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Biomedical subjects

A Edwards

Publications and source records attributed to A Edwards.

At least 109 records · Page 6Linked to original sources
PubMed1998

Novel tetranuclear orthometalated complexes of Pd(II) and Pt(II) derived from p-isopropylbenzaldehyde thiosemicarbazone with cytotoxic activity in cis-DDP resistant tumor cell lines. Interaction of these complexes with DNA.

The reaction of p-isopropylbenzaldehyde thiosemicarbazone [p-is.TSCN], 1, with palladium(II) acetate and potassium tetrachloroplatinate yielded two tetrameric orthopalladated isomers, [Pd(p-is.TSCN)]4 (complexes 2 and 3), and the platinum analogue [Pt(p-is.TSCN)]4 (complex 4), respectively. All of these complexes contain the thiosemicarbazone bonded as a terdentate ligand to the metallic atom, through the thiol sulfur, the azomethinic nitrogen and the ortho carbon of the p-isopropylphenyl ring to which the imine group is attached to as deduced from the study of the IR, NMR, and XRD spectra of complexes 2 and 4. Complexes 2 and 4 crystallize in the centrosymmetric monoclinic space group C2/c, with Z = 8. Unit cell parameters for complex 2 are as follows: a = 25.742(5) A, b = 19.560(4) A, c = 24.199(5) A, beta = 101.70(3)o. Unit cell parameters for complex 4 are as follows: a = 25.8728(19) A, b = 19. 5053(14) A, c = 24.0899(16) A, beta = 101.305(2)o. As can be deduced from the NMR study, the palladated isomers 2 and 3 interconvert in DMSO which may be a consequence of the existence in both complexes of a flexible eight-membered ring with alternating Pd-S atoms. The testing of the cytotoxic activity of these compounds against several human and murine cell lines sensitive and resistant to cisplatin (cis-DDP) suggests that compounds 2, 3, and 4 may be endowed with important anticancer properties since they elicit IC50 values in the microM range as does the clinically used drug cis-DDP, and, moreover, they display cytotoxic activity in tumor lines resistant to cis-DDP. The analysis of the interaction of these novel tetrameric cyclometalated compounds with DNA suggests that they form DNA interhelical cross-links.

Animals↗
PubMed1998

Acute plasticity in the human somatosensory cortex following amputation.

We studied a patient after amputation of an arm and found that in less than 24 h stimuli applied on the ipsilateral face were referred in a precise, topographically organized, modality-specific manner to distinct points on the phantom. Functional magnetic resonance imaging (fMRI) performed one month later showed that brush-evoked activity in the brain demonstrates objective signal changes which correlate with perceptual changes in the phantom hand. This finding in humans corresponds to the observations of immediate plasticity in cortical pathways described in animals, including primates. The results suggest that reorganization of sensory pathways occurs very soon after amputation in humans, potentially due to the unmasking of ordinarily silent inputs rather than sprouting of new axon terminals.

Adult↗
PubMed1998

Visual acuity and visual field impairment in Usher syndrome.

OBJECTIVE: To determine the extent of visual acuity and visual field impairment in patients with types 1 and 2 Usher syndrome. METHODS: The records of 53 patients with type 1 and 120 patients with type 2 Usher syndrome were reviewed for visual acuity and visual field area at their most recent visit. Visual field areas were determined by planimetry of the II4e and V4e isopters obtained with a Goldmann perimeter. Both ordinary and logistic regression models were used to evaluate differences in visual acuity and visual field impairment between patients with type 1 and type 2 Usher syndrome. RESULTS: The difference in visual acuity of the better eye between patients with type 1 and type 2 varied by patient age (P=.01, based on a multiple regression model). The maximum difference in visual acuity between the 2 groups occurred during the third and fourth decades of life (with the type 1 patients being more impaired), while more similar acuities were seen in both younger and older patients. Fifty-one percent (n=27) of the type 1 patients had a visual acuity of 20/40 or better in at least 1 eye compared with 72% (n=87) of the type 2 patients (age-adjusted odds ratio, 3.9). Visual field area to both the II4e (P=.001) and V4e (P<.001) targets was more impaired in the better eye of type 1 patients than type 2 patients. A concentric central visual field greater than 20 degrees in at least 1 eye was present in 20 (59%) of the available 34 visual fields of type 1 patients compared with 70 (67%) of the available 104 visual fields of type 2 patients (age-adjusted odds ratio, 2.9) with the V4e target and in 6 (21%) of the available 29 visual fields of type 1 patients compared with 36 (38%) of the available 94 visual fields of type 2 patients (age-adjusted odds ratio, 4.9) with the II4e target. The fraction of patients who had a visual acuity of 20/40 or better and a concentric central visual field greater than 20 degrees to the II4e target in at least 1 eye was 17% (n=5) in the type 1 patients and 35% (n=33) in the type 2 patients (age-adjusted odds ratio, 3.9). CONCLUSIONS: Visual acuity and visual field area were more impaired in patients with type 1 than type 2 Usher syndrome. Of note, 27 of 53 type 1 (51%) and 87 of 120 type 2 (72%) patients had a visual acuity of 20/40 or better in at least 1 eye. These data are useful for overall counseling of patients with Usher syndrome.

