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Biomedical subjects

J Allen

Publications and source records attributed to J Allen.

At least 145 records · Page 8Linked to original sources

Blister fluid for the diagnosis of subepidermal immunobullous diseases: a comparative study of basement membrane zone autoantibodies detected in blister fluid and serum.

The subepidermal immunobullous diseases bullous pemphigoid (BP), cicatricial pemphigoid (CP), pemphigoid gestationis (PG) and linear IgA disease (LAD) are characterized by circulating and in vivo deposition of antibodies to antigens in the cutaneous basement membrane zone (BMZ). Indirect immunofluorescence (IMF) of serum is a routine diagnostic test to detect circulating BMZ antibodies in these diseases. We have compared the titres of IgG and IgA and their subclasses, also of IgM and IgE BMZ antibodies in serum and aspirated blister fluid in 35 adult patients with subepidermal immunobullous diseases: BP (n = 30), PG (n = 2), CP (n = 1), and LAD (n = 2), by indirect IMF on intact and salt-split skin. The antibody titre in blister fluid was the same or one dilution less than serum in most cases and there was no significant difference between these results (P > 0.05). IgG1 and IgG4 were the predominant subclasses in both blister fluid and serum in BP. Indirect IMF of serum and blister fluid was also carried out on trypsinized epidermal cells in a subgroup of patients with BP (n = 19). Typical polar fluorescence was obtained in all 14 cases which had positive indirect IMF on intact and split skin. Our findings demonstrate that blister fluid can be used as an alternative to serum for indirect IMF in subepidermal immunobullous diseases. This avoids the need for venesection and has a practical application in children and those with poor venous access.

Adult↗

The association of HLA-DQ7 with bullous pemphigoid is restricted to men.

This study examines in detail the HLA associations of 74 patients (40 women and 34 men) with bullous pemphigoid (BP) and compares their immunogenetic profile with that of 604 unrelated control subjects (238 women and 366 men). Correlations were sought between HLA antigens and the various BP disease parameters investigated. The presence of milia was the only clinical or laboratory finding which was linked with a specific HLA antigen, HLA-DQ6, in both men and women with BP (P < 0.01). BP has previously been linked with the HLA-DQ7 antigen and this association was confirmed in 39 of our patients (14 women and 25 men). Twelve of these patients (four women and eight men) were homozygous for HLA-DQ7. The association of HLA-DQ7 with BP was gender-restricted and only significant for men (P < 0.01). No equivalent HLA disease susceptibility risk factor could be identified for our female BP patients. This difference in HLA association between men and women with BP has not been reported previously, and its significance for disease pathogenesis is not known. No specific link could be found between HLA-DQ7 and BP for any of the clinical, immunofluorescence, western blotting, treatment or prognostic disease factors studied.

Aged↗

The localization of target antigens and autoantibodies in linear IgA disease is variable: correlation of immunogold electron microscopy and immunoblotting.

Linear IgA disease (LAD) of adults and children is a dapsone-responsive, autoimmune subepidermal blistering disease characterized by linear IgA deposits at the basement membrane zone (BMZ) of the skin and mucosa. Circulating IgA antibodies to BMZ components are often present. In this study we investigated the ultrastructural localization of the antigens and autoantibodies in six patients with LAD (five adults and one child). Using a direct postembedding immunogold electron microscopy (EM) technique, three different patterns of IgA antibody deposition were seen in the skin of four patients with LAD. The IgA deposits localized within the uppermost part of the lamina lucida and to the basal surface of the hemidesmosome in two patients, to the lamina lucida in one, and to the lamina densa in the fourth patient. Using an indirect immunogold EM technique and serum or purified blister fluid from two additional LAD patients, we showed that the serum autoantibodies of one patient bound to the hemidesmosome of the BMZ, while the autoantibodies in the blister fluid of the other patient bound to the lamina densa and sublamina densa including the anchoring fibrils in a labelling pattern similar to that of the monoclonal antibody (LH7.2) to collagen VII. All the autoantibodies binding to the hemidesmosome or lamina lucida recognized a protein in epidermal extracts of molecular weight 180 kDa or its breakdown product of 97 kDa, 200 kDa or 230 kDa. The antibodies binding to the lamina densa recognized proteins of 180 and 285 kDa. The antibodies that bound to the lamina densa and anchoring fibrils recognized collagen VII. In this immunogold EM study we have shown four patterns of IgA labelling in six patients with LAD, associated with five different antigens as recognized by immunoblotting. These results, together with our previous immunofluorescence and immunoblotting findings add support to the contention that LAD is a heterogeneous disease as regards both the target antigens and epitopes.

