introduce a measles policy for its health care workers?

OBJECTIVES: First, to determine the prevalence of measles non-immunity in a group of health care workers (HCW), and secondly, to investigate what pre-employment screening for measles is carried out by NHS occupational health departments. METHODS: Two hundred and eighteen HCWs with patient contact on the medical wards at Addenbrooke's hospital provided an oral fluid sample and answered a questionnaire. A postal survey of Association of National Health Occupational Physicians Society (ANHOPS) members was conducted to assess whether UK NHS Trusts identify measles non-immune individuals. RESULTS: Of the HCWs tested, 3.3% of were found to be non-immune to measles (both oral fluid and confirmatory serum sample were measles IgG negative). Less than one third of a sample of 80 NHS occupational health departments enquired about measles immunity. CONCLUSION: The prevalence of measles non-immune health care workers is low, but with a fall in uptake of MMR immunization and increased likelihood of measles outbreaks, it is important to identify these at-risk individuals. Serum testing is the most reliable method to use. Oral fluid testing and history of measles disease or vaccination are unreliable methods of identifying non-immune individuals. To achieve complete immunity, it is cost-effective to screen and then offer immunization. NHS trusts vary greatly in their measles policies for health care workers.

Adult↗
PubMed2003

Risk factors, clinical features and genotype distribution of diagnosed hepatitis C virus infections: a pilot for a sentinel laboratory-based surveillance.

Hepatitis C is a global public health problem. A cross-sectional survey was undertaken to determine the frequency of reported risk factors and possible transmission routes in individuals in whom HCV antibody (anti-HCV) was newly detected. Seven public health laboratories in England and Wales reported persons with positive anti-HCV tests over a three-month period (1st November 1996-31st January 1997). A questionnaire was then sent to the clinician or general practitioner (GP) who requested the test. A total of 320 laboratory reports were received from participating laboratories and 221 (69%) questionnaires were received from clinicians and GPs. Of those patients from whom a questionnaire was received (median age 36 years; males 72.9%, females 23.1%), 86% had one or more risk factors for infection reported by the clinician/GP. Injecting drug use (68%) was the main risk factor reported. Reasons for testing included being in a known risk group (65%), liver disease (19%) and blood donation (1.4%). Of the total responders, 67% were asymptomatic, and of those that had had liver function tests 50% were abnormal. The most prevalent HCV genotypes were 3a and 1a. Risk factors for HCV infection can be identified using a simple postal questionnaire to clinicians/GPs who request patient screening.

Adult↗
PubMed2003

Outbreak of hepatitis A infection among intravenous drug users in Suffolk and suspected risk factors.

A prolonged outbreak of hepatitis A infection amongst drug users in Suffolk prompted a study of the natural immunity against hepatitis A in this population, and a retrospective analysis of the relationship between specific drug-taking behaviours and the risk of hepatitis A infection. Prior to the outbreak, age-specific seroprevalence of hepatitis A IgG in drug users was similar to that amongst blood donors in the region. Of those without effective immunity, intravenous drug users, multiple drug users and those injecting frequently were more likely to have developed hepatitis. The reported frequency of equipment sharing and the number of injecting partners were not related to the risk of infection. The potential for blood-to-blood, and a suggested faecal-blood transmission were considered to be important in propagating the outbreak in this population. We suggest that a single dose of hepatitis A vaccine administered opportunistically should be used in outbreaks involving drug users.

Adult↗
PubMed2002

Guidelines for laboratory monitoring of treatment of persistent virus infections.

A growing number of antiviral agents are available for treatment of persistent viral infections. This has increased the requirement for virology laboratories to undertake sophisticated assays for monitoring the efficacy of treatment and identifying drug failure at an early stage. The consensus guidelines within this article address the laboratory requirements for monitoring treatment of the herpes viruses, HIV-1, Hepatitis B and Hepatitis C.

Chickenpox↗
PubMed2002

Processing of cardiac valve allografts: 2. Effects of antimicrobial treatment on sterility, structure and mechanical properties.

