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Biomedical subjects

M Muir

Publications and source records attributed to M Muir.

At least 19 recordsLinked to original sources
PubMed2005

Anti-tumour activity in non-small cell lung cancer models and toxicity profiles for novel ruthenium(II) based organo-metallic compounds.

Novel ruthenium(II) organo-metallic compounds are active in ovarian cancer models [Aird RE, Cummings J, Ritchie AA, Muir M, Morris RE, Chen H, et al. In vitro and in vivo activity and cross resistance profiles of novel ruthenium(II) organometallic arene complexes in human ovarian cancer. Br J Cancer 2002;86(10):1652-7]. [(eta6-C6H5C6H5)Ru(en)Cl]+ (as a PF6 salt, where en=ethylenediamine (RM175)) has been evaluated in a 13-cell line panel. Particular sensitivity (approximately 10-fold lower than mean IC50) was noted in breast cancer and non-small cell lung cancer cell lines. In addition, IC50 in the A549 was 2 microM and RM175 (25 mg kg-1, days 1 and 5, i.p.) caused a significant (p=0.004) growth delay in a xenograft model. HC11 [(eta6-tetrahydroanthracene)Ru(en)Cl]PF6 was more potent in the A549 cell line (IC50 0.5 microM). HC11 (25 mg kg-1, days 1, 8 and 15, i.p.) was also active in vivo. Following RM175 25 mg kg-1, days 1 and 5, and 15 mg kg-1, days 1-5, HC11 25 and 40 mg kg-1, day 1, elevated alanine transaminase levels were detected, suggesting hepatotoxicity. No changes were observed in kidney or haematological parameters. In liver sections, multi-focal hepatic necrosis was seen, becoming confluent at high doses of HC11. In vitro studies confirmed that HC11 was more toxic than RM175 to fresh human hepatocytes and equitoxic to mithramycin. Liver toxicity may be related to the arene ligand and modification may reduce the potential for hepatic toxicity, while maintaining the anti-tumour activity seen.

Alanine Transaminase↗
PubMed2002

In vitro and in vivo activity and cross resistance profiles of novel ruthenium (II) organometallic arene complexes in human ovarian cancer.

Ruthenium complexes offer the potential of reduced toxicity, a novel mechanism of action, non-cross resistance and a different spectrum of activity compared to platinum containing compounds. Thirteen novel ruthenium(II) organometallic arene complexes have been evaluated for activity (in vitro and in vivo) in models of human ovarian cancer, and cross-resistance profiles established in cisplatin and multi-drug-resistant variants. A broad range of IC50 values was obtained (0.5 to >100 microM) in A2780 parental cells with two compounds (RM175 and HC29) equipotent to carboplatin (6 microM), and the most active compound (HC11) equipotent to cisplatin (0.6 microM). Stable bi-dentate chelating ligands (ethylenediamine), a more hydrophobic arene ligand (tetrahydroanthracene) and a single ligand exchange centre (chloride) were associated with increased activity. None of the six active ruthenium(II) compounds were cross-resistant in the A2780cis cell line, demonstrated to be 10-fold resistant to cisplatin/carboplatin by a mechanism involving, at least in part, silencing of MLH1 protein expression via methylation. Varying degrees of cross-resistance were observed in the P-170 glycoprotein overexpressing multi-drug-resistant cell line 2780AD that could be reversed by co-treatment with verapamil. In vivo activity was established with RM175 in the A2780 xenograft together with non-cross-resistance in the A2780cis xenograft and a lack of activity in the 2780AD xenograft. High activity coupled to non cross-resistance in cisplatin resistant models merit further development of this novel group of anticancer compounds.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

A randomized controlled trial to prevent patient lift and transfer injuries of health care workers.

