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Biomedical subjects

M Richards

Publications and source records attributed to M Richards.

At least 127 records · Page 7Linked to original sources
PubMed1996

Adjuvant cyclophosphamide, methotrexate, and fluorouracil versus fluorouracil, epirubicin, and cyclophosphamide chemotherapy in premenopausal women with axillary node-positive operable breast cancer: results of a randomized trial. The International Collaborative Cancer Group.

PURPOSE: To determine whether a combination chemotherapy regimen that contains epirubicin (fluorouracil, epirubicin, and cyclophosphamide [FEC]) is superior to the standard cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in premenopausal women with axillary node-positive operable breast cancer. PATIENTS AND METHODS: The International Collaborative Cancer Group (ICCG) conducted a large randomized trial in which two alternative schedules were used according to participating center: CMF1 versus FEC1 and CMF2 versus FEC2. RESULTS: Seven hundred fifty-nine patients were entered onto the trial. At a median follow-up time of 4.5 years, no significant benefit for the anthracycline-containing regimen was observed in terms of relapse-free (P = .61) or overall survival (P = .13). FEC1 and CMF1 appear to be of similar efficacy, but there is a suggestion that FEC2 may be superior to CMF2, since patients who received FEC2 had improved overall (P = .02) and relapse-free survival (P = .03) rates. Nausea and vomiting and alopecia were more common in the epirubicin-containing regimen (P = .001). CONCLUSION: We conclude that the FEC2 regimen, in which epirubicin replaced the methotrexate in CMF, is the preferable adjuvant chemotherapy regimen for premenopausal patients with operable axillary node-positive breast cancer.

Adult↗
PubMed1996

Paleolithic and neolithic lineages in the European mitochondrial gene pool.

Phylogenetic and diversity analysis of the mtDNA control region sequence variation of 821 individuals from Europe and the Middle East distinguishes five major lineage groups with different internal diversities and divergence times. Consideration of the diversities and geographic distribution of these groups within Europe and the Middle East leads to the conclusion that ancestors of the great majority of modern, extant lineages entered Europe during the Upper Paleolithic. A further set of lineages arrived from the Middle East much later, and their age and geographic distribution within Europe correlates well with archaeological evidence for two culturally and geographically distinct Neolithic colonization events that are associated with the spread of agriculture. It follows from this interpretation that the major extant lineages throughout Europe predate the Neolithic expansion and that the spread of agriculture was a substantially indigenous development accompanied by only a relatively minor component of contemporary Middle Eastern agriculturalists. There is no evidence of any surviving Neanderthal lineages among modern Europeans.

Agriculture↗
PubMed1996

The biological effectiveness of radon-progeny alpha particles. V. Comparison of oncogenic transformation by accelerator-produced monoenergetic alpha particles and by polyenergetic alpha particles from radon progeny.

Generation of estimates of risk caused by exposure to radon in the home, either from miner data or from A-bomb data, requires several scaling factors such as for dose, dose rate and radiation quality, and possible synergisms. Such scaling factors are best developed from laboratory-based studies. Two possible sources of alpha particles for such studies are (1) a polyenergetic spectrum, generated directly by radon and its progeny, or (2) a series of monoenergetic alpha particles. We compare here the results of oncogenic transformation from studies using both systems. At the Columbia University Radiological Research Accelerator Facility (RARAF), C3H 10T1/2 cells were irradiated with alpha particles of various energies, with defined LETs from 70 to 200 keV/mum. At Pacific Northwest Laboratory, cells from the same stock were exposed to alpha particles from radon gas and its progeny, which were in equilibrium with the culture medium. There was good agreement between the results of oncogenic transformation experiments using the two different exposure systems. Apart from the experimental transformation frequencies themselves, such a comparison requires (1) reliable dosimetry at both facilities and (2) estimated LET distributions for the polyenergetic alpha-particle irradiator. Thus this good agreement gives some confirmation to the technique which is used to fold together oncogenic transformation rates from monoenergetic alpha particles to yield a predicted rate for a spectrum of alpha particles.

Alpha Particles↗
PubMed1995

Clinical correlates of Alzheimer's disease with and without silent radiographic abnormalities.

