Biomedical subjects
Publications and source records attributed to J Richards.
The European Working Times Regulations have implications for staff throughout the NHS. In particular, theatre staff and others working on call and shifts need to be aware of the implications of these regulations. In this article, Jon Richards, National Officer for Unison, explains the background to and implications of these regulations for theatre staff.
PURPOSE: Pivotal trial E1684 of adjuvant high-dose interferon alfa-2b (IFNalpha2b) therapy in high-risk melanoma patients demonstrated a significant relapse-free and overall survival (RFS and OS) benefit compared with observation (Obs). PATIENTS AND METHODS: A prospective, randomized, three-arm, intergroup trial evaluated the efficacy of high-dose IFNalpha2b (HDI) for 1 year and low-dose IFNalpha2b (LDI) for 2 years versus Obs in high-risk (stage IIB and III) melanoma with RFS and OS end points. RESULTS: A total of 642 patients were enrolled (608 patients eligible), of whom a majority (75%) had nodal metastasis (50% had nodal recurrence). Unlike E1684, E1690 allowed entry of patients with T4 (> 4 mm) deep primary tumors, regardless of nodal dissection, and 25% of the patients entered onto this trial had deep primary tumors (compared with 11% in E1684). At 52 months' median follow-up, HDI demonstrated an RFS benefit exceeding that of LDI compared with Obs. The 5-year estimated RFS rates for the HDI, LDI, and Obs arms were 44%, 40%, and 35%, respectively. The hazards ratio for the intent-to-treat analysis of HDI versus Obs was 1.28 (P(2) =.05); for LDI versus Obs, it was 1.19 (P(2) =.17). By Cox analysis, the impact of HDI on RFS achieved significance (P(2) =.03). The RFS benefit was equivalent for node-negative and node-positive patients. Neither HDI nor LDI has demonstrated an OS benefit compared with Obs at this time. A major improvement in the median OS of patients in the E1690 Obs arm was noted in comparison with E1684 (6 years v 2.8 years). An analysis of salvage therapy for patients who relapsed on E1690 demonstrated that a significantly larger proportion of patients in the Obs arm received IFNalpha-containing salvage therapy compared with the HDI arm; this therapy was unavailable to patients during E1684, and patients with undissected regional nodes were not included in E1684. This study did not specify therapy at recurrence. Analysis of treatments received at recurrence demonstrated significantly more frequent use of IFNalpha2b at relapse from Obs than from HDI, which may have confounded interpretation of the survival benefit of assigned treatments in E1690. CONCLUSION: The results of the intergroup E1690 trial demonstrate an RFS benefit of IFNalpha2b that is dose-dependent and significant for HDI by Cox multivariable analysis.
This article explores the health concepts of community health care (CHC) nurses in relation to their potential roles as public health workers. On examining Ewen's (1998) study of CHC nurses' role perceptions, it is evident that an individualized, person-centred, holistic approach to care continues to dominate practice. The public health role within CHC nursing remains underdeveloped and is equated with primary prevention with the well population. A 'community-as-foreground' model is proposed as a useful way of redefining CHC nursing practice to incorporate public health. The discussion revolves around the need for a broader view of health to include a political and social dimension, and considers the role of education and practice in achieving this.
These guidelines for the microbiological quality of ready-to-eat foods represent a revision and expansion of guidelines first published by the PHLS in September 1992 and revised in March 1996. The latest guidelines incorporate many of the constructive comments received from food examiners and other microbiologists within and outside the PHLS and from environmental health officers throughout the United Kingdom. This document reviews the changes and the reasons they were made and sets out the new guidelines. It also clarifies the role of food examiners in interpreting the microbiological results of formal samples.
1. The effect has been examined of the accessory alpha2-delta and beta subunits on the properties of alpha1G currents expressed in monkey COS-7 cells and Xenopus oocytes. 2. In immunocytochemical experiments, the co-expression of alpha2-delta increased plasma membrane localization of expressed alpha1G and conversely, the heterologous expression of alpha1G increased immunostaining for endogenous alpha2-delta, suggesting an interaction between the two subunits. 3. Heterologous expression of alpha2-delta together with alpha1G in COS-7 cells increased the amplitude of expressed alpha1G currents by about 2-fold. This finding was confirmed in the Xenopus oocyte expression system. The truncated delta construct did not increase alpha1G current amplitude, or increase its plasma membrane expression. This indicates that it is the exofacial alpha2 domain that is involved in the enhancement by alpha2-delta. 4. Beta1b also produced an increase of functional expression of alpha1G, either in the absence or the presence of heterologously expressed alpha2-delta, whereas the other beta subunits had much smaller effects. 5. None of the accessory subunits had any marked influence on the voltage dependence or kinetics of the expressed alpha1G currents. These results therefore suggest that alpha2-delta and beta1b interact with alpha1G to increase trafficking of, or stabilize, functional alpha1G channels expressed at the plasma membrane.
