Search PubMed⌕ Search

Biomedical subjects

A Robinson

Publications and source records attributed to A Robinson.

At least 91 records · Page 5Linked to original sources
PubMed2000

Diclofenac sodium, 0.1% (Voltaren Ophtha), versus sodium chloride, 5%, in the treatment of filamentary keratitis.

PURPOSE: To compare the efficacy and short-term safety of diclofenac sodium, 0.1% (Voltaren Ophtha; Ciba-Vision) and of sodium chloride, 5% ophthalmic solution, in the treatment of filamentary keratitis (FK) in patients with dry-eye syndrome due to secondary Sjögren's syndrome. METHODS: Thirty-two patients (64 eyes) with dry-eye syndrome due to secondary Sjögren' syndrome were enrolled in a randomized study (patients and authors were aware of which medication was being used). All patients had FK. Sixteen patients were treated with sodium chloride, 5% drops, and 16 patients received diclofenac sodium, 0.1% eyedrops. Treatment regimen included instillation of 1 drop, 4 times a day for 28 days, for both groups. Clinical assessment was performed once a week during the study period. Data on the efficacy and safety of the different therapeutic regimens were collected and compared. RESULTS: Both medications achieved disappearance of filaments at the end of the study. Treatment with diclofenac sodium, 0.1%, revealed a significantly more rapid improvement of the clinical symptoms as compared with sodium chloride, 5%. No significant adverse effects were observed in both groups. CONCLUSION: Diclofenac sodium, 0.1%, may be an effective and safe topical therapy in patients with FK caused by secondary Sjögren's disease.

Aged↗
PubMed2000

Structure of the C123S mutant of dienelactone hydrolase (DLH) bound with the PMS moiety of the protease inhibitor phenylmethylsulfonyl fluoride (PMSF).

The structure of DLH (C123S) with PMS bound was solved to 2.5 A resolution (R factor = 15.1%). PMSF in 2-propanol was delivered directly to crystals in drops and unexpectedly caused the crystals to dissolve. New crystals displaying a different morphology emerged within 2 h in situ, a phenomenon that appears to be described for the first time. The changed crystal form reflected altered crystal-packing arrangements elicited by structural changes to the DLH (C123S) molecule on binding inhibitor. The new unit cell remained in the P2(1)2(1)2(1) space group but possessed different dimensions. The structure showed that PMS binding in DLH (C123S) caused conformational changes in the active site and in four regions of the polypeptide chain that contain reverse turns. In the active site, residues with aromatic side chains were repositioned in an edge-to-face cluster around the PMS phenyl ring. Their redistribution prevented restabilization of the triad His202 side chain, which was disordered in electron-density maps. Movements of other residues in the active site were shown to be related to the four displaced regions of the polypeptide chain. Their implied synergy suggests that DLH may be able to accommodate and catalyse a range of compounds unrelated to the natural substrate owing to an inherent coordinated flexibility in its overall structure. Implications for mechanism and further engineering studies are discussed.

Carboxylic Ester Hydrolases↗
PubMed2000

Levonorgestrel-releasing (20 microgram/day) intrauterine systems (Mirena) compared with other methods of reversible contraceptives.

OBJECTIVE: To assess the relative contraceptive effectiveness, tolerability and acceptability of the levonorgestrel-releasing (20 microg per day) intrauterine system (LNG-20) compared with reversible contraceptive methods in women of reproductive age. DESIGN: A systematic review and meta-analysis of randomised controlled trials. IDENTIFICATION: Studies were identified through seven databases, and by contacting investigators and organisations working in the contraceptive field. MAIN OUTCOME MEASURES: Unplanned pregnancy and continuation of contraceptive method. RESULTS: Five of the seven randomised controlled trials which met the inclusion criteria were included in the meta-analyses; four were comparisons of the LNG-20 intrauterine system with nonhormonal intrauterine devices. LNG-20 intrauterine systems were compared with intrauterine devices divided into two categories, those > 250 mm3 (Copper T 380 Ag and Copper T 380A intrauterine devices) and those < or = 250 mm3 (Nova-T, Copper T 220C and Copper 200 intrauterine devices). Pregnancy rates for the LNG-20 intrauterine system users were significantly less likely to become pregnant compared with users of intrauterine devices < or = 250 mm3, and significantly less likely to have an ectopic pregnancy. LNG-20 intrauterine system users were more likely to experience amenorrhoea and device expulsion than women using intrauterine devices > 250 mm3. LNG-20 intrauterine system users were significantly more likely than all the intrauterine device users to discontinue because of hormonal side effects and amenorrhoea. When the LNG-20 intrauterine system was compared with Norplant-2, the LNG-20 users were significantly more likely to experience oligo-amenorrhoea, but significantly less likely to experience prolonged bleeding and spotting. CONCLUSIONS: The effectiveness of the LNG-20 intrauterine system was similar to or better than other contraceptive methods with which it was compared. Amenorrhoea was the main reason for the discontinuation of the LNG-20 intrauterine system, usually unnecessarily, since this end-organ suppression of bleeding is benign, associated with normal oestrogen levels. Women choosing this method should be informed of potential amenorrhoea when having pre-contraceptive counselling and that absent bleeding may be viewed as a positive outcome.

