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Biomedical subjects

C Collins

Publications and source records attributed to C Collins.

At least 19 recordsLinked to original sources

Screening for Chlamydia trachomatis in asymptomatic women attending outpatient clinics in a large maternity hospital in Dublin, Ireland.

BACKGROUND: Chlamydia trachomatis can cause a sexually transmitted infection, which, untreated, may result in considerable morbidity. METHODS: A prevalence study was conducted for C trachomatis using nucleic acid amplification technology in asymptomatic women, and certain risk factors that may be used to direct future screening strategies were assessed. RESULTS: The study population comprised 945 asymptomatic women, of whom 783 were attending antenatal clinics, 91 were attending infertility clinics and 71 were attending family planning clinics. An overall C trachomatis prevalence of 3.7% (35/945) was found, with the highest prevalence of 11.2% (22/196) in Irish single women aged <25 years. Logistic regression analysis showed that single status and age <25 years were independent, statistically significant predictors of C trachomatis infection. CONCLUSION: These results support routine screening of asymptomatic women who are sexually active and aged <25 years. An opportunist active screening of all sexually active women independent of age should be additionally considered if resources permit.

Adult↗

A comprehensive study of chromosome 16q in invasive ductal and lobular breast carcinoma using array CGH.

We analysed chromosome 16q in 106 breast cancers using tiling-path array-comparative genomic hybridization (aCGH). About 80% of ductal cancers (IDCs) and all lobular cancers (ILCs) lost at least part of 16q. Grade I (GI) IDCs and ILCs often lost the whole chromosome arm. Grade II (GII) and grade III (GIII) IDCs showed less frequent whole-arm loss, but often had complex changes, typically small regions of gain together with larger regions of loss. The boundaries of gains/losses tended to cluster, common sites being 54.5-55.5 Mb and 57.4-58.8 Mb. Overall, the peak frequency of loss (83% cancers) occurred at 61.9-62.9 Mb. We also found several 'minimal' regions of loss/gain. However, no mutations in candidate genes (TRADD, CDH5, CDH8 and CDH11) were detected. Cluster analysis based on copy number changes identified a large group of cancers that had lost most of 16q, and two smaller groups (one with few changes, one with a tendency to show copy number gain). Although all morphological types occurred in each cluster group, IDCs (especially GII/GIII) were relatively overrepresented in the smaller groups. Cluster groups were not independently associated with survival. Use of tiling-path aCGH prompted re-evaluation of the hypothetical pathways of breast carcinogenesis. ILCs have the simplest changes on 16q and probably diverge from the IDC lineage close to the stage of 16q loss. Higher-grade IDCs probably develop from low-grade lesions in most cases, but there remains evidence that some GII/GIII IDCs arise without a GI precursor.

Breast Neoplasms↗

Prediction of maximum exposure in poor metabolizers following inhibition of nonpolymorphic pathways.

Marked increases in exposure of some substrates have been noted in poor metabolizers given inhibitors of nonpolymorphic enzymes. Among the small number of clinical trials conducted to investigate this problem, a wide variation in the degree of maximum exposure ratios (area under the curve in poor metabolizers in the presence of inhibitor/area under the curve in extensive metabolizers) among the different substrates has been reported, with some trials reporting profound increases (> tenfold), and others demonstrating less remarkable changes (< twofold). The conduct of such trials raises safety concerns for the trial participants, in addition to other ethical and logistic concerns; therefore, the possibility was investigated that maximum exposure (area under the curve in poor metabolizers in the presence of an inhibitor) could be predicted, and that substrates susceptible to large increases in exposure could be identified. Existing clinical trials were identified by data mining the literature. A theoretical approach was developed to predict maximum exposure in poor metabolizers from studies in extensive metabolizers treated with an inhibitor of the nonpolymorphic pathway. Maximum exposure was predicted in eleven instances and the mean percentage difference between predicted and observed was 11.9%. Substrates with a fraction of substrate dose metabolized by the polymorphic enzyme (fm(POLY)) higher than 75% are at greater risk of exhibiting maximum exposure ratios of more than tenfold.