Murine anti-CD3 (OKT3, Muromonab-CD3) is a potent human T-lymphocyte mitogen. A previous clinical Phase I trial examined OKT3 as an immunomodulator for the treatment of cancer. However, the murine monoclonal antibody triggered a potent humoral response that neutralized the antibody activity during subsequent administration. Thus, a "humanized" form of OKT3 (hOKT3gamma4) was developed to minimize immunogenicity. The genetically engineered human anti-CD3 retained its binding activity and effectively activated T cells in vitro. Therefore, we evaluated the safety and activity of hOKT3gamma4 in a Phase I clinical trial. hOKT3gamma4 was administered as a 10-min i.v. infusion every 2 weeks for three injections (one course of therapy). Six dose levels ranging from 50 to 1600 microg/injection were evaluated. Headache and fever were common, transient toxicities but were not dose limiting. The dose-limiting toxicities were rigors and dyspnea at the 1600-microg dose level, which defined 800 microg as the maximally tolerated dose in this trial. A dose-dependent in vivo T-lymphocyte activation was produced by this treatment, and the most significant T-lymphocyte activation occurred in patients treated at the two highest dose levels (800 and 1600 microg). Persistent CD3 modulation occurred after administration of 1600 microg of hOKT3gamma4. Anti-idiotypic antibodies were detected in only 6 of 24 patients after multiple injections and were not associated with attenuation of T-lymphocyte activation. Malignant ascites resolved in three patients, one each with peritoneal mesothelioma, pancreatic adenocarcinoma, and ovarian adenocarcinoma. hOKT3gamma4 can induce T-lymphocyte activation in patients with cancer, and the immunogenicity of the "humanized" antibody is sufficiently reduced relative to its murine "parent" to permit immunostimulation by repetitive i.v. administration. The therapeutic potential of biweekly i.v. hOKT3gamma4 at a dose of 800 microg should be further evaluated.
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PURPOSE: To present an Arg213Trp missense mutation in the XLRS1 gene in a family with juvenile X-linked retinoschisis in which one affected male had a normal electroretinogram scotopic b-wave amplitude. METHODS: Two affected males and one unaffected male from this family with X-linked retinoschisis underwent standard clinical examination including an electroretinogram. Mutations in the XLRS1 gene were detected by sequence analysis and by restriction enzyme assay for loss of an MSP-I restriction site. RESULTS: A missense mutation of C to T at nucleotide position 637 was identified in exon 6 of the XLRS1 gene. This changed the positively charged arginine to a nonpolar tryptophan (Arg213Trp) within the biologically important discoidin domain. Clinical examination revealed intraretinal cysts in a spoke-wheel distribution and early macular atrophy of the retinal pigment epithelium. Whereas the older affected patient had an "electronegative" electroretinogram typical of retinoschisis, the 13-year-old grandson with the same XLRS1 mutation had a normal electroretinogram scotopic b-wave. CONCLUSION: Although the electroretinogram is a key diagnostic test for X-linked retinoschisis, this report of a normal electroretinogram scotopic b-wave in a male with molecularly confirmed X-linked retinoschisis indicates that caution is advised in relying on the electroretinogram in differential diagnosis of this condition.
OBJECTIVES: To test the hypothesis that an interactive multimedia-based computer application may be used to teach urology to undergraduate medical students. METHODS: Third-year medical students rotating on their urology clerkship were studied. Student knowledge was measured with a multiple choice test administered in a pretest-post-test experimental design. The educational intervention was a multimedia-based application that presented a clinical module on hematuria, using natural language-like entries. Student attitudes toward the multimedia application were assessed by a survey. RESULTS: Twenty-three consecutive third-year medical students participated. Mean pretest and post-test scores +/- standard deviation were 35%+/-11% versus 74%+/-17%, respectively, P<0.0001. Student questionnaire responses indicated highly positive opinions that the multimedia-based module was easy to use, was fun, provided natural patient responses, had clear exercises, provided immediate feedback, was educational, and had a nonthreatening format, and that the multiple choice questions were clear and fair. CONCLUSIONS: Multimedia-based education may be used to teach urology to undergraduate medical students.
We evaluated the family-oriented care and counseling provided by the BC Children's Hospital Transport Team paramedies. One hundred families were asked to rate: (1) how they would like paramedies to communicate with them under ideal conditions; and (2) what they actually experienced during their child's transport. There were no significant differences in parents' preferences under ideal circumstances and what they actually experienced in five of nine behavioural areas studied. Nineteen paramedies also rated their use of elements of family-oriented communication and the strategies they would recommend other teams use when interacting with families. The elements that paramedies reported using most frequently were rated highly by parents and produced positive feelings in the majority of families. The study indicates that effective counseling can be achieved in 'critical', time-limited situations but improvements can be made; and it supports the value of appropriate selection and training of transport team personnel in family-oriented critical care.
