Hypercalcaemia and abdominal pain.
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Biomedical subjects
Publications and source records attributed to A Williams.
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We tested the role of interleukin-6 (IL-6) in sepsis-induced muscle proteolysis by determining ubiquitin mRNA levels and protein breakdown rates in incubated extensor digitorum longus muscles from septic and sham-operated IL-6 knockout and wild-type mice. In addition, the effect of treatment of mice with human recombinant IL-6 on muscle protein breakdown rates was determined. Finally, protein breakdown rates were measured in myotubes treated for up to 48 h with different concentrations of IL-6. Sepsis in wild-type mice resulted in an approximately ninefold increase in plasma IL-6 levels, whereas IL-6 was not detectable in plasma of sham-operated or septic IL-6 knockout mice. Total and myofibrillar muscle protein breakdown rates were increased by approximately 30% and threefold, respectively, in septic IL-6 wild-type mice with an almost identical response noted in septic IL-6 knockout mice. Ubiquitin mRNA levels determined by dot blot analysis were increased during sepsis in muscles from both IL-6 knockout and wild-type mice, although the increase was less pronounced in IL-6 knockout than in wild-type mice. Treatment of normal mice or of cultured L6 myotubes with IL-6 did not influence protein breakdown rates. The present results suggest that IL-6 does not regulate muscle proteolysis during sepsis.
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Long-term survival of lung transplant recipients is limited by the advent of obliterative bronchiolitis and irreversible airways obstruction, e.g. bronchiolitis obliterans syndrome (BOS). This study investigated whether inflammatory cells and their activation markers were increased in bronchoalveolar lavage (BAL) and transbronchial biopsies (TBB) from patients with BOS. Levels of antioxidants in BAL fluid were also assessed. BAL fluid and TBB from six single-lung, two bilateral-lung, and five heart-lung transplanted patients with diagnosis of BOS were compared with 13 transplant recipients without BOS. BAL fluid levels of myeloperoxidase (MPO), eosinophil cationic protein (ECP) and interleukin (IL)-8 were used as markers for the activation and attraction of neutrophils and eosinophils, respectively. Immunohistochemical staining of TBB with monoclonal antibodies to MPO and ECP (EG2) was performed. Significantly increased BAL percentages of neutrophils and levels of MPO were found in patients with BOS. The findings correlated well with the degree of monoclonal staining for MPO in TBB. BAL levels of ECP and IL-8 were significantly increased in BOS patients. BAL concentrations of the water-soluble antioxidants ascorbate, urate and glutathione were generally lower in BOS patients. The results indicate that neutrophil infiltration and activation, as well as oxidative stress, may play a role in the development and/or progression of bronchiolitis obliterans syndrome. Markers for neutrophil activation could have a potential role in monitoring disease activity in patients with this syndrome.
The costs of providing oncology services in three different ways were measured. Services were provided to a peripheral hospital by: conventional clinics, in which the oncologist worked at the hospital concerned; outreach clinics, in which an oncologist was flown in periodically from a central hospital; telemedicine clinics, in which the oncologist at the central hospital practised via a video-link. During a one-year study period, 2400 patients were seen in conventional clinics, 81 in outreach clinics and 103 in telemedicine clinics. At these workloads the average costs per patient were $149, $897 and $812, respectively. However, the average costs cannot be compared directly without further information about the shape of the unit cost curves.
The study uses a recently-developed scale for eliciting perceptions, expectations, and evaluations of intergenerational communication. As predicted, it is found that younger adults expect to experience more anxiety, receive more complaining, and receive lower levels of attunement from an older adult who is portrayed as "despondent" than one who is portrayed as a "perfect grandparent." In addition, younger adults with more negative attitudes toward older adults expect to experience more negative effect, anxiety, and communication apprehension, to feel more compassion for the older adult, and to receive lower levels of attunement and more complaining from the older adult than those with more positive attitudes. Surprisingly, younger adults with higher levels of young age identification expect to experience lower levels of apprehension, more attunement from the older adult, and to feel more compassion for the older adult than those with lower levels of age identity. These findings are discussed in terms of theoretical models of intergenerational communication, in particular the communication predicament model. In addition, younger people's feelings of having "helped" an older person are discussed in the context of intergroup theory.