OBJECTIVE: To determine whether patients with Alzheimer's disease (AD) who do not have historical or clinical evidence of stroke but who do have computed tomographic or magnetic resonance imaging evidence of noncortical lesions smaller than 2 cm or periventricular "caps" differ from other patients with AD. METHODS: The computed tomographic or magnetic resonance imaging scans of 158 patients meeting criteria of the National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association for probable AD were reviewed by one neuroradiologist. Two measures of disease severity--the Modified Mini-Mental State examination and the Blessed Dementia Rating Scale (Part I)--were subjected to two-way analysis of variance with scan type (computed tomography or magnetic resonance imaging) and lesion number as between-group factors and age and disease duration as covariates. RESULTS: No relationship was seen between lesion number or periventricular caps and disease severity. CONCLUSION: In this cross-sectional analysis using these clinical measures, patients with AD who have well-defined radiographic abnormalities cannot be differentiated from patients with AD who do not have them.

Adult↗
PubMed1995

A standardized technique for establishing onset and duration of symptoms of Alzheimer's disease.

OBJECTIVES: To develop an informant-based semistructured interview to determine the onset and duration of symptoms of Alzheimer's disease, and to use this instrument with informants to characterize a cohort of mildly impaired patients with Alzheimer's disease. DESIGN: In study 1, interrater and interinformant reliability was examined for the date of onset and the order of appearance for specific symptoms that were elicited by the semistructured onset interview. In study 2, the instrument was used to characterize disease onset in a cohort of patients with Alzheimer's disease who were participating in a large multicenter study. SUBJECTS: Informants of patients with Alzheimer's disease. RESULTS: In study 1, interrater reliability for duration of illness was excellent (intraclass correlation coefficient = .99, P < .001), and interinformant reliability was good (intraclass correlation coefficient = .86, P < .001). Agreement for the presence of a given symptom was highest for those that were most commonly reported (eg, memory and performance difficulty). In study 2, 89% of the cohort had memory problems, and 63.9% had performance difficulties as the first or second symptom. Depression and language problems were less commonly reported. Psychosis and behavioral disturbances were rarely reported as the first problem. CONCLUSION: This instrument provides a reliable procedure for standardizing the estimation of duration of illness based on retrospective report.

Aged↗
PubMed1995

V-Y advancement hamstring myocutaneous island flap repair of ischial pressure ulcers.

Thirty-seven ischial pressure ulcers were repaired in 27 patients (eight quadriplegic, 19 paraplegic) between 1988-1993 using the V-Y advancement hamstring myocutaneous island flap. Twenty-one ulcers (57%) arose de novo and 16 were recurrent, with five patients having bilateral ulcers. The average duration of the ulcer was 5 months (range 1-30). All ulcers extended through the deep fascia (clinical grade IV), with the average diameter being 4.7 cm (range 2-10). There were four major flap complications (11%). All but one of the ulcers healed at discharge (97%). Mean follow up was 20 months (range 5-54) in 21 patients (78%), with six patients being lost to follow up. Seven of the 21 (33%) patients developed recurrent ulcers, with four of these having flap re-advancement with successful healing, and one patient having two re-advancements. Overall, 18 of the 21 (86%) patients with follow up had healed ulcers at time of follow up. The V-Y advancement hamstring myocutaneous island flap is versatile, reliable, easy to perform, has few complications, and can be re-advanced in the event of recurrence.

Humans↗
PubMed1995

The biological effectiveness of radon-progeny alpha particles. II. Oncogenic transformation as a function of linear energy transfer.

Epidemiological studies have established an association between exposure to radon and carcinoma of the lung. However, based on data for either lung cancer in uranium miners exposed to radon or bronchial epithelial carcinomas in Japanese A-bomb survivors, it has not been possible to assign estimates of risk of lung cancer for the general population exposed to radon in their homes. Based on past success with the excellent quantitative properties of the C3H 10T1/2 in vitro oncogenic transformation assay system, the relative biological effectiveness (RBE) for radiation-induced transformation for charged particles of defined LET has been determined. As the LET of the radiation was increased, the rate of induction of oncogenic transformation increased and the RBEm approached 20. At higher LETs, RBE dropped precipitously. The rapid drop in effectiveness for alpha particles with LETs between 120 and 265 keV/microns implies a lower quality factor than the 20-25 currently considered appropriate when estimating lung cancer mortality.

Alpha Particles↗
PubMed1995

The origins of the Polynesians: an interpretation from mitochondrial lineage analysis.

