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Biomedical subjects

S Evans

Publications and source records attributed to S Evans.

At least 109 records · Page 6Linked to original sources

The Prosorba column for treatment of refractory rheumatoid arthritis: a randomized, double-blind, sham-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of the Prosorba column as a treatment for rheumatoid arthritis (RA) in patients with active and treatment-resistant (refractory) disease. METHODS: A sham-controlled, randomized, double-blind, multicenter trial of Prosorba versus sham apheresis was performed in patients with RA who had failed to respond to treatment with methotrexate or at least 2 other second-line drugs. Patients received 12 weekly treatments with Prosorba or sham apheresis, with efficacy evaluated 7-8 weeks after treatment ended. Patients were characterized as responders if they experienced improvement according to the American College of Rheumatology (ACR) response criteria at the efficacy time point. A data safety monitoring board (DSMB) evaluated interim analyses for the possibility of early completion of the trial. RESULTS: Patients in the trial had RA for an average of 15.5 years (range 1.7-50.6) and had failed an average of 4.2 second-line drug treatments prior to entry. After the completion of treatment of 91 randomized patients, the DSMB stopped the trial early due to successful outcomes. Of the 47 patients in the Prosorba arm, 31.9% experienced ACR-defined improvement versus 11.4% of the 44 patients in the sham-treated arm (P = 0.019 after adjustment for interim analysis). When results from 8 additional patients, who had completed blinded treatments at the time of DSMB action, were added to the analysis (n = 99), results were unchanged. The most common adverse events were a short-term flare in joint pain and swelling following treatment, a side effect that occurred in most subjects at least once in both treatment arms. Other side effects, although common, occurred equally as frequently in both treatment groups. CONCLUSION: Apheresis with the Prosorba column is an efficacious treatment for RA in patients with active disease who have failed other treatments.

Adult↗

QTc dispersion and complex ventricular arrhythmias in untreated newly presenting hypertensive patients.

Increased dispersion of ventricular repolarisation (increased QT dispersion) is believed to predispose to arrhythmias associated with sudden death in certain cardiac diseases. Hypertension is also associated with increased risk of sudden death, particularly in those with left ventricular hypertrophy (LVH). Therefore, the first aim of this study is to look into the possible pathogenic role of QT dispersion on the ventricular arrhythmias occurring in a group of never-treated hypertensive patients. The second aim is to look at other possible determinants of QT dispersion (ie, level of blood pressure, hypokalaemia, electrocardiographic LVH and presence or absence of strain pattern) in hypertensive patients, and their relevance to complex ventricular arrhythmias. QTc (corrected QT) was measured in 70 newly presenting (never-treated) hypertensive patients (47 male, 23 female, mean age 51.9 +/- 12.5 years) from a standard 12-lead surface electrocardiogram (ECG). Blood pressure measurements and 24-h ECG holter recordings were performed in all patients. Serum potassium level was measured in 51 of the patients. Ventricular arrhythmias were classified using a modified Lown's scoring system. Maximum QTc, minimum QTc and QTc dispersion for all patients were 442 +/- 30.3 ms, 380 +/- 26.7 ms and 61.5 +/- 21.6 ms respectively. High grade ventricular arrhythmias (Lown's score >/=3) were found in 43% of the patients. The QTc dispersion was strongly correlated with the Lown's classification of arrhythmia and the age of the patients. Patients with more severe ectopy (Lown's score >/=3) were significantly older (57.4 +/- 10.3 years) compared to those with score </=2 (48.3 +/- 12.6 years) (P = 0.0067) and had a significantly greater QTc dispersion (69.9 +/- 22.5 ms vs55.2 +/- 18. 8 ms; P = 0.002). Presence of electrocardiographic strain did not affect the severity of arrhythmia, as 29% of the patients with LVH and strain had grade >/=3 Lown's score compared to 39% in the group with LVH but without strain. In the presence of relative hypokalaemia, hypertensive patients with LVH showed more QTc dispersion (85.7 +/- 15.5 ms) and a greater tendency for complex ventricular arrhythmias (100% grade >/=3 Lown's score) compared to those with LVH and normal serum potassium levels (64.1 +/- 22.6 ms and 35%, QTc dispersion and Lown's score >/=3, respectively P = 0. 05). The level of blood pressure had no effect on either the QTc dispersion or the prevalence of complex ventricular arrhythmias. Prevalence of complex ventricular arrhythmias in hypertensive patients is strongly correlated with QTc dispersion and age. When hypertensive patients with LVH have low potassium levels the risk of developing complex ventricular arrhythmias is significantly increased.

