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Biomedical subjects

M Richards

Publications and source records attributed to M Richards.

At least 109 records · Page 6Linked to original sources
PubMed1998

Bone regeneration and fracture healing. Experience with distraction osteogenesis model.

The relation between physical forces and the processes of bone regeneration and healing remains incompletely understood. Gaps in understanding of these processes stem in part from models that produce inadequate amounts of new bone for study. Bone created through the use of distraction osteogenesis provides an attractive substrate for the study of mechanical forces and their effects on bone formation because this technique produces large volumes of new bone in a controlled fashion. The optimal mechanical environment in which bone formation occurs clinically has not been fully determined. In laboratory studies, however, the mechanical environment can be manipulated, and resultant changes in bone formation can be measured. To investigate how changes in strain environment influence patterns of bone formation, a bilateral New Zealand White rabbit model of bilateral distraction osteogensis was implemented. When a stiffener was applied to the external distractor, computation analyses predicted a sevenfold to eightfold decrease in all strain measures. These reductions in gap strains appeared to induce significant decreases in bone volume fraction and mean trabecular thickness. When osteotomies were created at a 30 degrees angle to the bony axis to generate more shear within the gap tissue, changes in the distribution of gap strains and resultant new bone architecture were observed. Specific correlations between changes in tissue level strains and the pattern of bone regeneration were seen in both experiments. These results provide direct in vivo evidence that pluripotential gap tissues are sensitive to their physical surroundings. Mechanisms responsible for this sensitivity might include vascularity, stem cell supply, and scaffolding architecture. The process of bone formation in distraction osteogenesis appears to be related to bone formation processes associated with more common conditions. The distraction osteogenesis model described suggests a mechanism for bone formation that seems applicable to other more common processes associated with bone formation, including fracture healing and impaired fracture healing.

Adult↗
PubMed1997

Activation of neurotensin receptors and purinoceptors in human colonic adenocarcinoma cells detected with the microphysiometer.

Activation of endogenous neurotensin (NT) receptors and P2-purinoceptors expressed by human colonic adenocarcinoma HT-29 cells increased extracellular acidification rates that were detected in the microphysiometer. NT (pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu), NT[8-13] (Arg-Arg-Pro-Tyr-Ile-Leu), NT[9-13] (Arg-Pro-Tyr-Ile-Leu), and NT1 (N alpha methyl-Arg-Lys-Pro-Trp-Tle-Leu [Tle = tert-leucine]) were full agonists, whereas XL 775 (N-[N-[2-[3-[[6-amino-1-oxo-2-[[(phenylmethoxy)carbonyl]-amino]hex yl]amino]phenyl]-3-(4-hydroxyphenyl)-1-oxo-2-propenyl]-L-isoleucyl]-L-le ucine) was a partial agonist for activating NT receptors expressed by HT-29 cells. Desensitization induced by NT was rapid and monophasic with 85% of the initial response lost by a 30-s exposure. Once initiated, the rate and extent of desensitization were similar for different concentrations of a given agonist, for agonists of different potencies, and for agonists of different efficacies, which suggests that desensitization may be independent of receptor occupancy or agonist efficacy. Resensitization was a much slower process, requiring 60 min before the full agonist response to NT was recovered. ATP, via P2-purinoceptors, also activated cellular acidification rates in a concentration-dependent manner. ATP induced a biphasic desensitization of purinoceptors with a loss of ca. 50% of the initial stimulation detectable between 30 and 90 s of exposure to the agonist. Desensitization of NT receptors did not influence the activation of P2-purinoceptors by ATP, suggesting there was no heterologous desensitization between the two types of receptors. Superfusion with NT receptor agonists for 15 min at concentrations that did not elicit changes in extracellular acidification rates blocked, in a concentration-dependent manner, the agonist response induced by 100 nM NT. This may reflect sequestration of the receptor. These results suggest that the high agonist affinity state of NT receptors may modulate receptor sequestration, whereas activation of the low agonist affinity state may be linked to cellular metabolism. Comparison of our results with published data found differences as well as similarities of NT responses among three lines of HT-29 cells.

Adenosine Triphosphate↗
PubMed1997

Development of a high-performance capillary isoelectric focusing technique with application to studies of microheterogeneity in chicken conalbumin.

