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Biomedical subjects

A Wright

Publications and source records attributed to A Wright.

At least 127 records · Page 7Linked to original sources
PubMed1998

Overview and meta-analysis of randomised trials of amiodarone in chronic heart failure.

Unlike other antiarrhythmic class I drugs, amiodarone showed in preliminary studies, benefits also in patients with left ventricular dysfunction. These positive results have induced the development of large randomised controlled studies: their results are reviewed and the controversial points are discussed. In a meta-analysis of randomised controlled trials the use of amiodarone in heart failure was associated with an approximate 20 to 25% reduction in deaths. However, amiodarone was also associated with a 120 to 124% increase in side effects.

Amiodarone↗
PubMed1998

Effect of C2-associated carbohydrate structure on Ig effector function: studies with chimeric mouse-human IgG1 antibodies in glycosylation mutants of Chinese hamster ovary cells.

The complex biantennary oligosaccharide at Asn297 of IgG is essential for some effector functions. To investigate the effect of carbohydrate structure on Ab function, we have now expressed mouse-human chimeric IgG1 Abs in Chinese hamster ovary (CHO) cells with defined defects in carbohydrate biosynthesis. We had previously shown that IgG1 Abs produced in the cell line Lec 1, which attaches a high-mannose intermediate carbohydrate, were severely deficient in complement activation, showed a slightly reduced affinity for Fc gammaRI, and had a reduced in vivo half-life. We have extended these studies by producing the same dansyl-specific IgG1 in cell lines deficient in attachment of sialic acid (Lec 2) and galactose (Lec 8). IgG1-Lec 1, IgG1-Lec 2, and IgG1-Lec 8 all showed varying reactivity with a mAb specific for an epitope in the amino terminal region of C(H)2, suggesting that the conformations of these proteins were altered by the different carbohydrate structures. Functionally, IgG1-Lec 2 and IgG1-Lec 8 were comparable to wild type with respect to in vivo half-life, affinity for Fc gammaRI, and capacity for complement-mediated hemolysis. While IgG1-Lec 2 was essentially identical to wild type in its capacity to interact with individual components of the classical complement activation pathway, IgG1-Lec 8 demonstrated equivalent maximal binding at lower concentrations and was preferentially bound by mannose-binding protein. Although IgG1-Lec 1 was deficient in activation of the classical pathway, it had a superior capacity to activate the alternative pathway. These studies demonstrate that Abs bearing C(H)2-linked carbohydrate of differing structures have different functional properties.

Animals↗
PubMed1998

Socioeconomic outcomes of combined spine surgery and functional restoration in workers' compensation spinal disorders with matched controls.

