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Biomedical subjects

C Clark

Publications and source records attributed to C Clark.

At least 19 recordsLinked to original sources
PubMed2006

Survey of pigs' kidneys with lesions consistent with PMWS and PDNS and ochratoxicosis. Part 2: pathological and histological findings.

One thousand condemned pigs' kidneys were collected in February 2002 from two pig abattoirs in England to assess the lesions due to postweaning multisystemic wasting syndrome (pmws) and porcine dermatitis and nephropathy syndrome (pdns) and the possible contribution of ochratoxicosis; 174 of the kidneys were pale, 295 were swollen and 81 were abnormally firm with the gross appearance of fibrosis. The main macroscopic finding was the presence of multifocal pale cortical lesions, observed in 446 of the kidneys, and there were large cysts in 266 of them. Histopathological lesions of non-suppurative tubulointerstitial nephritis, with degeneration and fibrosis of renal tubules, were identified in 213 of 250 (85.2 per cent) of the kidneys examined. These lesions were consistent with those reported in cases of pmws and pdns. The tubular degeneration and fibrosis were also consistent with ochratoxicosis. A higher mean concentration of ochratoxin A was significantly (P=0.020) associated with the presence of multifocal pale cortical lesions consistent with ochratoxicosis, but a causal relationship was not confirmed because histochemistry was not used to detect ochratoxin in the lesions directly. There was no significant correlation between the microscopic lesions and the concentration of ochratoxin. The degenerative lesions may have been caused by previous exposure to ochratoxin that had subsequently been excreted, but the microscopic lesions also included non-suppurative interstitial nephritis, which was unlikely to have been caused by ochratoxicosis.

Abattoirs↗
PubMed2006

Survey of pigs' kidneys with lesions consistent with PMWS and PDNS and ochratoxicosis. Part 1: concentrations and prevalence of ochratoxin A.

One thousand condemned pigs' kidneys were collected in February 2002 from two pig abattoirs in England to assess the possible contribution of ochratoxicosis to postweaning multisystemic wasting syndrome (PMWS) and porcine dermatitis and nephropathy syndrome (PDNS); 250 of the kidneys with macroscopic lesions consistent with nephrosis/nephritis (pale or white cortical lesions) were selected, and the concentration of ochratoxin A was measured in samples of renal cortex by high-performance liquid chromatography (HPLC). Low concentrations were detected in 230 (92 per cent) of the kidneys tested, and in 41 (16.4 per cent) of them the concentration was below the limit of quantification of 0.2 microg/kg. In 187 (74.8 per cent) of the kidneys, the concentration was more than 0.2 microg/kg, and the highest concentration detected was 2.3 microg/kg. The mean (sd) concentration was 0.31 (0.33) microg/kg. The identification of ochratoxin A was confirmed by mass spectrometry. The concentrations of ochratoxin A did not exceed the threshold assessed by the Food Standards Agency to be safe for human food.

Animals↗
PubMed2006

The impact of the physical and urban environment on mental well-being.

OBJECTIVES: To examine the strength of association between physical and social factors in the built environment and mental well-being, and to determine which factors are the most important. STUDY DESIGN: A postal survey based on a theoretical model of domains that might link the physical and urban environment with mental well-being was sent to 2696 adults aged 18 years or over, in four areas of Greenwich, London. Mental health was measured using the SF36 subscales for mental health (MH) and vitality (V). Additional household and area level data were appended for each respondent from a range of sources. RESULTS: 1012 questionnaires were returned (38% response rate). At the univariate level significant confounders that were associated with poorer mental well-being were being female, 85+ years, unemployed or retired, on housing benefit, council tenant, two or more children, and having requested re-housing Better mental well-being was associated with being aged 65 years to 84 years (better MH and V). Within domain analysis, adjusting for each of the confounding factors, resulted in the following factors being significantly associated with being in the lowest quartile for MH score: (i) control over the internal environment (damp), (ii) design and maintenance (not liking the look of the estate/road, (iii) noise (neighbour noise), (iv) density and escape (feeling over-crowded in the home, being dissatisfied with green spaces, dissatisfied with social and entertainment facilities) being dissatisfied with community facilities (such as libraries and community centres) was only significant for vitality, (v) fear of crime and harassment (feeling unsafe to go out in the day, feeling unsafe to go out at night, agreeing that needles and syringes left lying around are a problem) (vi) social participation (not enough events to get people together, not enough places to stop and chat). When these 12 factors were entered into a single model with the significant confounders five remained significantly associated with being in the lowest quartile for MH or V: neighbour noise MH OR 2.71 [95% CI 1.48, 4.98]; feeling over-crowded in the home MH OR 2.22 [1.42, 3.48]; being dissatisfied with access to green open spaces MH OR 1.69 [1.05, 2.74]; access to community facilities V OR 1.92, [1.24, 3.00]; feeling unsafe to go out in the day MH OR 1.64 [1.02, 2.64]; V OR 1.58 [1.00, 2.49]. CONCLUSIONS: This study confirms an association between the physical environment and mental well-being across a range of domains. The most important factors that operate independently are neighbour noise, sense of over-crowding in the home and escape facilities such as green spaces and community facilities, and fear of crime. This study highlights the need to intervene on both design and social features of residential areas to promote mental well-being.