Adult↗

A survey of psychiatric nurses' opinions of advanced practice roles in psychiatric nursing.

This postal survey established psychiatric nurses' opinions of the content of advanced practice psychiatric nursing roles. A random sample, consisting of 100 members of the Network for Psychiatric Nursing Research (NPNR), was surveyed. 78% returned completed questionnaires. Responses were analysed using the chi-square test, and the Mann-Whitney U-test. Elements of the normal nursing role identified included psychiatric assessment, patient and carer education, and basic psychotherapeutic practices. Identified advanced practice roles included psychiatric diagnoses, prescribing single emergency doses and modifying doses of a wide range of psychotropic medication. Enhanced autonomy in admission and discharge and additional powers under the Mental Health Act were also supported. The prescription of full courses of medication and the prescription and administration of electroconvulsive therapy were rejected as nursing roles. University and Trust employed nurses responded differently in a number of these areas. The study concluded that an advanced practice role which incorporates restricted elements of psychiatric practice is supported by psychiatric nurses, and recommends that pilot sites should be established which test the acceptability and effectiveness of the identified role.

Attitude of Health Personnel↗

Deletion analysis of yeast Sec65p reveals a central domain that is sufficient for function in vivo.

The Saccharomyces cerevisiae SEC65 gene encodes a 32 kDa subunit of yeast signal recognition particle that is homologous to human SRP19. Sequence comparisons suggest that the yeast protein comprises three distinct domains. The central domain (residues 98-171) exhibits substantial sequence similarity to the 144 residue SRP19. In contrast, the N-terminal and C-terminal domains (residues 1-97 and 172-273 respectively) share no similarity to SRP19, with the exception of a cluster of positively charged residues at the extreme C-terminus of both proteins. Here, we report the cloning of a Sec65p homologue from the yeast Candida albicans that shares the same extended domain structure as its S. cerevisiae counterpart. This conservation of sequence is reflected at the functional level, as the C. albicans gene can complement the conditional lethal sec65-1 mutation in S. cerevisiae. In order to examine the role of the N- and C- terminal domains in Sec65p function, we have engineered truncation mutants of S. cerevisiae SEC65 and tested these for complementing activity in vivo and for SRP integrity in vitro. These studies indicate that a minimal Sec65p comprising residues 76-209, which includes the entire central SRP19-like domain, is sufficient for SRP function in yeast.

Amino Acid Sequence↗

Treatment of intracranial ependymoma by surgery alone.

OBJECTIVE: This study aimed to determine the safety of deferring radiotherapy in pediatric intracranial ependymoma following a radiographically confirmed gross total resection in patients with localized disease. METHODS: Children over age 3 were recruited prospectively from 1990 to 1997, following a surgical impression and radiologic confirmation of a gross total resection of an intracranial ependymoma. RESULTS: 10/32 cases of intracranial ependymomas were both eligible and gave consent. 7 remain free of disease without further intervention. 3 recurred, 2 were salvaged with surgery and radiotherapy, none died. CONCLUSIONS: Deferral of radiotherapy following gross total resection alone is a safe option in supratentorial ependymomas. The pattern of recurrence is usually local and patients may be salvaged with additional surgery with or without radiotherapy.

Adolescent↗

Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors.

PURPOSE: To evaluate a strategy that avoids radiotherapy in children less than 6 years of age with newly diagnosed malignant brain tumors, by administering myeloablative consolidation chemotherapy with autologous bone marrow reconstitution (ABMR) after maximal surgical resection and conventional induction chemotherapy. PATIENTS AND METHODS: Between March 1991 and April 1995, 62 children (median age, 30 months) with newly diagnosed malignant brain tumors were enrolled onto this trial. Children received conventional induction chemotherapy with vincristine, cisplatin, cyclophosphamide, and etoposide, repeated every 3 weeks for five cycles. Children without disease progression on induction chemotherapy were offered consolidation with myeloablative chemotherapy that incorporated carboplatin, thiotepa, and etoposide followed by ABMR. Irradiation was used only for residual tumor at consolidation or for progressive/recurrent disease. RESULTS: Induction chemotherapy was well tolerated by most patients; however, progression was noted in 17 children (27%) and four (6%) died of treatment complications. Of 37 children who received consolidation chemotherapy with ABMR, 15 are free of disease progression (median post-ABMR without further treatment, >44 months). The remaining 22 all progressed within 15 months of ABMR; three of 37 (8%) died of treatment-related complications. The 3-year overall survival (OS) and event-free survival (EFS) rates from diagnosis for all children are 40% (95% confidence interval [CI], 28% to 52%) and 25% (95% CI, 13% to 37%), respectively. Radiotherapy was administered to 19 of 62 children: 17 for progressive disease (PD) and two for residual disease at the time of ABMR. CONCLUSION: A significant proportion of children with malignant brain tumors can avoid radiotherapy and prolonged maintenance chemotherapy yet still achieve durable remission with this brief intensive chemotherapy regimen.

