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Biomedical subjects

C Miller

Publications and source records attributed to C Miller.

At least 37 records · Page 2Linked to original sources
PubMed2003

Assessing health impact assessment: multidisciplinary and international perspectives.

Health impact assessment (HIA) seeks to expand evaluation of policy and programmes in all sectors, both private and public, to include their impact on population health. While the idea that the public's health is affected by a broad array of social and economic policies is not new and dates back well over two centuries, what is new is the notion-increasingly adopted by major health institutions, such as the World Health Organisation (WHO) and the United Kingdom National Health Services (NHS)-that health should be an explicit consideration when evaluating all public policies. In this article, it is argued that while HIA has the potential to enhance recognition of societal determinants of health and of intersectoral responsibility for health, its pitfalls warrant critical attention. Greater clarity is required regarding criteria for initiating, conducting, and completing HIA, including rules pertaining to decision making, enforcement, compliance, plus paying for their conduct. Critical debate over the promise, process, and pitfalls of HIA needs to be informed by multiple disciplines and perspectives from diverse people and regions of the world.

Evidence-Based Medicine↗
PubMed2003

Are district general hospital patients with unstable angina at a disadvantage?

OBJECTIVE: To determine whether patients with non-ST elevation acute coronary syndromes requiring coronary angiography and revascularisation have inferior access to these services if admitted to district general hospitals (DGHs) compared with similar patients admitted to a base hospital containing a tertiary cardiac centre. DESIGN: Prospective, consecutive monitoring of all patients with acute coronary syndromes accepted by the tertiary cardiac centre for angiography and revascularisation over a three month period (1 April to 30 June 2002). PARTICIPANTS: All patients accepted for angiography from DGHs and from within the base hospital with a diagnosis of acute coronary syndromes. SETTING: Tertiary cardiac facility (Manchester Heart Centre at Manchester Royal Infirmary (MRI)). MAIN OUTCOME MEASURE: Time waited from referral to angiography and revascularisation. RESULTS: A total of 184 patients with a diagnosis of non-ST elevation acute coronary syndromes underwent angiography with a view to revascularisation. Of these, 89 (48%) were admitted initially to MRI and 95 (52%) were admitted to a feeder DGH. DGH patients waited significantly longer from admission to angiography than MRI patients (median 13 days (25th-75th percentiles 7-19) v 5 days (3-8) respectively; p<0.0005). DGH patients therefore also waited longer from admission to revascularisation (15 days (6-20) v 6 days (3-9) respectively). Once transferred into the Manchester Heart Centre, DGH patients underwent angiography within a median of 1 day (1-2). More DGH patients than those from MRI underwent both coronary artery bypass grafting (21 (22%) v 8 (9%) respectively; p=0.015) and percutaneous coronary intervention (44 (46%) v 32 (36%) respectively; p=NS). CONCLUSION: Patients admitted to feeder DGHs with non-ST elevation acute coronary syndromes wait significantly longer for access to invasive coronary assessment and revascularisation than similar patients admitted in the hospital that incorporates the tertiary cardiac centre. This inequity of access is determined by postcode rather than clinical priority.

Adult↗
PubMed2003

Screening for multiple sclerosis cognitive impairment using a self-administered 15-item questionnaire.