Aging↗

High early mortality rate from acute pancreatitis in Scotland, 1984-1995.

BACKGROUND: Death from acute pancreatitis within the first week after admission is usually a consequence of multiple organ dysfunction. Reports from specialist centres suggest that, with improvements in resuscitation and supportive care, such deaths are becoming uncommon but it is unclear if this is reflected in a decrease in early mortality rate from acute pancreatitis in the general population. METHODS: Data concerning patients discharged with a diagnosis of acute pancreatitis (International Classification of Disease-9 code 577.0) between 1984 and 1995 were obtained from the Information and Statistics Division, National Health Service in Scotland, and analysed on a computer database. RESULTS: The incidence of acute pancreatitis in Scotland continues to increase in both sexes. The in-hospital mortality rate (death from all causes) was 7.5 per cent and showed a slight but significant downward trend over the period of study. Death within 7 days of hospital admission accounted for 53.7 per cent of all deaths and the proportion of early deaths did not decline over the study interval. CONCLUSION: These results suggest that scope remains for considerable improvement in the early management of acute pancreatitis. There is an urgent need to improve the early recognition of severe pancreatitis coupled to a willingness on behalf of clinicians to transfer these patients at an early stage to a centre with high-dependency and intensive care facilities supervised by a multidisciplinary team with expertise in the endoscopic, radiological and surgical management of these patients.

Acute Disease↗

Effect of blinding and unmasking on the quality of peer review.

The objectives of this study were to see whether, in the opinion of authors, blinding or unmasking or a combination of the two affects the quality of reviews and to compare authors' and editors' assessments. In a trial conducted in the British Medical Journal, 527 consecutive manuscripts were randomized into one of three groups, and each was sent to two reviewers, who were randomized to receive a blinded or an unblinded copy of the manuscript. Review quality was assessed by two editors and the corresponding author. There was no significant difference in assessment between groups or between editors and authors. Reviews recommending publication were scored more highly than those recommending rejection.

Authorship↗

Implementation of the ANA report card.

A major challenge in healthcare today is measuring the quality of care. To explore nursing's contribution to patients in acute care settings, the American Nurses Association commissioned the development of the "Nursing Report Card." This study explored whether these report card indicators capture quality care. The convenience sample comprised 1,500 patients and 300 nurses from 16 units at an academic medical center. Using regression analysis, the most consistent predictor of outcome indicators was the percentage of RNs of the total staff.

Adult↗

Sodium potassium adenosine triphosphatase activity in preterm and term infants and its possible role in sodium homeostasis during maturation.

AIM: To investigate sodium (NA(+)) potassium (K(+)) adenosine triphosphatase (ATPase) activity in newborn infants at different gestational ages, to elucidate the mechanism underlying poor renal sodium conservation in preterm infants. METHODS: Fifty three healthy newborn infants, gestational age 30-42 weeks, were studied. Umbilical cord red blood cell Na(+) K(+)ATPase activity, plasma renin activity, and plasma aldosterone activities were measured in all of them. Red blood cell Na(+) K(+)ATPase activity was re-examined in eight preterm infants, one and two weeks after birth. Total and ouabain sensitive ATPase activity was measured spectrophotometrically using a method that couples ATP hydrolysis with NADH oxidation. RESULTS: Red blood cell Na(+) K(+)ATPase activity was significantly lower (p<0.01) in preterm babies with a gestational age below 35 weeks, compared with those with aged 35 weeks and above: 2.3 (0.8) and 6.7 (1.3) nmol NADH/minute/mg protein, respectively. There was no correlation between gestational age, Na(+) K(+)ATPase, plasma renin activity and aldosterone values either in the preterm or term babies. Two weeks after birth, irrespective of gestational age, the enzyme activity of the preterm babies increased to values similar to those observed in the term neonates at birth. CONCLUSION: The differences in sodium homeostasis between term and preterm babies are modulated via changes in Na(+) K(+)ATPase activity.

