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Biomedical subjects

M Miller

Publications and source records attributed to M Miller.

At least 19 recordsLinked to original sources

Assessment of the relative skin sensitization potency of siloranes and bis-GMA using the local lymph node assay and QSAR predicted potency.

Siloranes are silicon and oxirane (epoxy) containing monomers used for new dental composite development. The siloranes 3,4-epoxycyclohexylethyl-cyclopolymethylsiloxane (Tet-Sil) and bis-3,4-epoxycyclohexylethyl-phenyl-methylsilane (Ph-Sil) have in common cycloaliphatic epoxy moieties. The epoxy group is of concern in their biocompatibility since most epoxy compounds are known skin sensitizers. The objective of this study was to determine the in vivo skin sensitization potency of the siloranes in the local lymph node assay. A comparison was made with well-known chemical allergens, bis-GMA and DNCB. Female mice (CBA/CaJ) were exposed topically (dorsum of both ears) to several doses of acetone:olive oil in the ratio of 4:1 v/v. Doses were defined by a predictive structure-activity model (QSAR) for contact sensitization. Lymph node cell (LNC) proliferation was measured on the sixth day by incorporation of radioactive thymidine into DNA of lymph node cells. The effective concentration (EC3) that produced a 3-fold stimulation in LNC proliferation relative to controls was extrapolated from dose-response curves. DNCB was a strong sensitizer (EC3 = 0.06%). The EC3 values of Ph-Sil and bis-GMA were 19% and 45%, respectively, making these weak contact sensitizers. Tet-Sil did not increase lymph node proliferation when compared with controls. In contrast to Tet-Sil, the unpolymerized monomers Ph-Sil and bis-GMA have the capacity to induce LNC proliferation, characteristic of a T-cell mediated skin contact sensitization.

Animals↗

Utilising handheld computers to monitor and support patients receiving chemotherapy: results of a UK-based feasibility study.

GOALS OF WORK: Recent changes in cancer service provision mean that many patients spend a limited time in hospital and therefore experience and must cope with and manage treatment-related side effects at home. Information technology can provide innovative solutions in promoting patient care through information provision, enhancing communication, monitoring treatment-related side effects and promoting self-care. PATIENTS AND METHODS: The aim of this feasibility study was to evaluate the acceptability of using handheld computers as a symptom assessment and management tool for patients receiving chemotherapy for cancer. A convenience sample of patients (n = 18) and health professionals (n = 9) at one Scottish cancer centre was recruited. Patients used the handheld computer to record and send daily symptom reports to the cancer centre and receive instant, tailored symptom management advice during two treatment cycles. Both patients' and health professionals' perceptions of the handheld computer system were evaluated at baseline and at the end of the project. MAIN RESULTS: Patients believed the handheld computer had improved their symptom management and felt comfortable in using it. The health professionals also found the handheld computer to be helpful in assessing and managing patients' symptoms. CONCLUSIONS: This project suggests that a handheld-computer-based symptom management tool is feasible and acceptable to both patients and health professionals in complementing the care of patients receiving chemotherapy.

Adult↗

Non-hyperinsulinemic hypoglycemia in a patient with a gastrointestinal stromal tumor.

One of the authors (JvD) recently reported a case of non-islet cell tumor hypoglycemia caused by the production of "big" IGF-II by a gastrointestinal stromal tumor (GIST). Here, we report a patient with a GIST in whom non-hyperinsulinemic hypoglycemia was not attributable to aberrant tumoral IGF-II processing, but instead was caused by a combination of cachexia, renal and hepatic dysfunction, and tumoral glucose consumption.

Journal Article↗

Improving the health of Indigenous Australians: reforms in nursing education. An opinion piece of international interest.

AIM: This paper overviews Indigenous disadvantage in relatively wealthy Australia. It describes efforts to increase the recruitment and retention of Indigenous people in nursing and to reform nursing education to be more inclusive of Indigenous culture, health and history. BACKGROUND: Indigenous people on average die 17 years younger than non-Indigenous people and have health problems similar to those of people in some underdeveloped countries. Moreover, social injustice and human rights issues affect their health and well-being and educational opportunities. They are under-represented in the health professions, including nursing, often through a lack of educational preparation and historical, socio-economic and cultural factors hindering them from entering and succeeding in university studies. METHODS: In 2000, a project was funded by the Australian commonwealth government and led by the Indigenous Nursing Education Working Group. This Group worked for five years on a wide range of methods that included consultation within the profession, information dissemination and longitudinal surveying of university schools of nursing and Indigenous support units. RESULTS: Findings show that collaborative efforts between key stakeholders in nursing education appear to be succeeding to increase the numbers of Indigenous students of nursing. Around two-thirds of schools of nursing now include Indigenous content in their undergraduate curricula, but the majority is yet to provide Indigenous cultural awareness/cultural safety training for faculty.

