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Biomedical subjects

J A Smith

Publications and source records attributed to J A Smith.

At least 19 recordsLinked to original sources

The association between body size, prostate volume and prostate-specific antigen.

Increasing prostate volume contributes to urinary tract symptoms and may obscure prostate cancer detection. We investigated the association between obesity and prostate volume, prostate-specific antigen (PSA) and PSA density among 753 men referred for prostate biopsy. Among men with a negative biopsy, prostate volume significantly increased approximately 25% from the lowest to highest body mass index (BMI), waist or hip circumference or height categories. PSA was 0.7 ng/ml lower with a high waist-to-hip ratio. These associations were less consistent among subjects diagnosed with high-grade prostatic intraepithelial neoplasia or cancer. Our data suggest that obesity and height are independently associated with prostate volume..

Abdomen↗

Application of a quantum cascade laser for time-resolved, in situ probing of CH4/H2 and C2H2/H2 gas mixtures during microwave plasma enhanced chemical vapor deposition of diamond.

First illustrations of the utility of pulsed quantum cascade lasers for in situ probing of the chemistry prevailing in microwave plasma activated hydrocarbon/Ar/H2 gas mixtures used for diamond thin film growth are reported. CH4 and C2H2 molecules, and their interconversion, have been monitored by line-of-sight single pass absorption methods, as a function of process conditions (e.g., choice of input hydrocarbon (CH4 or C2H2), hydrocarbon mole fraction, total gas pressure, and applied microwave power). The observed trends can be rationalized, qualitatively, within the framework of the previously reported modeling of the gas-phase chemistry prevailing in hot filament activated hydrocarbon/H2 gas mixtures (Ashfold et al. Phys. Chem. Chem. Phys. 2001, 3, 3471). Column densities of vibrationally excited C2H2(v5=1) molecules at low input carbon fractions are shown to be far higher than expected on the basis of local thermodynamic equilibrium. The presence of vibrationally excited C2H2 molecules (C2H2(double dagger)) can be attributed to the exothermicity of the C2H3 + H <==> C2H2 + H2 elementary reaction within the overall multistep CH4 --> C2H2 conversion. Diagnostic methods that sample just C2H2(v=0) molecules thus run the risk of underestimating total C2H2 column densities in hydrocarbon/H2 mixtures operated under conditions where the production rate of C2H2(double dagger) molecules exceeds their vibrational relaxation (and thermal equilibration) rates.

Journal Article↗

Objective measurement of cough during pulmonary exacerbations in adults with cystic fibrosis.

BACKGROUND: Little is known about cough frequency in adults with cystic fibrosis (CF). This study aimed to determine (1) daytime and overnight cough rates in patients with CF at the beginning and end of a course of antibiotics for treatment of an exacerbation; (2) the relationship between cough frequencies and standard clinical measures of disease; and (3) the relationship between objective cough rates and the subjective assessment of cough. METHODS: Nineteen adult patients admitted with a pulmonary exacerbation performed daytime and overnight sound recordings on admission; 13 had repeat recordings prior to discharge. Coughs were manually quantified in cough seconds (time spent coughing). Patients subjectively scored their cough using a visual analogue scale (VAS) and numerical score. Lung function, C-reactive protein (CRP) levels, and sputum weights were recorded. RESULTS: Cough rates fell substantially with treatment; median fall in cough rate was 51.3% (IQR 32.3-77.5) (p<0.001) for daytime and 72.2% (28.6-90.1) (p = 0.049) for overnight. Multivariate regression analyses showed that forced expiratory volume in 1 second and CRP levels predicted overnight cough rates on admission. On discharge, sputum volume predicted daytime cough rates. Only the change in overnight VAS correlated with the change in objective cough rates. CONCLUSIONS: The cough rate significantly decreases with treatment of a pulmonary exacerbation in adults with CF. Lung function, sputum volume, and CRP influences the cough rate, with the effects differing from day to night and between admission and discharge. Subjective reporting of a nocturnal cough may indicate a pulmonary exacerbation of CF in adults.

Adult↗

The personal experience of juvenile Huntington's disease: an interpretative phenomenological analysis of parents' accounts of the primary features of a rare genetic condition.