Gestational Age↗

Application and results of the Manchester Short Assessment of Quality of Life (MANSA).

BACKGROUND: Based on experiences and empirical evidence gained in studies using the Lancashire Quality of Life Profile (LQLP), the Manchester Short Assessment of Quality of Life (MANSA) has been developed as a condensed and slightly modified instrument for assessing quality of life. Its properties have been tested in a sample of community care patients. METHOD: Fifty-five randomly selected patients on the Care Programme Approach were interviewed using the LQLP, the MANSA and the Brief Psychiatric Rating Scale. RESULTS: Correlations between subjective quality of life scores on MANSA and LQLP were all 0.83 or higher (0.94 for the satisfaction mean score). Cronbach's alpha for satisfaction ratings was 0.74, and association with psychopathology was in line with results for LQLP as reported in the literature. CONCLUSIONS: The MANSA is a brief instrument for assessing quality of life focusing on satisfaction with life as a whole and with life domains. Its psychometric properties appear satisfactory.

Adult↗

Requirement of a novel gene, Xin, in cardiac morphogenesis.

A novel gene, Xin, from chick (cXin) and mouse (mXin) embryonic hearts, may be required for cardiac morphogenesis and looping. Both cloned cDNAs have a single open reading frame, encoding proteins with 2,562 and 1,677 amino acids for cXin and mXin, respectively. The derived amino acid sequences share 46% similarity. The overall domain structures of the predicted cXin and mXin proteins, including proline-rich regions, 16 amino acid repeats, DNA-binding domains, SH3-binding motifs and nuclear localization signals, are highly conserved. Northern blot analyses detect a single message of 8.9 and 5.8 kilo base (kb) from both cardiac and skeletal muscle of chick and mouse, respectively. In situ hybridization reveals that the cXin gene is specifically expressed in cardiac progenitor cells of chick embryos as early as stage 8, prior to heart tube formation. cXin continues to be expressed in the myocardium of developing hearts. By stage 15, cXin expression is also detected in the myotomes of developing somites. Immunofluorescence microscopy reveals that the mXin protein is colocalized with N-cadherin and connexin-43 in the intercalated discs of adult mouse hearts. Incubation of stage 6 chick embryos with cXin antisense oligonucleotides results in abnormal cardiac morphogenesis and an alteration of cardiac looping. The myocardium of the affected hearts becomes thickened and tends to form multiple invaginations into the heart cavity. This abnormal cellular process may account in part for the abnormal looping. cXin expression can be induced by bone morphogenetic protein (BMP) in explants of anterior medial mesoendoderm from stage 6 chick embryos, a tissue that is normally non-cardiogenic. This induction occurs following the BMP-mediated induction of two cardiac-restricted transcription factors, Nkx2.5 and MEF2C. Furthermore, either MEF2C or Nkx2.5 can transactivate a luciferase reporter driven by the mXin promoter in mouse fibroblasts. These results suggest that Xin may participate in a BMP-Nkx2.5-MEF2C pathway to control cardiac morphogenesis and looping.

Amino Acid Sequence↗

Effect of nappy liners on temperature stability in very preterm infants.