Attitude to Health↗

Voluntary activation and central activation failure in the knee extensors in young women and men.

Quadriceps muscle weakness is common after knee injuries. This weakness is caused, in part, by reduced voluntary activation (VA) because of central activation failure (CAF). Superimposed electrical stimulation techniques are used to assess VA and to detect CAF. The aim of this study was to assess VA during knee extension in young healthy women and men, and to evaluate subjective discomfort from the electrical stimulation. The quadriceps muscle in six young healthy women (mean age 22 years) and six young healthy men (mean age 29 years) was stimulated during maximal voluntary contractions using a 100 Hz pulse train. Data were collected from two test sessions separated by 6-8 days and each session comprised of two trials. A visual analog scale for pain (VAS-pain) was used to evaluate subjective discomfort. Overall, young healthy, moderately active men and women did have the ability to fully activate their knee extensors isometrically, but they did not achieve full activation on every trial. In those trials where a CAF was detected, the degree was small (mean less than 2%), and did not vary between the two test sessions. Subjective discomfort was generally moderate and tolerable (mean VAS-pain score 35 mm). These results will assist the clinical assessment of muscle weakness following a knee injury and facilitate the design and evaluation of appropriate rehabilitation interventions.

Adult↗

The association between changes in household firearm ownership and rates of suicide in the United States, 1981-2002.

OBJECTIVE: To explore whether recent declines in household firearm prevalence in the United States were associated with changes in rates of suicide for men, women, and children. METHODS: This time series study compares changes in suicide rates to changes in household firearm prevalence, 1981-2002. Multivariate analyses adjust for age, unemployment, per capita alcohol consumption, and poverty. Regional fixed effects controlled for cross sectional, time invariant differences among the four census regions. Standard errors of parameter estimates are adjusted to account for serial autocorrelation of observations over time. RESULTS: Over the 22 year study period household firearm ownership rates declined across all four regions. In multivariate analyses, each 10% decline in household firearm ownership was associated with significant declines in rates of firearm suicide, 4.2% (95% CI 2.3% to 6.1%) and overall suicide, 2.5% (95% CI 1.4% to 3.6%). Changes in non-firearm suicide were not associated with changes in firearm ownership. The magnitude of the association between changes in household firearm ownership and changes in rates of firearm and overall suicide was greatest for children: for each 10% decline in the percentage of households with firearms and children, the rate of firearm suicide among children 0-19 years of age dropped 8.3% (95% CI 6.1% to 10.5%) and the rate of overall suicide dropped 4.1% (2.3% to 5.9%). CONCLUSION: Changes in household firearm ownership over time are associated with significant changes in rates of suicide for men, women, and children. These findings suggest that reducing availability to firearms in the home may save lives, especially among youth.

Adolescent↗

The effect of simvastatin on triglyceride-rich lipoproteins in patients with type 2 diabetic dyslipidemia: a SILHOUETTE trial sub-study.

OBJECTIVE: To determine if simvastatin effectively decreases the elevated levels of triglyceride (TG), TG-rich lipoproteins, and small, dense LDL particles, which are characteristic of diabetic dyslipidemia. RESEARCH DESIGN AND METHODS: We conducted a prespecified analysis from a double-blind, placebo-controlled, randomized, 6-week crossover trial in patients with type 2 diabetes and low HDL-C (< 40 mg/dL). Each patient was randomized to 1 of 6 possible treatment arms; each patient received simvastatin 80 mg, simvastatin 40 mg, and placebo over 3 periods. We used the validated vertical auto profile (VAP) method to directly assess TG-rich lipoproteins and LDL subclasses. We assessed the efficacy of simvastatin to improve the lipoprotein profile in adult men (71%) and women (29%) (n = 151) with stable type 2 diabetes (HbA1C < 9%), LDL-C > 100 mg/dL, HDL-C < 40 mg/dL, and fasting TG level > 150 and < 700 mg/dL (median = 273 mg/dL). MAIN OUTCOME MEASURES: Percentage change from baseline in IDL and VLDL (TG-rich lipoproteins), LDL subclasses, and additional lipoproteins at the end of each 6-week treatment interval; percentage of patients who reached NCEP ATP III non-HDL goal of < 130 mg/dL by the end of each 6-week period. RESULTS: Both simvastatin 80 mg and 40 mg significantly reduced VLDL-C, VLDL3, and IDL, as well as the four LDL subclasses measured with VAP, compared with placebo. Simvastatin 80 mg, compared with simvastatin 40 mg, provided additional efficacy. With simvastatin 80 mg, 77.2% of patients not at their non-HDL-C goal of < 130 mg/dL at study baseline reached goal, compared with 65.7% following simvastatin 40 mg treatment, and 2.2% following placebo. CONCLUSIONS: Treatment with simvastatin effectively reduced the elevated levels of TG-rich lipoproteins and improved LDL composition in patients with type 2 diabetes. A large percentage of these patients attained the NCEP ATP III non-HDL-C goal of < 130 mg/dL, which demonstrates the improvement of the atherogenic profile in these patients.