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This qualitative study sought to explore the experience of the female nurse as patient, focusing on the power relations between the female nurse-patient and the female nurse providing care. A critical approach informed the interviews with six registered nurses regarding their hospitalised experiences, and why they chose to disclose or withhold their professional occupation. Thematic and deconstructive analysis revealed the subjugation and marginalisation of these nurse-patients, suggesting that nurses do not always view nurse-patients as individuals requiring holistic care, as well as the need for a more balanced sharing of power between these two groups.
Asymmetrical excision of sacrococcygeal pilonidal sinus has been shown to be associated with low recurrence rates. We report our experience with an asymmetric technique--the Karydakis operation. Of 28 patients who had the operation over a 4-year period, no recurrences were observed in 27 patients available for follow-up (median follow-up 3 years). Three patients had complications requiring surgical intervention. The operation is easy to teach and learn and is worth considering by both specialist and non-specialist surgeons.
This year will see the launch of the first chlorofluorocarbon (CFC)-free formulation of beclomethasone. Developed by 3M Health Care, its extrafine formulation gives significant benefits resulting from increased lung deposition and improved inhaler technology. Its difference from CFC-propelled inhalers is so marked that it will challenge views about about the risk-benefit profile of beclomethasone.
Post-transplant lymphoproliferative disease (PTLD) is a major cause of death and disease in transplant patients. We describe 4 cases with histologically confirmed malignant lymphoma arising in the Birmingham liver transplant programme between 1982 and 1995. One was an EBV-positive diffuse large B-cell lymphoma, 2 were EBV-positive Burkitt's lymphomas and the 4th was an EBV-negative Burkitt's lymphoma. Immunohistochemistry revealed expression of the EBV-encoded latent membrane protein LMP1 and of the BZLF1 trans-activator protein in 2 cases each, whereas the virus-encoded nuclear antigen EBNA2 was not detectable. All available post-transplant biopsies from the 3 patients with EBV-associated lymphoma were then studied to test whether the detection of EBV-positive cells in liver allograft biopsies could be used to identify patients at risk for the development of PTLD. Two patients showed infrequent EBV-positive cells in liver allograft biopsies up to 14 months before the occurrence of lymphoma and a marked increase in the number of such cells at the time of lymphoma diagnosis. Multiple biopsies from the 3rd patient did not reveal any EBV-carrying cells in the entire post-transplant period. Our results demonstrate a low incidence of PTLD in the Birmingham liver transplant programme. The PTLDs were morphologically high-grade malignant lymphomas. Only 3 cases were associated with EBV infection, and these showed heterogeneous patterns of EBV latent protein expression. Our results also suggest that the examination of liver allograft biopsies using EBER in situ hybridisation is not an appropriate method for identifying patients at risk of developing PTLD.
We have isolated and sequenced genomic clones encompassing more than 5 kb of the 5' flanking region of the cholesteryl ester transfer protein gene. This region contains multiple Alu repeats, a Mermaid repeat, and an extensive GA repeat, which made sequencing exceedingly difficult. To circumvent the problems that these repeats posed to traditional sequencing methodologies, we employed a novel transposon-facilitated technique, which greatly simplified sequencing of regions that had been difficult to accomplish otherwise. We utilized the artificial transposon, AT-2, a Bluescript derivative containing the dhfr gene and unique primer sites at both ends of the insertion DNA. Integration of the transposon occurred efficiently and covered the entire region of interest. Analysis of the sequence indicates a number of potential regulatory factor binding sites upstream of the previously characterized minimal promoter. The 5.7-kb regulatory region confers significant transcriptional activation in a conditionally transformed mouse hepatocyte line as compared to a minimal 137-bp promoter fragment. In addition, a tetranucleotide repeat of variable length that may provide a useful genetic marker has been identified 2 kb upstream of the CETP transcriptional start site.
A slot system allocating a set number of outpatient orthopaedic appointments to general practices in North West Anglia HA means all patients referred are seen in eight weeks. The system has provoked criticism from GPs on the grounds that the burden of waiting lists has shifted onto them, and it limits access to services. The scheme has improved communication between GPs and orthopaedic consultants.
