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Biomedical subjects

A Grant

Publications and source records attributed to A Grant.

At least 73 records · Page 4Linked to original sources
PubMed2000

Evidence-based medicine and health economics: a case study of end stage renal disease.

This paper explores the potential for use of an economic evaluation framework alongside systematic reviews. Clinical issues in dialysis therapy for end stage renal disease are used as case studies. The effectiveness data required were obtained from a systematic review of randomized controlled trials. Resource use and cost data were obtained from three sources; the identified randomized controlled trials, a separate review of observational studies and primary data collection. The results of the case studies show that, although simple economic evaluations were possible, issues arose, such as how transferable results are between settings and how appropriate it is to focus on the average patient. The interface between economic evaluation and systematic reviews needs to be further developed in order to ensure that the best available evidence can be used to inform future policy and research.

Chi-Square Distribution↗
PubMed2000

Elective versus selective caesarean section for delivery of the small baby.

BACKGROUND: Elective caesarean delivery for women in preterm labour might reduce the chances of fetal or neonatal death, but it might also increase the risk of maternal morbidity. OBJECTIVES: The objective of this review was to assess the effects of a policy of elective caesarean delivery versus selective caesarean delivery for women in preterm labour. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register was searched. SELECTION CRITERIA: Randomised trials comparing a policy of elective caesarean delivery with expectant management with recourse to caesarean section. DATA COLLECTION AND ANALYSIS: One reviewer assessed eligibility and trial quality. MAIN RESULTS: Five studies involving 104 women were included. All trials reported recruiting difficulties. No significant differences between elective and selective policies for caesarean delivery were found for fetal, neonatal or maternal outcomes. REVIEWER'S CONCLUSIONS: There is not enough evidence to evaluate the use of a policy for elective caesarean delivery for small babies. Randomised trials in this area are likely to continue to experience recruitment problems. However it still may be possible to investigate elective caesarean delivery in preterm babies presenting cephalically.

Cesarean Section↗
PubMed2000

Surgery for faecal incontinence in adults.

BACKGROUND: Faecal incontinence is a debilitating problem with significant medical, social and economic implications. Treatment options include conservative, non-operative interventions (e.g. pelvic floor muscle training, biofeedback, drugs) and surgical procedures. Surgery is used in selected groupsof people when the structural and functional defects in the pelvic floor muscles or the anal sphincter complex can be corrected mechanically. OBJECTIVES: To assess the effects of established surgical techniques for the treatment of faecal incontinence in adults who do not have rectal prolapse. Our aims were firstly to compare surgical management with non-surgical management and secondly, to compare the various surgical techniques. SEARCH STRATEGY: We searched the Cochrane Incontinence Group trials register, the Cochrane Colorectal Cancer Group trials register, the Cochrane Controlled Trials Register (Issue 2, 1999), Medline (up to March 1999), Embase (1998 up to January 1999), Sigle (1980 up to December 1996), Biosis (1998 up to March 1999), SCI (1998 up to March 1999), ISTP (1982 up to March 1999) and the reference lists of relevant articles. We specifically hand searched the British Journal of Surgery from 1995 to 1998 and the Diseases of the Colon and Rectum from 1995 to 1998. We also perused the proceedings of the Association of Coloproctology, meeting 1999. Date of the most recent literature searches: March 1999. SELECTION CRITERIA: All randomised or quasi-randomised trials of surgery in the management of adult faecal incontinence (other then surgery for rectal prolapse). DATA COLLECTION AND ANALYSIS: Two reviewers independently selected studies from the literature, extracted data and assessed the methodological quality of eligible trials. The three primary outcome measures were: change or deterioration in incontinence, failure to achieve full continence, and the presence of faecal urgency. MAIN RESULTS: Four trials were included with a total sample size of 110 participants. All trials excluded women with anal sphincter defects detected by endoanal ultrasound examination. No trial included a group managed non-surgically. Two trials (56 participants) compared three approaches to pelvic floor repair (anterior levatorplasty, postanal repair and their combination total pelvic floor repair). One trial (30 participants) evaluated adding plication of the anal sphincter to total pelvic floor repair. The fourth trial (24 participants) compared a neosphincter procedure with total pelvic floor repair. No differences in the primary outcomes were detected, but data were few and inconsistently reported. REVIEWER'S CONCLUSIONS: The small number of relevant trials identified together with their small sample sizes and other methodological weaknesses severely limit the usefulness of this review for guiding practice. It was impossible to identify or refute clinically important differences between the alternative surgical procedures. Larger rigorous trials are needed.