Algorithms↗

Pregnancy outcome in immigrant women in the Rotunda Hospital.

In recent years the numbers of immigrants attending maternity hospitals has risen. The amount of antenatal care these women receive varies widely. Analysis was performed of deliveries to immigrant women in the Rotunda Hospital in 2002. Women were sub-divided depending on antenatal care received in Ireland. Women who received no antenatal care were 'unbooked', those who attended the hospital two to 28 days before delivery were 'late bookers'. The remaining women were 'booked'. There were 1,954 deliveries to immigrant women; 1,1 73 (60%) 'booked', 391 (20%) 'late bookers' and 390 (20%) 'unbooked'. 'Unbooked' women had a higher rate of spontaneous vertex delivery (63%) (p < 0.01). 'Late bookers' had a higher rate of caesarean section (27.6%) (p < 0.01). The 'late bookers' infants were more likely to be preterm, low birth weight and had a higher rate of neonatal ICU (NICU) admissions (p < 0.01). This study has identified 'late booker' immigrants as a high-risk group.

Adolescent↗

Acceptability of routine enquiry regarding domestic violence in the antenatal clinic.

Domestic Violence poses a significant health risk for the woman and her baby. We wished to determine the acceptability of routine questioning for domestic violence in the maternity hospital setting. A non-anonymised questionnaire was completed by 481 women attending for booking antenatal appointment in a maternity hospital antenatal clinic. The doctor asked four questions regarding experience of partner abuse, The acceptability of these questions was determined. 468 (99%) patients found the questions acceptable and said it would be helpful to ask all patients. Sixty-one (12.9%) women gave a history of at least one form of partner abuse. We concluded that routine enquiry about domestic violence during hospital antenatal visits is acceptable to women and perceived by them to be worthwhile.

Communication↗

Smoking and alcohol in pregnancy. Survey in the immediate post-partum period.

This was a questionnaire-based study of 151 postnatal women. We found 42% of women were smokers prior to pregnancy and only 37% of these women succeeded in quitting smoking during pregnancy. Success in quitting was significantly related to the number of cigarettes smoked (p<0.05). However, 71% of pregnant smokers were aware of the associated risks. Alcohol was consumed by 89% of women and 10% admitted to binge drinking during pregnancy. Only 44% of the study group were aware of the associated risks of alcohol. We propose that we need to change our social acceptance of these behaviours before pregnancy, and provide support to those women during pregnancy.

Adolescent↗

Radionuclides in fruit systems: model-model intercomparison study.

Modeling is widely used to predict radionuclide distribution following accidental radionuclide releases. Modeling is crucial in emergency response planning and risk communication, and understanding model uncertainty is important not only in conducting analysis consistent with current regulatory guidance, but also in gaining stakeholder and decision-maker trust in the process and confidence in the results. However, while methods for dealing with parameter uncertainty are fairly well developed, an adequate representation of uncertainties associated with models remains rare. This paper addresses uncertainty about a model's structure (i.e., the relevance of simplifying assumptions and mathematical equations) that is seldom addressed in practical applications of environmental modeling. The use of several alternative models to derive a range of model outputs or risks is probably the only available technique to assess consistency in model prediction. Since each independent model requires significant resources for development and calibration, multiple models are not generally applied to the same problem. This study uses results from one such model intercomparison conducted by the Fruits Working Group, which was created under the International Atomic Energy Agency (IAEA) BIOMASS (BIOsphere Modelling and ASSessment) Program. Model-model intercomparisons presented in this study were conducted by the working group for two different scenarios (acute or continuous deposition), one radionuclide ((137)Cs), and three fruit-bearing crops (strawberries, apples, and blackcurrants). The differences between models were as great as five orders of magnitude for short-term predictions following acute radionuclide deposition. For long-term predictions and for the continuous deposition scenario, the differences between models were about two orders of magnitude. The difference between strawberry, apple, and blackcurrant contamination predicted by one model is far less than the difference in prediction of contamination for a single plant species given by different models. This study illustrates the importance of problem formulation and implementation of an analytic-deliberative process in risk characterization.