There has been a paucity of research into the psychosocial impact of juvenile Huntington's disease (JHD) on the child and the family. The study reported here is part of larger project that aimed to address this and investigate the social and health care needs of those affected by JHD. Ten semistructured interviews with the main caregiver(s) were carried out and were analyzed using the qualitative methodology interpretative phenomenological analysis. The main themes arising from the analysis are reported here: first becoming aware something is wrong; physical symptoms; speech and communication difficulties; behavioral problems; a slow but relentless process. These are discussed in relation to extant literature. We hope the article will be helpful to clinicians working with families where a child is affected by JHD and also contribute to the general literature on understanding symptoms in childhood illness.

Adolescent↗

Assessing the welfare of genetically altered mice.

In 2003, under the auspices of the main UK funders of biological and biomedical research, a working group was established with a remit to review potential welfare issues for genetically altered (GA) mice, to summarize current practice, and to recommend contemporary best practice for welfare assessments. The working group has produced a report which makes practical recommendations for GA mouse welfare assessment and dissemination of welfare information between establishments using a 'mouse passport'. The report can be found at www.nc3rs.org.uk/GAmice and www.lal.org.uk/gaa and includes templates for the recommended welfare assessment scheme and the mouse passport. An overview is provided below.

Animal Husbandry↗

The serine/threonine protein kinase, p90 ribosomal S6 kinase, is an important regulator of prostate cancer cell proliferation.

An increase in the activity of mitogen-activated protein kinase (MAPK) has been correlated with the progression of prostate cancer to advanced disease in humans. The serine/threonine protein kinase p90-kDa ribosomal S6 kinase (RSK) is an important downstream effector of MAPK but its role in prostate cancer has not previously been examined. Increasing RSK isoform 2 (RSK2) levels in the human prostate cancer line, LNCaP, enhanced prostate-specific antigen (PSA) expression, an important diagnostic marker for prostate cancer, whereas inhibiting RSK activity using a RSK-specific inhibitor, 3Ac-SL0101, decreased PSA expression. The RSK2 regulation of PSA expression occurred via a mechanism involving both RSK2 kinase activity and its ability to associate with the coactivator, p300. RNA interference of the androgen receptor (AR) showed that the AR was important in the RSK2-mediated increase in PSA expression. RSK levels are higher in approximately 50% of human prostate cancers compared with normal prostate tissue, which suggests that increased RSK levels may participate in the rise in PSA expression that occurs in prostate cancer. Furthermore, 3Ac-SL0101 inhibited proliferation of the LNCaP line and the androgen-independent human prostate cancer line, PC-3. These results suggest that proliferation of some prostate cancer cells is dependent on RSK activity and support the hypothesis that RSK may be an important chemotherapeutic target for prostate cancer.

Cell Growth Processes↗

Orbital socket contracture: a complication of inflammatory orbital disease in patients with Wegener's granulomatosis.

AIM: To describe the clinical characteristics of orbital socket contracture in patients with Wegener's granulomatosis (WG). METHODS: A retrospective cohort study The medical records of 256 patients with WG examined at the National Institutes of Health from 1967 to 2004 were reviewed to identify patients with orbital socket contracture. Details of the orbital disease including Hertel exophthalmometry readings, radiological findings, and results of eye examinations were recorded. Orbital socket contracture was defined as orbital inflammation with proptosis followed by the development of enophthalmos and radiographic evidence of residual fibrotic changes in the orbit. To examine for risk factors in the development of a contracted orbit, patients with orbital socket contracture were compared to patients without contracture with respect to multiple variables including history of orbital surgery, orbital disease severity, and major organ system involvement. The main outcome measures were the clinical characteristics of orbital socket contracture associated with inflammatory orbital disease in patients with WG. RESULTS: Inflammatory orbital disease occurred in 34 of 256 (13%) patients and detailed clinical data on 18 patients were available and examined. Orbital socket contracture occurred during the clinical course in six patients; the features included restrictive ophthalmopathy (five), chronic orbital pain (three), and ischaemic optic nerve disease (two) resulting in blindness (no light perception) in one patient. The orbital socket contracture occurred within 3 months of treatment with immunosuppressive medications for inflammatory orbital disease in five patients and was not responsive to immunosuppressive medications. The median degree of enophthalmos in the contracted orbit compared with the fellow eye was 2.8 mm (range 1.5-3.5 mm) by Hertel exophthalmometry. There were no risk factors that predicted development of orbital socket contracture. CONCLUSIONS: In six patients with WG and active inflammatory orbital disease, orbital socket contracture occurred during the treatment course with systemic immunosuppressive medications. The orbital socket contracture, presumably caused by orbital fibrosis, led to enophthalmos, restrictive ophthalmopathy, chronic orbital pain, and optic nerve disease and was not responsive to immunosuppressive therapy. Orbital socket contracture has not been previously reported as a complication of inflammatory orbital disease associated with WG and was an important cause of visual morbidity in our cohort of patients.