Adult↗
PubMed2006

Molecular epidemiology of tuberculosis after declining incidence, New York City, 2001-2003.

Tuberculosis incidence in New York City (NYC) declined between 1992 and 2000 from 51.1 to 16.6 cases per 100,000 population. In January 2001, universal real-time genotyping of TB cases was implemented in NYC. Isolates from culture-confirmed tuberculosis cases from 2001 to 2003 were genotyped using IS6110 and spoligotype to describe the extent and factors associated with genotype clustering after declining TB incidence. Of 2408 (91.8%) genotyped case isolates, 873 (36.2%) had a pattern indistinguishable from that of another study period case, forming 212 clusters; 248 (28.4%) of the clustered cases had strains believed to have been widely transmitted during the epidemic years in the early 1990s in NYC. An estimated 27.4% (873 minus 212) of the 2408 cases were due to recent infection that progressed to active disease during the study period. Younger age, birth in the United States, homelessness, substance abuse and presence of TB symptoms were independently associated with greater odds of clustering.

Adolescent↗
PubMed2006

Drinking histories of self-identified lifetime abstainers and occasional drinkers: findings from the 1958 British Birth Cohort Study.

AIMS: To investigate the validity of retrospective items used to distinguish people who have rarely or never consumed alcohol. METHODS: The 1958 British Birth Cohort Study has followed 9377 individuals until age 45. Previous drinking (at 16, 23, 33 and 42 years) was investigated for two groups of 45-year-old non-drinkers, those reporting never having consumed alcohol ('never drinkers', n = 143, 1.5%), and having only consumed very infrequently ('occasional-only drinkers', n = 1149, 12.3%). RESULTS: 67% of never drinkers previously reported drinking, 25% were past weekly/daily drinkers; 56% of occasional-only drinkers reported weekly/daily consumption. The validity of the retrospective items was progressively questionable when presumed to cover longer time periods. CONCLUSIONS: Substantial measurement error was evident when identifying 'occasional-only' and 'never' drinkers using retrospective items covering the lifecourse. Researchers investigating potential health benefits associated with moderate drinking need to incorporate more sophisticated methods when identifying sub-groups of non-drinkers.

Adolescent↗
PubMed2006

Annexin II binds progastrin and gastrin-like peptides, and mediates growth factor effects of autocrine and exogenous gastrins on colon cancer and intestinal epithelial cells.

We and others have reported the presence of novel progastrin (PG)/gastrin receptors on normal and cancerous intestinal cells. We had earlier reported the presence of 33-36 kDa gastrin-binding proteins on cellular membranes of colon cancer cells. The goal of the current study was to identify the protein(s) in the 33-36 kDa band, and analyse its functional significance. A carbodiimide crosslinker was used for crosslinking radio-labeled gastrins to membrane proteins from gastrin/PG responsive cell lines. Native membrane proteins, crosslinked to the ligand, were solubulized and enriched by >1000-fold, and analysed by surface-enhanced laser desorption/ionization-time of flight-mass spectrometry. The peptide masses were researched against the NCBInr database using the ProFound search engine. Annexin II (ANX II) was identified, and confirmed by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry. As HCT-116 cells express autocrine PG, the in situ association of PG with ANX II was demonstrated in pulldown assays. Direct binding of PG with ANX II was confirmed in an in vitro binding assay. In order to confirm a functional importance of these observations, sense and anti-sense (AS) ANX II RNA-expressing clones of intestinal epithelial (IEC-18) and human colon cancer (HCT-116) cell lines were generated. AS clones demonstrated a significant loss in the growth response to exogenous (IEC-18) and autocrine (HCT-116) PG. We have thus discovered that membrane-associated ANX II binds PG/gastrins, and partially mediates growth factor effects of the peptides.

Animals↗
PubMed2006

Noise exposure and children's blood pressure and heart rate: the RANCH project.