STUDY DESIGN: Randomized controlled trial (RCT). OBJECTIVES: To compare the effectiveness of training and equipment to reduce musculoskeletal injuries, increase comfort, and reduce physical demands on staff performing patient lifts and transfers at a large acute care hospital. SUMMARY OF BACKGROUND DATA: Back injury to nursing staff during patient handling tasks is a major issue in health care. The value of mechanical assistive devices in reducing injuries to these workers is unclear. METHODS: This three-armed RCT consisted of a "control arm," a "safe lifting" arm, and a "no strenuous lifting" arm. A medical, surgical, and rehabilitation ward were each randomly assigned to each arm. Both intervention arms received intensive training in back care, patient assessment, and handling techniques. Hence, the "safe lifting" arm used improved patient handling techniques using manual equipment, whereas the "no strenuous lifting" arm aimed to eliminate manual patient handling through use of additional mechanical and other assistive equipment. RESULTS: Frequency of manual patient handling tasks was significantly decreased on the "no strenuous lifting" arm. Self-perceived work fatigue, back and shoulder pain, safety, and frequency and intensity of physical discomfort associated with patient handling tasks were improved on both intervention arms, but staff on the mechanical equipment arm showed greater improvements. Musculoskeletal injury rates were not significantly altered. CONCLUSIONS: The "no strenuous lifting" program, which combined training with assured availability of mechanical and other assistive patient handling equipment, most effectively improved comfort with patient handling, decreased staff fatigue, and decreased physical demands. The fact that injury rates were not statistically significantly reduced may reflect the less sensitive nature of this indicator compared with the subjective indicators.

Back Injuries↗
PubMed2001

Oral health of patients with hepatitis C virus infection: a pilot study.

OBJECTIVES: This study examined the oral health of a cohort of hepatitis C virus (HCV) patients. In particular, the prevalence of lichen planus and xerostomia were determined. Experiences of discrimination against HCV-infected patients by their dentists were also recorded. METHODS: Forty patients infected with HCV, who were not undergoing anti-viral treatment, were examined. Patient information collected included demographic details together with patients' perception of their oral health and access to dental care since being diagnosed with hepatitis C. Both extra-oral and intra-oral examinations were conducted. Teeth present and visible caries were recorded, periodontal condition was measured using a Community Periodontal Index of Treatment Need (CPITN) probe and denture fit and hygiene were assessed where appropriate. The soft tissues were examined and lichen planus diagnosed clinically. Salivary flow rates were estimated by the Salivette system. RESULTS: The oral health of this cohort was poor. Eight patients had clinical evidence of oral lichen planus (OLP), although this was not confirmed histologically. The salivary flow rates were significantly lower (P < 0.001) than in previously reported healthy controls. Of the 15 (37.5%) regular dental attenders, two had encountered problems accessing dental care. CONCLUSIONS: Chronic hepatitis C patients have significant oral health needs. More effective oral health education is required for both HCV-infected patients and their carers, including dental practitioners.

Adult↗
PubMed2000

Dissociation of osmoregulation from plasma arginine vasopressin levels following thermal injury in childhood.

Although the syndrome of inappropriate anti-diuretic hormone secretion has been recognised as a complication associated with burn and other trauma in adults, relatively little is known about its incidence in children. The objective of this study was to investigate whether it is a complication associated with burn injury in children. Plasma and urine levels of arginine vasopressin (anti-diuretic hormone), sodium and osmolality were measured in samples collected from 16 burn-injured children admitted to the burns unit of the regional children's hospital. No significant correlations were found between plasma vasopressin and plasma sodium or osmolality levels, but there were significant correlations between plasma vasopressin and urine osmolality, 36 (r=0.74, p=0. 009), 60 (r=0.92, p=0.000) and 84 h (r=0.84, p=0.001) after admission, respectively. There were also significant correlations between plasma sodium and plasma osmolality, 24 (r=0.7, p=0.005), 36 (r=0.57, p=0.04) and 84 h (r=0.84, p=0.004) after admission. The data suggest dissociation between the osmolar control of vasopressin secretion and vasopressin levels after burn injury in children, but do not support the incidence of inappropriate secretion of antidiuretic hormone.

Arginine Vasopressin↗
PubMed1999

A high-density integrated genetic linkage and radiation hybrid map of the laboratory rat.

The laboratory rat (Rattus norvegicus) is a key animal model for biomedical research. However, the genetic infrastructure required for connecting phenotype and genotype in the rat is currently incomplete. Here, we report the construction and integration of two genomic maps: a dense genetic linkage map of the rat and the first radiation hybrid (RH) map of the rat. The genetic map was constructed in two F2 intercrosses (SHRSP x BN and FHH x ACI), containing a total of 4736 simple sequence length polymorphism (SSLP) markers. Allele sizes for 4328 of the genetic markers were characterized in 48 of the most commonly used inbred strains. The RH map is a lod >/= 3 framework map, including 983 SSLPs, thereby allowing integration with markers on various genetic maps and with markers mapped on the RH panel. Together, the maps provide an integrated reference to >3000 genes and ESTs and >8500 genetic markers (5211 of our SSLPs and >3500 SSLPs developed by other groups). [Bihoreau et al. (1997); James and Tanigami, RHdb (http:www.ebi.ac.uk/RHdb/index.html); Wilder (http://www.nih.gov/niams/scientific/ratgbase); Serikawa et al. (1992); RATMAP server (http://ratmap.gen.gu.se)] RH maps (v. 2.0) have been posted on our web sites at http://goliath.ifrc.mcw.edu/LGR/index.html or http://curatools.curagen.com/ratmap. Both web sites provide an RH mapping server where investigators can localize their own RH vectors relative to this map. The raw data have been deposited in the RHdb database. Taken together, these maps provide the basic tools for rat genomics. The RH map provides the means to rapidly localize genetic markers, genes, and ESTs within the rat genome. These maps provide the basic tools for rat genomics. They will facilitate studies of multifactorial disease and functional genomics, allow construction of physical maps, and provide a scaffold for both directed and large-scale sequencing efforts and comparative genomics in this important experimental organism.