Cesium Radioisotopes↗

Modelling and experimental studies on the transfer of radionuclides to fruit.

Although fruit is an important component of the diet, the extent to which it contributes to radiological exposure remains unclear, partially as a consequence of uncertainties in models and data used to assess transfer of radionuclides in the food chain. A Fruits Working Group operated as part of the IAEA BIOMASS (BIOsphere Modelling and ASSessment) programme from 1997 to 2000, with the aim of improving the robustness of the models that are used for radiological assessment. The Group completed a number of modelling and experimental activities including: (i) a review of experimental, field and modelling information on the transfer of radionuclides to fruit; (ii) discussion of recently completed or ongoing experimental studies; (iii) development of a database on the transfer of radionuclides to fruit; (iv) development of a conceptual model for fruit and (v) two model intercomparison studies and a model validation study. The Group achieved significant advances in understanding the processes involved in transfer of radionuclides to fruit. The work demonstrated that further experimental and modelling studies are required to ensure that the current generation of models can be applied to a wide range of scenarios.

Fruit↗

Design considerations for array CGH to oligonucleotide arrays.

BACKGROUND: Representational oligonucleotide microarray analysis has been developed for detection of single nucleotide polymorphisms and/or for genome copy number changes. In this process, the intensity of hybridization to oligonucleotides arrays is increased by hybridizing a polymerase chain reaction (PCR)-amplified representation of reduced genomic complexity. However, hybridization to some oligonucleotides is not sufficiently high to allow precise analysis of that portion of the genome. METHODS: In an effort to identify aspects of oligonucleotide hybridization affecting signal intensity, we explored the importance of the PCR product strand to which each oligonucleotide is homologous and the sequence of the array oligonucleotides. We accomplished this by hybridizing multiple PCR-amplified products to oligonucleotide arrays carrying two sense and two antisense 50-mer oligonucleotides for each PCR amplicon. RESULTS: In some cases, hybridization intensity depended more strongly on the PCR amplicon strand (i.e., sense vs. antisense) than on the detection oligonucleotide sequence. In other cases, the oligonucleotide sequence seemed to dominate. CONCLUSION: Oligonucleotide arrays for analysis of DNA copy number or for single nucleotide polymorphism content should be designed to carry probes to sense and antisense strands of each PCR amplicon to ensure sufficient hybridization and signal intensity.

Aneuploidy↗

Combined electric field and ultrasound therapy as a novel anti-tumour treatment.

The permeabilising effects of electric pulses on cell membranes and the use of ultrasound energy of various intensities, for both thermal effects and enhancement of drug and gene delivery, have led to extensive research into the potential applications of these systems in the development of novel anti-cancer treatments. In the present study we have demonstrated for the first time that the application of brief electric pulses 'sensitises' tumour cells to the effects of low intensity ultrasound. The studies were conducted in human tumours established in athymic nude mice and in many instances resulted in the reduction of tumour mass. The combined electric field and ultrasound approach (CEFUS) was applied in vivo to a murine colon adenocarcinoma (C26) and a human oesophageal adenocarcinoma (OE19). The experiments performed demonstrated the anti-tumour effects of the combined therapy. Varying the electrosensitisation parameters used (voltage, waveform, electrode type) contributed to optimise the procedure. Exponential electric pulses with a peak of 1000 V/cm were initially used, but square wave pulses (1000 V/cm, 1 ms, x2, 1 Hz) were found to be just as effective. All ultrasound application parameters were kept constant during the study. The growth rate of C26 tumours treated with CEFUS was significantly reduced with respect to untreated controls at day 7 (96% of average initial tumour volume in CEFUS group versus 615% for controls, P < 0.05). Similar reduction was observed in OE19 tumours treated with CEFUS by day 4 (82% versus 232%, P < 0.032). Our preliminary data suggest that this novel technology could potentially be of wide application in clinical practice for the treatment of solid tumours and is worth further investigation.