BACKGROUND: Conclusions that can be drawn from earlier studies on noise and children's blood pressure are limited due to inconsistent results, methodological problems, and the focus on school noise exposure. OBJECTIVES: To investigate the effects of aircraft and road traffic noise exposure on children's blood pressure and heart rate. METHODS: Participants were 1283 children (age 9-11 years) attending 62 primary schools around two European airports. Data were pooled and analysed using multilevel modelling. Adjustments were made for a range of socioeconomic and lifestyle factors. RESULTS: After pooling the data, aircraft noise exposure at school was related to a statistically non-significant increase in blood pressure and heart rate. Aircraft noise exposure at home was related to a statistically significant increase in blood pressure. Aircraft noise exposure during the night at home was positively and significantly associated with blood pressure. The findings differed between the Dutch and British samples. Negative associations were found between road traffic noise exposure and blood pressure, which cannot be explained. CONCLUSION: On the basis of this study and previous scientific literature, no unequivocal conclusions can be drawn about the relationship between community noise and children's blood pressure.

Aircraft↗
PubMed2006

Illicit and traditional drug use among ethnic minority adolescents in East London.

OBJECTIVES: To explore ethnic variations in the use of illicit and traditional drugs, and the association of indicators of acculturation with drug use among an ethnically diverse representative sample of early adolescents in East London. STUDY DESIGN: A cross-sectional questionnaire survey. METHODS: Confidential questionnaires were used to assess 2789 male and female pupils in years 7 and 9, aged 11-14 years old, from a representative sample of 28 secondary schools in East London. RESULTS: In total, 10.8% reported having ever tried illicit drugs and 7.3% reported ever using cannabis. Compared with white British adolescents, cannabis use in the previous month was significantly higher amongst black Caribbean adolescents. Lifetime cannabis use was significantly higher amongst black Caribbean and mixed ethnicity young people, but was lower amongst Bangladeshi, Indian and Pakistani adolescents. Living in UK for 5 years or less markedly reduced the risk of lifetime and recent cannabis use when controlled for ethnicity and social class. Glue or solvent use was reported in 3.2% of adolescents, with use significantly higher amongst Bangladeshi young people. Lifetime paan use was reported by 14.1% of the sample, and was almost completely confined to South Asian or mixed ethnicities. CONCLUSIONS: Ethnic differences in illicit drug use were found in the study population, and significant differences were found between ethnic groups often identified as 'black.' Further research is needed in understanding cultural-specific risk and protective factors in different ethnic groups, and the importance of cultural identity in mediating health risk behaviors. The high use of paan and glue/gas/solvents by Bangladeshi young people poses an unappreciated public health problem that may require targeted interventions.

Acculturation↗
PubMed2006

Concurrent end-phase boost high-dose radiation therapy for non-small-cell lung cancer with or without cisplatin chemotherapy.

The aim of this study was to audit the results of a high-dose, combined-modality prospective protocol for non-small-cell lung cancer in terms of survival, disease-specific survival and toxicity. One hundred and twenty-one patients with non-small-cell lung cancer were treated with a concurrent, end-phase, boost, high-dose radiotherapy protocol with 65 Gy in 35 fractions for more than 5 weeks. Sixty-six patients received radiotherapy alone (group 1), 29 received concurrent chemoradiation (group 2) and 26 received neoadjuvant and concurrent chemotherapy (group 3). Thirty-four patients had stage I disease, six had stage II and 81 had stage III. Overall median survival was 23 months: 75% at 1 year and 23% at 5 years. Median survivals for patients with stage I and stages II and III disease were 43 and 19 months, respectively. For stages II and III patients by groups 1-3, median survivals were 18, 25 and 18 months, respectively, and 2-year survivals were 36, 52 and 38%, respectively. Toxicity was acceptable. Overall, 9% had symptomatic pneumonitis and 7% had grades 3 and 4 oesophagitis. For those who had the mediastinum included in the volume, grade > or = 3 oesophagitis occurred in 0, 11 and 22% (n = 110, P = 0.001), respectively, for treatment groups 1-3. Overall treatment-related mortality was 3%, consisting of two septic deaths, one pneumonitis and possibly one late cardiac event, all occurring in patients who had chemotherapy (7% of 55 patients). Treatment-related mortality declined over the study period. Accelerated radiotherapy was well tolerated, with only moderate increased acute toxicity when combined with concurrent platinum chemotherapy. Toxicity was enhanced by induction chemotherapy. Overall survival outcomes were excellent for this condition. Continued use of this radiotherapy schedule is recommended as the platform for assessment of other chemotherapy schedules.