Adult↗
PubMed2000

Surgery for complete rectal prolapse in adults.

BACKGROUND: Complete rectal prolapse is a debilitating condition, which affects both the very young and the elderly and can cause faecal incontinence. The range of surgical methods available to correct the underlying anal sphincter or pelvic floor defects in complete rectal prolapse poses the question about the choice of the best operation. OBJECTIVES: To determine the effects of surgery on the treatment of rectal prolapse in adults. The following specific issues have been addressed: I. Whether surgical intervention is better than no treatment; II. Whether an abdominal approach to surgery is better then a perineal approach; III. Whether one method for performing rectopexy is better than another; IV. Whether laparoscopic access is better than open access for surgery; V. Whether resection should be included in the procedure. SEARCH STRATEGY: We searched the Cochrane Incontinence Group trials register, the Cochrane Colorectal Cancer Group trials register, the Cochrane Controlled Trials Register (Issue 2, 1999), Medline (up to March 1999), Embase (1998 up to January 1999), Sigle (1980 up to December 1996), Biosis (1998 up to March 1999), SCI (1998 up to March 1999), ISTP (1982 up to March 1999) and the reference lists of relevant articles. We hand searched the British Journal of Surgery 1995-8, and the Diseases of the Colon and Rectum 1995-8. We also searched the proceedings of the Association of Coloproctology, meeting 1999. Date of the most recent searches: March 1999. SELECTION CRITERIA: All randomised or quasi-randomised trials of surgery in the management of rectal prolapse. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected studies from the literature, extracted data and assessed the methodological quality of eligible trials. The three primary outcome measures were number of patients with recurrent rectal prolapse, or residual mucosal prolapse or faecal incontinence. MAIN RESULTS: Eight trials were included with a total of 264 participants. No trial included a group receiving no treatment, or anal encirclement, or Delormes procedure, or laparoscopic suture rectopexy, or laparoscopic resection rectopexy. One trial (20 participants) compared both perineal and abdominal resection rectopexy with pelvic floor repair; four trials (175 participants) compared different types of open rectopexy techniques; one trial (21 participants) compared laparoscopic with open mesh rectopexy; and two trials included comparisons between open resection rectopexy and rectopexy alone. In all comparisons data were few. There were no detectable differences in recurrent prolapse between abdominal and perineal approaches, although there was a suggestion that residual faecal incontinence was less common after abdominal surgery. There were no detectable differences between the methods used for fixation during rectopexy. Division, rather than preservation, of the lateral ligaments was associated with less recurrent prolapse but more post-operative constipation, although these findings were found in small numbers. There were too few data with which to compare laparoscopic with open surgery. Bowel resection during rectopexy was associated with lower rates of constipation, but again numbers were small. REVIEWER'S CONCLUSIONS: The small number of relevant trials identified, and their small sample sizes together with other methodological weaknesses severely limit the usefulness of this review for guiding practice. It was impossible to identify or refute clinically important differences between the alternative surgical operations. Larger rigorous trials are needed to improve the evidence with which to define optimum surgical treatment.

Adult↗
PubMed2000

Genomic and transcriptional characterization of the human ACHE locus: complex involvement with acquired and inherited diseases.

BACKGROUND: Abnormal levels of the acetylcholinesterase enzyme or aberrations involving the long arm of chromosome 7, harboring the ACHE gene at 7q22, occur in various diseases such as Alzheimer's, Parkinson's, and leukemias. However, the cause(s) of these abnormalities are still unknown. OBJECTIVE: To search for the genomic elements and transcriptional processes controlling ACHE gene expression and the plausible stability of its locus, by isolating, sequencing and characterizing the human (h)ACHE locus and its mRNA products. METHODS: Three clones containing the ACHE gene were isolated from a human chromosome 7 cosmid library. Two of these clones were thereafter sequenced and searched for repetitive elements, open reading frames and corresponding expressed sequence tags. Reverse transcription-polymerase chain reaction was employed to further explore these findings. RESULTS: The locus harboring the G,C-rich ACHE gene was found to be exceptionally rich in Alu repeats. It includes an additional, inversely oriented gene (ARS), tentatively associated with arsenite resistance. EST clones corresponding to both genes were found in cDNA libraries from 11 different human tissue sources, with ARS expressed in 10 additional tissues. Co-regulation of brain ACHE and ARS was suggested from their mutually increased expression following acute psychological stress. CONCLUSIONS: The abundance of Alu retrotransposones may predispose the ACHE locus to chromosomal rearrangements. Additionally, coordinated transcriptional regulation is implied from the joint ARS-AChE expression in stress insult responses. Disease-related changes in AChE may therefore reflect locus-specific regulation mechanisms affecting multiple tissues.

