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Biomedical subjects

E J Stewart

Publications and source records attributed to E J Stewart.

At least 19 recordsLinked to original sources
PubMed2006

A randomised, double-blind, placebo-controlled trial of a recombinant version of human alpha-fetoprotein (MM-093) in patients with active rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) tends to remit during pregnancy, with more patients achieving remission in the third trimester, coinciding with an increase in levels of alpha-fetoprotein (AFP). In vitro and animal studies have shown that AFP has immunomodulatory properties. MM-093 is a non-glycosylated, recombinant version of human AFP. OBJECTIVE: To assess the safety, tolerability and clinical effects of MM-093 during a 12-week, randomised, double-blind, placebo-controlled study. METHODS: 12 patients with RA, who had active disease and were on stable doses of methotrexate, received weekly subcutaneous injections of placebo or 21 mg of MM-093. Assessments were carried out at baseline and weekly thereafter. RESULTS: Baseline characteristics were similar in both groups. There was one dropout in the placebo group, due to flare of disease. Treatment with MM-093 was well tolerated. No serious adverse event was observed. By day 85, MM-093 produced a significant mean improvement from baseline in Disease Activity Score 28 (DAS28; 0.913 vs 0.008, p = 0.033) and patient's global assessment (28.9% vs -36.3%, p = 0.02) compared with placebo. CONCLUSION: This is the first randomised, controlled trial of MM-093, a recombinant version of human AFP, in patients with RA. MM-093 was well tolerated. Evidence of efficacy was observed, suggesting that MM-093 may have therapeutic potential in RA.

Arthritis, Rheumatoid↗
PubMed2001

Aggressive, extensive, vasculitic leg ulceration associated with hydroxyurea therapy and a fatal outcome.

The association of lower leg ulcer development and hydroxyurea therapy in patients with myeloproliferative disorders has been reported previously. In most of these cases the ulcers healed with cessation of the hydroxyurea together with meticulous attention to wound care. We report a patient who developed painful vasculitic ulcers secondary to hydroxyurea on both lower legs whilst on long-term hydroxyurea therapy for idiopathic thrombocytosis. The ulcers extended relentlessly despite stopping hydroxyurea, maximizing topical therapies and starting intensive systemic treatment. We discuss the association of hydroxyurea therapy with the development of painful ulceration.

Aged↗
PubMed2001

Comparison of costs and referral rates of 3 universal newborn hearing screening protocols.

OBJECTIVE: To investigate the costs and referral rates of 3 universal newborn hearing screening programs: transient evoked otoacoustic emissions (TEOAE), automated auditory brainstem response (AABR), and a combination, two-step protocol in which TEOAE and AABR are used. STUDY DESIGN: Clinical outcomes (referral rates) from 12,081 newborns at 5 sites were obtained by retrospective analysis. Prospective activity-based costing techniques (n = 1056) in conjunction with cost assumptions were used to analyze the costs based on an assumed annual birth rate of 1500 births. RESULTS: Referral rates differed significantly among the 3 screening protocols (AABR, 3.21%; two-step, 4.67%; TEOAE, 6.49%; P <.01), with AABR achieving the best referral rate at discharge. Although AABR had the lowest referral rate at discharge and the highest pre-discharge costs, the total pre- and post-discharge costs per infant screened (AABR, $32.81; two-step, $33.05; TEOAE, $28.69) and costs per identified child (AABR, $16,405; two-step, $16,527; TEOAE, $14,347) were similar among programs. CONCLUSION: Although AABR incurs higher costs during pre-discharge screening, it has lower referral rates than either the TEOAE or two-step program. As a result, the total costs of newborn hearing screening and diagnosis are similar among the 3 methods studied.

Costs and Cost Analysis↗
PubMed2000

Aetiological factors in vulvar dermatitis.

AIM: To determine aetiological factors in vulvar dermatitis. BACKGROUND: Dermatitis of the vulva is a common clinical diagnosis in the specialized vulva clinic, although the exact prevalence is unknown. Aetiological factors are poorly understood in particular the incidence of atopy and seborrhoeic dermatitis. Other factors implicated are iron deficiency and exogenous causes such as contact irritants and allergens. METHODS: During a 1-year period, 38 patients with an initial clinical diagnosis of vulvar dermatitis were questioned, examined and investigated with full blood count, serum ferritin, bacterial swab where indicated and punch biopsy. After three patients had been excluded with other diagnoses, prick testing and patch testing were carried out. RESULTS: Of the 35 patients with vulvar dermatitis, 34 (97%) had either an atopic background and/or seborrhoeic dermatitis. Iron deficiency occurred in seven patients (20%) and relevant positive patch tests in nine patients (26%). Twenty patients had biopsies and all had confirmatory histology. CONCLUSION: This study suggests that the main aetiological factor in vulvar dermatitis is an endogenous predisposition. Iron deficiency may also contribute, while contact with irritants and allergens may explain the localization and frequently complicates and exacerbates the picture. Secondary sensitization to multiple substances is common.