This is the second in a series of papers that report experiments to investigate the properties required for effective tissue valve implants. This paper is concerned with investigations into alternative antimicrobial treatments and the effect these treatments produce on the structural and biomechanical properties of ovine aortic valves. Six treatments were studied: heat, peracetic acid (at two concentrations), chlorine dioxide, a surfactant cleaning agent and a solvent/detergent treatment. Samples of myocardial tissue were exposed to a mixed bacterial culture or one of three virus cultures and then decontaminated. Two of the six treatments (0.35% peracetic acid and heat) were effective in removing both bacterial and viral contamination, reducing levels of contamination by 2.5 to 3 logs, whilst a third (chlorine dioxide) was effective against viruses ( approximately 3 log reduction). Valves subjected to these treatments were examined by microscopy and measurements of mechanical properties were made. All three treatments seriously damaged endothelial cells and leaflet fibroblasts. Heat treatment also damaged connective tissue components (collagen and elastin) but these changes were not seen after chemical treatment. Mechanical testing confirmed severe damage following heat treatment but chemical treatment showed only minor effects on the elasticity of the leaflets and none on extensibility. These minor effects could be mitigated by exposure to a lower dose of peracetic acid and this treatment could be safely combined with cryopreservation or storage in 85% glycerol. Peracetic acid was the preferred disinfection method for use in the subsequent in vivo studies in sheep.

Journal Article↗
PubMed2002

Causes of morbilliform rash in a highly immunised English population.

AIMS: To determine the causes of morbilliform rash and fever in a population with high vaccination coverage for measles and rubella. METHODS: Comprehensive laboratory investigation additional to routine oral fluid testing of children presenting to primary care physicians in East Anglia, England. RESULTS: Laboratory confirmation of infection was obtained in 93 (48%) of 195 children: parvovirus B19 in 34 (17%); group A streptococcus in 30 (15%); human herpesvirus type 6 in 11 (6%); enterovirus in nine (5%); adenovirus in seven (4%); and group C streptococcus in six (3%) (four individuals tested positive for two agents). None had measles or rubella. CONCLUSIONS: Oral fluid testing to cover infections additional to measles and rubella aids clinical management and is likely to maintain uptake of testing, which is essential for measles and rubella surveillance in highly immunised low incidence populations.

Adenoviridae Infections↗
PubMed1999

Pre-transplantation testing: who, when and why?

An ever-widening range of human organs and tissues is being transplanted, limited currently only by the ingenuity of surgeons and immunologists to overcome the physical and immune barriers. Microbiologists are in danger of being left behind. Although the major infective risks of human organ transplantation are now well understood, many details remain controversial, and the special risks associated with tissue banking have received little attention until recently. What should we do? Are we making mountains out of molehills? Are there any data on which to base a rational decision? Topics covered include: bacteriology of cadaveric heart valve transplantation (why are valves not cultured and only dunked in antibiotic solution for 24h, whereas endocarditis gets treated for 4 weeks?); screening for tissue-born viruses (why does everyone persist with serology when genomic methods are so much better?); screening organ donors for CMV (surely we should use the optimally sensitive combination of methods?); peripheral blood stem cell transplants (should we culture these, and what do the positive results mean if we do?); donor sputum screening before heart-lung transplantation (does this aid the post-operative management of the recipient?). With active participation from the floor some areas of consensus were identified and topics worthy of scientific investigation in the future were highlighted.

Heart Valves↗
PubMed1998

A randomized trial of solvent/detergent and standard fresh frozen plasma in the treatment of the coagulopathy seen during Orthotopic Liver Transplantation.