Alleles↗
PubMed1998

Antitumour activity and schedule dependency of 8-chloroadenosine-3',5'-monophosphate (8-ClcAMP) against human tumour xenografts.

8-Chloroadenosine-3',5'-monophosphate (8-ClcAMP) is a novel antitumour agent currently undergoing phase I clinical trials in several European centres. In this study, its antitumour activity against human tumour xenografts and its dependence on schedule were investigated. When administered by continuous infusion at doses of 100 or 50 mg/kg/day to nude mice bearing human tumour xenografts, 8-ClcAMP inhibited the growth of the HT 29 colorectal, ZR-75-1 breast, HOX 60 and PE04 ovarian and PANC-1 pancreatic carcinoma xenografts. However, these infusion schedules produced hypercalcaemia and severe weight loss. In an attempt to optimise antitumour activity and minimise toxicity, several other schedules were studied. In comparison with continuous administration of 8-ClcAMP at 50 mg/kg/day for 14 days which, although producing complete growth inhibition in the HOX 60 model, was associated with a marked body weight loss, schedules in which the infusion was interrupted (infusion on either days 0-4; 7-11 or days 0-2; 6-8) produced minimal weight loss but also reduced antitumour activity. However, co-administration of salmon calcitonin with continuous infusion of 8-ClcAMP prevented both hypercalcaemia and body weight loss in 3/6 animals while still producing marked inhibition of tumour growth. These data indicate that 8-ClcAMP has broad-spectrum antitumour activity and the major side-effect of hypercalcaemia may at least in part be ameliorated by the use of salmon calcitonin.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

Five-year incidence and prediction of dementia and cognitive decline in a population sample of women aged 70-79 at baseline.

OBJECTIVE: To determine the incidence of dementia and cognitive decline and their predictors in a population sample. SETTINGS: A rural geographically defined population served by a single health centre. SAMPLE: 75% of the 70-74-year-old, 100% of the 75-79-year-old women registered with the practice. METHOD: Interview the total sample using an augmented version of CAMDEX, including informant interview, and reaction times at baseline and 5 years later. IQ was estimated at baseline only. RESULTS: 365 women were interviewed at baseline, 237 at follow-up. Incidence of dementia of all severities was 3.1% per annum (95% CI, 2.2-4.3). CAMCOG declined by 12.6 points in those who became demented, MMSE by 3 points. Observed, self-reported and informant-reported cognitive difficulty at baseline all predicted later incidence of dementia. The additional use of estimated IQ and reaction times did not increase the efficiency of either cross-sectional detection of dementia or prediction of dementia at 5 years. CONCLUSIONS: The incidence of dementia was in the range reported by other studies; slight cognitive decline was noted in the total population, increasing with age and marked in incident dementia. Of clinical importance was the finding that both the individuals and the informants of those who subsequently demented were aware of decline 5 years earlier. Simple and relatively easily administered cognitive tests were found to be the most efficient method of detection of dementia.

Aged↗
PubMed1997

Health promotion and early detection of cancer in older adults: needs assessment for program development.

The greatest risk factor for developing cancer is age, yet little is known about the cancer-related knowledge, attitudes and beliefs of the older adult (age > 55 years). A community-based needs assessment was conducted to understand these dimensions in a large metropolitan community. Ten focus groups (n = 158 older adults) and 9 individuals were interviewed. Content analysis for the audiotaped sessions was completed. The study participants focused on "being active" and living a healthy lifestyle. Many worried about illness interfering with their ability to do what they wanted to do. Many had had exposure to cancer through family members or friends, but still had many unanswered questions about cancer. Age was not seen as a risk factor for cancer, and a range of attitudes existed regarding cancer prevention and early detection. Overall, despite fearing cancer, participants thought older adults needed to know about cancer and suggested a wide range of approaches to disseminate information effectively to older adults.