Antineoplastic Combined Chemotherapy Protocols↗

Simulated surgery.

Explore the source record for details and available documents.

Educational Measurement↗

Dialogue. Industry consolidation: what's at stake for consumers and purchasers?

The behavioral healthcare field has undergone massive consolidation, especially in the last year. Health plans, hospital systems, and community-based organizations have all been affected. Economists argue that consolidation is a logical consequence of the current, competitive healthcare market. But consumers and purchasers wonder if the mergers and acquisitions will benefit them. Efficient markets are supposed to stimulate competition in ways that reward purchasers and consumers of services. When prices go down and quality improves as a result of competitive market forces, then the market has functioned properly and has served its purpose. Behavioral healthcare, however, is an essential human service, not a commodity. And the consumers and purchasers of healthcare are typically not the same person or entity, which also makes the healthcare market different from the markets for cars, computers, food, or any other type of consumer product. More than 100 million Americans now receive managed behavioral health benefits from only three companies. With such intense power concentrated in the hands of such a small number of providers, the time has come to evaluate the impact of the consolidation trend. In the following dialogue article, leaders, representing different interest groups review the benefits and risks of massive industry consolidation, and propose solutions to the critical challenges that it raises.

Consumer Advocacy↗

Quantitative and qualitative performance of stroke versus normal elderly on six clock drawing systems.

The utility of the Clock Drawing Test (CDT) in localizing lesions has not been thoroughly examined to date. In the present study, six scoring systems (Freedman et al., 1994; Ishiai, Sugishita, Ichikawa, Gono, & Watabiki, 1993; Mendez, Ala, & Underwood, 1992; Rouleau, Salmon, Butters, Kennedy, & McGuife, 1992; Sunderland et al., 1989; Tuokko, Hadjistavropoulos, Miller, & Beattie, 1992; Watson, Arfken, & Birge, 1993; Wolf-Klein, Silverstone, Levy, & Brod, 1989) were used to assess clock drawings by 76 stroke patients and 71 normal controls. Significant differences were found between normals and stroke patients on all scoring systems for both quantitative and qualitative features of the CDT. Quantitative indices were not helpful in differentiating between various stroke groups (left versus right versus bilateral stroke; cortical versus subcortical stroke; anterior versus posterior stroke). Qualitative features were helpful in lateralizing lesion site and differentiating subcortical from cortical groups. Correlational analyses revealed that CDT performance was related to visuospatial processing and measures commonly used in cognitive screening.

Journal Article↗

Measurement of soluble transferrin receptor in serum of healthy adults.

The concentration of soluble transferrin receptor (sTfR) in serum is reported to be useful in the diagnosis of iron deficiency, especially for patients with concurrent chronic disease, where routine tests of iron status are compromised by the inflammatory condition. A new diagnostic assay for sTfR is calibrated against natural plasma sTfR, thus minimizing calibration discrepancies that result from differences between the analyte and the cellular transferrin receptor used in other assays. Use of the new assay to measure sTfR concentrations in 225 healthy, hematologically normal adults provided a reference interval against which pathological samples could be compared. There was no difference in the reference intervals for men and women and no correlation of [sTfR] with the age of the subject. Black subjects had significantly higher concentrations than nonblacks, and people living at high altitude had higher concentrations than those living closer to sea level. These differences were additive.

Age Factors↗

What you need to know: detecting alcohol problems in general medical practice.

In the US, about 11% to 20% of patients presenting to general medical clinics are diagnosed as suffering from alcohol abuse or dependence. Alcohol screening in primary care settings, whether in the US or Singapore, can utilise various strategies for the early detection of alcohol problems. This paper briefly reviews several self-reports and screening procedures to assist general practitioners in identifying problem drinkers. The use of CAGE questionnaire, MAST, and its variation, SAAST and the AUDIT, are discussed and evaluated. Likewise, useful biochemical markers of excessive alcohol consumption like the liver enzymes (AST, ALT, GGT), MCV, CDT are described. They can be combined with each other to improve validity or used in conjunction with self-report screening tests for more accurate detection of problem drinkers. In particular, use of the AUDIT for routine screening of alcohol problems in primary care settings is recommended. Selective administration to those with at least two drinks per setting can overcome time constraints. Alternatively, sequential screening utilising the TRAUMA questionnaire with frequency and quantity questions administered to higher frequency drinkers can circumvent concerns about direct questioning. Use of self-reports and when possible, biochemical screening for alcohol problems should be a standard part of primary care practice.