BACKGROUND: Viral transmission remains a residual risk in single unit blood component therapy. Virus inactivation of pooled fresh frozen plasma (FFP) by the solvent/detergent (SD) method can be used to reduce this risk but results in some loss of factor activity including factor VIII and (2-antiplasmin. This study was aimed at assessing the clinical effectiveness solvent/detergent treated pooled fresh frozen plasma (SDFFP) in the correction of the coagulopathy seen during Orthotopic Liver Transplantation (OLT) as compared with standard FFP. METHOD: Twenty eight patients with an underlying derangement of coagulation and who were due to undergo OLT were randomized to receive either FFP or SDFFP. They were assessed for side effects, correction of coagulopathy, and seroconversion for viral markers. RESULTS: Patients undergoing OLT showed equal correction of clotting factors and partial thromboplastin time (PTT) when treated with FFP or SDFFP. There was also a similar time course to return to baseline values in each group. There was no significant difference in correction of INR in either group. Usage of other blood components during the operation was identical in the two groups. No seroconversions were seen for HIV, HBC or HCV but only 12 patients were available for long term follow-up. CONCLUSION: SDFFP is an efficacious and safe source of coagulation factors for patients with liver disease undergoing Orthotopic Liver Transplantation. No adverse effects were seen during its administration. Further work is required to ascertain long term possibilities of seroconversion.

Adult↗
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↗
PubMed1997

Risk of inappropriate exclusion of organ donors by introduction of hepatitis B core antibody testing.

BACKGROUND: Hepatitis B virus infection originating from hepatitis B surface antigen-negative, hepatitis B core antibody (anti-HBc)-positive organ donors has been documented, and anti-HBc-positive donors have been excluded as liver donors. We assessed the prevalence of anti-HBc in UK organ donors and followed up recipients of organs from anti-HBc-positive donors for serological evidence of posttransplantation hepatitis B virus infection. METHODS: Serum samples from 400 hepatitis B surface antigen-negative organ donors were tested for anti-HBc. RESULTS: Only five (1.25%) of 20 sera in which anti-HBc was initially detected were confirmed as anti-HBc positive on further testing. Posttransplantation serum samples from four recipients of confirmed anti-HBc-positive organs showed no evidence of de novo hepatitis B infection. CONCLUSIONS: The poor specificity of some anti-HBc immunoassays was confirmed and suggests that donor exclusion on the basis of a single anti-HBc-positive result may result in the inappropriate loss of organs.

False Positive Reactions↗
PubMed1995

High prevalence of hepatitis C infection in Afro-Caribbean patients with type 2 diabetes and abnormal liver function tests.

Moderate elevations of serum transaminases are frequently found in patients with diabetes mellitus and are often attributed to fatty infiltration of the liver without further investigation. Recent studies of patients with end-stage liver disease have suggested a possible association between Hepatitis C virus (HCV) antibody positivity and the development of diabetes (mostly Type 2). As a first step in the examination of any potential association between HCV and Type 2 diabetes in subjects without overt liver disease, we examined 200 British patients with Type 2 diabetes (100 White Caucasians, 50 Asians, and 50 Afro-Caribbeans), recruited from the United Kingdom Prospective Study of Diabetes, half of whom had a significant elevation of alanine aminotransferase (ALT) on at least two occasions and half of whom had consistently normal ALT levels. In Afro-Caribbean Type 2 diabetic subjects 7/25 (28%) patients with abnormal ALT and 1/25 (4%) with normal ALT were HCV antibody positive. Among White Caucasian subjects 6/50 (12%) patients with abnormal LFTs and 0/50 with normal LFTs were HCV antibody positive and in Asians the prevalence was 2/25 (8%) and 0/25, respectively. This study suggests that persistent mild to moderate elevation of serum transaminases in a patient with Type 2 diabetes should not automatically be attributed to the metabolic disturbances of diabetes. Particularly in Afro-Caribbean subjects, HCV infection is a major diagnostic consideration. The question of whether HCV infection itself may have a diabetogenic action is worthy of further investigation.

Adult↗
PubMed1994

Evidence for a link between hepatitis C virus infection and diabetes mellitus in a cirrhotic population.