A robust, simple, reproducible isoelectric focusing method using capillary electrophoresis that exhibits high stability, migration time reproducibility and pH linearity over a wide pH gradient was developed. Consecutive runs (over 113 runs) of several proteins and one peptide with isoelectric points (p/s) ranging from 9.45 to 2.75 yielded excellent migration time reproducibility (< 2% R.S.D.). Experimental parameters including buffer aging and capillary-to-capillary variation were thoroughly examined and optimized to improve the migration time reproducibility. The capillary isoelectric focusing (CIEF) method was applied to the analysis of chicken conalbumin (ovotransferrin), an iron-binding protein in egg white. Conalbumin (low iron content) separated into three major components with p/s of 7.2, 6.6 and 6.2. When the protein was saturated with iron (2 Fe/mol), a shift to lower p/s was detected. Chicken serum transferrin subjected to CIEF gave a pattern similar to conalbumin with three p/s of 7.1, 6.6 and 6.1, indicating that it was not fully saturated with iron. Thus, CIEF can be used as a potential analytical method to provide information about the metal-binding properties of specific metalloproteins.

Animals↗
PubMed1997

Trabecular bone adaptation to variations in porous-coated implant topology.

Trabecular bone adaptation adjacent to porous-coated platen implants embedded within canine distal femoral metaphyses was evaluated following 24 weeks of daily compressive loading. The in vivo experimental model delivered controlled loads to five different platen implant topologies with variations in platen shape and porous coating distribution. Adaptive changes were evaluated based on three-dimensional stereological analyses of trabecular bone architecture underneath each platen and non-destructive mechanical tests of platen construct stiffness. Fully coated cylindrical platen designs possessed the highest construct stiffness in both tension and compression. Changes in local trabecular bone morphology were also found to be significantly influenced by platen implant topology. Cylindrical platens with fully coated bottom surfaces were associated with greater decreases in trabecular bone volume and connectivity than cylindrical platens with smooth bottom surfaces or fully coated conical platens. Comparisons to site-matched contralateral control bone volumes across all platen designs indicated significant decreases in the average bone volume fraction, trabecular plate number, and connectivity within experimental samples, but no change in trabecular plate thickness. In addition, analyses of microstructural anisotropy revealed a 20 degrees or 20.2 degrees trabecular reorientation towards the axis of loading in experimental tissue. This study demonstrates that trabecular bone adaptation near porous-coated surfaces is influenced by variations in local implant topology and provides insight into specific mechanisms of implant-mediated microstructural adaptation.

Analysis of Variance↗
PubMed1997

gamma-Interferon inhibits secretin-induced choleresis and cholangiocyte proliferation in a murine model of cirrhosis.

BACKGROUND/AIMS: Cholangiocyte proliferation is associated with increased secretin receptor gene expression and secretin-induced choleresis. Since gamma-interferon has antiproliferative effects, we tested the hypothesis that gamma-interferon inhibits ductal proliferation and secretin-stimulated choleresis associated with cirrhosis. METHODS: Mice were treated with 0.1 ml of 25% carbon tetrachloride intraperitoneally twice weekly and 5% alcohol in drinking water for 12 weeks to induce cirrhosis and subsequently gamma-interferon 10(5) intramuscularly was administered daily for 10 weeks. We measured the effects of carbon tetrachloride and gamma-interferon on liver collagen content by morphometric analysis and hydroxyproline content. We measured the effects of gamma-interferon on ductal mass by morphometry and on ductal secretion by assessment of secretin receptor gene expression and secretin-induced choleresis. RESULTS: Compared to controls, there was an increase in liver hydroxyproline content of carbon tetrachloride-treated mice with histologic evidence of cirrhosis. Gamma-interferon treatment significantly decreased collagen liver content with loss of histologic features of cirrhosis. Morphometry revealed an increased number of bile ducts in cirrhotic mice as compared to controls or cirrhotics who received gamma-interferon. Secretin receptor mRNA levels were higher in cirrhotic mice compared to controls but this increase was inhibited by gamma-interferon. Secretin stimulated ductal secretion in cirrhotic mice but not control or cirrhotic mice who received gamma-interferon. CONCLUSIONS: We have established a murine model for cirrhosis and have shown, consistent with our hypothesis, that gamma-interferon decreases collagen content, ductal mass and secretin-induced choleresis incirrhotic mice.

Animals↗
PubMed1997

The effects of divorce and separation on mental health in a national UK birth cohort.