Acetylcholinesterase↗
PubMed2000

Medical informatics and medical education in Canada in the 21st century.

The advances of health informatics over the last 50 years are briefly sketched to reveal the pervasiveness of their applications in health and health care. The relations to research in health informatics and health are pointed out. From this perspective it is argued that the evolution of consumer health informatics in the last decade has had a profound impact on the practice of medicine, on patient-physician relations and, hence, on the requirements for medical education. The different access to information and how it is used in educational environments will also dramatically affect how curricula are structured both at undergraduate and postgraduate levels. The impact of health informatics on medical education is further elaborated, and the requirements on infrastructure in support of this education are detailed. This infrastructure goes beyond instructional laboratories and includes academic units for medical informatics and, most importantly perhaps, funding resources and adjudication capacity for health informatics research and their integration into the Canadian research organization and the new Canadian Institutes of Health Research.

Canada↗
PubMed2000

Hearing thresholds under acute hypoxia and relationship to slowing in the auditory modality.

BACKGROUND: Acute hypoxia slows reaction time to visual stimuli and it has been proposed that this slowing can be accounted for by a decrease in perceived brightness. Auditory slowing could be accounted for in an analogous manner if hypoxia decreases perceived loudness, as reflected by an increase in pure-tone thresholds. However, evidence concerning the effects of hypoxia on auditory thresholds is contradictory and we performed an experiment to clarify this issue. Pilot work suggested that thresholds were raised due to noise from our breathing apparatus used to deliver the low O2 mixtures and we eliminated this artifact by measuring thresholds while the subjects held their breath. METHODS: The six subjects breathed either air as a control through an oro-nasal mask or low O2 mixtures to maintain arterial blood oxygen saturation at 74% while thresholds between 500-4000 Hz were measured with an audiometer during breathholding. RESULTS: Hypoxia produced a statistically significant but practically insignificant decrease in thresholds of 1 dB across all frequencies tested. CONCLUSIONS: Our results are consistent with the view that audition is relatively insensitive to hypoxia and that the slowing observed with auditory stimuli cannot be accounted for by an increase in auditory thresholds. Some alternative hypotheses which could account for this slowing are proposed.

Adult↗
PubMed2000

Early asthma prophylaxis, natural history, skeletal development and economy (EASE): a pilot randomised controlled trial.

