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Biomedical subjects

A Reynolds

Publications and source records attributed to A Reynolds.

At least 19 recordsLinked to original sources
PubMed2004

Comparison of autologous serum eye drops with conventional therapy in a randomised controlled crossover trial for ocular surface disease.

AIMS: To evaluate the efficacy of 50% autologous serum drops against conventional treatment in ocular surface disorders refractory to normal treatments in a prospective randomised crossover trial. METHOD: Patients fulfilling ophthalmological and haematological entry criteria were randomised to either 3 months of autologous serum 50% followed by 3 months of their conventional treatment, or 3 months of conventional treatment, followed by 3 months of autologous serum. Clinical assessments, including Schirmer's test, rose Bengal, and fluorescein staining, were carried out on entry and at monthly intervals. Impression cytology was performed at entry, 3 and 6 months. Grading was carried out on degrees of squamous metaplasia and goblet cell density. Subjective comfort was recorded daily using the "faces" scale. These categorical scores were converted to linear measurement using Rasch analysis. Statistical analysis was carried out using Wilcoxon's signed rank test and ANOVA. RESULTS: 16 patients were recruited with 31 eyes studied. The ocular surface diseases chiefly included Sjögren's syndrome (n = 6) and keratoconjunctivitis sicca (n = 5). Impression cytology available in 25 of 31 eyes showed significant improvement on serum treatment, p<0.02. Rasch weighted faces scores were statistically significantly better with serum, p<0.01. CONCLUSION: The results of this randomised study provide further evidence of the beneficial effects of autologous serum in severe ocular surface disorders. For most of these patients, autologous serum was superior to conventional treatment for improving ocular surface health and subjective comfort.

Adult↗
PubMed2003

Modelling the cost-effectiveness of etanercept in adults with rheumatoid arthritis in the UK.

OBJECTIVES: This model examines the cost-effectiveness of etanercept monotherapy under British Society for Rheumatology guidelines, i.e. adults previously failing two disease-modifying anti-rheumatic drugs (DMARDs). It compares a DMARD sequence with etanercept third line against the same sequence excluding etanercept. METHOD: The 6-monthly trend in Health Assessment Questionnaire (HAQ) disability score is simulated for 10 000 patients' lifetimes using clinical trial data and published literature. Switching to the next treatment is triggered by lack of response, loss of efficacy or adverse events. Patient mortality depends on rheumatoid arthritis life-tables and on epidemiological evidence relating reduced risk to HAQ improvement. Regression of HAQ/EuroQol (EQ-5D) utility provides quality-adjusted life years (QALY) gained. Primary analysis includes drug costs, monitoring and hospitalizations. RESULTS: The central estimate cost per QALY is pound 16 330. Sensitivity analyses ( pound 7800 to pound 42 000) showed long-term HAQ progression (etanercept, DMARDs, non-responders) as most sensitive variables. The inclusion of potential avoided nursing home admissions and indirect costs/lost employment further improves the cost-effectiveness. CONCLUSIONS: For adults in the UK, the results suggest that etanercept is cost-effective when compared with non-biologic agents. The National Institute for Clinical Excellence has accepted that etanercept is cost-effective and recommended its availability for use in patients who have failed at least two DMARDs. This model was an important component of that decision. The model is further suitable for use for a wide range of other cost-effectiveness questions in rheumatoid arthritis.

Antirheumatic Agents↗
PubMed2001

Breastfeeding and brain development.

Although biochemical evidence seems to support the fact that more DHA is incorporated into the brain of breastfed infants compared with formula-fed infants, whether the levels of DHA in the brain are clinically significant is unclear. Because randomized trials cannot be done, this issue is difficult to study. The effects of breastfeeding on developmental outcome in term infants seems to be small or insignificant. For otherwise healthy children the potential differences are not clinically relevant; however, these small differences distributed over an entire population might have a significant effect on society. Although significant methodologic concerns exist, the effects of breastfeeding on preterm infants may be greater than those for term infants. Extremely low birth weight, premature infants (< 750-1000 g) have been found to have IQs that are 13 points lower than term controls and a 50% to 60% risk for requiring special-education services when they are in school. In these infants, small improvements in IQ and neurologic function could have a much greater effect. Further study of neurodevelopmental outcome in premature infants fed breast milk compared with those fed preterm formula are indicated. This information should not change the practice of encouraging breastfeeding of term and preterm infants because other advantages to breastfeeding exist.