Adult↗
PubMed1998

Age-related macular degeneration. Clinical features in a large family and linkage to chromosome 1q.

OBJECTIVES: To identify the chromosomal location of a disease-causing gene and to describe the clinical characteristics of a large family with age-related macular degeneration (ARMD). METHODS: An ARMD pedigree was identified, and the disease state of family members was documented by stereoscopic fundus photography and was classified using a modified version of the Wisconsin Age-Related Maculopathy Grading System. A genome-wide screen at approximately 6-centimorgan spacing using a DNA-pooling strategy combined with shared-segment analysis was used to identify likely chromosomal regions. The entire family was then screened at each likely locus, and 1 positive locus was refined by screening with markers at an average density of 0.5 centimorgan and subjected to parametric linkage analysis. RESULTS: In the 10 affected family members, ARMD was manifest by the presence of large, soft, confluent drusen accompanied by varying degrees of retinal pigment epithelial degeneration and/or geographic atrophy. Age-related macular degeneration segregated as an autosomal-dominant trait, with the disease locus mapping to chromosome 1q25-q31 between markers D1S466 and D1S413, with a multipoint lod score of 3.00. CONCLUSION: Age-related macular degeneration localized to chromosome 1q25-q31 (gene symbol, ARMD1) as a dominant trait in a large family with a predominantly dry phenotype. CLINICAL RELEVANCE: Identification of ARMD genes will facilitate early diagnosis and aid in understanding the molecular pathophysiological mechanisms of ARMD. This knowledge will contribute to the development of preventive and improved treatment strategies.

Aged↗
PubMed1998

Comparison of three treatment regimens of inhaled sodium cromoglycate in the management of adult patients with severe, steroid-dependent asthma.

BACKGROUND: Asthmatic patients whose asthma remains poorly controlled despite treatment with high doses of inhaled corticosteroids and co-administration of oral corticosteroids are a difficult problem in therapeutics. OBJECTIVE: To investigate the relative efficacy of three treatment regimens of inhaled sodium cromoglycate in the treatment of adult, severe, corticosteroid-dependent patients as determined by the reduction in the dose of oral corticosteroids and change in lung function. METHODS: Open, randomized, group comparative trial of 12 weeks duration in asthmatic patients attending a hospital outpatient department. Patients whose asthma is (1) severe according to the classification of the Japanese Society of Allergology, (2) stable, and (3) needing treatment with at least 1600 microg of inhaled beclomethasone dipropionate and 5 mg or greater of oral prednisolone per day. The three treatment regimens of inhaled sodium cromoglycate were group A received sodium cromoglycate powder at a dose of 16 mg/day administered by a metered dose inhaler. Group N received sodium cromoglycate aqueous solution at a dose of 80 mg/day administered by a nebulizer. Group C received sodium cromoglycate aqueous solution (80 mg/day) combined with salbutamol (3 mg/day) administered by a nebulizer. The main outcome measures were a change in the daily dose of oral corticosteroids and in lung function with twice daily measurements of peak expiratory flow (PEF) recorded in the morning (PEF AM) and in the evening (PEF PM). RESULTS: Mean reduction in oral corticosteroid dose/day was group A, 3.68 mg (95% CI 1.35,5.95); group N, 3.59 mg (95% CI 0.73,6.45); and group C, 3.97 mg (95% CI 1.81,6.13). The dosage reductions are all significant but with no differences between the groups. The mean increase in PEF over the last 4 weeks of treatment compared with baseline values was significant in all groups. The increases in group C are significantly greater than those in the other groups. These changes are all significant and the increases in group C are significantly greater than those in the other groups. CONCLUSIONS: Inhaled sodium cromoglycate may be a useful additional treatment in the management of adult patients with severe, oral steroid-dependent asthma. Of the three methods of administration compared in this trial the most useful immediate results were obtained when the drug was administered as an aqueous solution mixed with salbutamol and delivered by a powered nebulizer.

Administration, Inhalation↗
PubMed1998

Communication about risk: diversity among primary care professionals.

