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Biomedical subjects

E Roberts

Publications and source records attributed to E Roberts.

At least 19 recordsLinked to original sources
PubMed2006

Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome.

Fuhrmann syndrome and the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome are considered to be distinct limb-malformation disorders characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia in humans. In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of chicken mesenchyme cell cultures and developing limbs. The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout). These findings illustrate the specific and conserved importance of WNT7A in multiple aspects of vertebrate limb development.

Amino Acid Sequence↗
PubMed2006

Medicare Part D coverage and its influence on transplant patients' out-of-pocket prescription expenses.

Since Medicare is available for qualifying individuals because of age (65 years or greater), disability, or end-stage renal disease, many transplant recipients have Medicare coverage. Everyone who is entitled to Medicare will qualify to enroll in a Part D plan-a voluntary prescription drug coverage option offered by private insurance companies who meet the standards established by Medicare. The addition of Medicare Part D may help reduce out-of-pocket medication expenses for transplant recipients who have Medicare; however, the reality of utilizing Part D to maximize recipients' benefits is not simple, but rather complicated. The intricacies of Part D involve not only understanding premium costs and benefit stages, but formularies, and, particularly for transplant patients, deciphering how Medicare Part B immunosuppressant coverage influences Part D coverage. This article details significant information concerning Part D that transplant health care professionals should know in order to maximize patients' benefits and minimize their out-of-pocket medication expenses.

Aged↗
PubMed2005

Dental project.

Explore the source record for details and available documents.

Charities↗
PubMed2005

The repeatability and criterion related validity of the 20 m multistage fitness test as a predictor of maximal oxygen uptake in active young men.

OBJECTIVE: To investigate the repeatability and criterion related validity of the 20 m multistage fitness test (MFT) for predicting maximal oxygen uptake (Vo(2max)) in active young men. METHODS: Data were gathered from two phases using 30 subjects (x+/-s; age = 21.8+/-3.6 years, mass = 76.9+/-10.7 kg, stature = 1.76+/-0.05 m). MFT repeatability was investigated in phase 1 where 21 subjects performed the test twice. The MFT criterion validity to predict Vo(2max) was investigated in phase 2 where 30 subjects performed a continuous incremental laboratory test to volitional exhaustion to determine Vo(2max) and the MFT. RESULTS: Phase 1 showed non-significant bias between the two applications of the MFT (x(diff)+/-s(diff) = -0.4+/-1.4 ml kg(-1) min(-1); t = -1.37, p = 0.190) with 95% limits of agreement (LoA) +/-2.7 ml kg(-1) min(-1) and heteroscedasticity 0.223 (p = 0.330). Log transformation of these data reduced heteroscedasticity to 0.056 (p = 0.808) with bias -0.007+/-0.025 (t = -1.35, p = 0.190) and LoA+/-0.049. Antilogs gave a mean bias on the ratio scale of 0.993 and random error (ratio limits) x/divided by 1.050. Phase 2 showed that the MFT significantly underpredicted Vo(2max) (x(diff)+/-s(diff) = 1.8+/-3.2 ml kg(-1) min(-1); t = 3.10, p = 0.004). LoA were +/-6.3 ml kg(-1) min(-1) and heteroscedasticity 0.084 (p = 0.658). Log transformation reduced heteroscedasticity to -0.045 (p = 0.814) with LoA+/-0.110. The significant systematic bias was not eliminated (x(diff)+/-s(diff) = 0.033+/-0.056; t = 3.20, p = 0.003). Antilogs gave a mean bias of 1.034 with random error x/divided by 1.116. CONCLUSIONS: These findings lend support to previous investigations of the MFT by identifying that in the population assessed it provides results that are repeatable but it routinely underestimates Vo(2max) when compared to laboratory determinations. Unlike previous findings, however, these results show that when applying an arguably more appropriate analysis method, the MFT does not provide valid predictions of Vo(2max).

Adolescent↗
PubMed2004

Congenital malformations of the diaphragm: findings of the West Midlands Congenital Anomaly Register 1995 to 2000.

OBJECTIVES: To describe trends in incidence, associated anomalies, clinical outcomes and sensitivity of prenatal diagnosis for congenital malformations of the diaphragm in the West Midlands Region between 1995 and 2000. METHODS: Information was retrieved from a population-based register of major congenital malformations in a health region of England, the West Midlands Congenital Anomaly Register (WMCAR), between 1995 and 2000. RESULTS: One hundred and sixty-one confirmed cases of congenital malformations of the diaphragm were notified from 396 577 births. This gives an incidence of 4.1 per 10,000 births. After natural losses and terminations, the incidence at birth was 2.9 per 10,000 registered births. For live-born cases, the infant mortality rate was 317 per 1000 births. 47% of the cases had additional structural or chromosomal anomalies; the infant mortality rate for these complex cases was 533 per 1000, an increased relative risk of 2.37 compared with isolated lesions. 66% of the cases were diagnosed prenatally, 51% of isolated lesions and 84% of complex cases. Fourteen prenatally diagnosed cases (12%) were false-positives; however, 11 of these cases had other significant pathology. These 14 cases were not included in the 161 confirmed cases. CONCLUSION: Congenital malformations of the diaphragm remain associated with considerable infant mortality. Most cases are now diagnosed before birth and the prognosis is adversely affected by the presence of other structural or chromosomal anomalies. This presents significant challenges for those involved in counselling the parents of affected fetuses.