Since there is a need for cost-effective screening techniques to identify neuropsychological impairment in multiple sclerosis (MS) patients, and because existing methods require cognitive testing with subsequent interpretation by a neuropsychologist, a brief self-report procedure was developed to screen for neuropsychological impairment in MS. In the first phase of the study, a pool of 80 items was generated based on a literature review and consultation with healthcare professionals. The set was reduced to 15 via Rasch analysis. Using these items, a brief (five minute) MS Neuropsychological Screening Questionnaire (MSNQ), including patient- and informant-report forms, was composed. In phase II, 50 MS patients and their caregivers completed the MSNQ. A comprehensive neuropsychological test battery was also administered. Analyses covered the reliability of the MSNQ and correlations between both patient- and informant-report scores and objective neuropsychological testing. Cronbach's alpha coefficients were 0.93 and 0.94 for the patient- and informant-report forms, respectively, and both forms of the test were strongly correlated with a more general cognitive complaints questionnaire. The patient MSNQ form correlated significantly with measures of depression but not with objective tests of cognitive function. In contrast, the informant form was correlated with patient cognitive performance but not depression. A cut-off score of 27 on the informant form of the MSNQ optimally separated patients based on a neuropsychological summary score encompassing measures of processing speed and memory. There were two false-negatives and one false-positive, giving the test a sensitivity of 0.83 and a specificity of 0.97. It is concluded, therefore, that this self-administered neuropsychological screening test is reliable and predicts neuropsychological impairment in MS patients with a reasonable degree of accuracy.

Adult↗
PubMed2003

[Living donor liver transplantation, adult to adult].

AIM: Since living donor liver transplantation (LDLT) can offer a viable response to the lack of transplantable cadaveric organs, our center instituted an LDLT program in 2001. METHODS: The authors report their experience with the first 35 LDLT procedures successfully completed at the Liver and Multiorgan Transplant Center of the University of Modena between 9 May 2001 and 21 May 2003. The case series comprised 35 patients, 7 of which received a left-half liver and 1 a left lobe. RESULTS: The global survival rate was 77.2% (27 out of 35 patients), with a mean follow-up period of 295 days; the survival rate at 1 year was 81%. In 4 cases (11%) retransplantation was performed. The donor demographics are described; all donors returned to their normal activities before transplantation, after a mean follow-up period of 373 days. No intraoperative complications were experienced by the donors, whereas during the postoperative period, 2 donors (5.7%) developed major complications (1 biliary fistula on the cut surface, 1 stenosis of the main bile duct). CONCLUSION: Our study shows that LDLT can be safely completed in the donor, with good results achieved in the recipient as well. Underlying these results is the accurate pretransplant assessment that continued into the operation itself. Even more important was the demonstrated ability and experience of the surgical team to attain results in the donor which we believe are necessary for carrying forth a LDLT program.

Adolescent↗
PubMed2002

Viremia and immunogenicity in nonhuman primates of a tetravalent yellow fever-dengue chimeric vaccine: genetic reconstructions, dose adjustment, and antibody responses against wild-type dengue virus isolates.

Chimeric yellow fever (YF)-dengue (DEN) viruses (ChimeriVax-DEN) were reconstructed to correct amino acid substitutions within the envelope genes of original constructs described by Guirakhoo et al. (2001, J. Virol. 75, 7290-7304). Viruses were analyzed and compared to the previous constructs containing mutations in terms of their growth kinetics in Vero cells, neurovirulence in mice, and immunogenicity in monkeys as monovalent or tetravalent formulations. All chimeras grew to high titers [ approximately 7 to 8 log(10), plaque-forming units (PFU)/ml] in Vero cells and were less neurovirulent than YF 17D vaccine in mice. For monkey experiments, the dose of DEN2 chimera was lowered to 3 log(10) PFU in the tetravalent mixture in an effort to reduce its dominant immunogenicity. The magnitude of viremia in ChimeriVax-DEN immunized monkeys was similar to that of YF-VAX, but significantly lower than those induced by wild-type DEN viruses. All monkeys developed high levels of neutralizing antibodies against homologous (chimeras) or heterologous (wild-type DEN viruses isolated from different geographical regions) viruses after a single dose of monovalent or tetravalent vaccine. Administration of a second dose of tetravalent vaccine 2 months later increased titers to both homologous and heterologous viruses. A dose adjustment for dengue 2 chimera resulted in a more balanced response against dengue 1, 2, and 3 viruses, but a somewhat higher response against chimeric dengue 4 virus. This indicates that further formulations for dose adjustments need to be tested in monkeys to identify an optimal formulation for humans.

Amino Acid Substitution↗
PubMed2002

Utility of clinical criteria in differentiating frontotemporal lobar degeneration (FTLD) from AD.