Animals↗
PubMed2001

Early predictors of neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection.

OBJECTIVE: To determine the ability of neonatal clinical, audiologic, and computed tomography (CT) findings to predict long-term neurodevelopmental outcome in children with symptomatic congenital cytomegalovirus (CMV) infection. METHODS: Longitudinal cohort study of children (n = 41) with symptomatic congenital CMV infection evaluated at birth and followed up with serial age-appropriate neurodevelopmental testing. The performance of birth characteristics as predictors of long-term outcome were determined, and clinical and CT scoring systems were developed and correlated with intellectual outcome. RESULTS: Microcephaly was the most specific predictor of mental retardation (100%; 95% CI 84.5-100) and major motor disability (92.3%; 95% CI 74.8-99). An abnormality detected by CT was the most sensitive predictor for mental retardation (100%; 95% CI 82.3-100) and motor disability (100%; 95% CI 78.2-100). A highly significant (P <.001) positive correlation was found between head size at birth and the intelligence/developmental quotient (IQ/DQ). Approximately 29% of children had an IQ/DQ >90. There was no association between sensorineural hearing loss at birth and cognitive outcome. However, children with sensorineural hearing loss on follow-up (congenital and late-onset) had a lower IQ/DQ (P =.006) than those with normal hearing. CONCLUSIONS: The presence of microcephaly at birth was the most specific predictor of poor cognitive outcome in children with symptomatic congenital CMV infection, whereas children with normal findings on head CT and head circumference proportional to weight exhibited a good cognitive outcome.

Cerebral Palsy↗
PubMed2001

No evidence to support an association between the oestrogen receptor beta gene and bipolar disorder.

Oestrogen, a sex steroid hormone, has long been hypothesized to be involved in alterations to pathways involved in neurotransmission, and therefore may be involved in neuropsychiatric conditions including bipolar disorder. Indeed, certain depressive disorders in women have been found to be associated with low levels of oestrogen and can be much improved by the administration of this hormone. As the effects of oestrogen are most probably mediated through the oestrogen receptors (ER alpha and ER beta), the genes encoding these receptors may be possible candidates for association studies with bipolar disorder and other neuropsychiatric disorders. A number of studies, including previous results from this group, have reported modest evidence of linkage between both bipolar disorder and schizophrenia and a region of chromosome 14 (q22-q24), where the ER beta gene has been localized. In the present study, a sample of 102 Irish parent-proband trios were genotyped for a single nucleotide polymorphism within the ER beta gene (3' untranslated region, A1730G). However, the transmission/disequilibrium test failed to reveal evidence of a distortion in allele transmission to bipolar I (BPI) probands.

Bipolar Disorder↗
PubMed2000

Oxidant stress in sled dogs subjected to repetitive endurance exercise.

OBJECTIVE: To determine whether repetitive endurance exercise in sled dogs was associated with substantial lipid peroxidation, decreases in antioxidant capacity of the serum, and skeletal muscle damage. ANIMALS: 24 lightly trained sled dogs. PROCEDURE: 16 dogs completed a 58-km run on each of 3 consecutive days; the other 8 dogs (control) did not exercise during the study. Blood samples were collected before the first exercise run and after the first and third exercise runs. Plasma isoprostane and serum vitamin E concentrations, total antioxidant status of plasma, and serum creatine kinase activity were measured. RESULTS: Plasma isoprostane concentrations in dogs in the exercise group were significantly increased after the first exercise run and further significantly increased after the third exercise run. Serum vitamin E concentration was significantly decreased after the first exercise run in dogs in the exercise group, and this change persisted after the third exercise run. There was a significant linear relationship between plasma isoprostane concentration and the logarithm of serum creatine kinase activity (adjusted ? = 0.84). CONCLUSIONS AND CLINICAL RELEVANCE: Results demonstrate that repetitive endurance exercise in dogs is associated with lipid peroxidation and a reduction in plasma antioxidant concentrations. We interpret these results as indicating that the antioxidant mechanisms of minimally trained dogs may, in some instances, be inadequate to meet the antioxidant requirements of repetitive endurance exercise.

