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Biomedical subjects

M Richards

Publications and source records attributed to M Richards.

At least 37 records · Page 2Linked to original sources
PubMed2002

Hormone replacement therapy for cognitive function in postmenopausal women.

BACKGROUND: As estrogens have been found in animal models to be associated with the maintenance and protection of brain structures, it is biologically plausible that maintaining high levels of estrogens in postmenopausal women by medication could be protective against cognitive decline. OBJECTIVES: To investigate the effect of ERT (estrogens only) or HRT (estrogens combined with a progestagen) in comparison with placebo in randomized controlled trials (RCTs) on cognitive function in postmenopausal women. SEARCH STRATEGY: The CDCIG Specialized Register was searched using the terms ORT, PORT, ERT, HRT, estrogen*, oestrogen*, progesteron* on 16 May 2002. In addition MEDLINE (1966-2002/01); EMBASE (1985-2000/11); PsycINFO (1967-2002/01) and CINAHL (1982-2001/12) were searched as the CDCIG Register does not contain all trials with healthy volunteers. SELECTION CRITERIA: All double-blind randomized controlled trials of the effect of ERT or HRT on cognitive function over a treatment period of at least two weeks in postmenopausal women. DATA COLLECTION AND ANALYSIS: Abstracts of the references retrieved by the searches were read by two reviewers in order to discard those that were clearly not eligible for inclusion. The two reviewers studied the full text of the remaining references and independently selected studies for inclusion. Any disparity in the resulting lists was resolved by discussion with all reviewers in order to arrive at the final list of included studies. The selection criteria ensured that the blinding and randomization of the included studies was adequate. Two reviewers (EH and KY) assessed the quality of other aspects including design and assessment of outcomes. One reviewer (EH) extracted the data from the studies. MAIN RESULTS: In total, 15 trials involving 566 postmenopausal women were included, but 6 studies did not have adequate data for analysis. Meta-analyses showed a positive effect of 10 mg of estradiol (E2) bolus injections intramuscularly monthly in relatively young surgically menopausal women on the Paired Associate learning test immediate recall (z=2.40, p<0.05, chi-square test=1.12, p=0.29, SMD=1.02, 95% C.I.=0.19-1.85), on a test of abstract reasoning (z=10.45, p<0.0001, WMD=6.80, 95% C.I.=5.52-8.08) and a test of speed and accuracy (z=9.16, p<0.0001 WMD=6.00, 95% C.I.=4.72-7.28). However, most studies showed no evidence of an effect on verbal or visuospatial memory, mental rotations, speed or accuracy measures. There was little evidence that Premarin, the most widely prescribed estrogen for postmenopausal use, had positive effects on cognitive function. The one effect of 9 months of treatment with Premarin (and a progestagen) on a measure of complex speed of information processing (the TMT-B) was probably explained by baseline differences, as it was not reported by the authors. REVIEWER'S CONCLUSIONS: There was little evidence regarding the effect HRT or ERT on overall cognitive function in healthy postmenopausal women. There was an effect on some verbal memory functions (immediate recall), on a test of abstract reasoning and a test of speed and accuracy in relatively young (47 years of age) surgically menopausal women who had been given a bolus intramuscular injection of 10 mg E2 every month for 3 months. These effects were from small studies from a single research group. It remains to be determined whether factors such as an older age (> 69 years of age), type of menopause (surgical or natural) and type of treatment (E2 with or without a progestagen), mode of delivery (transdermal, oral or intramuscular), dosage and duration (> 3 months) could alter the effect on memory functions to a clinically relevant level. In addition, whether the absence or presence of menopausal symptoms can modify treatment effects should be investigated in more detail. Longitudinal RCTs currently underway in the U.S.A., U.K. and Canada will be able to test these hypotheses by the year 2010.

Cognition↗
PubMed2002

Hormone replacement therapy to maintain cognitive function in women with dementia.