Aged↗
PubMed1997

Health promotion and early detection of cancer in older adults: a practical approach.

Little is known about the cancer-related knowledge, attitudes and health behaviours of older adults (> 55 years), or about designing health promotion and early detection interventions responsive to their learning needs. A collaborative project was established with the intent of designing an appropriate program for older adults. The initial work included a community needs assessment using focus groups, one-on-one interviews and self-report surveys. The use of key community contacts was effective in locating older adult subjects (> 55 years) through pre-established linkages with agencies. Various ethnocultural groups, low income communities and isolated individuals, as well as other pre-established groups, were included in this study. The needs assessment found that: age is not perceived as a cancer risk factor; transportation is a barrier to screening; fear inhibits people from being screened; physicians are viewed as both the main source of expert cancer knowledge and as the gatekeepers to screening; family and peers are the main source of support, ethnospecific groups have different information needs; and finally, that lifestyle suggestions can reduce the risk of cancer. The findings indicated that community health promotion programs for older adults will require multiple approaches with a combination of strategies in order to meet their learning needs.

Aged↗
PubMed1995

Motorcycle accidents in Strathclyde Region, Scotland during 1992: a study of the injuries sustained.

The purpose of this study was to describe the pattern and severity of injury, among motorcyclists involved in RTAs, in Strathclyde Region, Scotland, during 1992. This information was required to provide insight into the nature of motorcycle accidents and their consequences, as well as to provide a basis for work on preventive measures. Ninety-six motorcyclist casualties were studied using police and medical information. Their injury information was coded according to AIS 90 and some descriptive statistics applied. Most of the casualties were young and most of them sustained more than one injury. Eight of the casualties died. The legs, arms, head and thorax were the body regions most commonly injured. Serious injury to one or both of the latter two regions, appeared to be implicated in the fatal outcomes. This study confirms that motorcycling is a 'high risk activity', and for those who wish to take that risk, protective measures of optimum standard should be regarded as priority.

Accidents, Traffic↗
PubMed1994

Growth inhibition of oestrogen receptor-positive human ovarian carcinoma by anti-oestrogens in vitro and in a xenograft model.

This paper presents results of the in vitro and in vivo effects of anti-oestrogens on the growth of human ovarian cancer cells. Tamoxifen and the "pure" anti-oestrogens, ICI 164,384 and ICI 182,780, inhibited the oestrogen-stimulated growth of the oestrogen receptor (ER)-positive PE04 and PE01 cell lines grown in culture, the latter two compounds being more potent than tamoxifen. In the absence of 17 beta-oestradiol (E2), tamoxifen, but not the pure anti-oestrogens, produced a small degree of growth stimulation in the PE01 and PE04 lines at concentrations between 10((7) and 10(-9) M. In contrast, growth of the ER-negative PE014 line was unaffected by E2 and all three anti-oestrogens. The effects of tamoxifen and ICI 182,780 on PE04 cells grown as xenografts in nude mice were also studied. Both anti-oestrogens produce significant growth inhibitory effects. These results indicate that ovarian carcinoma cells may be sensitive to anti-oestrogens in vitro and in vivo, and support the view that anti-oestrogens merit further clinical studies in patients with ER-positive tumours.

Adenocarcinoma↗
PubMed1992

Broad spectrum neuropeptide antagonists inhibit the growth of small cell lung cancer in vivo.

The proliferation of small cell lung cancer (SCLC) cells appears sustained by multiple autocrine and paracrine circuits involving Ca2+ mobilizing neuropeptides. Consequently, broad spectrum neuropeptide antagonists which inhibit SCLC growth in vitro have been suggested as potential anticancer agents. Here we evaluated this hypothesis using xenografts of WX322 cells, a SCLC cell line that responds to multiple Ca2+ mobilizing neuropeptides. The broad spectrum neuropeptide antagonists [Arg6,D-Trp7,9,MePhe8]substance P(6-11) and [D-Arg1,D-Phe5,Trp7,9Leu11[substance P were shown to inhibit the growth of WX322 xenografts in nude mice. Similar results were obtained with xenografts of the SCLC cell line H69. The results indicate that broad spectrum neuropeptide antagonists can inhibit the growth of SCLC in vivo and suggest that these antagonists could be useful in the treatment of SCLC.