BACKGROUND: Many studies have reported a negative impact of divorce and separation on health although it is still unclear to what extent this is due to early vulnerability, the material and social consequences of divorce or to its direct emotional effects. METHOD: Measures of anxiety and depression and potential alcohol abuse at age 43 were compared in 2085 participants from the MRC National Survey of Health and Development who were either married and never divorced or separated, or who had divorced or separated at least once. Analyses were adjusted for sociodemographic features, early vulnerability factors and current stressors. RESULTS: Divorce and separation were associated with increased anxiety and depression, and increased risk of alcohol abuse. This was the case after adjusting for educational attainment, age at first marriage, parental divorce, childhood aggression and neuroticism, and current financial hardship, lack of a confidante and frequency of social contact with friends or family. The association between divorce and risk of alcohol abuse became non-significant when the latter variable was controlled for. Associations between divorce and psychopathology were observed even though half of those separated or divorced were re-married or reunited with their spouses at the time of the analysis. There was, furthermore, no association between these mental health measures and time since first separation or divorce.

Adult↗
PubMed1997

Inequalities in breast cancer care and outcome.

Comparisons across Europe suggest that survival from breast cancer is less good in the United Kingdom than in many countries. The care given in some UK breast cancer units is exemplary. However, it is difficult to escape the conclusion that a substantial number of women who present with breast cancer receive suboptimal care. Cancer registry-based studies have clearly demonstrated variations between surgeons and between hospitals in the management of early breast cancer. Although variations in surgical practice per se may have little impact on survival, there is evidence that differences in the use of systemic adjuvant therapy influence outcome. Five-year survival seems to be greater in women treated by surgeons seeing more than 30-50 new cases of breast cancer each year. This may be because such patients are more likely to be treated by a multidisciplinary team and to receive adjuvant therapy. Proposals that would increase the overall quality of breast cancer care and remove current inequalities must be carefully considered and should then be implemented.

Breast Neoplasms↗
PubMed1997

Mitochondrial footprints of human expansions in Africa.

mtDNA studies support an African origin for modern Eurasians, but expansion events within Africa have not previously been investigated. We have therefore analyzed 407 mtDNA control-region sequences from 13 African ethnic groups. A number of sequences (13%) were highly divergent and coalesced on the "mitochondrial Eve" in Africans. The remaining sequences also ultimately coalesced on this sequence but fell into four major clusters whose starlike phylogenies testify to demographic expansions. The oldest of these African expansions dates to approximately 60,000-80,000 years ago. Eurasian sequences are derived from essentially one sequence within this ancient cluster, even though a diverse mitochondrial pool was present in Africa at the time.

Africa South of the Sahara↗
PubMed1997

Is there any evidence for a protective effect of antithrombotic medication on cognitive function in men at risk of cardiovascular disease? Some preliminary findings.

To explore whether antithrombotic medication may protect against cognitive decline, tests of verbal memory, attention, abstract reasoning, verbal fluency, and mental flexibility were administered to 405 men at risk of cardiovascular disease. These subjects were a subgroup of those who had been participating in a randomised double blind factorial trial of low dose aspirin (75 mg daily) and low intensity oral anticoagulation with warfarin (international normalised ratio of 1.5) at 35 general practices across the United Kingdom for at least five years, were at least 55 years old at trial entry, and had been randomly allocated to one of four groups: active warfarin and active aspirin, active warfarin and placebo aspirin, placebo warfarin and active aspirin, and double placebo. Verbal fluency and mental flexibility were significantly better in subjects taking antithrombotic medication than in subjects taking placebo. Aspirin may have contributed more than warfarin to any beneficial effect. These results provide tentative evidence that antithrombotic medication may protect cognitive function in men at risk of cardiovascular disease.

Aged↗
PubMed1996

Three's a crowd.

Where do patients' rising expectations fit into the purchaser/provider relationship? John Spiers, Harry Burns and Michael Richards look at this question from a patient, purchase, and provider perspective.

Health Care Rationing↗
PubMed1996

Cyclin D1 and prognosis in human breast cancer.