Adult↗
PubMed1999

Six conserved cysteines of the membrane protein DsbD are required for the transfer of electrons from the cytoplasm to the periplasm of Escherichia coli.

The active-site cysteines of the Escherichia coli periplasmic protein disulfide bond isomerase (DsbC) are kept reduced by the cytoplasmic membrane protein, DsbD. DsbD, in turn, is reduced by cytoplasmic thioredoxin, indicating that DsbD transfers disulfidereducing potential from the cytoplasm to the periplasm. To understand the mechanism of this unusual mode of electron transfer, we have undertaken a genetic analysis of DsbD. In the process, we discovered that the previously suggested start site for the DsbD protein is incorrect. Our results permit the formulation of a model of DsbD membrane topology. Also, we show that six cysteines of DsbD conserved among DsbD homologs are essential for the reduction of DsbC, DsbG and for a reductive pathway leading to c-type cytochrome assembly in the periplasm. Our findings suggest a testable model for the DsbD-dependent transfer of electrons across the membrane, involving a cascade of disulfide bond reduction steps.

Alkaline Phosphatase↗
PubMed1998

Disulfide bond formation in the Escherichia coli cytoplasm: an in vivo role reversal for the thioredoxins.

Cytoplasmic proteins do not generally contain structural disulfide bonds, although certain cytoplasmic enzymes form such bonds as part of their catalytic cycles. The disulfide bonds in these latter enzymes are reduced in Escherichia coli by two systems; the thioredoxin pathway and the glutathione/glutaredoxin pathway. However, structural disulfide bonds can form in proteins in the cytoplasm when the gene (trxB) for the enzyme thioredoxin reductase is inactivated by mutation. This disulfide bond formation can be detected by assessing the state of the normally periplasmic enzyme alkaline phosphatase (AP) when it is localized to the cytoplasm. Here we show that the formation of disulfide bonds in cytoplasmic AP in the trxB mutant is dependent on the presence of two thioredoxins in the cell, thioredoxins 1 and 2, the products of the genes trxA and trxC, respectively. Our evidence supports a model in which the oxidized forms of these thioredoxins directly catalyze disulfide bond formation in cytoplasmic AP, a reversal of their normal role. In addition, we show that the recently discovered thioredoxin 2 can perform many of the roles of thioredoxin 1 in vivo, and thus is able to reduce certain essential cytoplasmic enzymes. Our results suggest that the three most effective cytoplasmic disulfide-reducing proteins are thioredoxin 1, thioredoxin 2 and glutaredoxin 1; expression of any one of these is sufficient to support aerobic growth. Our results help to explain how the reducing environment in the cytoplasm is maintained so that disulfide bonds do not normally occur.

Alkaline Phosphatase↗
PubMed1997

Neuropeptide stimulation of the nitric oxide signaling pathway in Drosophila melanogaster Malpighian tubules.

Activation of the nitric oxide (NO) and guanosine 3', 5'-cyclic monophosphate (cGMP) signaling pathway stimulates fluid secretion by the Drosophila melanogaster Malpighian tubule. The neuropeptide cardioacceleratory peptide 2b (CAP2b) has been previously shown to stimulate fluid secretion in this epithelium by elevating intracellular cGMP levels. Therefore, it was of interest to investigate if CAP2b acts through NO in isolated tubules and thus presumably through stimulation of a tubule NO synthase (NOS). We show here by reverse-transcription polymerase chain reaction that Drosophila NOS (dNOS) is expressed in Malpighian tubules. Biochemical assays of NOS activity in whole tubules show that CAP2b significantly stimulates NOS activity. Additionally, fluid secretion and cyclic nucleotide assays show that CAP2b-induced elevation of intracellular cGMP levels and fluid secretion rates are dependent on the activation of a soluble guanylate cyclase. Treatment of tubules with a specific NOS inhibitor abolishes the CAP2b-induced rise in intracellular cGMP levels. These data indicate that CAP2b stimulates NOS and therefore, endogenous NO production, which, in turn, stimulates a soluble guanylate cyclase. This is the first demonstration of stimulation of an endogenous NOS by a defined peptide in Drosophila.