OBJECTIVES: (1) To establish recruitment rates of newly presenting asthmatic children. (2) To establish acceptability of study protocols. (3) To pilot age-specific quality of life (QoL) assessment. (4) To assess short-term (6 months) outcomes of inhaled corticosteroids (ICS) treatment. (5) To refine sample size calculations for a definitive study. DESIGN: A randomised pragmatic longitudinal trial design was used, with no blinding or placebo, to examine early ICS introduction similar to its use in practice. Subjects were assessed at entry, 3 and 6 months. SETTING: Subjects were recruited from six general practices. Children under 6 years were assessed at the Craig Research and Investigation Unit, Royal Aberdeen Children's Hospital, or their family home, and subjects 6 years and over were assessed at their general practice. SUBJECTS: Children (aged 6 months-16 years) with symptoms suggestive of asthma/wheeze that had commenced no longer than 12 months before were identified retrospectively and prospectively from general practices. Subjects were also required to be naïve to prophylactic therapy with no other lung disease/concomitant illness. INTERVENTIONS: Subjects were randomised to ss2-agonist (ss2-only group) or ss2-agonist and ICS (ICS group) for 6 months. Physicians could later prescribe ICS in controls if needed. MAIN OUTCOME MEASURES: (1) Pulmonary function. (2) Asthma symptom diary. (3) Symptomatic health status questionnaire. (4) Caregiver's and child's QoL. (5) Growth. (6) Bone mass. (7) Bone turnover. (8) Economic issues. RESULTS: Of over 15,000 children yielded from general practice records, 11% had symptoms suggestive of asthma/wheeze, and two-thirds of these already used ICS. Of the remaining, 141 subjects met the criterion of early asthma, and 86 were randomised. Two-thirds of those randomised were < 6 years old, the males:females ratio was 2:1, and 67% had a family history of atopy. RESULTS - PHYSIOLOGICAL DEVELOPMENT: Pulmonary function did not significantly improve in the older children. Although tidal breathing measures in the pre-school children were significantly higher at 6 months in the ss2-only group, there was great variability. Incidence of wheeze and night-time cough reduced equally in both groups. Reduction of night-time symptom score and reliever use, and increase in symptom-free days were only significant in the ss2-only group. No significant differences were found in growth and bone mass between the two groups, but bone metabolism was significantly reduced at 6 months in the ICS group. RESULTS - PSYCHOLOGICAL DEVELOPMENT: The caregiver's QoL questionnaire was sensitive to child symptom changes over 3 months, but absolute impact of child symptoms on their QoL varied, whereas the child-centred questionnaire was not sensitive to change. RESULTS - ECONOMICS: There were no significant differences in medical consultation costs between the groups, but, as expected, prescription costs in the ICS group were higher over 6 months. Combined healthcare costs were significantly higher for patients assigned to ICS, but there were no significant differences in any effectiveness measures between the groups. CONCLUSIONS: Most (96%) of the proposed sample was recruited, and the low drop-out rate (8%) demonstrated acceptability of the study protocol. Most children first presenting with symptoms suggestive of asthma were < 6 years old and represented a group biased towards mild to moderate asthma, or virally induced wheeze. The caregiver's QoL questionnaire was found to better reflect a child's symptom changes than a child-centred instrument. In the short term, no adverse effects were seen on growth, but ICS treatment significantly reduced bone metabolism. Most of the young children with asthma/wheeze improved over time with ss2-agonist treatment alone, and clinical benefits of early ICS intervention amongst these children were not detected; however, there was inadequate power in this pilot study to establish this. (AB

Adolescent↗
PubMed1999

Exo84p is an exocyst protein essential for secretion.

The exocyst is a multiprotein complex that plays an important role in secretory vesicle targeting and docking at the plasma membrane. Here we report the identification and characterization of a new component of the exocyst, Exo84p, in the yeast Saccharomyces cerevisiae. Yeast cells depleted of Exo84p cannot survive. These cells are defective in invertase secretion and accumulate vesicles similar to those in the late sec mutants. Exo84p co-immunoprecipitates with the exocyst components, and a portion of the Exo84p co-sediments with the exocyst complex in velocity gradients. The assembly of Exo84p into the exocyst complex requires two other subunits, Sec5p and Sec10p. Exo84p interacts with both Sec5p and Sec10p in a two-hybrid assay. Overexpression of Exo84p selectively suppresses the temperature sensitivity of a sec5 mutant. Exo84p specifically localizes to the bud tip or mother/daughter connection, sites of polarized secretion in the yeast S. cerevisiae. Exo84p is mislocalized in a sec5 mutant. These studies suggest that Exo84p is an essential protein that plays an important role in polarized secretion.

Amino Acid Sequence↗
PubMed1999

Elasticity analysis as an important tool in evolutionary and population ecology.

Elasticity analysis estimates the proportional change in the population growth rate for a proportional change in a vital rate (i.e. survival, growth or reproduction). It can be used to pinpoint those parts of an organism's life history that should be the focus of management effort, or those that contribute most to fitness. Recent theoretical work has emphasized some limitations of the technique, has overcome other problems, and has shown that it is robust to some violations of its underlying assumptions. Thus, although care is needed, elasticity analysis is a simple first step in answering important questions in evolutionary and population ecology.

Journal Article↗
PubMed1999

Barriers to participation in randomised controlled trials: a systematic review.