Contraception↗
PubMed2000

The potential use of decision analysis to support shared decision making in the face of uncertainty: the example of atrial fibrillation and warfarin anticoagulation.

The quality of patient care is dependent upon the quality of the multitude of decisions that are made daily in clinical practice. Increasingly, modern health care is seeking to pursue better decisions (including an emphasis on evidence-based practice) and to engage patients more in decisions on their care. However, many treatment decisions are made in the face of clinical uncertainty and may be critically dependent upon patient preferences. This has led to attempts to develop decision support tools that enable patients and clinicians to make better decisions. One approach that may be of value is decision analysis, which seeks to create a rational framework for evaluating complex medical decisions and to provide a systematic way of integrating potential outcomes with probabilistic information such as that generated by randomised controlled trials of interventions. This paper describes decision analysis and discusses the potential of this approach with reference to the clinical decision as to whether to treat patients in atrial fibrillation with warfarin to reduce their risk of stroke.

Aged↗
PubMed2000

Home screening for chlamydial genital infection: is it acceptable to young men and women?

OBJECTIVES: To determine the acceptability, to young men and women, of home screening for chlamydial infection. METHODS: We wrote to a random sample of 208 women aged 18-25 years and 225 men aged 18-35 years from three general practices, inviting them to undergo home screening for chlamydial infection. They were asked to return, by normal post, a urine specimen (for men and half of the women) or a vulval swab (other half of the women) for ligase chain reaction (LCR) testing for chlamydial infection. They were also asked to return a short questionnaire about risk status and the acceptability of this approach. RESULTS: The participation rate among the available sample was 39% for women and 46% for men (p = 0.3). However, among women, the rate was slightly higher (p = 0.05) for urine samples (47%) than for vulval swabs (32%). Six per cent of women and 9% of men declined to take part, while 42% of women and 33% of men failed to respond. Two men objected to receiving the package at home. We received few other comments, positive and negative in about equal measure. CONCLUSION: Home screening for chlamydial infection is a potentially efficient method of reaching young people who may have little contact with health services. Men were at least as likely as women to respond to this screening approach. Home screening might form a useful component of a future chlamydial screening programme in the United Kingdom.

Adolescent↗
PubMed2000

Socioeconomic issues affecting the treatment of obesity in the new millennium.

The prevalence of obesity among the populations of most developed countries has increased to such an extent that the healthcare and social security/disability system will accumulate direct and indirect costs related to obesity that will be more substantial than those for any other primary disease within this generation. For the past decade, the Healthcare Financing Agency, which oversees the Medicare and Medicaid programmes, has required all physicians and healthcare agencies serving beneficiaries of these programmes to include diagnoses using codes established by the ninth revision of the World Health Organization's International Classification of Diseases. This coding system actually distorts data collection and undermines appropriate medical insurance reimbursement for the treatment of obesity. Societal prejudices, inability of governmental agencies to address future concerns and the business community's attempts to control healthcare costs without addressing the underlying issues contributing to these costs have led to confusion on how to confront this emerging epidemic. How will we develop the scientific knowledge and the political willpower to confront this epidemic? First, we need more accurate methods for classifying obesity and for measuring the cost of treatment. We can then determine if it is more cost effective to prevent or treat obesity early in its evolution or pay for its consequences in the form of treatment costs associated with its multiple comorbid diseases, such as hypertension, other cardiovascular disorders, diabetes mellitus, osteoarthritis and cancers, plus the lost productivity from absenteeism, premature retirement and death.

