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Biomedical subjects

J Skinner

Publications and source records attributed to J Skinner.

At least 37 records · Page 2Linked to original sources

A pooled analysis of magnetic fields and childhood leukaemia.

Previous studies have suggested an association between exposure to 50-60 Hz magnetic fields (EMF) and childhood leukaemia. We conducted a pooled analysis based on individual records from nine studies, including the most recent ones. Studies with 24/48-hour magnetic field measurements or calculated magnetic fields were included. We specified which data analyses we planned to do and how to do them before we commenced the work. The use of individual records allowed us to use the same exposure definitions, and the large numbers of subjects enabled more precise estimation of risks at high exposure levels. For the 3203 children with leukaemia and 10 338 control children with estimated residential magnetic field exposures levels < 0.4 microT, we observed risk estimates near the no effect level, while for the 44 children with leukaemia and 62 control children with estimated residential magnetic field exposures >/= 0.4 microT the estimated summary relative risk was 2.00 (1.27-3.13), P value = 0.002). Adjustment for potential confounding variables did not appreciably change the results. For North American subjects whose residences were in the highest wire code category, the estimated summary relative risk was 1.24 (0.82-1.87). Thus, we found no evidence in the combined data for the existence of the so-called wire-code paradox. In summary, the 99.2% of children residing in homes with exposure levels < 0.4 microT had estimates compatible with no increased risk, while the 0.8% of children with exposures >/= 0.4 microT had a relative risk estimate of approximately 2, which is unlikely to be due to random variability. The explanation for the elevated risk is unknown, but selection bias may have accounted for some of the increase.

Adolescent↗

Hysterosalpingocontrastsonography in clinical practice.

The aim of this study was to review the indication, source of referral and findings at hysterosalpingocontrastsonography (HyCoSy) of the first 100 patients referred for this new service in the gynaecological outpatients department of the Coombe Women's Hospital, Dublin. Of the first 100 women referred for HyCoSy, the indication for referral was investigation of infertility in 72%, recurrent miscarriage in 22% and other reasons in 6%. Sixty-four women were referred from general gynaecological clinics, 29 from the specialised infertility clinic and seven women were referred from other hospitals. The procedure was completed in 97% of cases and tubal patency successfully assessed in 95%. Saline hysterosonography was performed in 96 cases. Tubal assessment with Echovistt showed bilateral tubal patency in 73%, bilateral occlusion in 10% and unilateral patency in 12%. All women were discharged within 30 minutes of the procedure. We concluded that hysterosalpingocontrastsonography is an easily introduced, successful outpatient technique, which is well tolerated by women and provides clinically relevant information in women with infertility or recurrent miscarriage.

Journal Article↗

Are the immediate complications of conisation with the large loop similar to those with the knife?

One hundred patients underwent conisation with large loop excision of the transformation zone. The overall immediate complication rate was 6%. There were no preoperative complications. Three patients were treated with antibiotics for infection and three patients had a secondary haemorrhage. No patient required a blood transfusion or cervical suturing and no patient returned to the operating theatre.

Journal Article↗

Are routine sensitivity test data suitable for the surveillance of resistance? Resistance rates amongst Escherichia coli from blood and CSF from 1991-1997, as assessed by routine and centralized testing.

Surveillance of antibiotic resistance can be undertaken by compilation of routine data or by central testing of isolates. Routine results can be obtained cheaply and in sufficient quantities for correlation with population and prescribing denominators but there is concern about their quality. As one of a series of ongoing studies to assess this quality, we compared the proportions of resistance amongst Escherichia coli from patients with bacteraemia or meningitis between 1991 and 1997 (i) as recorded in routine data reported to the PHLS and (ii) as found in tests performed at the PHLS Laboratory of Enteric Pathogens (LEP). These two data sets both showed an overall upward trend in the proportion of isolates resistant to ampicillin, trimethoprim, gentamicin and ciprofloxacin. The average annual percentage increase in resistance was estimated in separate logistic regression models, and 95% confidence intervals (CI) were determined. The annual percentage increases in the proportions of isolates reported resistant were similar in the two data sets for trimethoprim, gentamicin and ciprofloxacin but differed for ampicillin. The upward trends were statistically significant except for gentamicin resistance in the LEP data set, where the 95% CI straddled zero. The proportions of resistant isolates for each antibiotic in the two data sets each year were in poorer agreement than the trends; however, the 95% CI of the difference of proportions resistant between the routine and LEP data sets straddled zero in 4 or 5 of the 7 years studied. Some discrepancies might be explained by geographical bias in the sampling or by differences in definitions of resistance. Thus (i) the proportion of resistant isolates tested at LEP almost always fell within the ranges bounded by the highest and lowest proportions for individual Regional Health Authorities, as recorded in the routine data, and (ii) the fact that LEP consistently recorded less gentamicin resistance but more ciprofloxacin resistance than the routine could be explained by breakpoint differences. We conclude that routine susceptibility data for ampicillin, ciprofloxacin, gentamicin and trimethoprim appear sound for E. coli and might be suitable for correlation with other data, e.g. for prescribing.

