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J Shaw

Publications and source records attributed to J Shaw.

At least 19 recordsLinked to original sources
PubMed2000

Quantitation of Epstein-Barr virus DNA in the blood of adult liver transplant recipients.

BACKGROUND: Posttransplant lymphoproliferation is most often observed in pediatric transplant recipients who experience primary Epstein-Barr virus (EBV) infection at the time of or after transplantation. Lymphoproliferation is believed to be caused by impaired control of EBV-infected cells, which may be of recipient or donor origin. Most studies of EBV infection and lymphoproliferation have focused on the pediatric age group. METHODS: We have undertaken a prospective study of EBV infection in adult liver transplant recipients. Sequentially collected peripheral blood lymphocytes were examined with a recently developed quantitative polymerase chain reaction assay. The assay quantitates EBV DNA genomic titre over a 5 log10 range. RESULTS: Compared with healthy EBV seropositive people not undergoing immunosuppressive therapy, blood EBV DNA titre is elevated in patients with liver disease before transplantation. Overall, highest titres were observed during the first posttransplant month, and in the context of antilymphocyte therapy. In one patient, lymphoproliferation was associated with high titres which fell during reduction of immunosuppressive therapy. In another patient with lymphoproliferation of donor lymphocyte origin, blood EBV DNA titre was not as high. CONCLUSIONS: EBV proliferation is seen in the context of advanced liver disease and after liver transplantation. EBV DNA quantitation is a useful tool to examine the effects of immunosuppression on EBV-associated lymphoproliferation, and may be an essential technique for programs exploring the merits of EBV adoptive immunotherapy.

Adult↗
PubMed2000

Release of TNFalpha in response to SiC fibres: differential effects in rodent and human primary macrophages, and in macrophage-like cell lines.

Asbestos has been implicated in the pathogenesis of several lung diseases, but its mechanism of action is not fully understood. However, asbestos-induced oxidative stress and production of inflammatory cytokines may play a significant role. TNFalpha is an inflammatory cytokine which has a central role in inflammation and fibrosis due to its ability to stimulate fibroblasts and collagen deposition. In this study, a panel of fibres designated either pathogenic or non-pathogenic in recent animal studies, were utilized. The amount of TNFalpha released after a 16-hour exposure to the panel of fibres was compared in four different cell types; two primary macrophage cell types and two cell lines. TNFalpha release by cells exposed to the panel did not equate to pathogenicity, although the most pathogenic fibre caused three out of the four cell types tested, to produce the greatest amount of TNFalpha. Primary rat cells and primary human cells behaved in a similar manner as regards to TNFalpha production; the cell lines behaved quite differently to their primary counterparts with regards to TNFalpha production in this study.

Animals↗
PubMed2000

Increased calcium influx in a monocytic cell line on exposure to ultrafine carbon black.

Ultrafine particles have been shown to induce pro-inflammatory effects both in vivo and in vitro. Increased expression of pro-inflammatory genes probably requires the activation of specific transcription factors such as nuclear factor kappa B (NF-kappaB) via a number of possible pathways including Ca2+ and reactive oxygen species. The fluorescent dye fura 2, was used to measure cytosolic Ca2+ in the human monocytic cell line, Monomac 6 on exposure to 66 microg x mL(-1) of either ultrafine carbon black (ufCB; diameter 14 nm), carbon black (CB; diameter 260 nm), quartz (diameter 1.45 microm), or medium alone. UfCB but not fine CB induced a 1.6-fold increase (p<0.01) in the resting cytosolic Ca2+ concentration of Monomac 6 cells. In addition ufCB induced a 2.6-fold increase (p<0.001) in the response to the endoplasmic reticulum Ca2+- adenosine triphosphatase (ATPase) inhibitor, thapsigargin, suggesting the Ca2+ release-activated Ca2+ current across the plasma membrane was enhanced. This response was inhibited by the removal of extracellular Ca2+ and by the Ca2+ channel blocker, verapamil. In addition, ufCB stimulated the entry of extracellular Mn2+. Finally, the antioxidants mannitol and nacystelin both inhibited the effects of ufCB on the response to thapsigargin. These data suggest that ultrafine carbon black particles stimulated an increase in cytosolic Ca2+, possibly through the entry of extracellular Ca2+ via Ca2+ channels in the plasma membrane. The particles may in part activate the opening of Ca2+ channels via a mechanism involving reactive oxygen species.