Chromosome Aberrations↗
PubMed2003

DHEA treatment of Alzheimer's disease: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To compare the efficacy and tolerability of dehydroepiandrosterone (DHEA) vs placebo in AD. METHOD: Fifty-eight subjects with AD were randomized to 6 month's treatment with DHEA (50 mg per os twice a day; n = 28) or placebo (n = 30) in a multi-site, double-blind pilot trial. Primary efficacy measures assessed cognitive functioning (the AD Assessment Scale-Cognitive [ADAS-Cog]) and observer-based ratings of overall changes in severity (the Clinician's Interview-Based Impression of Change with Caregiver Input [CIBIC-Plus]). At baseline, 3 months, and 6 months, the ADAS-Cog was administered, and at 3 and 6 months, the CIBIC-Plus was administered. The 6-month time point was the primary endpoint. RESULTS: Nineteen DHEA-treated subjects and 14 placebo-treated subjects completed the trial. DHEA was relatively well-tolerated. DHEA treatment, relative to placebo, was not associated with improvement in ADAS-Cog scores at month 6 (last observation carried forward; p = 0.10); transient improvement was noted at month 3 (p = 0.014; cutoff for Bonferroni significance = 0.0125). No difference between treatments was seen on the CIBIC-Plus at either the 6-month or the 3-month time points. CONCLUSIONS: DHEA did not significantly improve cognitive performance or overall ratings of change in severity in this small-scale pilot study. A transient effect on cognitive performance may have been seen at month 3, but narrowly missed significance.

Aged↗
PubMed2003

Cree encephalitis is allelic with Aicardi-Goutiéres syndrome: implications for the pathogenesis of disorders of interferon alpha metabolism.

Aicardi-Goutiéres syndrome (AGS) is an early onset, progressive encephalopathy characterised by calcification of the basal ganglia, white matter abnormalities, and a chronic cerebrospinal fluid (CSF) lymphocytosis. Cree encephalitis shows phenotypic overlap with AGS although the conditions have been considered distinct because of immunological abnormalities observed in Cree encephalitis. We report that levels of interferon alpha (IFN-alpha), a marker of AGS, are raised in Cree encephalitis. Moreover, linkage analysis indicates that the disorders are allelic and refines the AGS1 locus to a 3.47 cM critical interval. Our data show that a CSF lymphocytosis is not necessary for the diagnosis of AGS and strongly suggest that AGS and pseudo-TORCH syndrome are the same disorder. Recognition of immunological dysfunction as part of the AGS phenotype provides further evidence of a primary pathogenic role for abnormal IFN-alpha production in AGS.

Abnormalities, Multiple↗
PubMed2002

Autosomal recessive primary microcephaly: an analysis of locus heterogeneity and phenotypic variation.

BACKGROUND AND OBJECTIVES: Locus heterogeneity is well established in autosomal recessive primary microcephaly (MCPH) and to date five loci have been mapped. However, the relative contributions of these loci have not been assessed and genotype-phenotype correlations have not been investigated. DESIGN: A study population of 56 consanguineous families resident in or originating from northern Pakistan was ascertained and assessed by the authors. A panel of microsatellite markers spanning each of the MCPH loci was designed, against which the families were genotyped. RESULTS: The head circumference of the 131 affected subjects ranged from 4 to 14 SD below the mean, but there was little intrafamilial variation among affecteds (+/- 1 SD). MCPH5 was the most prevalent, with 24/56 families consistent with linkage; 2/56 families were compatible with linkage to MCPH1, 10/56 to MCPH2, 2/56 to MCPH3, none to MCPH4, and 18/56 did not segregate with any of the loci. CONCLUSIONS: MCPH5 is the most common locus in this population. On clinical grounds alone, the phenotype of families linked to each MCPH locus could not be distinguished. We have also shown that further MCPH loci await discovery with a number of families as yet unlinked.

Adolescent↗
PubMed2002

Analysis of result variability from high-density oligonucleotide arrays comparing same-species and cross-species hybridizations.