Bacteremia↗

Evidence for a telomere-independent "clock" limiting RAS oncogene-driven proliferation of human thyroid epithelial cells.

An initiating role for RAS oncogene mutation in several epithelial cancers is supported by its high incidence in early-stage tumors and its ability to induce proliferation in the corresponding normal cells in vitro. Using retroviral transduction of thyroid epithelial cells as a model we ask here: (i) how mutant RAS can induce long-term proliferation in an epithelial cell in contrast to the premature senescence observed in fibroblasts; and (ii) what is the "clock" which eventually triggers spontaneous growth arrest even in epithelial clones generated by mutant RAS. The early response to RAS activation in thyroid epithelial cells showed two features not seen in fibroblasts: (i) a marked decrease in expression of the cyclin-dependent kinase inhibitor (CDKI) p27(kip1) and (ii) the absence of any induction of p21(waf1). When proliferation eventually ceased (after up to 20 population doublings) this occurred despite undiminished expression of mutant RAS and was tightly correlated with a return to the initial high level of p27(kip1) expression, together with the de novo appearance of p16(ink4a). Importantly, neither the CDKI changes nor the proliferative life span of RAS-induced epithelial clones was altered by induction of telomerase activity through forced expression of the catalytic subunit, hTERT, at levels sufficient to immortalize human fibroblasts. These data provide a basis for cell-type differences in sensitivity to RAS-induced proliferation which may explain the corresponding tumor-type specificity of RAS mutation. They also show for the first time in a primary human cell model that a telomere-independent mechanism can limit not only physiological but also oncogene-driven proliferation, pointing therefore to a tumour suppressor mechanism additional, or alternative, to the telomere clock.

Catalytic Domain↗

Centralisation of oesophageal cancer services; the view from the periphery.

There is debate as to whether patients requiring resection for oesophageal cancer should be referred to specialist centralised units rather than being managed by general surgeons in district general hospitals (DGH). The aim of this study was to determine the effects of centralising oesophageal cancer surgery on outcome and quality of service for patients with oesophageal cancer in a peripheral region. Patients with biopsy proven oesophageal cancer diagnosed over a 4 year period were identified from pathology records. Patients were divided into two groups; Group 1 (n = 60) from the first two years of the study who had any surgery performed by a general surgeon within the DGH and Group 2 (n = 53) from the latter two years of the study who had any surgery performed in a regional cardiothoracic unit. The post-operative mortality rate was lower in the specialist unit, 5.6% vs. 12.5%, but this was not statistically significant. There were no significant differences in survival rates; 3 month, 1 year, 2 year and 3 year survival rates were 63% vs. 62%, 24% vs. 25%, 12% vs. 8% and 7% vs. 6% in Groups 1 and 2, respectively. Referral rates for a surgical opinion were significantly lower in Group 2--92% vs. 63% p < 0.01 by Chi-squared test. Patients waited significantly longer from diagnosis to definitive treatment in Group 2--median 15 days vs. 23 days p = 0.17 by Mann-Whitney test. In conclusion, survival rates are not necessarily improved by centralisation of oesophageal cancer surgery and quality of service may be poorer.

Adenocarcinoma↗

Infant feeding practices of Anglo American and Asian Indian American mothers.

OBJECTIVE: To compare infant feeding practices of Anglo-American (AA) (n = 25) and Asian-Indian American (AIA) mothers (n = 25) residing in the southeastern United States. METHODS: Feeding practices (breast-feeding, formula-feeding, introduction of solid foods) were assessed at infant ages one, three, six, nine and twelve months for a total of 250 interviews conducted in the home. Mothers' sources of information about infant feeding practices and dietary intakes of their infants were collected (24-hour recalls). RESULTS: Compared to their AIA counterparts, AA mothers breast-fed for significantly longer durations and introduced formula and solid foods into the infants' diet at a later age (p<0.05). Throughout the first year, AA mothers relied primarily upon health professionals for infant feeding information compared to AIA mothers, who sought information primarily from the family network during the first six months and relied more on health professionals during the second six months of the infant's life. Throughout the first twelve months, infants of both groups exceeded 100% of the RDA for energy, protein, calcium, iron, vitamin A, and vitamin C. CONCLUSION: Health professionals, including nutrition educators, should educate AIA mothers about and encourage AA mothers to follow current feeding recommendations and guidelines about breast-feeding, formula-feeding and introducing solid foods.