The appearance of immunoreactive interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha, prostaglandin (PG) E2 and lipocortin-1 in the central nervous system was investigated during the development of lesions in a 301V/VM murine scrapie model. Focal PrP(Sc) deposition was present after 30 days of the 115-120 day incubation period; this immunoreactivity increased in intensity and distribution thereafter. Staining for IL-1beta and TNF alpha in perivascular macrophages, and PGE2 immunoreactivity in astrocytes, was detected in those areas showing PrP(Sc) deposition from 60 days. Increased GFAP and F4/80 immunoreactivity, indicating activation of astrocytes and microglia, was also evident in these areas from 60 days. Glial cytokine and lipocortin immunoreactivity was detected after 90 days, in the absence of clinical signs. The disease-induced cytokine, PG and lipocortin immunoreactivity occurred only in those brain areas showing PrP(Sc) deposition, glial activation and, in later stages, vacuolation. These findings support the concept that PrP(Sc) deposition induces glial cytokine production. These glial cytokines may contribute to the development of the pathological lesions in scrapie.
Rabbit muscle adenylate kinase (EC 2.7.4.3) is completely inhibited, or nearly so, at 2 mM ascorbate, concentrations that are found in tissues. Kinetically, the inhibitions show classic non-competitive inhibition patterns against both substrates. Ascorbate inhibitions reverse completely in the presence of low concentrations of sulfhydryl compounds, such as mercaptoethanol, dithiothreitol, cysteine and glutathione. Dehydroascorbate inhibition is relatively poor and is also reversed by sulfhydryl compounds. Examination of the adenylate kinase inhibited by ascorbate with CD methodology showed no significant change in alpha-helix and beta-pleated sheet composition.
Following a dose of 4 Gy 250 kVp X-rays to the blood lymphocytes from three healthy donors the frequency of micronuclei was enumerated by three scorers. Eight slides were prepared from each blood sample with 1000 cytokinesis-blocked binucleate cells being scored for micronuclei and a recount undertaken 4 weeks later. Seven possible sources of variation were investigated: differences between donors, scorers, the four stages of sample preparation and time. A complete factorial analysis indicated that the major sources of variation were differences between donors and differences between scorers. One scorer identified fewer micronuclei than did the other two scorers in all slides of the irradiated blood samples and gave wide and inconsistent results for baseline counts. These results suggest that the performance of scorers should be screened before undertaking analysis of micronuclei. The most striking result, however, was the consistent performance of the scorers on the repeat counts compared with the very large differences between the scorers.
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OBJECTIVE: To evaluate the immunogenicity and reactogenicity of a new triple S recombinant hepatitis B vaccine in a cohort of healthy people in whom currently licensed hepatitis B vaccines had persistently not induced an immune response. DESIGN: Single centre, randomised, double blind, dose-response study. SETTING: Research vaccine evaluation centre at a teaching hospital. SUBJECTS: 100 healthcare workers aged 18-70 years with a history of failure to seroconvert after at least four doses of a licensed hepatitis B vaccine containing the S component. INTERVENTION: Each subject was randomly allocated two doses of 5, 10, 20, or 40 micrograms of a new hepatitis B vaccine two months apart. MAIN OUTCOME MEASURES: Immunogenicity of the four doses. Seroconversion and seroprotection were defined as an antibody tire > 10 IU/l and > 100 IU/l respectively against an international antibody standard. RESULTS: 69 subjects seroconverted after a single dose of the vaccine. After the booster vaccination one other subject seroconverted, bringing the overall seroconversion rate to 70%. Fifteen subjects given 5 micrograms of vaccine, 19 given 10 micrograms, 16 given 20 micrograms, and 20 given 40 micrograms seroconverted. Seroconversion rates in the four antigen dose groups were 60% (15/25), 76% (19/25), 64% (16/25), and 80% (20/25). After the booster dose there was no significant dose-response effect on the overall seroconversion rate, although the small sample size meant that a clinically important dose-response could not be ruled out. CONCLUSION: A single dose of 20 micrograms of the vaccine was as effective as two doses of either 40 micrograms or 20 micrograms of this vaccine formulation in terms of seroconversion, seroprotection, and geometric mean titres.