OBJECTIVE: We aimed to identify the important clinical topics and to report current practice of communication about risk in primary care. METHODS: We carried out a qualitative study using six semi-structured focus group discussions with primary care professionals. The subjects were 36 primary care professionals from general practice, practice nurse, district nurse, community psychiatric nurse and health visitor disciplines. RESULTS: All clinical topics were felt to raise issues of effective risk communication. Participants expressed concern about the lack of accessible up-to-date information and the problems of conveying information to patients. They described the circumstances and contexts in which communication varies and is difficult, and identified media and medico-legal influences and professional uncertainty as also contributing to the problems of risk communication. Specific training in risk communication was identified as an important need. CONCLUSIONS: The complexity of risk communication and diversity of influences on it will require wide-ranging interventions in order to address them. Standardized communication may be a difficult goal to attain.

Communication↗
PubMed1998

Communication about risk: the responses of primary care professionals to standardizing the 'language of risk' and communication tools.

OBJECTIVE: We aimed to gauge responses of primary care professionals to standardization of the 'language of risk' and risk communication tools. METHODS: We carried out a qualitative study using six semi-structured focus group discussions. The subjects were 36 primary care professionals from general practice, practice nurse, district nurse, community psychiatric nurse and health visitor disciplines. RESULTS: Between professionals, the standardization of the language of risk was felt to have potential benefit in making professionals consistent in their appreciation of risks and communication with each other. Between professionals and patients, standardized language was thought inappropriate or insufficient because of contextual variation in communication and interpretation of risk information by patients. The use of more-detailed comparisons of risks was felt to be a potentially effective development of risk communication in practice. CONCLUSIONS: A standard language of risk communication was perceived as being potentially helpful for communication between professionals, but many respondents were sceptical about its usefulness in communication with patients.

Communication↗
PubMed1998

Mutations in the gene encoding starch synthase II profoundly alter amylopectin structure in pea embryos.

Mutations at the rug5 (rugosus5) locus have been used to elucidate the role of the major soluble isoform of starch synthase II (SSII) in amylopectin synthesis in the developing pea embryo. The SSII gene maps to the rug5 locus, and the gene in one of three rug5 mutant lines has been shown to carry a base pair substitution that introduces a stop codon into the open reading frame. All three mutant alleles cause a dramatic reduction or loss of the SSII protein. The mutations have pleiotropic effects on the activities of other isoforms of starch synthase but apparently not on those of other enzymes of starch synthesis. These mutations result in abnormal starch granule morphology and amylopectin structure. Amylopectin contains fewer chains of intermediate length (B2 and B3 chains) and more very short and very long chains than does amylopectin from wild-type embryos. The results suggest that SSII may play a specific role in the synthesis of B2 and B3 chains of amylopectin. The extent to which these findings can be extrapolated to other species is discussed.

Amylopectin↗
PubMed1998

A multiunit model of solute and water removal by inner medullary vasa recta.

A recent model of volume and solute microcirculatory exchange in the renal medulla based on a single descending vasa rectum (DVR) was extended to account for the varying number of vessels along the corticomedullary axis. The assumption that concentration polarization at the walls of ascending vasa recta (AVR) during volume uptake eliminates transmural oncotic pressure gradients was examined. In this limiting case, small hydrostatic pressure gradients can drive AVR volume uptake if the pressure in the interstitium exceeds that in the AVR lumen. The calculated hydraulic pressure difference across AVR yielding agreement between predicted and measured values of AVR-to-DVR blood flow rate ratios was found to be smaller than the reported maximum pressure difference AVR can sustain. Simulations also confirmed previous conclusions suggesting that the presence of urea transporters in DVR counterbalances that of water channels that would otherwise decrease the efficiency of small solute trapping in the renal medulla.

Capillaries↗
PubMed1998

Research and the Goal of Improving Patient Care.

The goal of this article is to raise issues associated with the underlying assumptions of our research approaches and the nature of health/disease in conventional medical care and complementary and alternative medical care. Different types of efficacy are discussed in terms of randomized controlled trials and outcomes research. The demands of different audiences for research results suggest that researchers need to carefully specify the research question in the context of the state-of-the-knowledge. Appropriate matching of the study design, the nature of the disease, the nature of the treatment and what is known is essential to designing and implementing research that actually could improve patient care.

Journal Article↗
PubMed1998

Carbon dioxide embolism following diagnostic hysteroscopy.

A 50-year-old woman ASA 2 underwent carbon dioxide hysteroscopy under general anaesthesia. Monitoring showed a sudden and rapid fall in end-tidal carbon dioxide followed by oxygen desaturation. She became pulseless and cyanosed. Resuscitation with oxygen, intravenous adrenaline and head-down tilt restored her to haemodynamic stability. Hyperbaric therapy was also administered as air embolism could not be excluded.

Anesthesia, General↗
PubMed1998

In vitro and in vivo biodurability of a compliant microporous vascular graft.