Calcium↗
PubMed2000

Selection of multiresistant hepatitis B virus during sequential nucleoside-analogue therapy.

Hepatitis B virus (HBV) drug resistance to lamivudine is always accompanied by mutations in the viral polymerase gene at position 550, termed group 1 (M550V with L526M) or group 2 (M550I) mutations. The latter mutation has not been associated with famciclovir resistance. Thus, the addition of famciclovir to lamivudine therapy in persons with group 2 lamivudine resistance may lead to virus suppression. The effect of lamivudine/famciclovir combination therapy on HBV infection was monitored in 5 lamivudine-resistant patients by quantitative polymerase chain reaction and polymerase gene sequencing of serum virus. No patients treated with combination therapy had a decline in HBV load >1 log10. Continual evolution of the viral polymerase was detected in association with virologic resistance to both drugs. Cloning experiments identified the preexistence of these multidrug-resistant virus variants as minority species prior to addition of famciclovir therapy. HBV resistance to lamivudine monotherapy is associated with a complex mixture of variants that limit the efficacy of second-line nucleoside-analogue therapy. First-line potent combination therapy may reduce the emergence of HBV drug resistance.

2-Aminopurine↗
PubMed2000

Outcome of lamivudine resistant hepatitis B virus infection in the liver transplant recipient.

BACKGROUND: In many transplant centres lamivudine is an important component of prophylaxis against, and treatment of, hepatitis B virus (HBV) graft infection. Drug resistant HBV species with specific polymerase mutations may emerge during lamivudine treatment. AIMS: To examine the clinical consequences of graft infection by lamivudine resistant virus. METHODS: The clinical course of four liver transplant patients who developed graft infection with lamivudine resistant virus was reviewed. The response of HBV infection to reduction of immunosuppression and to manipulation of antiviral therapy was assessed. For each patient, serum viral titre was measured and the viral polymerase gene was sequenced at multiple time points. RESULTS: High serum titres were observed following emergence of the lamivudine resistant species. Wild type HBV re-emerged as the dominant serum species after lamivudine withdrawal. All patients developed liver failure, and onset of liver dysfunction was observed when resistant virus was the dominant serum species. In three patients, liver recovery was observed when immunosuppression was stopped and when alternative antivirals were given. Wild type virus appeared to respond to ganciclovir, and to reintroduction of lamivudine. For one patient, introduction of famciclovir was associated with clinical, virological, and histological response. CONCLUSIONS: Failure of lamivudine prophylaxis may identify patients at special risk for the development of severe graft infection. Treatment of graft reinfection should include reduction of immunosuppression, and systematic exposure to alternative antivirals. Viral quantitation and genetic sequencing are essential components of therapeutic monitoring.

Adult↗
PubMed2000

Automated measurement of unsaturated iron binding capacity is an effective screening strategy for C282Y homozygous haemochromatosis.

BACKGROUND: C282Y hereditary haemochromatosis is an appropriate condition for population screening. Transferrin saturation, the best screening test to date, is relatively expensive, labour intensive, and cannot be automated. Unsaturated iron binding capacity is a surrogate marker of transferrin saturation and its measurement can be automated. AIMS: To evaluate a screening strategy for C282Y hereditary haemochromatosis in a tertiary hospital environment based on unsaturated iron binding capacity as the initial screening test. METHODS: Measurement of unsaturated iron binding capacity was adapted to the main laboratory analyser. An unsaturated iron binding capacity of less than 30 micromol/l was identified as an appropriate decision point and 5182 consecutive subjects were screened over 28 consecutive days. RESULTS: Of those screened, 697 had an unsaturated iron binding capacity less than 30 micromol/l. Of these, transferrin saturation was greater than 40% in 294. A total of 227 were able to be genotyped for the C282Y mutation. Nine subjects homozygous for C282Y were identified. Based on full cost recovery, affected persons were identified at a cost of Aus$2268.77 per case (approximately US$1496). CONCLUSION: Automated measurement of unsaturated iron binding capacity enables a cost effective, large scale population screening programme for C282Y hereditary haemochromatosis to be developed.