We have used immunohistochemical staining to assess the expression of cyclin D1 in formalin-fixed sections of 345 breast carcinomas, dating back 20 years. Clinical follow-up data were available on all patients. Approximately 50% of the tumours showed excessive nuclear staining for cyclin D1 as compared with normal epithelium. Some tumours showed strong cytoplasmic staining in the absence of nuclear staining, and around 25% of the tumours were judged to be negative for nuclear cyclin D1. Contrary to expectations, moderate/strong staining for cyclin D1 was associated with improved relapse-free and overall survival relative to patients whose tumours stained weakly or negatively. Conversely, tumours that were considered negative for cyclin D1 staining had an adverse prognosis, and the poor outcome was further accentuated if the tumours were also oestrogen receptor-negative. A possible explanation for our findings is that tumours in which cyclin D1 levels are abnormally low may have sustained mutations in other genes, such as RBI and that it is this abnormality that has the more significant impact on survival from breast cancer.

Adult↗
PubMed1996

Relative effects of wound healing and mechanical stimulus on early bone response to porous-coated implants.

We hypothesized that early bone adaptation to well fixed porous-coated implants is influenced more by wound healing than by mechanical loading. To test this hypothesis, two groups of dogs with identical, hydraulically controlled porous-coated implants interference fit within distal femoral trabecular bone were used. One group had no load: the other had 35 N of load applied to the implants. At 5 weeks after surgery, the resulting adaptation of bone around the implants was quantified on a cellular basis by cytochemical analysis of type-I procollagen synthesis and on a structural basis using three-dimensional micro-computed tomography imaging. The percentage of trabecular surfaces covered by osteoblasts expressing type-I procollagen was significantly increased in bone surrounding the implant in both groups compared with contralateral control bone tissue. There was no difference between the groups with no load or 35 N of load. In addition, measures of trabecular bone structure did not differ significantly between the load and no-load groups. Taken together, these results suggest that wound healing plays a much greater role in the early response of bone to well fixed porous-coated implants than does mechanical stimulus.

Animals↗
PubMed1996

Physiological responses to repeated endotoxin challenge are selectively affected by recombinant bovine somatotropin administration to calves.

The study determined 1) whether the pretreatment of calves with recombinant bovine somatotropin (bST, sometribove) would alter the change in packed cell volume (PCV), rectal temperature (RT), and the plasma concentrations of Ca2+, Fe2+, glucose (G), urea N (PUN), nonesterified free fatty acids (NEFA), albumin (ALB), and blood cell populations after endotoxin challenge (EC) and 2) whether the natural development of physiologic tolerance to repeated EC was affected by bST. Twelve steer beef calves were assigned to either control (-bST) or +bST treatment in equal numbers. Calves were injected intramuscularly with either HCO3(-)-buffered saline or bST (0.1 mg/kg) daily for 5 d. On Day 6, the first EC was administered (Escherichia coli, 055:B5, 0.2 microgram/kg, intravenous bolus in pyrogen-free saline). Saline or bST injections were continued from Day 7 up to the repeat of EC on Day 11. RT and PCV were measured hourly through 12 and 6 hr, respectively. Jugular blood was obtained at 0, +1, 2, 3, 4, 6, 8, 12, and 24 hr relative to each EC. bST had no effect on the increase in RT, the hyperglycemic phase of the G response, the biphasic change in Fe2+, or increases in NEFA and PUN. PCV increased after each EC only in -bST. The mean decrease in G during the hypoglycemic phase was less in +bST. Hypocalcemic responses were significantly less in +bST. ALB concentrations decreased after each challenge; the response was unaffected by bST. CD2+, CD4+, and CD8+ T-lymphocyte populations were unaffected by bST and EC. Overall, the magnitude of change in all plasma variables was less after the second EC compared with the first, either in terms of magnitude or duration. The data suggest that the treatment of calves with bST diminishes the magnitude of hypoglycemic, hypocalcemic, and PCV changes after EC and does not compromise fever response, changes in blood cell populations, or tolerance to repeated EC.

Animals↗
PubMed1996

Can the computerized physical examination differentiate normal subjects from abnormal subjects with benign mechanical low back pain?