STUDY DESIGN: A longitudinal cohort study (n = 448) comparing functionally restored discectomy (n = 123) and fusion (n = 101) workers' compensation patients to matched, unoperated control patients (n = 123 and n = 101, respectively). OBJECTIVES: To determine successful treatment outcomes uniquely important in a workers' compensation environment when spine surgery is combined with comprehensive tertiary rehabilitation, to optimize anatomic and social sequelae. SUMMARY OF BACKGROUND DATA: Multiple recent studies confirm suboptimal socioeconomic outcomes for spinal surgery for degenerative conditions in a workers' compensation venue. In other musculoskeletal regions, there is a clear relationship between the quality of postsurgical rehabilitation and the impact on disability, recurrent injury, and future health care use. It is hypothesized that poor surgical outcomes in compensation injuries may result from outmoded postoperative methods, rather than failures of patient selection or surgical technique. No previous combination of surgery plus rehabilitation has been carefully evaluated with disabled workers undergoing spine surgery. Functional restoration is an individualized medically directed, interdisciplinary program using quantitatively directed exercise progression, psychotherapeutic interventions, and monitoring of specific socioeconomic outcomes for chronically disabled workers. METHODS: This study prospectively evaluated a cohort of consecutive functional restoration program graduates (n = 1202). Two surgical groups, discectomy (n = 123) and fusion (n = 101) were matched to two groups of unoperated control patients, control/discectomy and control/fusion, selected from the same cohort of patients with chronic spinal disorders based on age, gender, race, length of disability, and workers' compensation jurisdiction. A structured clinical interview was administered 12 months after program completion, with a contact rate of 95% to 98%. RESULTS: Socioeconomic outcomes for work return, health care use, and recurrent lost-time injury were assessed. All groups demonstrated a return-to-work incidence of more than 85%, but work retention at 1 year was higher for the fusion group than for the discectomy or control/fusion groups. Health care use was significantly higher for the discectomy group than the control/discectomy or fusion groups for reoperation (8% vs. 4%/ 2%), as well as other factors. All groups showed comparable recurrent lost-time injury rates (2-3.3%), and made comparable improvements in prospectively collected physical and psychological measures. CONCLUSIONS: Discectomy patients had work, health care utilization, and recurrent injury outcomes comparable with those for unoperated control patients. Fusion patients had better outcomes of work retention, reoperation, and health care use compared with the unoperated control patients and even with discectomy patients, in spite of more cases of previous surgery and greater duration of disability. The discectomy and fusion cohorts of operated chronic spinal disorder compensation patients with subsequent functional restoration had the best documented outcomes found in the literature for this population. In spite of the common presumption that spine surgery patients fare poorly in a workers' compensation environment, these results demonstrate that such patients can show remarkably successful objective outcomes if accompanied by effective rehabilitation, documenting efficacy and clinical utility. A new clinical approach is required to evaluate prospectively the combination of surgery and rehabilitation in chronic pain/disability workers' compensation patients, in which the surgical role is to correct an anatomic lesion, but the socioeconomic outcomes either occur spontaneously or are effected through some form of rehabilitation.

Adult↗
PubMed1998

South American camelids in the United Kingdom: reproductive failure, pregnancy diagnosis and neonatal care.

The results of a postal questionnaire survey conducted between December 1992 and March 1993 indicated that a third of mated female South American camelids in the United Kingdom failed to produce offspring. This failure did not include abortions or stillbirths, which accounted for up to 4 per cent and up to 3 per cent of further reproductive losses respectively. The most common method of pregnancy diagnosis was observation (40 to 70 per cent). Plasma progesterone estimations and ultrasonography were used by a small proportion of respondents. A combination of methods was seldom used. Between 25 and 46 per cent of camelid owners housed their animals at parturition and 50 to 82 per cent routinely dipped the navel of the newborn calf. Neonatal mortality was an important cause of loss.

Animal Husbandry↗
PubMed1998

South American camelids in the United Kingdom: population statistics, mortality rates and causes of death.

A survey of the health of South American camelids in the United Kingdom was carried out between December 1992 and June 1993; 123 members of the British Camelid Owners and Breeders Association and 19 non-members were sent questionnaires and usable responses were received from 84 (59 per cent). In total 689 camelids were included, and in 1992, 66 per cent were Ilama, 21 per cent alpaca and 13 per cent guanaco. Their ages ranged from less than six months to over 10 years, with animals aged two to five years constituting the largest proportion. The mortality rates between 1990 and 1992 were 2.7 to 3.3 per cent for Ilama, 3.5 to 6.9 per cent for alpaca and 0 to 11.4 per cent for guanaco. The highest mortality was in animals less than six months and more than 10 years old; 4 to 11 per cent of Ilama deaths and 17 to 33 per cent of alpaca deaths were in animals aged less than six months and a high proportion of these occurred during the first week of life. In the cases for which a cause was reported, accidents and injury accounted for 20 per cent of Ilama deaths, and perinatal deaths accounted for 22 per cent of alpaca deaths. A third of the deaths were reported as being of unknown cause, and a veterinary diagnosis was reported in less than half of the cases. These data suggest that attention to the environment and housing conditions of Ilama, the neonatal care of alpaca and improvements in diagnosis are priorities for reducing the mortality and improving the health of South American camelids in the UK.

Animals↗
PubMed1998

Review of uptake of interventions to reduce mother to child transmission of HIV by women aware of their HIV status.