Animals↗
PubMed1996

Poikilodermatous and verrucous mycosis fungoides.

Mycosis fungoides (MF) is a cutaneous lymphoma of presumed T-helper cell origin. It usually presents with patches and infiltrated plaques, but a wide range of atypical forms have also been described. We report a 48-year-old man who had a 2-year history of a pruritic, warty plaque on the right palm with surrounding poikilodermatous changes. He subsequently developed additional macules of poikiloderma atrophicans vasculare (PAV) on the right upper limb and abdomen. Biopsies from the arm showed poikilodermatous changes, and the warty plaque had features of MF. Verrucous or hyperkeratotic lesions appear to be an uncommon presenting feature of MF with few case reports in the literature to date. This presentation may be associated with considerable diagnostic delay, and MF should be considered in the differential diagnosis of acquired verrucous lesions. This case also illustrates that PAV may herald cutaneous malignancy, and that patients with this condition require close follow up.

Hand Dermatoses↗
PubMed1996

Assessment of patient's benefit from rhinoplasty.

It is standard practice for most rhinoplasty surgeons to assess what they perceive to be the cosmetic outcome of their surgery. There have, however, been few attempts to gauge the degree of success of rhinoplasty from the patient's perspective. The aim of this study was to measure the benefit of rhinoplasty in an unselected group of patients who had undergone this procedure under the National Health Service (NHS). Two hundred and twenty-four patients who had undergone rhinoplasty or septorhinoplasty in the Department of Otolaryngology at Glasgow Royal Infirmary from 1990 to 1994 were surveyed by post; two questionnaires were administered. The Glasgow Benefit Inventory has four subscales which assess the patient's perception of the success of surgery, and the influence of surgery on the patients physical health, psychosocial function and social interaction. The Nasal Symptom Questionnaire (Fairley et al., 1993)--previously validated as an outcome measure in the context of FESS--was used to assess nasal symptoms. Multivariate and factor analysis was used to analyse the results. Four factors were extracted from the 103 responses to the Glasgow Benefit Inventory. The major factor of the benefit score was perception of surgical success which explained 50% of the variance. Three other factors (improvements in psychosocial functioning, social interaction and physical health after surgery) accounted for 10%, 5%, and 6% of the variance, respectively. Analysis of the Nasal Symptom Questionnaire yielded one predominant factor which was inversely related to perceived benefit. The outcome of rhinoplasty is influenced by the presence of nasal symptoms. Greater attention to nasal function would increase the benefit of rhinoplasty.

Humans↗
PubMed1995

A double counter-selection system for the study of null alleles of essential genes in Escherichia coli.

The ability to analyze null alleles of genes can be an important means of studying both a protein's function and its interactions with other proteins involved in a particular process. However, if the gene encodes a protein that is essential to the viability of the cell, such analysis becomes complicated because a complementing copy of the gene must be present in the cell. In order to study the effects caused by the null allele, the complementing copy must be inactivated or lost. We report the development of a system in Escherichia coli which facilitates the manipulation of null alleles of essential genes. It consists of a strain deleted chromosomally for the essential gene and complemented for its function by a wild-type (wt) copy expressed from a plasmid counter-selectable for two markers bracketing the gene. Using this system, we have (i) searched for bypass suppressors of a deletion of the essential secE gene, (ii) ascertained the ability of various mutant secE genes to complement a deletion of the wt copy and (iii) isolated intragenic pseudorevertants of a null missense allele of secE. This methodology should be widely applicable to other cases in which essential genes are to be studied genetically.

Alleles↗
PubMed1993

The influence of beta-adrenoceptors on nasal mucosal function.