Animal Feed↗
PubMed1999

Iris crystals in chronic uveitis.

AIMS: To analyse the unusual physical sign of iris crystals occurring in patients with uveitis. METHODS: Demographic details and clinical features were documented in 24 patients with chronic uveitis and iris crystals. Plasma immunoglobulin subclasses were measured, and a histopathological review of iridectomy specimens from 33 patients with chronic uveitis was also undertaken. RESULTS: The mean age of patients was 38 years, with a slight preponderance of females. 17 patients had Fuchs' heterochromic cyclitis although a number of other uveitis entities were represented. There was no correlation between severity of clinical signs and presence of iris crystals. Over a mean follow up period of 15 months no significant change in the number, size, or position of the crystals was seen except in four patients who underwent intraocular surgery. Only three patients had raised plasma IgG1. The review of the histology of iridectomy specimens failed to show evidence of Russell body formation in any patient. CONCLUSIONS: Iris crystals appear to be rare but may be underreported as they are small and can easily be missed. They are likely to be associated with disease processes in which there is active immunoglobulin production within the anterior chamber, such as Fuchs' heterochromic cyclitis.

Adolescent↗
PubMed1998

Molecular cloning of the human p120ctn catenin gene (CTNND1): expression of multiple alternatively spliced isoforms.

Catenins were discovered as proteins that are linked to the cytoplasmic domain of transmembrane cadherins. Among these junctional plaque proteins are several members of the Armadillo gene family: beta-catenin, plakoglobin, and p120ctn. Recently it became clear that some catenins also mediate nuclear signaling. We performed a detailed analysis of the human p120ctn gene (HGMW-approved symbol CTNND1) and its transcripts. The human p120ctn gene comprises 21 exons, potentially encoding up to 32 protein isoforms as products of alternative splicing. Human isoforms, designated 1 to 4, differ from each other by the start codon used. Additional isoforms are derived from combinations with alternatively used exons A (exon 18) and B (20), near the end of the open reading frame, and also with exon C (11) in the middle of the open reading frame. Hence, the longest isoform is of type 1ABC and comprises 968 amino acid residues. The functional consequence of the observed multitude of p120ctn splice variants awaits further study, but tissue-specific expression was obvious. Further, we demonstrate that the exon organization, which is not simply related to the Armadillo repeat structure, is very well conserved between the p120ctn gene and the related ARVCF gene, but not at all between these two genes and the beta-catenin or plakoglobin genes. The present data favor the concept that p120ctn is the prototype of a subfamily of Armadillo proteins, comprising ARVCF, p0071, delta-catenin/NPRAP, and plakophilins 1 and 2, that are more related to each other than to other Armadillo proteins.

Alternative Splicing↗
PubMed1998

Harpin and hydrogen peroxide both initiate programmed cell death but have differential effects on defence gene expression in Arabidopsis suspension cultures.

Programmed cell death is increasingly viewed as a key component of the hypersensitive disease resistance response of plants. The generation of reactive oxygen species (ROS) such as H2O2 triggers a cell death programme in Arabidopsis suspension cultures following challenge with the bacterial elicitor harpin. Both harpin and exogenous H2O2 initiate a cell death pathway that requires gene expression, and also act as signalling molecules to induce the expression of plant defence genes encoding enzymes such as phenylalanine ammonia-lyase (PAL), glutathione S-transferase (GST) and anthranilate synthase (ASA1), an enzyme of phytoalexin biosynthesis in Arabidopsis. H2O2 induces the expression of PAL1 and GST but not that of ASA1. Harpin initiates two signalling pathways, one leading to increased ROS generation and expression of PAL1 and GST mRNA, and another leading to increased GST and ASA1 expression, independent of H2O2.

Anthranilate Synthase↗
PubMed1998

Congenital myotonic dystrophy requiring prolonged endotracheal and noninvasive assisted ventilation: not a uniformly fatal condition.