OBJECTIVE: To determine whether absorbent liners used in posturally supportive cloth nappies influence temperature stability in infants < 31 weeks gestation. METHODOLOGY: Randomized cross-over trial conducted at King Edward Memorial Hospital for Women, Perth, Western Australia. Twenty-three infants nursed in incubators on Infant Servo Control were randomly assigned to wear cloth postural support nappies alternately with or without absorbent liners for 24-h periods over 4 days. Measurements of skin and incubator temperatures were recorded hourly. Times of all nappy changes and infant handling procedures were also recorded. RESULTS: There was no change in any temperature measurement over time, between days, or between day/night periods. Infants nursed with the liner demonstrated a higher skin temperature (0.04 degrees C), and a lower incubator temperature (1.05 degrees C). A drop in skin temperature of 0.02 degrees C and an increase in incubator temperature of 0.28 degrees C occurred following handling of infants. There was no effect due to sex, gestational age, or actual age of the infants. CONCLUSION: Use of an absorbent liner within a cloth postural support nappy promotes better temperature regulation in infants < 31 weeks gestation, by reducing incubator temperature and increasing skin temperature.

Analysis of Variance↗

Platelet indices during normal pregnancy and pre-eclampsia.

Platelet count and mean platelet volume (MPV) were estimated in 349 normal pregnancies at various gestational stages, and in 30 cases of pre-eclampsia. A probability plot was constructed from these data using discriminant analysis of MPV versus platelet count for the pre-eclamptic versus normal pregnancies. The sensitivity for pre-eclampsia was 90% (27/30) and the specificity was 83.3%. This plot may be of use in confirming risk of pre-eclampsia.

Blood Platelets↗

Daily injections of fluoxetine induce dose-dependent desensitization of hypothalamic 5-HT1A receptors: reductions in neuroendocrine responses to 8-OH-DPAT and in levels of Gz and Gi proteins.

The present studies examined the dose-response relationship of fluoxetine-induced desensitization of hypothalamic postsynaptic 5-HT1A receptors, as measured from the reduced neuroendocrine responses to a 5-HT1A agonist. Because hypothalamic Gz proteins mediate the ACTH and oxytocin responses to 5-HT1A receptor activation, we also determined the effect of fluoxetine on the levels of Gz proteins in the hypothalamus. Rats were injected daily for 14 days with saline or with fluoxetine doses of 0.3, 1, 3, 5, 7. 5, or 10 mg/kg/day. Fluoxetine produced a dose-dependent reduction in the oxytocin, ACTH, and corticosterone responses to the 5-HT1A agonist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT, 50 micrograms/kg, s.c.). The lowest fluoxetine dose that significantly, although incompletely, reduced the neuroendocrine responses to 8-OH-DPAT was 5 mg/kg/day. The 10 mg/kg/day dose of fluoxetine maximally inhibited all neuroendocrine responses to 8-OH-DPAT. Hypothalamic levels of Gz protein were reduced by both the 7.5 and 10 mg/kg/day doses of fluoxetine, whereas Gi1 protein levels were reduced only after the highest dose (10 mg/kg/day) of fluoxetine. Gi2, Gi3, and Go levels were not reduced by any fluoxetine dose. Cytosolic levels of Gi1 and Gz proteins were unaltered, indicating that reductions in Gz and Gi1 proteins are not caused by a redistribution of the proteins from the membrane into the cytosol. The results from the present study indicate that fluoxetine-induced desensitization of hypothalamic postsynaptic 5-HT1A receptor systems is dose-dependent and may be caused in part by reductions in the hypothalamic levels of Gz proteins.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Differential rescue of visceral and cardiac defects in Drosophila by vertebrate tinman-related genes.