Adult↗
PubMed1999

8-aminoquinolines as anticoccidials - Part III.

Analogues of the antimalarial pentaquine, 1, in which the nature of the side-chain on the 8-amino position was varied, were prepared and evaluated for anticoccidial activity both in vitro and in vivo. Specifically, both the inter-nitrogen distance and the nature of the terminal amino group were investigated. Novel analogues of equal or improved efficacy in vitro and in vivo to pentaquine were discovered.

Aminoquinolines↗
PubMed1999

Suicide within 12 months of contact with mental health services: national clinical survey.

OBJECTIVE: To describe the clinical circumstances in which psychiatric patients commit suicide. DESIGN: National clinical survey. SETTING: England and Wales. SUBJECTS: A two year sample of people who had committed suicide, in particular those who had been in contact with mental health services in the 12 months before death. MAIN OUTCOME MEASURES: Proportion of suicides in people who had had recent contact with mental health services; proportion of suicides in inpatients; proportion of people committing suicide and timing of suicide within three months of hospital discharge; proportion receiving high priority under the care programme approach; proportion who were recently non-compliant and not attending. RESULTS: 10 040 suicides were notified to the study between April 1996 and March 1998, of whom 2370 (24%; 95% confidence interval 23% to 24%) had had contact with mental health services in the year before death. Data were obtained on 2177, a response rate of 92%. In general these subjects had broad social and clinical needs. Alcohol and drug misuse were common. 358 (16%; 15% to 18%) were psychiatric inpatients at the time of death, 21% (17% to 25%) of whom were under special observation. Difficulties in observing patients because of ward design and nursing shortages were both reported in around a quarter of inpatient suicides. 519 (24%; 22% to 26%) suicides occurred within three months of hospital discharge, the highest number occurring in the first week after discharge. 914 (43%; 40% to 44%) were in the highest priority category for community care. 488 (26% excluding people whose compliance was unknown; 24% to 28%) were non-compliant with drug treatment while 486 (28%; 26% to 30%) community patients had lost contact with services. Most people who committed suicide were thought to have been at no or low immediate risk at the final service contact. Mental health teams believed suicide could have been prevented in 423 (22%; 20% to 24%) cases. CONCLUSIONS: Several suicide prevention measures in mental health services are implied by these findings, including measures to improve compliance and prevent loss of contact with services. Inpatient facilities should remove structural difficulties in observing patients and fixtures that can be used in hanging. Prevention of suicide after discharge may require earlier follow up in the community. Better suicide prevention in psychiatric patients is likely to need measures to improve the safety of mental health services as a whole, rather than specific measures for people known to be at high risk.

Adolescent↗
PubMed1999

Mental disorder and clinical care in people convicted of homicide: national clinical survey.

OBJECTIVES: To estimate the rate of mental disorder in those convicted of homicide and to examine the social and clinical characteristics of those with a history of contact with psychiatric services. DESIGN: National clinical survey. SETTING: England and Wales. SUBJECTS: Eighteen month sample of people convicted of homicide. MAIN OUTCOME MEASURES: Offence related and clinical information collected from psychiatric court reports on people convicted of homicide. Detailed clinical data collected on those with a history of contact with psychiatric services. RESULTS: 718 homicides were reported to the inquiry between April 1996 and November 1997. Of the 500 cases for whom psychiatric reports were retrieved, 220 (44%; 95% confidence interval 40% to 48%) had a lifetime history of mental disorder, while 71 (14%; 11% to 17%) had symptoms of mental illness at the time of the homicide. Of the total sample, 102 (14%; 12% to 17%) were confirmed to have been in contact with mental health services at some time, 58 (8%; 6% to 10%) in the year before the homicide. The commonest diagnosis was personality disorder (20 cases, 22%; 13% to 30%). Alcohol and drug misuse were also common. Only 15 subjects (18%; 10% to 26%) were receiving intensive community care, and 60 (63%; 53% to 73%) were out of contact at the time of the homicide. CONCLUSIONS: There are substantial rates of mental disorder in people convicted of homicide. Most do not have severe mental illness or a history of contact with mental health services. Inquiry findings suggest that preventing loss of contact with services and improving the clinical management of patients with both mental illness and substance misuse may reduce risk, but clinical trials are needed to examine the effectiveness of such interventions.