BACKGROUND: As estrogens have been shown to have several potentially beneficial effects on the central nervous system, it is biologically plausible that maintaining high levels of estrogens in postmenopausal women by means of estrogen replacement therapy (ERT) could be protective against cognitive decline and the development of Alzheimer's disease (AD) or other dementia syndromes. OBJECTIVES: To investigate the effects of ERT (estrogens only) or HRT (estrogens combined with a progestagen) compared with placebo in randomized controlled trials (RCTs) on cognitive function of postmenopausal women with dementia. SEARCH STRATEGY: The CDCIG Specialized Register, which contains up-to-date records from many medical databases was searched using the terms ORT, PORT, ERT, HRT, estrogen*, oestrogen*, progesteron* and Alzheim* on 16th of May 2002. In addition, MEDLINE (1966-2002/01); EMBASE (1985-2002/01); and PsyINFO (1967-2002/01) were searched. SELECTION CRITERIA: All double-blind randomized controlled trials (RCTs) into the effect of ERT or HRT for cognitive function with a treatment period of at least two weeks in postmenopausal women with AD or other types of dementia. DATA COLLECTION AND ANALYSIS: Abstracts of the references retrieved by the searches were read by two reviewers (EH and KY) independently in order to discard those that were clearly not eligible for inclusion. The two reviewers studied the full text of the remaining references and independently selected studies for inclusion. Any disparity in the ensuing lists was resolved by discussion with all reviewers in order to arrive at the final list of included studies. The selection criteria ensured that the blinding and randomization of the included studies was adequate. The two reviewers also assessed the quality of other aspects of the included trials. One reviewer (EH) extracted the data from the studies, but was aided and checked by JB from Cochrane. MAIN RESULTS: A total of five trials including 210 women with AD were analysed. Meta-analyses showed that there was a limited positive effect from low dosage of conjugated equine estrogens (CEE, 0.625 mg once a day) but not from higher dosage (1.25 mg of CEE once a day) on the Mini-Mental Status Examination after 2 months (WMD=1.28, 95% C.I.=0.26 to 2.30, z=2.45, p<0.01) and the effect disappeared after 3, 6 and 12 months of treatment. This effect was small and not clinically relevant as there was only a difference of 1 point on average in comparison with the placebo users (the scale range is 0-30). There were also short-term effects of 1.25 mg of CEE on tests of concentration and executive function, namely the Trail Making Test-B (WMD=-40.90, 95% C.I.-79.29 to -2.51, z=2.09, p<0.05) and Digit Span backward (WMD=0.67, 95% C.I.=-0.01 to 1.34, z=1.94, p<0.05). With regard to memory, only cued delayed recall of a word list was positively affected by 2 months of transdermal diestradiol (E2) (WMD=6.50, 95% C.I.=4.04 to 8.96, z=5.19, p<0.0001). No HRT effects were seen on other word lists, Paragraph Recall or Paired Associate Learning. In addition, no effects were seen on visual memory, language functions, most speeded tests, clinical rating scales or depression. Controls had better performance on the delayed recall of the Paragraph Test (overall WMD=-0.45, 95% C.I.=-0.79 to -0.11, z=2.60, p<0.01) after 1 month and on Finger Tapping after 12 months (WMD=-3.90, 95% C.I.=-7.85 to 0.05, z=1.93, p<0.05). Clinicians also gave controls a better score on a dementia rating scale (CDR, overall WMD=0.35, 95% C.I.=0.01 to 0.69, z=1.99, p<0.05). Positive findings in favour of treatment or placebo could have been random effects caused by multiple analyses. After correction for multiple testing, only the short-term positive treatment effect of E2 on memory remained. REVIEWER'S CONCLUSIONS: Currently, HRT or ERT for cognitive improvement or maintenance is not indicated for women with AD. As we did not have data on women with other types of dementia (e.g. vascular dementia) this remains to be investigated. As most studies only used CEE and our earlier review in healthy women found effects only after a bolus injection of E2, it remains possible that different preparations or types of ERT or HRT could have a different effects. Several questions are raised in this review, including whether factors such as age, dementia onset (early AD), or the use of a particular preparation for a longer duration of treatment could have different effects. Perhaps the most important question is whether ERT or HRT can delay the time of onset of dementia. For answers to these questions, we have to await the results of the large RCTs currently in progress in the UK, USA, and Canada.