Adolescent↗

Cough in chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) most commonly complain of cough, production of phlegm and breathlessness. The cough reflex sensitivity is heightened compared with that in healthy volunteers and is similar to that in subjects with asthma. The degree of airflow obstruction does not predict cough reflex sensitivity or objective cough counts, implying an independent process. Objective cough rates seem to be relatively low in COPD, despite frequent reporting of the symptom by patients. The relative contribution of cough to disability in COPD seems to be small, if assessed by subjective reporting. Effective treatments for cough in COPD have not yet been identified. Improved outcome measures of cough, a better understanding of the mechanisms underlying cough, and the importance of cough to patients is required to progress in this field.

Clinical Trials as Topic↗

An overview of the status of imaging screening technology for breast cancer.

With breast cancer incidence rates showing no signs of abating, advances in risk stratification and increasing awareness of cancer control, there is interest in expanding the breast imaging arsenal. Mammography is still the standard of care, and a recent meta-analysis of seven large studies supports its value as a screening tool. There is, however, clear need for improved sensitivity and specificity. Imaging of function, metabolism and molecular activity in breast tissue is of potential benefit in addressing these issues. In this article we provide an overview of the current methods of imaging in breast cancer, including mammography, ultrasound, digital mammography, magnetic resonance, positron emission tomography and magnetic resonance spectroscopy. Screening and surveillance should, ideally, be tailored to an individual's cancer risk and breast tissue. Current evidence questions the recent move toward magnetic resonance imaging as a single or multimodality strategy for breast cancer screening. In a high-risk group, the cost effectiveness of technical innovations may be justified.

Breast Neoplasms↗

Structure of the BoLA-DRB3 gene and promoter.

The cattle major histocompatibility complex (MHC) class II DR gene product is a heterodimer encoded by the BoLA-DRA and -DRB3 genes. Several groups have isolated cDNA and genomic clones for these genes, but their full genomic organization has not been described. We used a combination of long-range polymerase chain reaction (PCR), cloning and sequencing to define the organization of the DRB3 gene on existing genomic clones and in genomic DNA. We estimate the size of the coding region to be 11.4 kbp. Sequencing of full-length PCR clones from two different haplotypes confirmed that they carried complete DRB3 genes and allowed the design of probes and primers to isolate and characterize the DRB3 promoter and 3' end. Fragments carrying the 5' end of the DRB3 gene and its promoter were identified on bacterial artificial chromosome (BAC) clones carrying the BoLA-DR genes. A 10-kbp promoter fragment was subcloned from one clone and a 1.7-kbp region including exon 1 and the promoter was sequenced. A 3-kbp fragment encoding exons 4-6 and the entire 3' untranslated region of the DRB3 gene was isolated from lambda clone A1 and sequenced. This provides us with improved characterization of the DRB3*0101 and DRB3*2002 alleles, and also subcloned 5' and 3' flanking regions of the polymorphic DRB3 gene for use in functional studies.

3' Flanking Region↗

The problem of appraising qualitative research.

Qualitative research can make a valuable contribution to the study of quality and safety in health care. Sound ways of appraising qualitative research are needed, but currently there are many different proposals with few signs of an emerging consensus. One problem has been the tendency to treat qualitative research as a unified field. We distinguish universal features of quality from those specific to methodology and offer a set of minimally prescriptive prompts to assist with the assessment of generic features of qualitative research. In using these, account will need to be taken of the particular method of data collection and methodological approach being used. There may be a need for appraisal criteria suited to the different methods of qualitative data collection and to different methodological approaches. These more specific criteria would help to distinguish fatal flaws from more minor errors in the design, conduct, and reporting of qualitative research. There will be difficulties in doing this because some aspects of qualitative research, particularly those relating to quality of insight and interpretation, will remain difficult to appraise and will rely largely on subjective judgement.