Aged↗

A comparison of MicroCog and the Wechsler Memory Scale (3rd ed.) in older adults.

In recent years, computerized assessment of cognitive functions such as memory has increased in popularity. Here we contrast the performance of 33 community-dwelling older adults (mean age 71.2 years, SD = 7.62) on the computer-based MicroCog with the conventional Wechsler Memory Scale-3rd Edition (WMS-III). Participants were screened for possible depression using the Geriatric Depression Scale and completed both memory tests in counterbalanced order. WMS-III General Memory correlated moderately with both the MicroCog Memory index and the General Cognitive Functioning index. Correlations between the visual memory measures of the 2 tests were not statistically significant. Agreement between the tests on the classification of participants as lying within the average, below average, or above average ranges was fair at best. We conclude that the correspondence between the 2 measures is not sufficient to substitute 1 for the other for clinical decision making as to the memory functioning of older adults.

Aged↗

The dimerization of SnCl2(g): mass spectrometric and theoretical studies.

The vaporization of SnCl2(s) was investigated in the temperature range between 382 and 504 K by the use of Knudsen effusion mass spectrometry. The Sn+, SnCl+, SnCl2+, Sn2Cl3+, and Sn2Cl4+ ions were detected in the mass spectrum of the equilibrium vapor. The SnCl2(g) and Sn2Cl4(g) gaseous species were identified, and their partial pressures were determined. The structure and vibrational properties of both species and corresponding fragmentation products were studied applying density functional theory and second-order Møller-Plesset perturbation theoretical approaches. Molecular parameters yielded thermodynamic functions by the use of statistical thermodynamics. The sublimation enthalpies of SnCl2(g) and Sn2Cl4(g) at 298 K resulting from the second- and third-law methods are evaluated as 130.9 +/- 6.2 kJ mol(-1) and 155.8 +/- 7.3 kJ mol(-1), respectively. The enthalpy changes of the dissociation reactions Sn2Cl4(g) = 2 SnCl2(g) were obtained as delta(d)H degrees(298) = 106.8 +/- 6.2 kJ mol(-1). The corresponding theoretical value amounts to 103.4 kJ mol(-1). The change of monomer properties due to the dimerization reaction is also discussed.

Journal Article↗

Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia.

Activating mutations in RAS and receptor tyrosine kinases such as KIT and FLT3 are hypothesized to cooperate with chimeric transcription factors in the pathogenesis of acute myeloid leukemia (AML). To test this hypothesis, we genotyped 150 pediatric AML samples for mutations in KIT (exons 8, 17), NRAS and KRAS (exons 1, 2) and FLT3/ITD. This is the largest cohort of pediatric AML patients reported thus far screened for all four mutations. Of the children with AML, 40% had a mutation in KIT (11.3%), RAS (18%) or FLT3/ITD (11.1%), and 70% of cases of core-binding factor (CBF) leukemia were associated with a mutation of KIT or RAS. Mutations in RAS or FLT3/ITD were frequently found in association with a normal karyotype. Patients with a FLT3/ITD mutation had a significantly worse clinical outcome. However, the presence of a KIT or RAS mutation did not significantly influence clinical outcome. We demonstrate that KIT exon 8 mutations result in constitutive ligand-independent kinase activation that can be inhibited by clinically relevant concentrations of imatinib. Our results demonstrate that abnormalities of signal transduction pathways are frequent in pediatric AML. Future clinical studies are needed to determine whether selective targeting of these abnormalities will improve treatment results.

Acute Disease↗

Amelotin--a Novel Secreted, Ameloblast-specific Protein.