Using mitochondrial lineage analysis of 1,178 individuals from Polynesia, the western Pacific, and Taiwan, we show that the major prehistoric settlement of Polynesia was from the west and involved two or possibly three genetically distinct populations. The predominant lineage group, accounting for 94% of Polynesian mtDNA, shares a 9-bp COII/tRNA(Lys) intergenic deletion and characteristic control region transition variants, compared to the Cambridge reference sequence. In Polynesia, the diversity of this group is extremely restricted, while related lineages in Indonesia, the Philippines, and Taiwan are increasingly diverse. This suggests a relatively recent major eastward expansion into Polynesia, perhaps originating from Taiwan, in agreement with archeological and linguistic evidence, but which experienced one or more severe population bottlenecks. The second mitochondrial lineage group, accounting for 3.5% of Polynesian mtDNA haplotypes, does not have the 9-bp deletion and its characterized by an A-C transversional variant at nt position 16265. Specific oligonucleotides for this variant were used to select individuals from the population sample who, with other sequences, show that the Polynesian lineages were part of a diverse group in Vanuatu and Papua New Guinea. The very low overall diversity of both lineage groups in Polynesia suggests there was severe population restriction during the colonization of remote Oceania. A third group, represented by only four individuals (0.6%) in Polynesia but also present in the Philippines, shares variants at nt positions 16172 and 16304. Two Polynesians had unrelated haplotypes matching published sequences from native South Americans, which may be the first genetic evidence of prehistoric human contact between Polynesia and South America.

Base Sequence↗
PubMed1994

Conducting clinical research in the new NHS: the model of cancer. United Kingdom Coordinating Committee on Cancer Research.

The United Kingdom Coordinating Committee on Cancer Research represents the major organizations funding cancer research in the United Kingdom. The deliberations of a working party convened by the committee to evaluate recently expressed concerns that the changes in the NHS threaten research, especially clinical trials to evaluate new treatments, are reported. A survey of contributors to trials coordinated by the committee showed that half are now experiencing difficulties in continuing to participate in clinical trials. The two major problems identified were lack of time and of staff, especially for NHS staff in non-teaching hospitals. Recent changes in junior doctors' hours and proposed reductions in the length of time for training will exacerbate this. It is possible to identify the direct and indirect excess costs of conducting research in the NHS, but currently the mechanism does not exist to designate funds specifically for this purpose. Consultation with the regional directors of research and development confirmed that the service increment for teaching and research is not the solution for this. Proposals are made to secure future clinical research in the NHS, including finance, indemnity, the licensing of new drugs, the greater use of nurse counsellors, and the value of cancer registries.

Clinical Trials as Topic↗
PubMed1994

Negative feedback regulation of IgE synthesis by murine CD23.

Immunoglobulin E is found in nanogram amounts in normal human and mouse serum. It is increased during parasitic infestations and mediates allergy. CD23, the low-affinity receptor for IgE (Fc epsilon RII), has been proposed as an important regulator of IgE synthesis. The type-II transmembrane lectin CD23 is expressed in the mouse on B cells and follicular dendritic cells. In humans there are two forms of CD23 which differ in their intracellular amino-terminal 6/7 amino acids; expression of the A-form corresponds to that of murine CD23, whereas the B-form is also found on T and other haematopoietic cells. CD23 has been implicated in cellular adhesion, antigen presentation, as a growth and differentiation factor for human B, T and plasma cells, and as a signal transduction molecule (reviewed in refs 3, 8). Here we disrupt the gene coding for murine CD23 (ref. 9) to clarify the role of CD23 in vivo and find that B- and T-cell development is normal in these CD23-deficient mice. Immune responses to the helminth Nippostrongylus brasiliensis are unaffected. In contrast, immunization with thymus-dependent antigens leads to increased and sustained specific IgE antibody titres compared with controls. Formation of germinal centres is normal. These results suggest that murine CD23 acts as a negative feedback component of IgE regulation.

Animals↗
PubMed1994

Molecular genetic analyses of the Tyrolean Ice Man.