OBJECTIVE: To assess the ability of the current diagnostic criteria for frontotemporal lobar degeneration (FTLD) to differentiate FTLD from AD. METHODS: Thirty cases with autopsy-proven FTLD and 30 cases of AD, matched for Mini-Mental State Examination score, were identified from the clinical databases of three dementia subspecialty centers, and their charts were reviewed for the presence of clinical features described in the current criteria for FTLD. The proportion of patients with each clinical feature at the first clinical presentation was compared across groups. RESULTS: A significantly larger proportion of patients with FTLD showed behavioral abnormalities, particularly social and personal conduct disorders and emotional blunting, than patients with AD. Few differences in language features were seen between the groups, and many of the language features detailed in the criteria were found in only a small proportion of patients. In both groups, many patients showed neuropsychological abnormalities, except for perceptual difficulties, which were present in many patients with AD but only in a few patients with FTLD. Extrapyramidal motor symptoms were more likely to be present in FTLD. Logistic regression revealed that five features-social conduct disorders, hyperorality, akinesia, absence of amnesia, and the absence of a perceptual disorder-correctly classified 93% of patients with FTLD and 97% of patients with AD. CONCLUSION: A combination of behavioral, neuropsychological, and physical findings is most useful in distinguishing FTLD from AD. Future studies should be directed at establishing more objective methods of identifying these clinical features.

Aged↗
PubMed2002

Microsatellite DNA and recent statistical methods in wildlife conservation management: applications in Alpine ibex [Capra ibex(ibex)].

We evaluated the usefulness of microsatellites and recently developed statistical methods for the conservation management of fragmented and reintroduced populations, using the alpine ibex (Capra ibex) as a model species. First, we assessed the effects of past reintroduction programmes on genetic diversity and population differentiation considering different population sizes and histories. We show that genetic variability in ibex populations (HE 0.13) is among the lowest reported from microsatellites in mammal species, and that the Alpi Marittime-Mercantour population has suffered from a severe genetic bottleneck associated with its reintroduction. Second, using a computer-simulation approach, we provide examples and rough guidelines for translocation programmes concerning the number and origin of individuals for future reintroductions and for the reinforcement of populations with low genetic variability. Finally, we use the ibex microsatellite data to assess the usefulness of several published statistical tests for detecting population bottlenecks and assigning individuals to their population of origin. This study illustrates that microsatellites allow: (i) evaluation of alternative translocation scenarios by simulating different numbers and origins of migrants; (ii) identification of bottlenecked populations (especially using the Wilcoxon signed-ranks test); and (iii) population assignment with a high certainty (P < 0.001) of almost 100 of the individuals (or trophies or carcasses) from two distant populations (especially using stucture or whichrun software).

Animals↗
PubMed2002

Mutations in the factor V, prothrombin and MTHFR genes are not risk factors for recurrent fetal loss.

OBJECTIVE: Recurrent fetal loss, defined as the occurrence of three or more consecutive spontaneous abortions regardless of previous live birth, is a condition that affects about 2% of all reproductive-aged women. The role of gene mutations in recurrent pregnancy loss is not fully understood. The present research examined the relationship between factor V Leiden, factor V HR2, prothrombin G20210A and MTHFR and recurrent fetal loss in a case-control study. METHODS: Women aged 22-45 with a history of three or more fetal losses, being seen at a perinatal medicine clinic in New Jersey or Georgia, were eligible as cases. Overall, the study consisted of 60 women with three or more fetal losses and 92 women with at least one successful pregnancy. RESULTS: Factor V HR2 and MTHFR were not related to recurrent fetal loss. The prothrombin G20210A mutation appeared to confer an elevation in risk but the association was based upon small numbers and was not statistically significant (OR 4.8, 95% CI 0.50-47.2). Cases were 90% less likely to have the factor V Leiden mutation than controls (OR 0.10, 95% CI 0.01-0.81). CONCLUSIONS: Our study did not demonstrate that women who are carriers of the factor V, prothrombin, or MTHFR mutations are at higher risk of recurrent fetal loss than women without these mutations. In regards to factor V Leiden, the prevalence in our cases (1.7%) was not statistically different from the known population prevalence of 5%. However, the high prevalence in our controls (14%) was unusual. Factor V Leiden may protect against bleeding in early pregnancy.