Inconsistencies among physicians in the evaluation of benign low back conditions make standardization desirable. A computerized physical examination device was used to evaluate low back pain patients and compare their results with a normative database obtained from a selection of healthy subjects. A high-resolution motion analysis system tracked the movement of skin markers placed on the midline and pelvis. Surface electromyography electrodes placed above L(5) collected data from multifidus. From the kinematics of skin markers during flexion extension with lifts up to 32 kg, and lateral bending with lifts up to 4.6 kg, the following parameters were estimated: lumbosacral angle and elongation, contribution of each lumbar segment to the lordosis reduction, relative pelvic/spine motion and trunk velocity. First, the average normal value for each estimated parameter was determined using 40 normal subjects. For each subject, the difference between his parameter and the normal was processed by an expert system generating a normality index varying from zero (perfect abnormal) to one (perfect normal). To develop the expert system's rules, a preliminary group of 20 very abnormal subjects were used, such that the normality index separated them from the normals. For validation, a set of 29 WCB sprain patients and another set of 42 discogram positive were selected. Each subject was tested and his computerized normality index calculated without any clinicians' input. The computerized normality index was compared with the clinicians' evaluation which was taken to be the gold standard. The Receiver Operating Characteristic technique was used to quantify the discrepancies. Results show that the expert system can detect clinically abnormal subjects with accuracy (sensitivity 83-91% and specificity >/=90%) while providing quantitative information on workers' functional capacities.

Journal Article↗
PubMed1996

Lay understanding of genetics: a test of a hypothesis.

There have been growing calls for more education in genetics for the public and in schools. However, studies of the public, school children, and those who have received genetic counselling show that understanding of scientific genetics is very limited. A hypothesis to explain this limited understanding is proposed and tested. It is argued that there is a widespread lay knowledge of inheritance which conflicts in a number of aspects with scientific explanations and which impedes the assimilation of the latter. It is suggested that this lay knowledge is derived from concepts of the social relationships of kinship. Concepts of kinship ties are sustained by everyday social activities and relationships which may make them resistant to change. A prediction which follows from the hypothesis that the lay understanding of genetics is derived from concepts of family and kinship relationships is that closeness in genetic terms will be determined by the closeness of the family ties of social relationship and social obligation. While the proportion of genes shared with parents, children, and sibs is, on average, the same, kin relationships and obligations are much stronger between parents and children than between sibs. The hypothesis was tested in a questionnaire study of two samples of adult women (n = 64 and n = 113) and one of social science students (n = 73). In all three groups a higher proportion of subjects gave the correct response for the proportion of shared genes with a father and child than with a sister, uncle, or grandmother. In the cases of sisters and uncle (and grandmother), there was a consistent tendency to underestimate the degree of genetic connection as predicted by the hypothesis. Answers to other questions are consistent with the hypothesis. The fundamental implications of the hypothesis for genetic education in the clinic and classroom are outlined.

Adult↗
PubMed1996

Family history and perceived vulnerability to some common diseases: a study of young people and their parents.

During the last two decades, health promotion has concentrated on lifestyle factors. However, recent research in genetics has shown that inherited susceptibility may be important in many common conditions. This raises questions about how these two different messages are integrated into people's beliefs about their own susceptibility. We report a study based on interviews with 58 young people, who had all recently completed the National Curriculum science course including basic human genetics, and 54 of their parents. We aimed to examine the extent to which people take account of family history when considering their susceptibility to health risks, with comparisons being made between generations, gender, and between different diseases. Family health histories were compared between generations and the relationship between reported family history and perceived vulnerability was examined. Family health history was seen as more relevant for a perceived vulnerability to heart disease and diabetes than cancer, while actions and behaviour were seen as important in determining the chance of developing heart disease and cancer but less so for diabetes. Chance was seen as an important factor in the risk of cancer and diabetes, but was barely mentioned in connection with heart disease. Nearly half of those who reported affected family members with heart disease or cancer did not perceive this to have any effect on their own susceptibility. Notably, women were much more likely than men to see the presence or absence of affected relatives as being relevant to the chances of developing cancer. Differences were found between generations in the reporting of the family tree and in knowledge of health of family members. Although words such as genes, chromosomes, and DNA were used by both generations there was no evidence of any understanding of the process of inheritance in scientific terms.

Adolescent↗
PubMed1996

Parkinson's disease in populations of African origin: a review.

Several studies have reported a lower prevalence of Parkinson's disease (PD) in populations of African origin than in populations of European origin, raising the possibility that the former are protected against PD. However, the confounding effects of low case ascertainment and high selective mortality on PD prevalence estimates in populations of African origin cannot be ruled out at this time. One hypothesis consistent with available data is that populations of African origin are vulnerable to vascular parkinsonism, which is associated with high mortality.

Africa↗