Adult↗
PubMed1999

Prevalence and detection of serious psychiatric disorder in defendants attending court.

BACKGROUND: Diversion programmes in magistrates' courts are designed to provide immediate advice or access to mental-health treatment facilities for defendants when appropriate. The prevalence of serious psychiatric disorder and the proportion of defendants who might require transfer are unknown. We undertook a study to address these issues and to find out whether defendants with such disorders are reliably detected by court personnel and referred to psychiatric staff in court diversion programmes. METHODS: A two-phase screening method used questionnaires for psychiatric disorder (the general health questionnaire and psychotic screening questionnaire) and screening instruments for alcohol and substance misuse followed by standard psychiatric interview (schedules for clinical assessment in neuropsychiatry). The detection rate of defendants with serious psychiatric disorder by court staff was observed. FINDINGS: The frequency of serious psychiatric disorder was 1.31% (three of 229) among defendants appearing in court direct from the community and 6.57% (96 of 1460) among those held in custody overnight. Of the 99 defendants with serious psychiatric disorder, 34 had schizophrenia and other psychoses and 55 had depressive disorders. 42 (76%) of the 55 individuals with depressive disorders had suicidal ideas, which were recorded on the first-phase screening questionnaire in many cases. Only 14 of 96 defendants from overnight custody with serious psychiatric disorder were detected by court staff and referred to the court diversion programme. INTERPRETATION: There is a substantial rate of psychiatric disorder in the court population, which is not satisfactorily detected with the current system. Brief screening questionnaires and training of court staff are probably necessary for detection of people with serious psychiatric disorder passing through the courts.

Adult↗
PubMed1999

Cost-efficacy modeling of functional testing with perfusion imaging to detect asymptomatic restenosis following percutaneous transluminal coronary angioplasty.

The objective of this study was to perform a theoretical cost-efficacy analysis on the use of routine functional testing with perfusion imaging to identify patients with asymptomatic restenosis following percutaneous transluminal coronary angioplasty (PTCA) procedures. Approximately 50% of patients with restenosis following PTCA are asymptomatic. Routine functional testing is commonly performed at 3 to 6 months to identify these patients. The cost-efficacy associated with this strategy is unknown. Theoretical models were constructed based on assumed costs for functional testing (U.S. $1,300) and coronary angiography (U.S. $3,000). Restenosis rates were assumed to be 40%, and half of patients with restenosis were assumed to be asymptomatic. To provide a range of costs to identify a patient with asymptomatic restenosis, three scenarios were constructed based on the diagnostic test characteristics of functional testing. Sensitivity analyses were performed using a range of costs for functional testing, restenosis rates, and proportion of patients with restenosis who are asymptomatic. Depending on the diagnostic accuracy of functional testing, it costs $8,200 to $22,400 to identify an asymptomatic patient with restenosis following PTCA. The cost to identify a patient with asymptomatic restenosis varies inversely with the rates of restenosis. When restenosis rates are < 20%, the cost to identify a patient with asymptomatic restenosis exceeds $10,000. Similarly, the cost to identify a patient with asymptomatic restenosis increases when the proportion of patients with asymptomatic restenosis decreases. The cost, associated with the use of routine functional testing for the identification of asymptomatic patients with restenosis appears exorbitant. However, a formal study is warranted to determine the cost-efficacy of such a strategy. Cathet. Cardiovasc. Intervent. 48:352-356, 1999.