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In this paper, we describe a miniature analytical thermal cycling instrument (MATCI) to amplify and detect DNA via the polymerase chain reaction in real-time. The MATCI is an integrated, miniaturized analytical system that uses silicon-based, high-efficiency reaction chambers with integrated heaters and simple, inexpensive electronics to precisely control the reaction temperatures. Optical windows in the silicon and solid-state, diode-based detection components are employed to perform real-time fluorescence monitoring of product DNA production. The entire system fits into a briefcase and runs on rechargeable batteries. The applications of this miniaturized nucleic acid analysis system include clinical, research, environmental, and agricultural analyses as well as others which require rapid, portable, and accurate analysis of biological samples for nucleic acids. This paper describes the MATCI and presents results from ultrafast thermal cycling and real-time PCR detection. Examples include human genes and pathogenic viruses and bacteria.
Haemophilus influenzae undergoes phase variation in expression of the phosphorylcholine (ChoP) epitope, a structure present on several invasive pathogens residing in the human respiratory tract. In this study, structural analysis comparing organisms with and without this epitope confirmed that variants differ in the presence of ChoP on the cell surface-exposed outer core of the lipopolysaccharide. During nasopharyngeal carriage in infant rats, there was a gradual selection for H. influenzae variants that express ChoP. In addition, genotypic analysis of the molecular switch that controls phase variation predicted that the ChoP+ phenotype was predominant in H. influenzae in human respiratory tract secretions. However, ChoP+ variants of nontypable H. influenzae were more sensitive to the bactericidal activity of human serum unrelated to the presence of naturally acquired antibody to ChoP. Serum bactericidal activity required the binding of C-reactive protein (CRP) with subsequent activation of complement through the classical pathway. Results of this study suggested that the ability of H. influenzae to vary expression of this unusual bacterial structure may correlate with its ability both to persist on the mucosal surface (ChoP+ phenotype) and to cause invasive infection by evading innate immunity mediated by CRP (ChoP- phenotype).
Occupational exposure to residual oil fly ash (ROFA) particulate has been associated with adverse respiratory health effects in humans. We hypothesized that ROFA collected at different sites within an oil burning power plant, by virtue of its differing metal and sulfate composition, will induce differential lung injury. Ten ROFA samples collected at various sites within a power plant were analyzed for water- and 1.0 M HCl-leachable arsenic (As), beryllium (Be), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb), vanadium (V), zinc (Zn), and sulfur by inductively coupled plasma-atomic emission spectroscopy. All ROFA samples contained variable amounts of leachable (water-extractable) and 1.0 M HCl-extractable Fe, V, and/or Ni. All other metals, except Zn (ROFA No. 1 contained 3.43 and No. 3, 6.35 micrograms/mg Zn), were present in negligible quantities (< 1.0 microgram/mg) in the water extract. In vivo pulmonary injury from exposure to whole saline suspensions of these ROFA was evaluated. Male, SD rats (60 days old) were intratracheally instilled with either saline or saline suspension of whole ROFA (< 3.0 mass median aerodynamic diameter) at three concentrations (0.833, 3.33, or 8.33 mg/kg). After 24 h, lungs were lavaged and bronchoalveolar lavage fluid (BALF) was analyzed for cellular influx and protein content as well as lactate dehydrogenase (LDH) and N-acetyl glucosaminidase (NAG) activity and total hemoglobin as indicators of lung injury. ROFA-induced increases in BALF protein and LDH, but not neutrophilic inflammation, were associated with its water-leachable total metal, Ni, Fe, and sulfate content. However, the neutrophilic response following ROFA exposure was positively correlated with its water-leachable V content. Modest lung injury was observed with the ROFA samples which contained the smallest amounts of water-leachable metals. The ability of ROFA to induce oxidative burst in alveolar macrophage (AM) was determined in vitro using a chemiluminescence (CL) assay. AM CL signals in vitro were greatest with ROFA containing primarily soluble V and were less with ROFA containing Ni plus V. In summary, ROFA-induced in vivo acute pulmonary inflammation appears to be associated with its water-leachable V content; however, protein leakage appears to be associated with its water-leachable Ni content. ROFA-induced in vitro activation of AM was highest with ROFA containing leachable V but not with Ni plus V, suggesting that the potency and the mechanism of pulmonary injury will differ between emissions containing V and Ni.
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An immunoassay for the detection of Clostridium difficile toxin A in stool samples (Clearview C. DIFF A; Unipath, UK) was evaluated against the cell cytotoxicity assay using 407 stool samples from patients suspected to have, or considered at risk of, antibiotic-associated diarrhoea. Of the samples tested, 98 were positive and 280 were negative by both tests (sensitivity 83.1%, specificity 96.9%). Following resolution of the 29 discrepant results, the sensitivity and specificity of the immunoassay were 91% and 98%, respectively, and the sensitivity for the cell cytotoxicity assay was calculated as 91.5%, with a specificity of 99%. The Clearview C. DIFF A test proved to be a rapid simple assay for the detection of Clostridium difficile toxin A in stool samples. The test was equally suited to single or batch testing, required minimal sample handling, and provided results within 30 min of applying the sample to the test unit.