Adenocarcinoma↗

Probiotics: an emerging therapy.

There is considerable clinical interest in the utility of probiotic therapy--the feeding of (live) non-pathogenic bacteria, originally derived from the alimentary tract, for disease treatment or health promotion. The microflora of the gastrointestinal tract is essential for mucosal protection, for immune education and for metabolism of fecal residue. Physiological disturbances of these processes, when they occur, result from: i) alteration of a microbial ecosystem, originally conserved by evolution; ii) reduced consumption of microorganisms; iii) invasion of pathogens; or iv) modern interventions. Recent data support the use of proven probiotic organisms in prevention and treatment of flora-related gastrointestinal disorders including inflammatory bowel disease, infectious and antibiotic related diarrheas, and post-resection disorders including pouchitis. Therapeutic activity of probiotic bacteria can be due to competition with pathogens for nutrients and mucosal adherence, production of antimicrobial substances, and modulation of mucosal immune functions. Although a promising treatment, controlled clinical trials are necessary to validate the benefit of probiotics.

Animals↗

Calcium absorption and bone mineral density in celiacs after long term treatment with gluten-free diet and adequate calcium intake.

Calcium malabsorption, hypocalcemia and skeletal demineralization are well-recognized features of untreated celiac disease. This study investigates calcium absorption and bone mineral density (BMD) after a prolonged, over 4 years, treatment with a gluten-free diet. Twenty-four adult females with treated celiac disease and twenty age- and sex-matched control subjects were studied. Mean body mass index (MBI), energy intake, serum calcium, and serum 25(OH)D concentrations in treated celiacs did not differ from controls. However, while both dietary calcium and protein intake were significantly higher in celiacs (P<0.012), fractional calcium absorption was lower (mean percentage+/-SD; treated 39.8+/-12 versus controls 52.3+/-10, P<0.001). Thus, after adjusting for calcium intake, the estimated amount of calcium absorbed daily was similar in both groups. Whole body, spine and trochanter BMD were significantly lower in treated celiac patients compared with controls (P<0.05). There were significant inverse correlations between: serum parathyroid hormone (PTH) and femoral neck or total body BMD (P<0.01), PTH and duration of gluten-free diet (P=0.05), and fractional calcium absorption and alkaline phosphatase (P=0.022). Increased calcium intake could potentially compensate for the reduced fractional calcium absorption in treated adult celiac patients, but may not normalize the BMD. In addition, the inverse correlation between PTH and time following treatment is suggestive of a continuing long-term benefit of gluten withdrawal on bone metabolism in celiac patients.

Absorption↗

Small margin excision of periocular basal cell carcinoma: 5 year results.

BACKGROUND: The traditional surgical management of nodular adnexal basal cell carcinomas (BCC) involves excision with 3-4 mm margins and primary repair. This may remove a significant area of healthy tissue, often necessitating a complicated reconstruction, without the confirmation that tumour excision is complete. METHODS: Nodular adnexal BCCs were excised with 2 mm margins, and the repair delayed for 2 days, providing time for histological confirmation of complete excision with formal paraffin sections. Any incompletely excised tumours underwent further resection, which was facilitated by the undisturbed wound edges. Repair was again delayed until further histological examination had confirmed complete excision. RESULTS: 5 year follow up data were available for 55 patients who had undergone small margin BCC excision with delayed repair. 10 patients required more than one excision to achieve clear margins. There were no recurrences. CONCLUSION: Small margin excision of nodular adnexal BCCs with delayed repair is a safe and efficient method. Delayed repair allows histological confirmation of complete excision and assists further resection if required. Preservation of healthy tissue is maximised allowing less radical reconstructive surgery without resorting to Mohs' labour intensive technique.