Abortion, Habitual↗
PubMed2001

See potassium run.

Explore the source record for details and available documents.

Cell Membrane↗
PubMed2001

Modulation of dopamine uptake in rat nucleus accumbens: effect of specific dopamine receptor antagonists and sigma ligands.

The ability of dopamine (DA) antagonists and sigma receptor ligands to alter [(3)H]-DA uptake was examined using synaptosomes prepared from the nucleus accumbens of female rats. Pre-incubation with compounds having a high affinity for sigma (rimcazole, haloperidol, and spiperone) receptors produced dose dependent inhibition of (3)H-DA uptake. Sulpiride, a pure DA D(2) antagonist had no effect. In contrast, DA uptake was potentiated in response to (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine, a mixed sigma receptor antagonist and DA D(2) receptor agonist. Similarly, SKF-10,047, a selective sigma receptor agonist, and progesterone, a putative endogenous ligand for the sigma receptor, produced significant increases in (3)[H]-DA uptake. These data suggest a potential role for sigma and DA ligands in the regulation of DA uptake in the nucleus accumbens.

Animals↗
PubMed2001

In vivo gene expression revealed by cDNA arrays: the pattern in relapsing-remitting multiple sclerosis patients compared with normal subjects.

OBJECTIVES: To use DNA arrays to identify differences in gene expression associated with relapsing-remitting (RR) MS. METHODS: Total RNA was isolated from monocyte depleted peripheral blood mononuclear cells of 15 RR MS patients and 15 age- and sex-matched controls. The RNA was reverse transcribed to radiolabeled cDNA and the resultant cDNA was used to probe a DNA array containing over 4000 named human genes. The binding of radiolabeled cDNA to the probes on the array was measured by phosphorimager. RESULTS: Of more than 4000 genes tested, only 34 were significantly different in RR-MS patients from controls. Of these, 25 were significantly increased and 9 significantly decreased in the RR MS patients. Twelve of these genes have inflammatory and/or immunological functions that could be relevant to the MS disease process. The potentially relevant genes that were elevated (15% to 28%) were P protein, LCK, cAMP responsive element modulator, IL-7 receptor, matrix metalloproteinase-19, M130 antigen, and peptidyl-prolyl isomerase. Those that were significantly decreased (15% to 35%) were SAS transmembrane 4 superfamily protein, STRL22 (C-C chemokine receptor 6), AFX protein, DNA fragmentation factor-45 and immunoglobulin gamma 3 (Gm marker). CONCLUSIONS: The RR-MS disease effect was relatively restricted and most of the mRNAs tested were not different from the normal controls. However, there were significant differences identified in the expression of a subset of mRNAs, including 13 with inflammatory/immune functions that could be relevant to MS. The systematic use of DNA arrays can provide insight into the dynamic cellular pathways involved in MS pathogenesis and its phenotypic heterogeneity.

Adult↗
PubMed2001

Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation.