Cognition↗
PubMed2002

Ovarian function in the Nile hippopotamus and the effects of Depo-Provera administration.

The preliminary results of an investigation into the reproductive endocrinology of the hippopotamus (Hippopotamus amphibius) and the effects of the progestin Depo-Provera on ovarian function are presented. Faecal progestagen analysis indicated that hippos have an oestrous cycle of 29.2 +/- 0.9 days and faecal progestagen concentrations of 323.6 +/- 31.4 ng g(-1) during the luteal phase. Concentrations were higher (765.9 +/- 162.4 ng g(-1); P < 0.05) during pregnancy than during the luteal phase and remained high until parturition. A lactational anoestrus was usually, but not always, observed during nursing. The onset of puberty was observed in three animals and started at 2.5-3.5 years of age. After Depo-Provera treatment, increases in faecal progestagens indicative of ovulation were observed and were not significantly different from luteal concentrations observed before treatment (236.3 +/- 24.4 versus 340.1 +/- 47.9 ng g(-1), respectively); however, the duration of the luteal phase was shorter (P < 0.05) than before treatment (11.3 +/- 1.0 versus 18.9 +/- 1.0 days, respectively). Females returned to normal cyclicity at day 100.7 +/- 15.3 (range 70-116 days) after administration and one female conceived on day 100 after administration.

Analysis of Variance↗
PubMed2001

Do the four clades of the mtDNA haplogroup L2 evolve at different rates?

Forty-seven mtDNAs collected in the Dominican Republic and belonging to the African-specific haplogroup L2 were studied by high-resolution RFLP and control-region sequence analyses. Four sets of diagnostic markers that subdivide L2 into four clades (L2a-L2d) were identified, and a survey of published African data sets appears to indicate that these clades encompass all L2 mtDNAs and harbor very different geographic/ethnic distributions. One mtDNA from each of the four clades was completely sequenced by means of a new sequencing protocol that minimizes time and expense. The phylogeny of the L2 complete sequences showed that the two mtDNAs from L2b and L2d seem disproportionately derived, compared with those from L2a and L2c. This result is not consistent with a simple model of neutral evolution with a uniform molecular clock. The pattern of nonsynonymous versus synonymous substitutions hints at a role for selection in the evolution of human mtDNA. Regardless of whether selection is shaping the evolution of modern human mtDNAs, the population screening of L2 mtDNAs for the mutations identified by our complete sequence study should allow the identification of marker motifs of younger age with more restricted geographic distributions, thus providing new clues about African prehistory and the origin and relationships of African ethnic groups.

Base Sequence↗
PubMed2001

A signal, from human mtDNA, of postglacial recolonization in Europe.

Mitochondrial HVS-I sequences from 10,365 subjects belonging to 56 populations/geographical regions of western Eurasia and northern Africa were first surveyed for the presence of the T-->C transition at nucleotide position 16298, a mutation which has previously been shown to characterize haplogroup V mtDNAs. All mtDNAs with this mutation were then screened for a number of diagnostic RFLP sites, revealing two major subsets of mtDNAs. One is haplogroup V proper, and the other has been termed "pre*V," since it predates V phylogenetically. The rather uncommon pre*V tends to be scattered throughout Europe (and northwestern Africa), whereas V attains two peaks of frequency: one situated in southwestern Europe and one in the Saami of northern Scandinavia. Geographical distributions and ages support the scenario that pre*V originated in Europe before the Last Glacial Maximum (LGM), whereas the more recently derived haplogroup V arose in a southwestern European refugium soon after the LGM. The arrival of V in eastern/central Europe, however, occurred much later, possibly with (post-)Neolithic contacts. The distribution of haplogroup V mtDNAs in modern European populations would thus, at least in part, reflect the pattern of postglacial human recolonization from that refugium, affecting even the Saami. Overall, the present study shows that the dissection of mtDNA variation into small and well-defined evolutionary units is an essential step in the identification of spatial frequency patterns. Mass screening of a few markers identified using complete mtDNA sequences promises to be an efficient strategy for inferring features of human prehistory.