Angioplasty, Balloon, Coronary↗
PubMed1999

High pre-treatment serum hepatitis B virus titre predicts failure of lamivudine prophylaxis and graft re-infection after liver transplantation.

BACKGROUND/AIMS: Orthotopic liver transplantation has an established role for the treatment of patients with chronic liver failure secondary to hepatitis B virus (HBV) infection. Unfortunately, recurrent infection of the graft can be associated with aggressive disease, and with diminished graft and patient survival. Currently, the role of nucleoside analogues for prevention of graft re-infection is being evaluated. Preliminary results are encouraging, but treatment failure has been associated with emergence of drug-resistant virus. METHODS: We have studied ten consecutive patients who received lamivudine prophylaxis for prevention of HBV graft reinfection. Sequential sera, collected prelamivudine then during treatment before and after liver transplantation, were examined. Conventional serological markers were measured, as were serum viral DNA levels with a sensitive quantitative polymerase chain reaction assay. RESULTS: Lamivudine treatment effected a reduction in serum HBV levels, but six patients still had measurable viral DNA at the time of transplantation. Five patients developed graft re-infection with lamivudine-resistant virus. Resistant virus emerged 8 to 15 months post-transplant. The likelihood of emergence of resistant virus was related to the pre-treatment serum HBV titre. Persistent serum viral DNA positivity and evidence of graft re-infection during the early post-transplant period did not predict the subsequent emergence of resistant virus. CONCLUSIONS: Our observations suggest that the resistant species may be present in the viral quasispecies in the serum and liver of patients with high-level replication prior to lamivudine exposure. The resistant species can persist during lamivudine treatment prior to transplantation, and emerge following transplantation. These observations suggest strategies which might prevent the emergence of drug-resistant species, and imply that graft re-infection may be a preventable phenomenon.

Antiviral Agents↗
PubMed1999

Vascular surgical society of great britain and ireland: superficial femoral angioplasty

BACKGROUND: Superficial femoral angioplasty (percutaneous transluminal angioplasty, PTA) is a widely performed therapeutic modality used throughout the UK in the treatment of intermittent claudication. However, there is still concern over its efficacy in the management of atherosclerotic occlusive disease. Long-term outcome was examined in patients undergoing PTA for short (less than 10 cm) occlusions or stenoses. METHODS: Data were collected prospectively for 413 patients undergoing femoral angioplasty and entered into a database for long-term outcome analysis. Patients were seen at 3, 6 and 12 months and at yearly intervals. Doppler ultrasonography and clinical assessment were performed in all patients and duplex imaging was carried out in those in whom there was doubt about patency. Finally, surviving patients were simply questioned as to whether they felt the original PTA to have been worthwhile. RESULTS: Mean follow-up time was 7 (range 2-11) years. Excluding an initial technical failure rate of 8 per cent, cumulative primary patency at 1, 2, 3, 4 and 5 years was 64, 55, 36, 21 and 14 per cent respectively. Moreover, clinical assessment revealed improvement of the presenting complaint in only 40, 29, 17, 9 and 7 per cent respectively. CONCLUSION: Superficial femoral PTA does not appear to be effective in the management of intermittent claudication in most patients.

Journal Article↗
PubMed1999

Bladder augmentation surgery--what about the malignant risk?

Augmentation cystoplasty has become a common surgical treatment for the neuropathic bladder. However, malignancy in bladder augmentations has been well-described and in time is estimated to occur in 1.3% of cases. We surveyed 36 paediatric surgeons from the UK with a special interest in paediatric urology to ascertain how many bladder augmentations were being performed in children each year and whether the surgeons were warning patients/parents of the malignant risks involved with this surgery. Over 150 bladder augmentations were being performed in the UK each year. Surgeons surveyed were concerned about the malignant risks and nearly all agreed that a Central Registry of patients with bladder augmentations should be established to keep track of developments.