Cost-Benefit Analysis↗
PubMed2000

Diagnostic radiology residents in the classes of 1999 and 2000: fellowship and employment.

OBJECTIVE: Most diagnostic radiology residents undergo fellowship training. Applications for fellowship positions are submitted during the third year of residency. We compared the number of residents undertaking fellowship, accepting jobs, and rescinding accepted fellowship positions to accept jobs. MATERIALS AND METHODS: During the 47th Association of University Radiologists meeting, participants from the American Association of Academic Chief Residents in Radiology completed a questionnaire regarding the intentions of third- and fourth-year residents in their programs. RESULTS: Seventy programs, representing 402 fourth-year and 395 third-year residents, responded. Of fourth-year residents, 322 (80.1%) accepted fellowships and 41 (10.2%) accepted jobs. Of third-year residents, 335 (84.8%) accepted fellowships. Eighty-eight (27.3%) fourth-year residents and 95 third-year residents (28.4%) accepted interventional radiology fellowships, and 104 (32.3%) fourth-year residents and 96 (28.7%) third-year residents accepted body imaging fellowships. Most residents who accepted fellowships did so in the same city in which they completed their residency training. Of fourth-year residents who accepted fellowship positions the year before, 14 (4.3%) withdrew their acceptance to pursue employment. CONCLUSION: Most residents opt for fellowship training in interventional radiology or body imaging. We postulate that the practice of accepting fellowships during the third year of residency may contribute to the percentage of residents who rescind fellowship acceptance to pursue employment. We suggest that consideration be given to changing this practice.

Data Collection↗
PubMed2000

Mining for putative regulatory elements in the yeast genome using gene expression data.

We have developed a set of methods and tools for automatic discovery of putative regulatory signals in genome sequences. The analysis pipeline consists of gene expression data clustering, sequence pattern discovery from upstream sequences of genes, a control experiment for pattern significance threshold limit detection, selection of interesting patterns, grouping of these patterns, representing the pattern groups in a concise form and evaluating the discovered putative signals against existing databases of regulatory signals. The pattern discovery is computationally the most expensive and crucial step. Our tool performs a rapid exhaustive search for a priori unknown statistically significant sequence patterns of unrestricted length. The statistical significance is determined for a set of sequences in each cluster with respect to a set of background sequences allowing the detection of subtle regulatory signals specific for each cluster. The potentially large number of significant patterns is reduced to a small number of groups by clustering them by mutual similarity. Automatically derived consensus patterns of these groups represent the results in a comprehensive way for a human investigator. We have performed a systematic analysis for the yeast Saccharomyces cerevisiae. We created a large number of independent clusterings of expression data simultaneously assessing the "goodness" of each cluster. For each of the over 52,000 clusters acquired in this way we discovered significant patterns in the upstream sequences of respective genes. We selected nearly 1,500 significant patterns by formal criteria and matched them against the experimentally mapped transcription factor binding sites in the SCPD database. We clustered the 1,500 patterns to 62 groups for which we derived automatically alignments and consensus patterns. Of these 62 groups 48 had patterns that have matching sites in SCPD database.

Gene Expression Profiling↗
PubMed1999

Efficient discovery of inhibitory ligands for diverse targets from a small combinatorial chemical library of chimeric molecules.

Living systems are mainly composed and regulated by compounds in four biochemical classes and their polymers-nucleotides, carbohydrates, lipids, and amino acids. Early combinatorial chemistry libraries consisted of peptides. The present report describes the general bioactivity and biophysical properties of a combinatorial chemical library that used glyco, nucleotidyl, and lipid building blocks. The resulting chimeric combinatorial library of 361 compounds had a confirmed cumulative hit rate of 0.16%, which is 8-fold higher than a commonly claimed industrial benchmark of 0. 02%. It produced 7 structurally confirmed hits for a third of 12 proprietary drug discovery projects, and these comprised a variety of molecular targets. Diversity analyses demonstrated that despite the small number of compounds, a wider range of diversity space was covered by this library of biochemical chimeras than by a branched tripeptide library of the same size and similar generic formula.

Binding Sites↗
PubMed1999

A multicenter, randomized, double-blinded trial of pyridostigmine in postpolio syndrome.