Africa, Northern↗
PubMed2001

Genetic evidence for different male and female roles during cultural transitions in the British Isles.

Human history is punctuated by periods of rapid cultural change. Although archeologists have developed a range of models to describe cultural transitions, in most real examples we do not know whether the processes involved the movement of people or the movement of culture only. With a series of relatively well defined cultural transitions, the British Isles present an ideal opportunity to assess the demographic context of cultural change. Important transitions after the first Paleolithic settlements include the Neolithic, the development of Iron Age cultures, and various historical invasions from continental Europe. Here we show that patterns of Y-chromosome variation indicate that the Neolithic and Iron Age transitions in the British Isles occurred without large-scale male movements. The more recent invasions from Scandinavia, on the other hand, appear to have left a significant paternal genetic legacy. In contrast, patterns of mtDNA and X-chromosome variation indicate that one or more of these pre-Anglo-Saxon cultural revolutions had a major effect on the maternal genetic heritage of the British Isles.

Cultural Evolution↗
PubMed2001

Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus.

Generalized epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome characterized by the presence of febrile and afebrile seizures. The first gene, GEFS1, was mapped to chromosome 19q and was identified as the sodium-channel beta1-subunit, SCN1B. A second locus on chromosome 2q, GEFS2, was recently identified as the sodium-channel alpha1-subunit, SCN1A. Single-stranded conformation analysis (SSCA) of SCN1A was performed in 53 unrelated index cases to estimate the frequency of mutations in patients with GEFS+. No mutations were found in 17 isolated cases of GEFS+. Three novel SCN1A mutations-D188V, V1353L, and I1656M-were found in 36 familial cases; of the remaining 33 families, 3 had mutations in SCN1B. On the basis of SSCA, the combined frequency of SCN1A and SCN1B mutations in familial cases of GEFS+ was found to be 17%.

Amino Acid Sequence↗
PubMed2001

Birth weight and cognitive function in the British 1946 birth cohort: longitudinal population based study.

OBJECTIVE: To examine the association between birth weight and cognitive function in the normal population. DESIGN: A longitudinal, population based, birth cohort study. PARTICIPANTS: 3900 males and females born in 1946. MAIN OUTCOME MEASURES: Cognitive function from childhood to middle life (measured at ages 8, 11, 15, 26, and 43 years). RESULTS: Birth weight was significantly and positively associated with cognitive ability at age 8 (with an estimated standard deviation score of 0.44 (95% confidence interval 0.28 to 0.59)) between the lowest and highest birthweight categories after sex, father's social class, mother's education, and birth order were controlled for. This association was evident across the normal birthweight range (>2.5 kg) and so was not accounted for exclusively by low birth weight. The association was also observed at ages 11, 15, and 26, and weakly at age 43, although these associations were dependent on the association at age 8. Birth weight was also associated with education, with those of higher birth weight more likely to have achieved higher qualifications, and this effect was accounted for partly by cognitive function at age 8. CONCLUSIONS: Birth weight was associated with cognitive ability at age 8 in the general population, and in the normal birthweight range. The effect at this age largely explains associations between birth weight and cognitive function at subsequent ages. Similarly, the association between birth weight and education was accounted for partly by earlier cognitive scores.

Adolescent↗
PubMed2001

A predominantly indigenous paternal heritage for the Austronesian-speaking peoples of insular Southeast Asia and Oceania.