Child↗
PubMed1999

Selection of hepatitis B surface "escape" mutants during passive immune prophylaxis following liver transplantation: potential impact of genetic changes on polymerase protein function.

CASE REPORT: A patient is described who developed hepatitis B virus (HBV) reinfection five months following liver transplantation. Failure of hepatitis B immunoglobulin prophylaxis was associated with the emergence of mutations. HBV gene sequencing identified nucleotide substitutions associated with amino acid changes, one within the major hydrophilic region (MHR) of the HBV surface antigen at amino acid position 144 and one outside the MHR. Because of the overlapping reading frames of surface and polymerase genes, the latter surface antigen change was associated with an amino acid change in the polymerase protein. The patient developed significant allograft hepatitis and was treated with lamivudine (3TC) 100 mg daily. Rapid decline of serum HBV DNA was observed with loss of HBV e antigen and HBV surface antigen from serum. There was normalisation of liver biochemistry, and liver immunohistochemistry showed a reduction in HBV core and disappearance of HBs antigen staining. CONCLUSION: Surface antigen encoding gene mutations associated with HBIg escape may be associated with alteration of the polymerase protein. The polymerase changes may affect sensitivity to antiviral treatment. Selection pressure on one HBV reading frame (for example, HBIg pressure on HBsAg, or nucleoside analogue pressure on polymerase protein) may alter the gene product of the overlapping frame. Such interactions are relevant to strategies employing passive immune prophylaxis and antiviral treatment.

Aged↗
PubMed1999

Breeding structure of the sand fly Lutzomyia longipalpis (Lutz & Neiva) in Brazil.

Eleven populations of Lutzomyia longipalpis (Lutz & Neiva), the sand fly vector of Leishmania chagasi, from different areas of Brazil were analyzed for genetic variation at 16 enzyme loci. In this region, the prevalence of visceral leishmaniasis (VL) caused by L. chagasi is spotty and reproductive isolation among populations of Lu. longipalpis has been reported. It is thought that morphologically similar cryptic species with varying vectorial capacity may be responsible for the discontinuous distribution of VL. The aim was to study the genetic structure of populations within this region and to identify demes that may represent sibling species. Genotypic frequencies within populations were in close compliance to Hardy-Weinberg expectations, suggesting there are no sympatric species among these 11 populations. Levels of genetic distance between pairs of populations were very low (< 0.03), consistent with local populations within a single sand fly species. When genotypic frequency data for all populations were pooled, 9 of the 13 polymorphic loci deviated from Hardy-Weinberg expectations, indicating some degree of genetic substructuring. Estimates of effective migration rates (N(e)m) among all populations were low, 2.73, suggesting that gene flow is restricted among populations, which is probably the reason for the observed genetic substructuring.

Alleles↗
PubMed1999

Life history variation in gametophyte populations of the moss Ceratodon purpureus (Ditrichaceae).

The life cycles of mosses and other bryophytes are unique among land plants in that the haploid gametophyte stage is free-living and the diploid sporophyte stage is ephemeral and completes its development attached to the maternal gametophyte. Despite predictions that populations of haploids might contain low levels of genetic variation, moss populations are characterized by substantial variation at isozyme loci. The extent to which this is indicative of ecologically important life history variation is, however, largely unknown. Gametophyte plants from two populations of the moss Ceratodon purpureus were grown from single-spore isolates in order to assess variation in growth rates, biomass accumulation, and reproductive output. The data were analyzed using a nested analysis of variance, with haploid sib families (gametophytes derived from the same sporophyte) nested within populations. High levels of life history variation were observed within both populations, and the populations differed significantly in both growth and reproductive characteristics. Overall gametophytic sex ratios did not depart significantly from 1:1 within either population, but there was significant variation among families in both populations for progeny sex ratio. Some families produced predominantly male gametophytes, while others yielded predominantly females. Because C. purpureus has a chromosomal mechanism of sex determination, these observations suggest differential (but unpredictable) germination of male and female spores. Life history observations showed that male and female gametophytes are dimorphic in size, maturation rates, and reproductive output.

Journal Article↗