An approximately 5000-year-old mummified human body was recently found in the Tyrolean Alps. The DNA from tissue samples of this Late Neolithic individual, the so-called "Ice Man," has been extracted and analyzed. The number of DNA molecules surviving in the tissue was on the order of 10 genome equivalents per gram of tissue, which meant the only multi-copy sequences could be analyzed. The degradation of the DNA made the enzymatic amplification of mitochondrial DNA fragments of more than 100 to 200 base pairs difficult. One DNA sequence of a hypervariable segment of the mitochondrial control region was determined independently in two different laboratories from internal samples of the body. This sequence showed that the mitochondrial type of the Ice Man fits into the genetic variation of contemporary Europeans and that it was most closely related to mitochondrial types determined from central and northern European populations.

Animals↗
PubMed1994

Plasma brain natriuretic peptide in assessment of acute dyspnoea.

Recognition of heart failure (HF) may be difficult in patients presenting with acute dyspnoea, particularly in the presence of chronic airways obstruction. Since increased secretion of the cardiac hormones atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) occurs early in the course of HF, we have assessed the value of measuring these hormones in plasma in the diagnosis of suspected HF in 52 elderly patients presenting with acute dyspnoea, and compared values with left-ventricular ejection fraction (LVEF), a standard measure of left-ventricular function, by radionuclide angiography. Patients were enrolled prospectively. On the basis of clinical findings, conventional tests, and response to specific treatment, 20 of the 52 patients were classified as having primary lung disorder (PLD), 12 as HF alone, and 20 as HF with underlying PLD (HF/PLD). Compared with findings in PLD patients, LVEF was significantly depressed in HF and HF/PLD patients (p < 0.001), whereas both plasma ANP and BNP were significantly increased (p < 0.001). Admission plasma BNP concentration more accurately reflected the final diagnosis of HF (93% sensitivity and 90% specificity when BNP > or = 22 pmol/L) than LVEF or plasma ANP concentration. When all patients were considered together, there were strong negative correlations between LVEF and log BNP (r = -0.7, p < 0.001) and log ANP (r = -0.59, p < 0.001). Our finding that plasma BNP is raised in dyspnoeic patients with HF but not in acutely breathless patients with PLD, suggests that rapid BNP assays may assist in the diagnosis of patients with acute dyspnoea.

Acute Disease↗
PubMed1994

Interrater reliability of the Unified Parkinson's Disease Rating Scale motor examination.

Interrater reliability of the Unified Parkinson's Disease Rating Scale (UPDRS) motor examination was assessed by three neurologists experienced in the administration of this scale. Intraclass correlation coefficients indicated good-to-excellent agreement for speeded repeated movements, resting tremor, arising from a chair, and gait; moderate agreement for action tremor, rigidity, posture, postural stability, and bradykinesia; and poor agreement for speech disorder and facial immobility. Overall, these results indicate that satisfactory interrater reliability is attainable with the UPDRS motor examination.

Adult↗
PubMed1994

Reliability of symptom onset assessment in Parkinson's disease.

Test-retest reliability of onset date and type of initial symptoms of Parkinson's disease (PD) was assessed in 45 patients with PD who were drawn from a community-dwelling cohort in New York City. Patients were the sole information providers on both rating occasions. Reliability of symptom-onset data was found to be high, even when the interval between test and retest was up to 3 years and when the information was elicited by different neurologists. However, these patients were less consistent about the type of early symptoms. When interpreting their own disease history, patients with PD may attach more importance to when their disease began than to how it began.

Cohort Studies↗
PubMed1994

Assessing patient dependence in Alzheimer's disease.

BACKGROUND: While cognitive and functional deficits are the hallmark of Alzheimer's disease (AD), loss of social function (and the dependence this implies) is also critical, especially in early stages of disease. Little attention has been directed to this facet of dementing disease. We describe a scale for assessing dependency in AD and present a baseline profile of dependency in a cohort of AD patients. METHODS: In a study of the predictors of the course of AD, 233 patients in early stages of disease (modified MMS > or = 30) were assessed. Psychometric properties of the dependence scale were established. To validate the scale, dependence scores at baseline were correlated with a series of measures assessing cognition and function. The course of dependency over 18 months of follow-up was also analyzed. RESULTS: The scale shows adequate reliability (test-retest, intraclass correlation). Dependence stage was related to other measures of disease severity. Scalogram analysis shows that the dependence scale is consistent with the course of functional loss established for dementing disease. Prospective data indicate sensitivity of the scale to disease progression. CONCLUSION: Dependency is a distinct, measurable component of dementing disease and should be considered an important outcome in studies of AD.

Activities of Daily Living↗