We aimed to analyze the differential gene expression in various murine dental tissues, expecting to find novel factors that are involved in tooth formation. We here describe the identification of a novel ameloblast-specific gene, amelotin (AMTN), by differential display polymerase chain-reaction (DD-PCR) analysis of microdissected ameloblasts, odontoblasts, dental pulp, and alveolar bone cells of 10-day-old mouse incisors. The conceptually translated protein sequence was unique and showed significant homology only with its human orthologue. The amelotin genes from mouse and human displayed a similar exon-intron structure and were expressed from loci on chromosomes 5 and 4, respectively, which have been associated with various forms of amelogenesis imperfecta. Expression of amelotin mRNA was restricted to maturation-stage ameloblasts in developing murine molars and incisors. Amelotin protein was efficiently secreted from transfected cells in culture. Taken together, our findings suggest that amelotin is a novel factor produced by ameloblasts that plays a critical role in the formation of dental enamel.

Alveolar Process↗

Pancreatic cancer--is an aggressive approach justified?

INTRODUCTION: Surgery is the only curative treatment for carcinoma of the pancreas. Resection rates can be low (4.5%), figures of 30% have also been suggested as possible. The approach undertaken in this unit is to consider all patients as potentially resectable unless otherwise proven. PATIENTS & METHODS: 140 patients were studied over 6-year period; 113 underwent palliative treatment (48% distant metastases, 40% local spread, 11% high operative risk); 14 had a triple bypass (14/113 = 12%), 99 were managed conservatively, 43 received palliative chemotherapy. 23/140 (16%) underwent Whipple's procedure (n = 23; 12 females, 11 males; mean age, 60 years); 4/23 had chronic pancreatitis. Distal pancreatectomy was undertaken in 4 patients. RESULTS: Median survival time for patients undergoing a triple bypass was 5 months (range, 0.1-20 months), 3 months for patients treated conservatively (range, 0.1-30 months) and 5 months for patients undergoing palliative chemotherapy (range, 1-30 months). 30-day mortality for Whipple's procedure was 4% (1/23) with median survival rate for patients with carcinoma of 13 months (range, 5-66 months); 31 months for patients with clear resection margins and negative nodes (n = 5). CONCLUSION: This policy allows a resection rate of 19% with increased median survival rate for patients with cancer by 8 months more than those who where not resected. Aggressive staging and pancreatic biopsies allow patients to be entered into chemotherapy trials with improvement in survival and potential future benefits.

Aged↗

Gastric glassy cells: a study of 3202 gastrectomy specimens from dwellers of the Atlantic and Pacific basins.

Fifteen years ago we detected gastric cells with glassy cytoplasm (GCs) in the human pyloric antrum. The frequency of these cells was subsequently investigated in sections from gastrectomies carried on in populations dwelling on the rim of the Atlantic and Pacific basins. In this work we compared the results obtained in these disparate geographic regions. We reviewed sections from 3203 gastrectomies (1942 in the Atlantic basin and 1261 in the Pacific basin). In the Atlantic basin 12/1942 (0.6%) of the gastrectomies had GCs, whereas in the Pacific basin 26/1261 (2.1%) of the gastrectomies had GCs. The difference was significant (p<0.05). The proportion of gastrectomies with GCs was higher in patients in Vancouver, Canada, than in New York, and higher in Santiago de Chile than in Buenos Aires, despite the fact that these populations reside at approximately the same geographic latitude. Previous studies with the same material indicated that both the extension of intestinal metaplasia and the frequency of ciliated metaplasia were significantly higher in the Pacific than in the Atlantic basin. Hence, the difference in the frequencies of GCs appears to be a new indication that dissimilar environmental exposures in the two basins might have influenced the histological make-up of the gastric mucosa.

Aged↗

Cardiovascular risk factors and probability for cardiovascular events in HIV-infected patients - part III: age differences.