BACKGROUND: Postpoliomyelitis syndrome (PPS) is likely due to degeneration and dysfunction of terminal axons of enlarged postpolio motor units. Age-related decline in growth hormone and insulin-like growth factor (IGF-I) may be a contributing factor. Neuromuscular junction abnormalities and decreased IGF-I levels may respond to the anticholinesterase pyridostigmine, with consequent improvement in strength, fatigue, and quality of life. OBJECTIVES: To determine the effect of pyridostigmine in PPS on health-related quality of life, isometric muscle strength, fatigue, and serum IGF-I levels; and to assess the safety of pyridostigmine in PPS. METHODS: The study was a multicenter, randomized, double-blinded, placebo-controlled trial of a 6-month course of pyridostigmine 60 mg three times per day in 126 PPS patients. The primary data analysis compared mean changes of outcomes between treatment and control groups at 6 months using an intention to treat approach. Secondary analyses included a comparison of outcomes at 6 and 10 weeks, and in compliant patients. RESULTS: The study showed no significant differences in pyridostigmine and placebo-treated patients with regard to changes in quality of life, isometric strength, fatigue, and IGF-I serum levels at 6 months in the primary analysis and in compliant patients. There were no differences in outcomes at 6 and 10 weeks between groups. However, very weak muscles (1 to 25% predicted normal at baseline) were somewhat stronger (p = 0.10, 95% CI of difference -9.5 to 73.3%), and in compliant patients IGF-I was somewhat increased (p = 0.15, 95% CI of difference -6.4 to 44.8 ng/mL) at 6 months with the medication. Pyridostigmine was generally well tolerated. CONCLUSIONS: This study showed no significant differences between pyridostigmine and placebo-treated PPS patients on measures of quality of life, isometric strength, fatigue, and serum IGF-I.

Aged↗
PubMed1999

Inhibition of endothelin-converting enzyme attenuates transplant vasculopathy and rejection in rat cardiac allografts.

BACKGROUND: Transplant vasculopathy in kidney and heart allografts is associated with marked elevation of endothelin-1 (ET-1), but a role for ET-1 in the pathogenesis of transplant vasculopathy and chronic rejection has not been established. We, therefore, tested whether inhibition of ET-1-converting enzyme by phosphoramidon (PA) would attenuate rejection in a rat model of chronic cardiac allograft rejection (Lewis [LEW] to F344). METHODS: Donor LEW rats were pretreated 24 hr before transplantation with a bolus injection of vehicle (water) or PA. Twenty- four hour after transplantation, water or PA was continuously administered through an osmotic mini-pump. Plasma ET-1 levels in Fisher 344 (F344) recipients were 0.8+/-0.1 pg/ml in water-treated rats and 0.2+/-0.2 pg/ml (P<0.01) in PA-treated rats, demonstrating that the PA treatment protocol effectively lowered ET-1 biosynthesis. RESULTS: LEW cardiac allografts treated with water survived (i.e., palpable heart beat) for 16.0+/-0.5 days (n=6). Inhibition of ET-1 secretion by PA improved allograft survival to 28.8+/-3.3 days (P<0.01, n=8). An analysis of cardiac arteries demonstrated that PA treatment attenuated transplant vasculopathy. A morphometric scale of neointima formation (0-5) was 1.4+/-0.2 and 3.6+/-0.2 in PA- or water-treated rats, respectively (P<0.01). The percent of luminal occlusion, as measured by microscopic image analysis, was 19+/-6% in PA-treated animals and 38+/-6% (P<0.01) in animals treated with water. PA treatment also reduced infiltration of ED-1-positive monocytes/macrophages into the vascular neointima. CONCLUSIONS: We conclude that, even in the absence of concomitant immunosuppression, inhibition of ET-1 biosynthesis significantly attenuates transplant vasculopathy and improves survival of LEW to F344 cardiac allografts.

Animals↗
PubMed1999

Psychosocial competence of unselected young adults with sex chromosome abnormalities.

Very little is known about the adult adaptation of individuals with sex chromosome abnormalities (SCA) except for a few reports based upon biased samples of clinically identified patients. This first report from the Denver SCA study on the adult psychosocial adaptation of 36 unselected propositi, identified at birth, shows a continuation of mild psychological and social problems. Psychiatric interviews and self-reported information revealed that adaptation is quite variable, with many of the nonmosaic propositi not faring as well as their siblings, but in a few instances exceeding the success of brothers and sisters. Within this group of SCA subjects a subset demonstrated more marked pathology and a tendency to over-rate their social adaptation relative to the psychiatric interviewer, suggesting that the exclusive use of self-report questionnaires may not provide accurate assessment of psychological characteristics in this and other special populations. The full adult SCA behavioral phenotype has not yet been established but is emerging through additional reports from this and other studies of unselected SCA adults.