PURPOSE: To explore the relationship between oral mucositis and selected clinical and economic outcomes in blood and marrow transplant patients. PATIENTS AND METHODS: Subjects consisted of 92 transplant patients from eight centers who participated in a multinational pilot study of a new oral mucositis scoring system (Oral Mucositis Assessment Scale [OMAS]). In the pilot study, patients were evaluated for erythema and ulceration/pseudomembrane formation beginning on the first day of conditioning and continuing for 28 days. We examined the relationship between patients' peak OMAS scores and days with fever (body temperature > 38.0 degrees C), the occurrence of significant infection, days of total parenteral nutrition (TPN), and days of injectable narcotic therapy (all over 28 days), days in hospital (over 60 days), total hospital charges for the index admission, and vital status at 100 days. RESULTS: Patients' peak OMAS scores spanned the full range of possible values (0 to 5) and were significantly (P <.05) correlated with all of the outcomes of interest except days with fever (P =.21). In analyses controlling for type of graft (autologous v allogeneic) and study center, a 1-point increase in peak OMAS score was associated with (1) 1.0 additional day with fever (P <.01), (2) a 2.1-fold increase in risk of significant infection (P <.01), (3) 2.7 additional days of TPN (P <.0001), (4) 2.6 additional days of injectable narcotic therapy (P <.0001), (5) 2.6 additional days in hospital (P <.01), (6) $25,405 in additional hospital charges (P <.0001), and (7) a 3.9-fold increase in 100-day mortality risk (P <.01). Mean hospital charges were $42,749 higher among patients with evidence of ulceration compared with those without (P =.06). CONCLUSION: Oral mucositis is associated with significantly worse clinical and economic outcomes in blood and marrow transplantation.

Adult↗
PubMed2001

Insights into a plasma membrane signature.

The plasma membrane (PM) is an organized biological system that serves as a structural barrier and communication interface with the extracellular environment. Many basic questions regarding the PM as a system remain unanswered. In particular, we do not understand the scope of similarity and differences in protein expression at the PM. This study takes an initial step toward addressing these questions by comparing the PM proteomes of fibroblasts and mammary carcinoma cells. Three sets of proteins were revealed by the study. The first set comprises between 9 and 23% of all proteins at the PM and appears to be common to both fibroblasts and mammary carcinoma. A second group of proteins, comprising approximately 40% of the proteins at the PM, is tightly linked to cell lineage. The third set of proteins is unique to each cell line and is independent of cell lineage. It is reasonable to hypothesize then, that this third group of proteins is responsible for unique aspects of cell behavior. In an effort to find proteins linked to the metastatic phenotype, we identified several proteins that are uniquely expressed at the PM of the metastatic MDA-MB-435 cells. These proteins have functions ranging from cell adhesion to the regulation of translation and the control of oxidant stress.

Breast Neoplasms↗
PubMed2001

Projection structure of a ClC-type chloride channel at 6.5 A resolution.

Virtually all cells in all eukaryotic organisms express ion channels of the ClC type, the only known molecular family of chloride-ion-selective channels. The diversity of ClC channels highlights the multitude and range of functions served by gated chloride-ion conduction in biological membranes, such as controlling electrical excitability in skeletal muscle, maintaining systemic blood pressure, acidifying endosomal compartments, and regulating electrical responses of GABA (gamma-aminobutyric acid)-containing interneurons in the central nervous system. Previously, we expressed and purified a prokaryotic ClC channel homologue. Here we report the formation of two-dimensional crystals of this ClC channel protein reconstituted into phospholipid bilayer membranes. Cryo-electron microscopic analysis of these crystals yields a projection structure at 6.5 A resolution, which shows off-axis water-filled pores within the dimeric channel complex.

Chloride Channels↗
PubMed2001

Association of SV40 with human tumours.

SV40 was discovered as a contaminant of poliovirus vaccines that were inadvertently administered to millions of people in Europe and the United States between 1955 and 1963. Shortly afterwards, SV40 was proven to be oncogenic in rodents and capable of transforming human and animal cells in vitro. The possibility that SV40 might cause tumours in humans thus became a subject of scientific and public interest and scrutiny. However, largely due to a lack of significant epidemiological evidence, interest in assessing SV40's potential carcinogenic role in humans diminished. Recently, many laboratories have reported the presence of SV40-like DNA in a high proportion of human mesotheliomas, ependymomas and osteosarcoma (the three main types of tumours caused by virus in hamsters), renewing the question whether SV40 might be a human tumour virus. Molecular data from these studies are reviewed to re-evaluate the potential role of SV40 as a human carcinogen.

Animals↗