OBJECTIVE: In recent years, concerns have been growing about an elevated rate of cardiovascular diseases in HIV-infected patients due to side effects of antiretroviral therapy. The present study analyses the cardiovascular risk profile and the probability of cardiovascular events with regard to the age of HIV-infected patients. METHODS: Cardiovascular risk factors of 309 HIV-infected adults were analysed. Patients were divided into four groups: 18-30 years (group 1), 31-40 years (group 2), 41-50 years (group 3), > 50 years (group 4). Overall 10-years probability for cardiovascular events was evaluated by the Framingham algorithm. RESULTS: Differences between the groups were detected in cardiovascular risk factors including changes in lipid- and glucose metabolism. Lipid values increased with elevated age, such as total cholesterol concentration (Mean +/- SEM in group 1 vs. group 4: 4.71 +/- 0.20 to 6.36 +/- 0.21 mmol/L, p < 0.05), LDL-cholesterol concentration (2.86 +/- 0.17 vs. 4.17 +/- 0.21 mmol/L, p < 0.05) and triglyceride concentration (1.56 +/- 0.14 vs. 3.48 +/- 0.40 mmol/L, p < 0.05). HDL-cholesterol concentration did not show a significant difference (1.15 +/- 0.03 mmol/L). Glucose concentration increased with elevated age in HIV-infected patients (5.28 +/- 0.19 vs. 6.46 +/- 0.24 mmHg, p < 0.05), but there was no significant difference in HbA1c - concentration, blood pressure and smoking rate between the groups. The overall 10-years probability for cardiovascular events was higher in group 1 (median: 1.9%) than in group 4 (20.5%; p < 0.01). CONCLUSIONS: The risk of cardiovascular events is related to the age in HIV-infected patients. Therefore, an increased duration of life due to a more effective antiretroviral therapy will have a significant impact on the rate of cardiovascular events in this patient population. In the future, further increase of cardiovascular events in HIV-infected patients may be expected.

Adolescent↗

Perceptions of older people with cancer of information, decision making and treatment: a systematic review of selected literature.

BACKGROUND: Several studies have identified inadequacies in the care and treatment received by older patients with cancer, as opposed to their younger counterparts. These include over or under diagnosis, ineffective symptom management and lower survival rates in older people with cancer. Despite these inadequacies, there is a lack of evidence of older peoples' perspectives regarding their cancer diagnosis and treatment. MATERIALS AND METHODS: Studies for review were identified from systematic searches of literature published between January 1990 and November 2003, using PubMed, CINAHL and PsycINFO. Studies were selected for inclusion by using a number of criteria (i.e. date and language of publication, age of participants and thematic area). The aims of the review were to summarize and evaluate previous evidence on the views of older patients with cancer, regarding information, decision making and treatment. RESULTS: Eighteen studies of various methodologies met the criteria of the present review. In summary, older people with cancer are generally content with the information they receive, but not entirely satisfied with the quantity and quality of care and contact. They present with various needs, which are not always well met. Finally, they wish to be kept informed of their cancer diagnosis and treatment progress, but often do not wish to be told about progression of their illness and length of survival. CONCLUSIONS: Previous research has suffered a number of limitations regarding sampling procedures and methods of data collection. Other limitations included lack of consideration of the heterogeneity of older people with cancer and lack of a well-defined theoretical framework to guide design and data analysis. These may compromise not only rigour and the ability to generalize findings, but also the provision of patient-focused care. The difficulties of doing research in this area are also discussed and suggestions for future research are made.

Aged↗

Chemotherapy-related nausea and vomiting - past reflections, present practice and future management.

Although much progress has occurred in the last decade regarding the management of chemotherapy-induced nausea and vomiting, these remain among the most intolerable side-effects of treatment and patients continue to report the negative impact such symptoms have on their ability to enjoy life. Inadequate control of nausea and vomiting reduces patients' quality of life and functional status and jeopardizes the delivery of optimal treatment, so making its management a priority for oncology health care workers. This article will reflect on past and present evidence regarding the management of chemotherapy-induced nausea and vomiting while highlighting some of the most recent scientific advances before drawing conclusions about the future management of this troublesome symptom for patients receiving chemotherapy.

Aged↗

Outpatient rehabilitative treatment of chronic fatigue syndrome (CFS/ME).

AIMS: To assess the outcome of outpatient multidisciplinary rehabilitative treatment (graded activities/exercise programme, family sessions, and supportive care) compared with supportive care alone for children and adolescents with chronic fatigue syndrome (CFS/ME). METHODS: Fifty six young people (aged 9-17 years) with CFS/ME by standard criteria were followed up for 3-24 months. All subjects received supportive care. Families additionally opted to either enter the rehabilitation programme (supportive care plus graded activities/exercise programme and family sessions) or have no additional treatment. RESULTS: Twenty two (39%) subjects had supportive care alone and 26 (46%) entered the programme. Treatment groups were comparable at baseline in terms of age, severity and duration of illness, Wellness score, and school attendance. At end of follow up, those in the programme group had significantly higher Wellness score and school attendance than those having supportive care alone. The programme significantly reduced the overall severity of illness: after the programme, 43% had complete resolution of CFS/ME compared to only 4.5% of those having supportive care alone. The presence of depressed mood and family beliefs about the aetiology of CFS/ME were not significantly associated with outcomes. CONCLUSIONS: Outpatient rehabilitative treatment offers significant potential to improve the prognosis of CFS/ME in childhood and adolescence.

Adolescent↗