Adult↗
PubMed2005

Human sealpox resulting from a seal bite: confirmation that sealpox virus is zoonotic.

The case of a marine mammal technician who sustained a seal-bite to the hand that produced a lesion clinically very similar to orf is described. Sequence analysis of the viral DNA amplified from the lesion by the polymerase chain reaction indicated that it was sealpox virus in origin. This is the first report providing unequivocal evidence that sealpox may be transmitted to humans and causes lesions very similar to orf.

Adult↗
PubMed2005

An international outbreak of salmonellosis associated with raw almonds contaminated with a rare phage type of Salmonella enteritidis.

During the winter of 2000 to 2001, an outbreak due to Salmonella Enteritidis (SE) phage type 30 (PT30), a rare strain, was detected in Canada. The ensuing investigation involved Canadian and American public health and food regulatory agencies and an academic research laboratory. Enhanced laboratory surveillance, including phage typing and pulsed-field gel electrophoresis, was used to identify cases. Case questionnaires were administered to collect information about food and environmental exposures. A case-control study with 16 matched case-control pairs was conducted to test the hypothesis of an association between raw whole almond consumption and infection. Almond samples were collected from case homes, retail outlets, and the implicated processor, and environmental samples were collected from processing equipment and associated farms for microbiological testing. One hundred sixty-eight laboratory-confirmed cases of SE PT30 infection (157 in Canada, 11 in the United States) were identified between October 2000 and July 2001. The case-control study identified raw whole almonds as the source of infection (odds ration, 21.1; 95% confidence interval, 3.6 to infinity). SE PT30 was detected in raw whole natural almonds collected from home, retail, distribution, and warehouse sources and from environmental swabs of processing equipment and associated farmers' orchards. The frequent and prolonged recovery of this specific organism from a large agricultural area was an unexpected finding and may indicate significant diffuse contamination on these farms. Identification of almonds as the source of a foodborne outbreak is a previously undocumented finding, leading to a North American recall of this product and a review of current industry practices.

Adolescent↗
PubMed2004

Treatment of superficial cutaneous vascular lesions: experience with the KTP 532 nm laser.

Whilst most facial telangiectasias respond well to short-pulse-duration pulsed dye laser therapy, studies have shown that for the treatment of larger vessels these short-duration pulses are sub-optimal. Long-pulse frequency-doubled neodymium:YAG lasers have been introduced with pulse durations ranging from 1-50 ms and treatment beam diameters of up to 4 mm. We report the results of KTP/532 nm laser treatment for superficial vascular skin lesions. The aim was to determine the efficacy of the KTP/532 nm laser in the treatment of superficial cutaneous vascular lesions at a regional dermatology centre in a 2 year retrospective analysis. Patients were referred from general dermatology clinics to a purpose-built laser facility. A test dose was performed at the initial consultation and thereafter patients were reviewed and treated at 6 week intervals. Outcome was graded into five classifications by the patient and operator independently based on photographic records: clear, marked improvement, partial response, poor response, and no change or worsening. Over the 2 year period, 204 patients with 246 diagnoses were treated [156 female; median age 41 (range 1-74) years; Fitzpatrick skin types I-III]. Equal numbers of spider angioma (102) and facial telangiectasia (102) were treated. Of those patients who completed treatment and follow up, 57/58 (98%) of spider angiomas and 44/49 (90%) of facial telangiectasia markedly improved or cleared. Satisfactory treatment outcomes, with one clearance and two partial responses, occurred in three of five patients with port-wine stain. Few patients experienced adverse effects: two declined further treatment due to pain, and a small area of minimal superficial scarring developed in one case. Two patients developed mild persistent post-inflammatory hyperpigmentation, and one subject experienced an episode of acute facial erythema, swelling and blistering after one treatment. The KTP/532 nm frequency-doubled neodymium:YAG laser is a safe and effective treatment for common superficial cutaneous vascular lesions in patients with Fitzpatrick skin types I-III.

Adolescent↗
PubMed2004

Gene expression during formation of earlywood and latewood in loblolly pine: expression profiles of 350 genes.

The natural variability of wood formation in trees affords opportunities to correlate transcript profiles with the resulting wood properties. We have used cDNA microarrays to study transcript abundance in developing secondary xylem of loblolly pine (Pinus taeda) over a growing season. The cDNAs were selected from a collection of 75 000 ESTs that have been sequenced and annotated (http://web.ahc.umn.edu/biodata/nsfpine/). Cell wall thickness and climatic data were related to earlywood and latewood formation at different time points during the growing season. Seventy-one ESTs showed preferential expression in earlywood or latewood, including 23 genes with no significant similarity to genes in GenBank. Seven genes involved in lignin synthesis were preferentially expressed in latewood. The studies have provided initial insights into the variation of expression patterns of some of the genes related to the wood formation process.