tinman, a mesodermal NK2-type homeobox gene, is absolutely required for the subdivision of the early Drosophila mesoderm and for the formation of the heart as well as the visceral muscle primordia. Several vertebrate relatives of tinman, many of which are predominately expressed in the very early cardiac progenitors (and pharyngeal endoderm), also seem to promote heart development. Here, we show that most of these vertebrate tinman-related genes can readily substitute for Drosophila tinman function in promoting visceral mesoderm-specific marker gene expression, but much less in promoting cardiac-specific gene expression indicative of heart development. In addition, another mesodermal NK2-type gene from Drosophila, bagpipe, which is normally only needed for visceral mesoderm but not heart development, cannot substitute for tinman at all. These data indicate that the functional equivalence of the tinman-related subclass of NK2-type genes (in activating markers of visceral mesoderm development in Drosophila) is specific to this subclass and distinct from other homeobox genes. Despite the apparent overall conservation of heart development between vertebrates and invertebrates, the differential rescue of visceral mesoderm versus heart development suggests that some of the molecular mechanisms of organ formation may have diverged during evolution.

Animals↗

What makes a good reviewer and a good review for a general medical journal?

CONTEXT: Selecting peer reviewers who will provide high-quality reviews is a central task of editors of biomedical journals. OBJECTIVES: To determine the characteristics of reviewers for a general medical journal who produce high-quality reviews and to describe the characteristics of a good review, particularly in terms of the time spent reviewing and turnaround time. DESIGN, SETTING, AND PARTICIPANTS: Surveys of reviewers of the 420 manuscripts submitted to BMJ between January and June 1997. MAIN OUTCOME MEASURES: Review quality was assessed independently by 2 editors and by the corresponding author using a newly developed 7-item review quality instrument. RESULTS: Of the 420 manuscripts, 345 (82%) had 2 reviews completed, for a total of 690 reviews. Authors' assessments of review quality were available for 507 reviews. The characteristics of reviewers had little association with the quality of the reviews they produced (explaining only 8% of the variation), regardless of whether editors or authors defined the quality of the review. In a logistic regression analysis, the only significant factor associated with higher-quality ratings by both editors and authors was reviewers trained in epidemiology or statistics. Younger age also was an independent predictor for editors' quality assessments, while reviews performed by reviewers who were members of an editorial board were rated of poorer quality by authors. Review quality increased with time spent on a review, up to 3 hours but not beyond. CONCLUSIONS: The characteristics of reviewers we studied did not identify those who performed high-quality reviews. Reviewers might be advised that spending longer than 3 hours on a review on average did not appear to increase review quality as rated by editors and authors.

Data Collection↗

Effect of blinding and unmasking on the quality of peer review: a randomized trial.

CONTEXT: Little research has been conducted into the quality of peer review and, in particular, the effects of blinding peer reviewers to authors' identities or masking peer reviewers' identities. OBJECTIVE: To determine whether concealing authors' identities from reviewers (blinding) and/or revealing the reviewer's identity to a coreviewer (unmasking) affects the quality of reviews, the time taken to carry out reviews, and the recommendation regarding publication. DESIGN AND SETTING: Randomized trial of 527 consecutive manuscripts submitted to BMJ, which were randomized and each sent to 2 peer reviewers. INTERVENTIONS: Manuscripts were randomized as to whether the reviewers were unmasked, masked, or uninformed that a study was taking place. Two reviewers for each manuscript were randomized to receive either a blinded or an unblinded version. MAIN OUTCOME MEASURES: Mean total quality score, time taken to carry out the review, and recommendation regarding publication. RESULTS: Of the 527 manuscripts entered into the study, 467 (89%) were successfully randomized and followed up. The mean total quality score was 2.87. There was little or no difference in review quality between the masked and unmasked groups (scores of 2.82 and 2.96, respectively) and between the blinded and unblinded groups (scores of 2.87 and 2.90, respectively). There was no apparent Hawthorne effect. There was also no significant difference between groups in the recommendations regarding publication or time taken to review. CONCLUSIONS: Blinding and unmasking made no editorially significant difference to review quality, reviewers' recommendations, or time taken to review. Other considerations should guide decisions as to the form of peer review adopted by a journal, and improvements in the quality of peer review should be sought via other means.

Authorship↗