OBJECTIVES: To examine the change in uptake of interventions to reduce transmission of HIV from mothers to infants from January 1994 to July 1997. DESIGN: Review of mother-infant pairs who presented for infant diagnosis of HIV infection. SETTING: Central London hospital with facilities for diagnosis of infant HIV infection. SUBJECTS: 57 consecutive mother-infant pairs, mainly from central London but also referred from surrounding hospitals. INTERVENTIONS: Data were collected on mother's country of origin; CD4 count at delivery; plasma HIV RNA copies/ml; mode of delivery; antiretroviral therapy; infant feeding; and HIV infection in infants. MAIN OUTCOME MEASURES: HIV infection of infants. RESULTS: The vertical transmission rate was 12% (7 pairs; 95% confidence interval 3% to 22%). All mothers chose not to breast feed. The caesarean section rate was 53% (30/57). Antiretroviral therapy was taken by 68.5% (39/57) of mother-infant pairs. With antiretroviral therapy or caesarean section, or both, transmission occurred in 6% (0% to 13%) of pairs (3/50). During the 24 months of 1994 and 1995, 21% (4/19) of infants were infected with HIV; 7.9% (3/38) were infected over the 19 months January 1996 to July 1997. The caesarean section rate did not change over these periods. Use of antiretroviral therapy increased from 31.5% (6/19) to 86.8% (33/38) (P < 0.0001). CONCLUSION: Women with a diagnosis of HIV infection acted to reduce the risk of transmission to their infants. Uptake of antiretroviral therapy increased significantly over time, and the caesarean section rate was persistently high.

Africa↗
PubMed1998

The central lysine in the P-loop motif of the Escherichia coli DnaA protein is essential for initiating DNA replication from the chromosomal origin, oriC, and the F factor origin, oriS, but is dispensable for initiation from the P1 plasmid origin, oriR.

The Escherichia coli DnaA protein is essential for initiation of DNA replication from the chromosomal origin, oriC, and from certain plasmid origins such as oriR of P1, oriS of F, and ori of pSCS101. The DnaA protein binds ATP with high affinity and contains a P-loop motif assumed to be the binding site. Three mutations in the E. coli dnaA gene were constructed by oligonucleotide-directed mutagenesis that changed amino acids in the P-loop. A DnaA protein, K178T, in which the central lysine was changed to the smaller amino acid threonine, was able to initiate DNA replication from P1 oriR, but was unable to initiate replication from E. coli oriC or F oriS in vivo. Mutant and wild-type DnaA proteins were overexpressed, partially purified, and tested for replication activity in vitro. The K178T DnaA protein could initiate replication from oriR, although with a decreased activity compared to the wild-type DnaA protein. No replication activity was detected for this mutant protein from oriC. The different responses of the oriR and oriC replicons to the K178T DnaA protein indicate that the role of DnaA is different in the two systems.

Bacterial Proteins↗
PubMed1998

The epidermoid formation and its affinity to congenital cholesteatoma.

The epidermoid formation was reinvestigated in stained step sections of foetal and neonatal temporal bones to assess its relationship to congenital cholesteatoma. Epidermoid formations were found in 88 of 211 temporal bones (42%) at from 12 weeks gestation to 6 months post-partum. The site was usually near the roof of the anterolateral epitympanum at an average of 389 microns anterior to the anterior edge of the tympanic membrane. Seven epidermoid formations however, were sited on the medial anterosuperior tympanic membrane surface. The mean surface diameter of epidermoid formations was 242 microns. Some were greater than 1500 microns, which approaches the size of small congenital cholesteatomas. They are often in proximity to a developmental epithelial fold which could close off to produce a cyst. These features support the concept that the epidermoid formation is a precursor of the small anterosuperior congenital cholesteatoma.

Cholesteatoma↗
PubMed1998

Intrapartum mucosal exposure to human immunodeficiency virus type 1 (HIV-1) of infants born to HIV-1-infected mothers correlates with maternal plasma virus burden.