METHOD: A systematic review of three bibliographic databases from 1986 to 1996 identified 78 papers reporting barriers to recruitment of clinicians and patients to randomised controlled trials. RESULTS: Clinician barriers included: time constraints, lack of staff and training, worry about the impact on the doctor-patient relationship, concern for patients, loss of professional autonomy, difficulty with the consent procedure, lack of rewards and recognition, and an insufficiently interesting question. Patient barriers included: additional demands of the trial, patient preferences, worry caused by uncertainty, and concerns about information and consent. CONCLUSIONS: To overcome barriers to clinician recruitment, the trial should address an important research question and the protocol and data collection should be as straightforward as possible. The demands on clinicians and patients should be kept to a minimum. Dedicated research staff may be required to support clinical staff and patients. The recruitment aspects of a randomised controlled trial should be carefully planned and piloted. Further work is needed to quantify the extent of problems associated with clinician and patient participation, and proper evaluation is required of strategies to overcome barriers.

Data Collection↗
PubMed1999

Selected spin probes for the electron spin resonance study of the dynamics of water and lipids in doughs.

New water-soluble and lipid-soluble spin probes suitable for the ESR investigation of the physical states and interactions of components of dough have been developed. This paper reports some preliminary findings on the suitability of these probes for this type of investigation. Rotational correlation times have been measured for the spin probes in water, dough, oil, and a starch/water mixture. An increase in rotational correlation time of the spin probe corresponds to an increase in microviscosity of the medium. Changes observed in correlation times of the water-soluble spin probes in doughs and in water/starch mixtures clearly correspond to a gelatinization process when the mixtures are heated above 60 degrees C. These irreversible changes, clearly important in the baking process, were monitored by following the change of mobility of a spin probe in doughs over a wide temperature range. The similarity of the results from the two sets of experiments suggests that the phenomenon of the increase of correlation times with temperature in doughs is attributable to the starch component. The lipid-soluble spin probe was found to be located preferentially in the lipid phase of the dough.

Electron Spin Resonance Spectroscopy↗
PubMed1999

Results of complete soft tissue clubfoot release combined with calcaneocuboid fusion in the 4-year to 8-year age group following failed clubfoot release.

A subset of postoperative recurrent clubfeet was isolated in a group of patients 4 to 8 years old. Twenty-seven consecutive patients who underwent redo surgery consisting of complete soft tissue clubfoot release combined with a calcaneocuboid fusion were reviewed for this study. Twenty-six feet of 27 feet in 20 patients had a long-term good result, suggesting that this procedure is the one of choice for this age group.

Algorithms↗
PubMed1998

Loss of Drs2p does not abolish transfer of fluorescence-labeled phospholipids across the plasma membrane of Saccharomyces cerevisiae.

The yeast DRS2 gene, which is required for growth at 23 degreesC or below, encodes a member of a P-type ATPase subgroup reported to transport aminophospholipids between the leaflets of the plasma membrane. Here, we evaluated the potential role of Drs2p in phospholipid transport. When examined by fluorescence microscopy, a drs2 null mutant showed no defect in the uptake or distribution of fluorescent-labeled 1-palmitoyl-2[6-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl (NBD))aminocaproyl]phosphatidylserine) or 1-myristoyl-2[6-NBD-aminocaproyl]phosphatidylethanolamine. Quantification of the amount of cell-associated NBD fluorescence using flow cytometry indicated a significant decrease in the absence of Drs2p, but this decrease was not restricted to the aminophospholipids (phosphatidylserine and phosphatidylethanolamine) and was dependent on culture conditions. Furthermore, the absence of Drs2p had no effect on the amount of endogenous PE exposed to the outer leaflet of the plasma membrane as detected by labeling with trinitrobenzene sulfonic acid. The steady state pool of Drs2p, which was shown to reside predominantly in the plasma membrane, increased upon shift to low temperature or exposure to various divalent cations (Mn2+, Co2+, Ni2+, and Zn2+ but not Ca2+ or Mg2+), conditions that also inhibited the growth of a drs2 null mutant. The data presented here call into question the identification of Drs2p as the exclusive or major aminophospholipid translocase in yeast plasma membranes (Tang, X., Halleck, M. S., Schlegel, R. A., and Williamson, P. (1996) Science 272, 1495-1497).

4-Chloro-7-nitrobenzofurazan↗