Expressed Sequence Tags↗
PubMed2004

MRI and CSF studies in the early diagnosis of Alzheimer's disease.

The main goal of our studies has been to use MRI, FDG-PET, and CSF biomarkers to identify in cognitively normal elderly (NL) subjects and in patients with mild cognitive impairment (MCI), the earliest clinically detectable evidence for brain changes due to Alzheimer's disease (AD). A second goal has been to describe the cross-sectional and longitudinal interrelationships amongst anatomical, CSF and cognition measures in these patient groups. It is now well known that MRI-determined hippocampal atrophy predicts the conversion from MCI to AD. In our summarized studies, we show that the conversion of NL subjects to MCI can also be predicted by reduced entorhinal cortex (EC) glucose metabolism, and by the rate of medial temporal lobe atrophy as determined by a semi-automated regional boundary shift analysis (BSA-R). However, whilst atrophy rates are predictive under research conditions, they are not specific for AD and cannot be used as primary evidence for AD. Consequently, we will also review our effort to improve the diagnostic specificity by evaluating the use of CSF biomarkers and to evaluate their performance in combination with neuroimaging. Neuropathology studies of normal ageing and MCI identify the hippocampal formation as an early locus of neuronal damage, tau protein pathology, elevated isoprostane levels, and deposition of amyloid beta 1-42 (Abeta42). Many CSF studies of MCI and AD report elevated T-tau levels (a marker of neuronal damage) and reduced Abeta42 levels (possibly due to increased plaque sequestration). However, CSF T-tau and Abeta42 level elevations may not be specific to AD. Elevated isoprostane levels are also reported in AD and MCI but these too are not specific for AD. Importantly, it has been recently observed that CSF levels of P-tau, tau hyperphosphorylated at threonine 231 (P-tau231) are uniquely elevated in AD and elevations found in MCI are useful in predicting the conversion to AD. In our current MCI studies, we are examining the hypothesis that elevations in P-tau231 are accurate and specific indicators of AD-related changes in brain and cognition. In cross-section and longitudinally, our results show that evaluations of the P-tau231 level are highly correlated with reductions in the MRI hippocampal volume and by using CSF and MRI measures together one improves the separation of NL and MCI. The data suggests that by combining MRI and CSF measures, an early (sensitive) and more specific diagnosis of AD is at hand. Numerous studies show that neither T-tau nor P-tauX (X refers to all hyper-phosphorylation site assays) levels are sensitive to the longitudinal progression of AD. The explanation for the failure to observe longitudinal changes is not known. One possibility is that brain-derived proteins are diluted in the CSF compartment. We recently used MRI to estimate ventricular CSF volume and demonstrated that an MRI-based adjustment for CSF volume dilution enables detection of a diagnostically useful longitudinal P-tau231 elevation. Curiously, our most recent data show that the CSF isoprostane level does show significant longitudinal elevations in MCI in the absence of dilution correction. In summary, we conclude that the combined use of MRI and CSF incrementally contributes to the early diagnosis of AD and to monitor the course of AD. The interim results also suggest that a panel of CSF biomarkers can provide measures both sensitive to longitudinal change as well as measures that lend specificity to the AD diagnosis.

Aged↗
PubMed2004

Does a single bolus thrombolytic reduce door to needle time in a district general hospital?

OBJECTIVES: To answer the question "In patients presenting with ST elevation acute myocardial infarction (STEMI) and no contraindication to thrombolysis, does the introduction of Tenecteplase reduce door to needle times?" METHODS: Firstly, an observational study was performed to compare the time taken to prepare standard thrombolytic therapy with Tenecteplase. Secondly, door to needle times were compared before and after the introduction of Tenecteplase. The study was powered to be 80% sure of finding a change of 10% in the number of patients meeting the national service framework standard of a 30 minute door to needle time. RESULTS: Tenecteplase takes 10.5 minutes less time to prepare than standard treatment (p value <0.001). After the introduction of Tenecteplase the percentage of patients receiving thrombolysis in 30 minutes increased from 58% to 76% (p value <0.01) CONCLUSION: Tenecteplase is quicker to prepare than standard therapy, resulting in a significant improvement in performance against the national service framework target.

Emergencies↗