Consensus↗

A comparison of a forced-air warming system to traditional thermal support for rodent microenvironments.

Thermal homeostasis is important for the well-being of laboratory rodents during experimental investigations involving chemical restraint. Anaesthesia-induced hypothermia may alter physiological processes, prolong recovery times, or result in death. Therefore, active warming may be needed to prevent excess heat loss from the rodent to the environment. Three methods of active warming were evaluated in typical rodent procedural areas and recovery cages: a forced-air warming system, infra-red heat emitter and circulating-water blanket. The first experiment involved recording the temperature of the immediate environment of the three devices, with and/or without the accompanying plastic drape, to simulate a surgical situation. In the second experiment, temperatures were recorded within cages that simulated a recovery situation with the same modalities. Forced-air warmer blankets (FAWB) were either wrapped around or placed underneath standard polycarbonate rodent cages and the results were compared with cage temperatures warmed by the heat emitter and circulating-water blanket. Temperatures were recorded at 0, 20, 40, and 60 min for each warming treatment, to determine mean temperature (+/- SEM) and the magnitude of increase (+/- SEM) between 0 and 60 min. All three devices showed an increase in temperature, but the FAWB with a plastic drape heated the procedural area microenvironment (Experiment 1) quickly and to a final temperature of 38.6 degrees C (101.5 degrees F) at 60 min, compared with 25 degrees C (77 degrees F) for the heat emitter and 28 degrees C (82.4 degrees F) for the circulating-water blanket. The magnitude of increase was significantly different for each treatment, but the FAWB with a plastic drape climbed 16.3 degrees C (29.3 degrees F) in 60 min. In Experiment 2, the FAWB wrapped around a cage, covered with a plastic drape, heated recovery cages to 32.5 degrees C (90.5 degrees F) compared to the heat emitter 26.4 degrees C (79.5 degrees F) and circulating-water blanket with drape 26.3 degrees C (79.3 degrees F). The magnitude of increase in the microenvironmental temperature was significantly higher for the FAWB, with the plastic drape wrapped around the recovery cage, compared to the other treatments. In both experiments, forced-air warming proved superior to the more traditional thermal support treatments in heating the microenvironments quickly and to an optimum ambient temperature. Forced-air warming devices should be considered when thermal support is required for rodent procedural areas and recovery cages.

Anesthesia↗

Helicobacter pylori (H. pylori) molecular signature in conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma.

Conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal marginal zone B-cell lymphoma that is characterized by an exaggerated clonal expansion of B cells, which implicate a pathological proliferative response to antigen(s) including bacteria. Helicobacter pylori (H. pylori) infection is recognized as one of the causative agents of gastric MALT lymphoma; however, it has not been reported in extra gastric MALT lymphoma. We studied 5 patients (4 adults and 1 child) with salmon-colored conjunctival lesions. One patient also had a history of abnormal bone marrow biopsy a year earlier with lymphoid aggregates involving 5% of the overall bone marrow. The conjunctival lesions of the 5 patients were biopsied. Histopathological diagnoses were consistent with conjunctival MALT lymphoma. Lymphoma and normal conjunctival cells were microdissected using laser capture microscopy or manual techniques. DNA was extracted and subjected to PCR amplification using H. pylori gene-specific primers from the urease B and vac/m2 gene. Cells from chronic conjunctivitis (normal lymphocytes), conjunctival human T-cell lymphotropic virus type-1/adult T-cell leukemia/lymphoma (HTLV-1/ATL), and orbital B-cell lymphoma were also microdissected, processed and analyzed. PCR amplification and Southern blot hybridization demonstrated H. pylori DNA in the conjunctival MALT lymphoma cells of 4/5 cases. The negative case was the one with a history of abnormal bone marrow. In contrast, H. pylori gene was not detected in normal conjunctival cells from the cases of MALT lymphoma or the lymphocytes, ATL and orbital B-lymphoma cells from the controls. These data suggest that H. pylori may play a role in conjunctival MALT lymphoma.

Aged↗