Polyurethanes have unique mechanical and biologic properties that make them ideal for many implantable devices. However, certain polyurethanes are affected by some in vivo degradation mechanisms. For example, poly(ester)urethanes are subject to hydrolytic degradation and are no longer used in long-term implanted devices. Poly(ether)urethanes while hydrolytically stable, are subject to oxidative degradation in several forms, including environmental stress cracking and metal ion oxidation. We have developed a second-generation poly(carbonate)urethane with superior biostability. This material has been fabricated by our patented method into small diameter microporous vascular grafts. We evidenced the biodurability of our vascular graft by in vitro qualification tests which compared the poly(carbonate)urethane with a traditional poly(ether)urethane. This poly(carbonate)urethane graft has also proven to be biodurable in in vivo experimental implants up to twenty months duration with no evidence of hydrolysis or environmental stress cracking (ESC).

Animals↗
PubMed1998

The use of specialist palliative care services by patients with human immunodeficiency virus-related illness in the Yorkshire Deanery of the northern and Yorkshire region.

To examine the use of palliative care services by patients affected by human immunodeficiency virus (HIV) in hospices which do not specialize in the care of HIV patients, a tape-recorded, semistructured interview was carried out in 12 hospices in the UK. The interview explored concerns about such provision, as well as actual issues encountered. The study revealed that all 12 hospices accepted referrals for people affected by HIV and had clear working practices on infection control. between 1990 and 1996, 48 individuals affected by HIV had contact with the hospices. The number of referrals was not related to the size of the hospice. Thirty-nine individuals had a total of 655 days of inpatient care (range 1-35 days); mean length of stay 12.7 days. Twenty-four (62%) died during their first admission. Referrals came from disparate sources and this affected the amount and type of specialist HIV support available to the hospice. The paucity of referrals raised concerns in most of the units as to how to maintain skills. Issues about maintaining confidentiality of diagnosis in a multiprofessional team, and after death were highlighted. All units expressed concerns about the impact on fundraising of HIV-related admissions. Overall it was felt that the hospice units were failing to meet the palliative care needs of the majority of people affected by HIV or acquired immunodeficiency syndrome (AIDS) in the region. Possible reasons for this are given.

Advance Directives↗
PubMed1998

Criteria for evaluating alternative MEDLINE search engines.

With so many options available for searching MEDLINE on the World Wide Web or as a component of an online service, evaluation criteria are suggested as a means of assisting librarians in determining the positive and negative aspects of alternative MEDLINE sites. A set of searches was utilized to systematically compare MEDLINE sites. Sites evaluated included Avicenna, America Online, HealthGate, PubMed, Medscape, and Physicians' Online. Some features used to evaluate these sites were: default fields; operators (default); access to MeSH; subheadings; stop words protected in MeSH; truncation; and stemming. This article will describe the group process used to arrive at the evaluation criteria, as well as some general conclusions which will help librarians in directing their users to a particular MEDLINE site.

Abstracting and Indexing↗
PubMed1998

Improved detection of familial hypercholesterolemia by determining low density lipoprotein receptor expression in mitogen-induced proliferating lymphocytes.

In view of the presence of some 190 mutations in the low density lipoprotein receptor (LDL-R) gene and a lack of simple detection methods, we have developed an improved assay system for detecting familial hypercholesterolemia (FH) using mitogen-induced proliferating lymphocytes. Freshly isolated mononuclear cells were cultured for 3 days in RPMI 1640 supplemented with 10% human lipoprotein-deficient serum (LPDS) and 1% phytohemagglutinin (PHA). LDL-R expression was measured by flow cytometry using a monoclonal anti-LDL-R antibody or DiI-LDL. Mitogenic responses were monitored by cell size (FSC), interleukin-2 receptor (IL2-R) expression, and stimulation index (SI). The LDL-R expression in PHA-stimulated lymphocytes was significantly higher than lymphocytes or monocytes cultured without PHA (15.2- and 3.6-fold, respectively). The gradation of the LDL-R expression was highly correlated to FSC, IL2-R expression, and SI (r > 0.9 in each case). However, no difference in FSC, IL2-R expression, or SI existed between 30 clinically diagnosed FH and 42 normolipemic control subjects. The significantly lower LDL-R expression in the FH group (45.2 +/- 15.3% versus 100 +/- 14.1%; unpaired t test, P < 0.0001) indicated the presence of genetic defects. Normocholesterolemic first degree relatives and non-FH hypercholesterolemic subjects demonstrated normal LDL-R expression as did the controls. The assay carries an efficiency of 97% and both sensitivity and specificity of 98.5%. Measurement of low density lipoprotein receptor expression in phytohemagglutinin- and lipoprotein-deficient serum-stimulated lymphocytes offers a simple method for detecting familial hypercholesterolemia with improved sensitivity.

Adolescent↗