Alcoholism↗

Simulated surgery in the summative assessment of general practice training: results of a trial in the Trent and Yorkshire regions.

BACKGROUND: General practice registrars are now required to undertake a summative assessment of their consulting skills. Simulated surgeries have been developed as an alternative to the existing method of assessing video-recorded consultations. AIM: To evaluate the simulated surgery assessment method, developed in the General Practice Postgraduate Education Department in Leicester, for use in assessing general practice consultation skills. METHOD: General practice registrars in Leicester performed two eight-patient simulated surgeries separated by four weeks. Assessment outcomes were compared to demonstrate the consistency of the method. Pilot surgeries in Yorkshire were videotaped, and then rated by video-raters trained for summative assessment. RESULTS: The method consistently identified those registrars who were competent and those who were not yet competent in consulting skills. It proved acceptable to candidate doctors and has fewer resource requirements for both examiners and candidates than other consulting skills assessment methods. CONCLUSION: The method developed in Leicester and successfully transferred to Yorkshire is feasible on a large scale, and offers an acceptable alternative to other consulting skills assessment methods. In this study it consistently identified competent from incompetent candidate doctors.

Clinical Competence↗

What determines competence within a general practice consultation? Assessment of consultation skills using simulated surgeries.

A method for assessing the consultation skills required in general practice using patient simulators within a simulated surgery has been developed in Leicester, aimed at registrars coming to the end of their three-year training programme. This paper addresses the issues of validity, describing the technique as it has evolved over the past three years, and paying particular attention to ways in which the consultation was made to feel 'real' for candidates. As well as testing clinical issues during consultations, simulated surgery incorporates the views of the patient into the assessment process. Feedback from registrars has been positive and the method presents an alternative to video-recording the consultation for the purpose of assessment.

Clinical Competence↗

The use of APACHE II scores to select candidates for left ventricular assist device placement. Acute Physiology and Chronic Health Evaluation.

BACKGROUND: The growth in left ventricular assist device (LVAD) use has been hampered by high morbidity and mortality rates and cost. The purpose of this study was to help improve patient selection for LVAD placement by determining whether the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system, a multiparameter, physiology-based predictor of outcome, could be used to predict outcome after LVAD placement and thus help determine optimum timing of LVAD placement. METHODS: This was a retrospective analysis of a prospective cohort observational study consisting of 2 groups: (1) 50 patients with severe heart failure who did not receive LVAD placement after initial evaluation and (2) 31 patients who did receive LVAD placement. Patients included in the study were in severe heart failure on the basis of 3 of the following: lung crackles, S3, peripheral edema, ejection fraction < 0.30, systolic blood pressure < 80 mm Hg, progressive prerenal azotemia, altered level of consciousness, gastrointestinal ischemia or congestion, or persistent although reversible pulmonary hypertension in spite of maximal medical therapy, including intravenous inotropes. The decision for LVAD placement was at the discretion of the attending physician. RESULTS: Both LVAD- and non-LVAD-treated patients were similar in cause of heart failure, APACHE II scores, and other baseline laboratory parameters. Survival time with a log-logistic model was better for LVAD-treated patients, p=.0266. Although Kaplan Meier analysis showed a trend toward better survival rates in the LVAD-treated patient, the Cox proportional hazards revealed that LVAD-treated patients had better survival (relative risk ratio, 95% confidence interval=0.305, 0.110 to 0.892; p=.0219) after adjustment for APACHE II score. Each unit increase in APACHE II independently predicted death (relative risk ratios, 95% confidence interval=1.139, 1.055 to 1.231; p=.0009). Patients with medium APACHE II (11 to 20) scores in particular benefitted from LVAD treatment. CONCLUSION: LVAD placement for severe heart failure (not restricted to cardiogenic shock) improves survival. APACHE II can aid in deciding the timing of LVAD placement in patients with heart failure who may not have attained conventional hemodynamic criteria for LVAD placement. Patients who had APACHE II scores between 11 and 20 derived the greatest benefit from LVAD placement.

APACHE↗

Deliberate self-harm: developing clinical guidelines.

Nurses in an acute admissions psychiatric ward are using reflective practice to develop clinical guidelines for the management of patients who deliberately self-harm. In this article, they describe the cyclical learning processes and reflective techniques involved.

Clinical Nursing Research↗