In this report we present two infants with congenital myotonic dystrophy (CMD) who were successfully weaned from prolonged ventilatory support using nasal continuous positive airway pressure (N-CPAP). The first infant received 127 days of endotracheal mechanical ventilation as part of 141 days of total ventilatory support, including N-CPAP; the second infant received 27 days of endotracheal mechanical ventilation as part of 84 days of total ventilatory support. Noninvasive N-CPAP facilitated weaning these two infants from ventilatory support, thereby minimizing the morbidity associated with prolonged intubation. The developmental outcomes of our two infants were comparable to infants not requiring prolonged endotracheal mechanical ventilation. We suggest that this noninvasive modality of ventilatory support may be advantageous in the management and beneficial to the outcome of infants with CMD who are respirator-dependent >30 days.

Adult↗
PubMed1998

TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues.

TRAF-4 was discovered because of its expression in breast cancers and is a member of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) family of putative signal-transducing proteins. In vitro binding assays demonstrated that TRAF-4 interacts with the cytosolic domain of the lymphotoxin-beta receptor (LT beta R) and weakly with the p75 nerve growth factor receptor (NGFR) but not with TNFR1, TNFR2, Fas, or CD40. Immunofluorescence analysis of TRAF-4 in transfected cells demonstrated localization to cytosol but not nucleus. Immunohistochemical assays of normal human adult tissues revealed prominent cytosolic immunostaining in thymic epithelial cells and lymph node dendritic cells but not in lymphocytes or thymocytes, paralleling the reported patterns of LT beta R expression. The basal cell layer of most epithelia in the body was very strongly TRAF-4 immunopositive, including epidermis, nasopharynx, respiratory tract, salivary gland, and esophagus. Similar findings were obtained in 12- to 18-week human fetal tissue, indicating a highly restricted pattern of expression even during development in the mammary gland, epithelial cells of the terminal ducts were strongly TRAF-4 immunopositive whereas myoepithelial cells and most of the mammary epithelial cells lining the extralobular ducts were TRAF-4 immunonegative. Of 84 primary breast cancers evaluated, only 7 expressed TRAF-4. Ductal carcinoma in situ (DCIS) lesions were uniformly TRAF-4 immunonegative (n = 21). In the prostate, the basal cells were strongly immunostained for TRAF-4, whereas the secretory epithelial cells were TRAF-4 negative. Basal cells in prostate hypertrophy (n = 6) and prostatic intraepithelial neoplasia (PIN; n = 6) were strongly TRAF-4 positive, but none of the 32 primary and 16 metastatic prostate cancer specimens examined contained TRAF-4-positive malignant cells. Although also expressed in some types of mesenchymal cells, these findings suggest that TRAF-4 is a marker of normal epithelial stem cells, the expression of which often ceases on differentiation and malignant transformation.

Adult↗
PubMed1997

The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88.

The oncogenic nucleoporin CAN/Nup214 is essential in vertebrate cells. Its depletion results in defective nuclear protein import, inhibition of messenger RNA export and cell cycle arrest. We recently found that CAN associates with proteins of 88 and 112 kDa, which we have now cloned and characterized. The 88 kDa protein is a novel nuclear pore complex (NPC) component, which we have named Nup88. Depletion of CAN from the NPC results in concomitant loss of Nup88, indicating that the localization of Nup88 to the NPC is dependent on CAN binding. The 112 kDa protein is the human homologue of yeast CRM1, a protein known to be required for maintenance of correct chromosome structure. This human CRM1 (hCRM1) localized to the NPC as well as to the nucleoplasm. Nuclear overexpression of the FG-repeat region of CAN, containing its hCRM1-interaction domain, resulted in depletion of hCRM1 from the NPC. In CAN-/- mouse embryos lacking CAN, hCRM1 remained in the nuclear envelope, suggesting that this protein can also bind to other repeat-containing nucleoporins. Lastly, hCRM1 shares a domain of significant homology with importin-beta, a cytoplasmic transport factor that interacts with nucleoporin repeat regions. We propose that hCRM1 is a soluble nuclear transport factor that interacts with the NPC.

Amino Acid Sequence↗