Animals↗
PubMed1992

Seasonal and climatic variation in cholesterol and vitamin C: effect of vitamin C supplementation.

Vitamin C (ascorbic acid) is an important anti-oxidant which may help to reduce free radical damage and atheroma formation in blood vessels. In a study in which a group of healthy volunteer subjects were followed up for 12 months and a group of patients with vascular disease taking Vitamin C supplements were followed for 23 months, we confirmed previous findings of seasonal variations in ascorbic acid and cholesterol and have shown an inverse relationship between leucocyte ascorbic acid and serum cholesterol levels. In healthy control subjects the increase in ascorbate and fall in cholesterol during the summer months was reversed when the weather changed to a more winter pattern, presumably due to dietary alterations. We found that ascorbic acid levels were lower in patients with peripheral vascular disease and that although normal ascorbic acid levels were achieved with Vitamin C supplementation, when supplements were stopped at the height of a normal summer, there was a fall in ascorbic acid and a rise in serum cholesterol to winter levels. Given these findings we suggest that patients with vascular disease should have Vitamin C supplements throughout the year.

Adult↗
PubMed1992

Patient controlled analgesia: the relation of psychological factors to pain and analgesic use in adolescents with postoperative pain.

OBJECTIVE: To examine the relationship of psychological variables to pain and patient-controlled analgesia (PCA) use in adolescents undergoing orthopedic surgeries. DESIGN: Cohort. PATIENTS: Fifty adolescents and their parents. MAIN OUTCOME MEASURES: Visual analogue scales of pain, the McGill Pain Questionnaire, and questionnaires that assessed overall psychological distress, anxiety, and family environment. RESULTS: Correlations of the psychological variables with measures of pain and PCA use showed that high levels of anxiety and distress in adolescents were related to higher postoperative pain. Adolescents from controlling and conflicted families also had higher pain ratings and made more frequent PCA demands during the lockout interval when drug was unavailable. Parent anxiety and distress were also related to adolescent pain and PCA use. CONCLUSIONS: The psychological status of adolescents and their parents can significantly influence postoperative pain and PCA use.

Adolescent↗
PubMed1990

Patient-controlled analgesia in postoperative pain: the relation of psychological factors to pain and analgesic use.

The surgical experience is often characterized by fear, stress, and pain. Whenever an individual has to confront a painful or stressful event such as surgery, the individual's opportunity to control some aspect of the situation may actually influence the degree of pain experienced. Patient-controlled analgesia (PCA) is a relatively new method of analgesic administration that allows the postoperative patient to self-administer analgesic drug. The present study examined the relationship of psychological variables, including anxiety, depression, coping strategies, and social support, to pain and PCA use in a sample of 80 adults who underwent orthopaedic surgeries. Regression analyses controlling for age and type of opioid revealed that the psychological measures were important predictors of pain and PCA use. Patients with higher anxiety levels and less social support had higher postoperative pain and made more frequent PCA demands.

Age Factors↗
PubMed1986

Substrate specificity of the Escherichia coli maltodextrin transport system and its component proteins.

Maltooligosaccharides up to maltoheptaose are transported by the maltodextrin transport system of Escherichia coli. The overall substrate specificity of the transport system was investigated by using 15 maltodextrin analogues with various modifications at the reducing end of the oligosaccharides as competing substrates. The binding interaction of the analogues with maltoporin in the outer membrane and the periplasmic maltose-binding protein, the two protein components of the transport system with known specificity for maltodextrins, was also investigated. All analogues containing several alpha, 1----4-glucosyl linkages were bound with high affinity by maltoporin and maltose-binding protein, regardless of O-methyl, O-nitrophenyl, beta-glucosyl or beta-fructosyl substitutions at the reducing end of the dextrins. Introduction of a negative charge or lack of a ring structure at the reducing end were also ineffective in abolishing binding by these two proteins. These results suggest that the structure of the reducing glucose is not important in the binding specificity of maltoporin or maltose-binding protein. However, the high affinity of these proteins for analogues was not in itself sufficient for recognition by the transport system overall. Maltohexaitol, 4-nitrophenyl alpha-maltotetraoside and 4-beta-D-maltopentaosyl-D-glucopyranose were bound with the same affinity as comparable maltodextrins by both maltoporin and maltose-binding protein but were poorly recognized by the transport system. These results suggest that another, yet uninvestigated component of the transport system has a more restricted specificity towards changes at the reducing end of the maltodextrin molecule.

ATP-Binding Cassette Transporters↗