The majority of vertical infections with human immunodeficiency virus type 1 (HIV-1) occur at or near delivery, strongly suggesting a mucosal route of transmission. The frequency and level of intrapartum mucosal exposure to HIV-1 of 22 infants born to infected mothers was investigated. Maternal plasma HIV-1 RNA and CD4 cell count were measured at delivery. Infant oropharyngeal aspirates obtained at birth were examined for HIV-1 RNA by reverse transcription-polymerase chain reaction and qualitative nucleic acid sequence-based amplification. Nine infants (41%) had detectable levels of HIV-1 RNA, 3 of which were quantifiable (mean, 3000 copies/mL). This mucosal exposure to HIV-1 during delivery did not lead to infection of any infant. Cesarian delivery did not reduce mucosal exposure to HIV-1. Mucosal exposure did not correlate with maternal CD4 cell count but did correlate with maternal plasma virus load and was reduced by antiretroviral therapy.

Adult↗
PubMed1998

Nursing interventions with advanced osteoporosis.

The patient with advanced osteoporosis presents with multisystem dysfunction, a decrease in ability to perform activities of daily living (ADLs), and often both acute and chronic pain. These men and women may experience depression and loss of self-esteem as well as future disability and increasing physical dependence. In the short time and limited visits allowed, the home care nurse can act as advocate, teacher, and caregiver in helping these patients to reach the goals of maintaining function and improving their quality of life.

Aged↗
PubMed1998

Evidence for interspecies gene transfer in the evolution of 2,4-dichlorophenoxyacetic acid degraders.

Small-subunit ribosomal DNA (SSU rDNA) from 20 phenotypically distinct strains of 2,4-dichlorophenoxyacetic acid (2,4-D)-degrading bacteria was partially sequenced, yielding 18 unique strains belonging to members of the alpha, beta, and gamma subgroups of the class Proteobacteria. To understand the origin of 2,4-D degradation in this diverse collection, the first gene in the 2,4-D pathway, tfdA, was sequenced. The sequences fell into three unique classes found in various members of the beta and gamma subgroups of Proteobacteria. None of the alpha-Proteobacteria yielded tfdA PCR products. A comparison of the dendrogram of the tfdA genes with that of the SSU rDNA genes demonstrated incongruency in phylogenies, and hence 2,4-D degradation must have originated from gene transfer between species. Only those strains with tfdA sequences highly similar to the tfdA sequence of strain JMP134 (tfdA class I) transferred all the 2,4-D genes and conferred the 2,4-D degradation phenotype to a Burkholderia cepacia recipient.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1998

Characterization and optimization of in vitro assay conditions for (1,3)beta-glucan synthase activity from Aspergillus fumigatus and Candida albicans for enzyme inhibition screening.

(1,3)Beta-D-glucan synthase (E.C.2.4.1.34. UDP-glucose: 1,3-beta-D-glucan 3-beta-glucosyl transferase) catalyzes the polymerization of glucose ([1-3]-beta-linkages) using UDP-glucose as substrate. We have determined optimal in vitro conditions for the assay of (1,3)beta-glucan synthase activity from Aspergillus fumigatus and Candida albicans. These included lysis of cells in the following for C. albicans, 100 mM HEPES, pH 8.0, 10 microM guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS), 2 mM ethylenediaminetetraacetic acid (EDTA), disodium salt, 5 mM NaF, 250 mM sucrose, and 10 mM NaH2PO4; and for A. fumigatus, 50 mM HEPES, 10mM EDTA, 750 mM sucrose, 10 mM NaH2PO4, 100 mM cellobiose and 50 microM GTPgammaS. Resulting low-speed supernatants were used as enzyme sources to determine the optimal in vitro assay conditions. We have characterized the resulting enzyme activities and tested the optimized assays with known (1,3)beta-glucan synthase inhibitors including cilofungin, papulacandin, aculeacin A, and echinocandin B. We have used both optimized assays to screen > 1000 extracts of marine macroorganisms and, using bioassay-guided purification, have identified (1,3)beta-glucan synthase inhibitors.

Antifungal Agents↗
PubMed1998

Two novel mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene in X-linked retinitis pigmentosa (RP3). Mutations in brief no. 172. Online.

Recently a new gene called RPGR (retinitis pigmentosa GTPase regulator) was isolated in Xp21.1 and found to be mutated in patients with RP3 type X-linked retinitis pigmentosa. Two new mutations, the first a single base pair deletion and the other a two base pairs deletion, have been found in one Spanish and one Italian family.

Carrier Proteins↗