There exists a significant limitation in the variety of organismsfor which microarrays have been developed because of a lack of genomic sequence data. A near-term solution to this limitation is to use microarrays designed for one species to analyze RNA samples from closely related species. The assumption is that conservation of gene sequences between species will be sufficient to generate a reasonable amount of good-quality data. While there have been relatively few published reports describing the use of microarrays for cross-species hybridizations, this technique is potentially a powerful tool for understanding genomics in model organisms such as nonhuman primates. Here we describe the analysis and comparison of hybridization characteristics and data variability from a set of cross-species (rhesus macaque) and same-species (human) hybridization experiments using human high-density Affymetrix oligonucleotide arrays. The data reveal that a large fraction of probe sets are effective at transcript detection in the cross-species hybridization, validating the application of cross-species hybridizations for nonhuman primate genomics research.

Analysis of Variance↗
PubMed2001

Turn structures in CGRP C-terminal analogues promote stable arrangements of key residue side chains.

The 37-amino acid calcitonin gene-related peptide (CGRP) is a potent endogenous vasodilator thought to be implicated in the genesis of migraine attack. CGRP antagonists may thus have therapeutic value for the treatment of migraine. The CGRP C-terminally derived peptide [D(31),P(34),F(35)]CGRP(27-37)-NH(2) was recently identified as a high-affinity hCGRP(1) receptor selective antagonist. Reasonable CGRP(1) affinity has also been demonstrated for several related analogues, including [D(31),A(34),F(35)]CGRP(27-37)-NH(2). In the study presented here, conformational and structural features in CGRP(27-37)-NH(2) analogues that are important for hCGRP(1) receptor binding were explored. Structure-activity studies carried out on [D(31),P(34),F(35)]CGRP(27-37)-NH(2) resulted in [D(31),P(34),F(35)]CGRP(30-37)-NH(2), the shortest reported CGRP C-terminal peptide analogue exhibiting reasonable hCGRP(1) receptor affinity (K(i) = 29.6 nM). Further removal of T(30) from the peptide's N-terminus greatly reduced receptor affinity from the nanomolar to micromolar range. Additional residues deemed critical for hCGRP(1) receptor binding were identified from an alanine scan of [A(34),F(35)]CGRP(28-37)-NH(2) and included V(32) and F(37). Replacement of the C-terminal amide in this same peptide with a carboxyl, furthermore, resulted in a greater than 50-fold reduction in hCGRP(1) affinity, thus suggesting a direct role for the amide moiety in receptor binding. The conformational properties of two classes of CGRP(27-37)-NH(2) peptides, [D(31),X(34),F(35)]CGRP(27-37)-NH(2) (X is A or P), were examined by NMR spectroscopy and molecular modeling. A beta-turn centered on P(29) was a notable feature consistently observed among active peptides in both series. This turn led to exposure of the critical T(30) residue to the surrounding environment. Peptides in the A(34) series were additionally characterized by a stable C-terminal helical turn that resulted in the three important residues (T(30), V(32), and F(37)) adopting consistent interspatial positions with respect to one another. Peptides in the P(34) series were comparatively more flexible at the C-terminus, although a large proportion of the [D(31),P(34),F(35)]CGRP(27-37)-NH(2) calculated conformers contained a gamma-turn centered on P(34). These results collectively suggest that turn structures at both the C-terminus and N-terminus of CGRP(27-37)-NH(2) analogues may help to appropriately orient critical residues (T(30), V(32), and F(37)) for hCGRP(1) receptor binding.

Alanine↗
PubMed2001

Growth and change in the prescribing of anti-depressants in New Zealand: 1993-1997.

AIMS: To examine changes in the prescribing of anti-depressants in New Zealand from 1993-1997, in terms of expenditure, the number of dispensings and days of therapy supplied. METHOD: Data on subsidised dispensings of anti-depressant drugs during 1993 to 1997 were obtained from PHARMAC and analysed using SAS. RESULTS: The overall size of the anti-depressant market increased considerably over the study period. Government expenditure rose 2.25 times, and 1.65 times as many days of anti-depressant medication were supplied in 1997 as in 1993. Most of this was due to the growth in prescribing of newer anti-depressants, but the use of older drugs remained constant. CONCLUSIONS: In common with other countries, the use of newer agents is contributing to increased overall use of anti-depressant medication and government expenditure in New Zealand. Use of older drugs has not diminished substantially.

Antidepressive Agents↗
PubMed2001

Regional variation in anti-depressant dispensings in New Zealand: 1993-1997.

AIMS: To examine regional differences in the prescribing of anti-depressants in New Zealand from 1993 to 1997, and to examine the composition and dynamics of these differences. METHODS: Data on every subsidised dispensing of anti-depressant drugs 1993 to 1997 were obtained from PHARMAC and analysed using SAS. Each dispensing was allocated to a regional council area on the basis of the location of the dispensing pharmacy. RESULTS: Prescribing of anti-depressants increased with time in all regions. However, there was substantial regional variation in prescribing rates per-capita, the highest being 2.28 to 2.49 times the lowest in every year. Regions also varied substantially in the mix of newer and older drugs used, although newer drugs became increasingly important in every region. CONCLUSIONS: Regional differences in anti-depressant prescribing are large. Further research with different data sources is required to explore the reasons for this variation.

Antidepressive Agents↗