Abnormalities of carbohydrate metabolism, including hyperinsulinaemia and insulin resistance, are well recognised complications of cirrhosis. While diabetes mellitus can be explained in many instances on the basis of coincident pancreatic disease, in most the characteristic glucose intolerance of cirrhosis is not readily explicable. A previous clinical observation that hepatitis C virus infection and diabetes mellitus appeared to be associated was formally tested by a retrospective review of 100 consecutive adult patients with cirrhosis undergoing assessment for liver transplantation. Hepatitis C virus was diagnosed by conventional serological and histological criteria. Twenty-three patients had diabetes mellitus, of whom 18 were being treated with insulin. Of the 34 patients with hepatitis C virus-related cirrhosis, 17 (50%) had diabetes mellitus, in contrast to just six (9%) of the 66 patients with cirrhosis unrelated to hepatitis C virus (chi2 = 19.1, p < 0.0001) with an odds ratio for hepatitis C virus by diabetes mellitus status 10.0 (95% confidence interval 3.4 to 29.3). Hierarchical loglinear model analysis of those factors of potential relevance to the development of diabetes mellitus revealed that only hepatitis C virus interacted significantly with diabetes mellitus while the relation between diabetes mellitus and origin, sex, body mass index and severity of cirrhosis was conditional. By multiple logistic regression analysis of diabetes mellitus status in relation to the same variables, only hepatitis C virus status was statistically significant (p < 0.0001). Origin, sex, severity of cirrhosis, body mass index and therapy were not significantly associated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Risk factors for survival following combined heart-lung transplantation. The first 100 patients.

As the numbers of heart and lung transplant recipients have increased it has become possible to identify major risk factors for early (within 3 months) and later (after 3 months) death after this procedure. For 100 patients receiving organs between April 1984 and February 1991, and followed up until February 1992, patient characteristics, operative details, and early morbidity were assessed for their effects on early and later deaths. Recipient age, sex, and preoperative diagnosis did not have a significant effect on early (within 3 months) or later death. Positive cytomegalovirus antibody status of donor or recipient conferred greater risk of death within 90 days (odds ratio [OR] = 3.24, P = 0.06). Greater than 2 L blood in the first 24 hr after operation (OR = 6.00, P = 0.05), and ventilation for greater than 24 hr (OR = 4.87, P = 0.006) were significant prognostic indicators of early death. After the first 3 months, the main risk factor for death was rejection in the first 3 months (OR = 1.38 per episode, P = 0.008). Early infection in general and CMV infection in particular were associated with a small increase in risk. This study confirms the importance of matching donor and recipient for CMV and shows that difficulties during operation, reflected in postoperative bleeding and ventilation times increased the chance of early death. Later death was associated with early acute rejection. A detrimental effect of infection, including CMV infection, either does not exist, or is too small to be detected in a study of this size.

Actuarial Analysis↗
PubMed1993

Chlamydial infection of the respiratory tract.

Chlamydial infection of the human respiratory tract was first described over 100 years ago, when outbreaks of psittacosis were linked to imported pet birds. The causative organism was identified subsequently as Chlamydia psittaci. However, C. pneumoniae, has also been recognised recently as an important cause of human respiratory tract infection. Approximately 300 cases of human chlamydial respiratory tract infection are reported to CDSC each year, mainly in adults aged 15 to 44 years. A prospective study in Cambridgeshire showed that 76% of cases were associated with C. psittaci and 24% of cases with C. pneumoniae. There are several laboratory tests for diagnosing chlamydial infections. The complement fixation test is still the most commonly used but it cannot distinguish between different species of chlamydiae. Other serological tests, which can distinguish between different species, are only carried out in specialist laboratories. C. pneumoniae is particularly difficult to culture and C. psittaci is a grade 3 pathogen. Chlamydial antigens can be detected in sputum samples but these are not routinely sought in human chlamydial respiratory infections. There is a need to improve diagnostic techniques because rapid and accurate diagnosis leads to the use of appropriate antibiotics and will help to elucidate the epidemiology of these infections.

Adolescent↗