The aim of the study was to elucidate the role of beta-adrenoceptors in normal human nasal mucosa. In two studies, beta-receptor function was tested by the application of agonists and antagonists. Measurements of nasal secretion and nasal peak expiratory flow were performed at 4-min intervals, during 12 min of rest, pre- and post-treatment, 12 min of exercise and 20 min of recovery. In Study 1, placebo was compared with 100 micrograms salbutamol and 2 mg propranolol. Neither placebo nor 100 mg salbutamol affected nasal secretion production at rest, but propranolol caused a transient significant increase (p < 0.05). Exercise significantly increased secretion production in all three treatment groups (p < 0.05). Nasal peak expiratory flow was not altered at rest, but increased significantly (p < 0.05) during exercise in the three treatment groups. In Study 2 placebo was compared with 200 mg salbutamol, 80 micrograms isoprenaline and 2 mg atenolol. Secretion production was not altered at rest by any treatment and increased during exercise in all four (p < 0.05). There was no significant difference between weights of secretions produced between any of the treatment groups during exercise. Salbutamol significantly decreased nasal peak expiratory flow at rest compared with placebo (p < 0.05). During exercise nasal peak flow increased in all groups, but peak exercise values were significantly reduced by both salbutamol and isoprenaline (p < 0.05). Atenolol appeared to have no effect on nasal peak expiratory flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The effect of methacholine on nasal transmucosal potential difference in normal human subjects.

This study was proposed to test the hypothesis that the parasympathetic system might attribute to the transmucosal potential difference. In a double-blind, placebo-controlled study six volunteers had nasal transmucosal potential difference (NTPD) recorded at 4-min intervals during 12-min periods of rest, before and after treatment, as well as during exercise and recovery. Application of placebo did not significantly alter NTPD at rest. There was a significant rise during exercise (p < 0.05). The application of methacholine significantly increased NTPD at rest (p < 0.01); there was a further rise during exercise (p < 0.02). We conclude that parasympathetic stimulation can increase the transmucosal potential difference.

Adult↗
PubMed1992

The effects of diuretics on nasal transmucosal potential difference.

The effects of application of frusemide, amiloride and bumetanide on nasal transmucosal potential difference (NTPD), at rest and during exercise, were studied in 8 normal subjects. In a double-blind placebo controlled study, 8 volunteers had NTPD recorded at 4-min intervals during 12-min periods of rest, before and after treatment, during 12 min of exercise, and recovery. Application of placebo, frusemide and bumetanide did not significantly alter NTPD at rest. Amiloride caused a significant reduction (P less than 0.025). During exercise there was a significant rise in NTPD with placebo (P less than 0.05), frusemide (P less than 0.05) and amiloride (P less than 0.05). There was no increase in NTPD during exercise with bumetanide.

Adult↗
PubMed1989

Klippel-Feil syndrome and conductive deafness.

The Klippel-Feil syndrome is usually associated with sensorineural deafness and reports of conductive or mixed deafness are rare. Four additional cases are presented in this paper. The middle ear anomalies found in this syndrome are discussed. The results of middle ear surgery are reviewed and found to be poor.

Adolescent↗
PubMed1989

A clinical and audiological investigation of osteogenesis imperfecta.

Fifty-six patients with osteogenesis imperfecta underwent clinical and audiological assessment. They completed questionnaires regarding their physical and otological disabilities, and attended various centres for audiological testing. It was found that 31 patients had a hearing loss. Hearing loss began in the second and third decades as a conductive loss, and progressed to a mixed loss. Eight patients, found in all age groups, had a pure sensorineural loss in one or both ears. Patients with osteogenesis imperfecta congenita suffered more fractures, became more physically disabled and had more severe hearing loss than those with osteogenesis imperfecta tarda. Tympanometry was found to give unpredictable results and was unhelpful in assessing middle ear function in these patients.

Acoustic Impedance Tests↗
PubMed1984

Diabetes and insurance: a survey of patient experience.

A survey of 186 diabetic patients examined their collective experience of life and motor insurance. Some form of life insurance policy had been obtained by 150 patients, with a combined total of 204 policies, 107 of which had been agreed before the diagnosis of diabetes. Most patients had declared diabetes to the insurer but 12 patients had been refused acceptance. Only 15 patients sought alternative quotations. The premium had been loaded by 10-40% for 36 patients because of diabetes, and 48 required a medical report. Of 147 diabetic drivers, 95 (65%) had declared diabetes either to the Licensing authority, or to the motor insurer, but only 62 (42%) had informed both. Fourteen patients had been refused motor insurance cover by individual companies, and 36 patients were aware of having had their premium increased, but only 16 patients had sought alternative quotations. Major differences in attitude with regard to diabetes as a risk factor for insurance are evident, and patients should be advised to approach several companies when seeking insurance cover.

Accidents, Traffic↗