Modern humans reached Southeast Asia and Oceania in one of the first dispersals out of Africa. The resulting temporal overlap of modern and archaic humans-and the apparent morphological continuity between them-has led to claims of gene flow between Homo sapiens and H. erectus. Much more recently, an agricultural technology from mainland Asia spread into the region, possibly in association with Austronesian languages. Using detailed genealogical study of Y chromosome variation, we show that the majority of current Austronesian speakers trace their paternal heritage to Pleistocene settlers in the region, as opposed to more-recent agricultural immigrants. A fraction of the paternal heritage, however, appears to be associated with more-recent immigrants from northern populations. We also show that the northern Neolithic component is very unevenly dispersed through the region, with a higher contribution in Southeast Asia and a nearly complete absence in Melanesia. Contrary to claims of gene flow (under regional continuity) between H. erectus and H. sapiens, we found no ancestral Y chromosome lineages in a set of 1,209 samples. The finding excludes the possibility that early hominids contributed significantly to the paternal heritage of the region.

Asia, Southeastern↗
PubMed2001

Cognitive function in UK community-dwelling African Caribbean elders: normative data for a test battery.

Many 'first generation' African Caribbean residents in the UK have now reached ages where risk of cognitive impairment and dementia starts to increase. In addition, conditions which may impair cognitive function, such as hypertension, diabetes and stroke, have high prevalence rates in African Caribbean populations. However, there is a lack of normative data for cognitive tests in this ethnic group. Cognitive assessment was carried out in a south London community population of 285 African Caribbean participants aged 55-75 years. Tests were drawn principally from the consortium to establish a registry for Alzheimer's disease (CERAD) battery (Boston Naming Test, verbal fluency, word list recall, and Trailmaking Tests A and B) and also included orientation items from the Mini-Mental State Examination (MMSE) and the Clock Drawing Test. Independent effects of age, sex, education and occupation were identified on scores for most but not all cognitive tests. Compared with normative data for African American populations, lower scores on verbal fluency and the Boston Naming Test were observed but scores on memory tests were comparable. Normative data for the tests are presented, stratified by level of education.

Aged↗
PubMed2001

Identification and management of intravagal parathyroid adenoma.

Intravagal parathyroid adenomas are rare, with only three cases reported in the English literature. The objective of this report is to describe two additional patients with hyperfunctioning parathyroid glands found within the vagus nerve and to define the anatomy of this finding. Both patients presented with a history of persistent hyperparathyroidism despite multiple therapeutic interventions. A high cervical localization was established in both cases by selective venous sampling. In each patient successful removal of the intravagal parathyroid gland was achieved with subsequent resolution of calcium and parathyroid levels. Each adenoma was located within the vagus nerve below the level of the carotid bifurcation and was enucleated without sacrificing the vagus nerve. In our cases and those reported previously, the parathyroid glands were supernumerary, representing parathyroid tissue embryologically derived from the third branchial pouch. Exploration for hyperparathyroidism requires a complete, meticulous surgical dissection to identify all parathyroid glands and to search for possible accessory tissue in selected cases. Our experience and a review of the literature serve to emphasize that, although rare, intravagal parathyroid adenomas do occur. Examination of the vagus nerve should therefore be strongly considered when four normal glands are found, as intravagal adenomas appear to represent accessory ectopically located parathyroid tissue.

Adenoma↗
PubMed2001

Detecting errors in mtDNA data by phylogenetic analysis.

Sequencing and documenting a sample of homologous DNA stretches is prone to copying errors in a way rather analogous to the biological replication process. Previous attempts at obtaining representative mtDNA sequences, typically of the control region, for evolutionary studies or forensic purposes have yielded rather unsatisfactory results in many cases. The key ingredient in pinpointing problems with given data is the phylogenetic analysis of closely related mtDNAs within the framework of an established worldwide phylogeny that is supported by coding region information. We develop some general rules by which likely errors in data tables can readily be detected without rereading whole sequences repeatedly. Following these guidelines, one can expect to lower the error rate by at least an order of magnitude, although it will still be hard to beat the mitochondrial gamma polymerase in precision.

DNA, Mitochondrial↗