Adaptation, Psychological↗
PubMed1999

The strategic and operational characteristics of a distributed phased archive for a multivendor incremental implementation of picture archiving and communications systems.

The long-term (10 years) multimodality distributed phased archive for the Medical Information, Communication and Archive System (MICAS) is being implemented in three phases. The selection process took approximately 10 months. Based on the mandatory archive attributes and desirable features, Cemax-Icon (Fremont, CA) was selected as the vendor. The archive provides for an open-solution allowing incorporation of leading edge, "best of breed" hardware and software and provides maximum flexibility and automation of workflow both within and outside of radiology. The solution selected is media-independent, provides expandable storage capacity, and will provide redundancy and fault tolerance in phase II at minimum cost. Other attributes of the archive include scalable archive strategy, virtual image database with global query, and an object-oriented database. The archive is seamlessly integrated with the radiology information system (RIS) and provides automated fetching and routing, automated study reconciliation using modality worklist manager, clinical reports available at any Digital Imaging and Communications in Medicine (DICOM) workstation, and studies available for interpretation whether validated or not. Within 24 hours after a new study is acquired, four copies will reside within different components of the archive including a copy that can be stored off-site. Phase II of the archive will be installed during 1999 and will include a second Cemax-Icon archive and database using archive manager (AM) Version 4.0 in a second computer room.

Computer Communication Networks↗
PubMed1999

Integration, acceptance testing, and clinical operation of the Medical Information, Communication and Archive System, phase II.

The Medical Information, Communication and Archive System (MICAS) is a multivendor incremental approach to picture archiving and communications system (PACS). It is a multimodality integrated image management system that is seamlessly integrated with the radiology information system (RIS). Phase II enhancements of MICAS include a permanent archive, automated workflow, study caches, Microsoft (Redmond, WA) Windows NT diagnostic workstations with all components adhering to Digital Information Communications in Medicine (DICOM) standards. MICAS is designed as an enterprise-wide PACS to provide images and reports throughout the Strong Health healthcare network. Phase II includes the addition of a Cemax-Icon (Fremont, CA) archive, PACS broker (Mitra, Waterloo, Canada), an interface (IDX PACSlink, Burlington, VT) to the RIS (IDXrad) plus the conversion of the UNIX-based redundant array of inexpensive disks (RAID) 5 temporary archives in phase I to NT-based RAID 0 DICOM modality-specific study caches (ImageLabs, Bedford, MA). The phase I acquisition engines and workflow management software was uninstalled and the Cemax archive manager (AM) assumed these functions. The existing ImageLabs UNIX-based viewing software was enhanced and converted to an NT-based DICOM viewer. Installation of phase II hardware and software and integration with existing components began in July 1998. Phase II of MICAS demonstrates that a multivendor open-system incremental approach to PACS is feasible, cost-effective, and has significant advantages over a single-vendor implementation.

Compact Disks↗
PubMed1999

The combination of topical ceftazidime and aminoglycosides in the treatment of refractory pseudomonal keratitis.

BACKGROUND: Pseudomonal keratitis is a serious and potentially blinding infection. METHODS: We treated 12 patients with culture-positive fulminant pseudomonal keratitis with a topical combination of ceftazidime ophthalmic solution (50 mg/ml) and aminoglycosides (14 mg/ml). None of these patients had responded to the standard initial therapy with topical fortified gentamicin or tobramycin (14 mg/ml) combined with cefazolin (50 mg/ml). RESULTS: Substitution of cefazolin by ceftazidime achieved a remarkable clinical improvement during the first 24-48 h of administration in all cases. The average time of healing after initiation of the combination of ceftazidime and fortified aminoglycosides was 21+/-15 days. No serious side effects accompanied ceftazidime administration. In vitro susceptibility testing showed resistance to gentamicin or tobramycin in 33% of cases (4/12) and sensitivity to ceftazidime in all cases. CONCLUSIONS: The combination of ceftazidime, in a 5% solution, and fortified aminoglycosides (1.4%) may be a useful, safe and effective topical therapy for the treatment of pseudomonal keratitis resistant to aminoglycosides.

Acute Disease↗