Adult↗

Acute gastroenteritis in northern Ireland and the Republic of Ireland: a telephone survey.

Most people with acute gastroenteritis do not seek medical care and are therefore not captured by routine surveillance. For this reason, population-based studies are needed to measure the burden of illness. A study of acute gastroenteritis in Northern Ireland and the Republic of Ireland surveyed 9,903 people by telephone over the 12-month period from December 2000 to November 2001. The rate of acute gastroenteritis was 0.60 episodes per person per year. A general practitioner was consulted by 29.2% of those reporting illness, and 2.0% submitted a stool sample. The use of antibiotics was reported by 7.4% of ill respondents and 14.8% took anti-diarrhoeals. Taking days off work due to illness, was reported by 17.4% of respondents. Acute gastroenteritis causes a large amount of illness in the community. There are established and effective measures to prevent this condition and the challenge is to find new ways of promoting these precautions.

Absenteeism↗

Genome sequence and splice site analysis of low-fidelity DNA polymerases H and I involved in replication of damaged DNA.

POLH and POLI are paralogs encoding low-fidelity, class Y, DNA polymerases involved in replication of damaged DNA in the human disease xeroderma pigmentosum variant. Analysis of genomic regions for human and mouse homologs, employing the analytic tool Genome Cryptographer, detected low-repetitive or unique regions at exons and other potential control regions, especially within intron I of human POLH. The human and mouse homologs are structurally similar, but the paralogs have undergone evolutionary divergence. The information content of splice sites for human POLH, the probability that a base would contribute to splicing, was low only for the acceptor site of exon II, which is preceded by a region of high information content that could contain sequences controlling splicing. This analysis explains previous observations of tissue-specific skipping during mRNA processing, resulting in the loss of the transcription start site in exon II, in human tissues.

Alternative Splicing↗

Anti-transglutaminase antibodies and the serological diagnosis of coeliac disease.

Tissue transglutaminase (tTG) has recently been identified as the antigenic target recognised by anti-endomysial antibodies in patients with coeliac disease. In this study, an enzyme-linked immunosorbent assay (ELISA) is used to measure IgA, IgG and IgM antibodies to tTG in patients with coeliac disease and a variety of other inflammatory disorders; and is compared to the standard immunofluorescence test used to detect endomysial antibodies (EMA). In the samples tested, 3% control sera (n=146), 83% EMA-positive sera (n=29), 9% patients with Graves' disease (n=94), 12% antimitochondrial antibody-positive sera (n=53), 11% rheumatoid arthritis patients (n=53) and 22% systemic lupus erythematosus (SLE) patients (n=46) were positive for anti-tTG antibodies. In contrast, none of the controls, 1% of patients with Graves' disease, 2% antimitochondrial antibody-positive sera, 2% rheumatoid arthritis patients and none of the SLE patients were positive for EMA. Measurement of IgG or IgM antibodies to tTG was much less reliable than IgA anti-tTG antibody for the serological diagnosis of coeliac disease. The addition of calcium to the coating buffer improved the assay characteristics of the anti-tTG ELISA. However, the IgA anti-tTG ELISA, with and without calcium, performed less well than the standard EMA test used for the serological diagnosis of coeliac disease. In particular, the anti-tTG ELISA gave a higher rate of non-specific positive reactions.

Antibodies↗

Relationship between milk urea concentration and the fertility of dairy cows.

The relationship between milk urea concentration and the fertility of dairy cows was examined in two studies. The first examined the relationship between bulk milk urea concentration and overall herd fertility, using data collected from 250 herds in the UK. There was no relationship either between bulk milk urea concentration and fertility, or between changes in bulk milk urea concentration and fertility. The second study compared the relationship between the milk urea concentration five days after service, and the fertility of individual cows on 11 UK dairy farms. There was no significant difference between the milk urea concentration of the cows that became pregnant and those that did not.

Animals↗