Adult↗

Levomepromazine for nausea and vomiting in advanced cancer.

Levomepromazine (previously known as methotrimeprazine), despite virtually no high quality scientific data to support its use, has become a very popular antiemetic for use in patients with advanced cancer. This article considers the reasons for this.

Dopamine Antagonists↗

Characterisation of regulatory sequences at the Epstein-Barr virus BamHI W promoter.

Epstein-Barr virus, a human gammaherpesvirus, possesses a unique set of latent genes whose constitutive expression in B cells leads to cell growth transformation. The initiation of this growth transforming infection depends on a viral promoter in BamHI W (Wp) whose regulation is poorly understood. Using Wp reporter constructs in in vitro transfection assays, we found that Wp was 11- to 190-fold more active in B cell than in non-B cell lines and that three regions of the promoter (termed UAS1, UAS2, and UAS3) contributed to transcriptional activation. The upstream regions UAS3 (-1168 to -440) and UAS2 (-352 to -264) both functioned in a cell lineage-independent manner and were together responsible for the bulk of Wp activity in non-B cells; mutational analysis indicated the importance of a YY1 binding site in UAS2 in that context. By contrast, UAS1 (-140 to -87) was B cell specific and was the key determinant of the promoter's increased activity in B cell lines. Mutational analysis of UAS1 sequences combined with in vitro bandshift assays revealed the presence of three binding sites for cellular factors in this region. When mutations that abolished factor binding in bandshift assays were introduced into a Wp reporter construct, the loss of any one of the three UAS1 binding sites was sufficient to reduce promoter activity by 10- to 30-fold in B cells. From sequence analysis, two of these appear to be novel transcription factor binding sites, whereas the third was identified as a cyclic AMP response element (CRE). Our data indicate that this CRE interacts with CREB and ATF1 proteins present in B cell nuclear extracts and that this interaction is important for Wp activity.

Activating Transcription Factors↗

Does increased resistance on umbilical artery Doppler preclude a trial of labour?

OBJECTIVE: To determine whether patients with increased resistance on umbilical artery Doppler velocimetry could be safely allowed a trial of labour. DESIGN: The Coombe Womens' Hospital is a university teaching hospital which takes tertiary referrals. All singleton pregnancies found to have increased resistance (>2 SD above the mean for gestational age) on umbilical artery Doppler ultrasound between 1993 and 1995 inclusively were identified from the ultrasound database and reviewed, retrospectively. Cases where the umbilical artery waveform reverted to normal or deteriorated to absent end diastolic flow on a subsequent scan were excluded. The 118 cases identified were divided into two groups, those that were delivered by elective caesarean section and those that laboured. RESULTS: Forty-five patients were delivered by elective caesarean section and 73 were allowed to labour. In the group that laboured over 90% delivered vaginally and 9.8% were delivered by emergency caesarean section. Three babies had a cord pH less than 7.20 in the group that laboured. Two babies had an Apgar score of less than 7 at 5 min in the group that were delivered electively. There were no neonatal seizures or perinatal deaths in either of the two groups. CONCLUSIONS: This study shows that patients with increased resistance on umbilical artery Doppler can be allowed a trial of labour without compromising the fetal outcome. We would suggest that consideration be given to induction of labour in selected patients as an alternative to elective section.

Adult↗

The phenomenon of "picky eater": a behavioral marker in eating patterns of toddlers.

OBJECTIVE: To determine if toddlers who were considered "picky eaters" had lower dietary scores than non-picky eaters, and if family environment and socioeconomic status were significantly related to picky eater status and dietary scores. METHODS: An incomplete block design provided two interviews at randomly assigned times (24, 28, 32, or 36 months) of Caucasian mothers from upper socioeconomic (n=74) and lower socioeconomic status (n=44). Using trained interviewers, 6 days of food intake, two administrations of a questionnaire about toddler's eating behavior, and one administration of the Family Environment Scales were collected in the home. MANOVA, discriminant function analysis, and logistic regression procedures were used to determine significant differences between picky and non-picky eater groups. RESULTS: Picky eaters had lower dietary variety (p=.03) and diversity scores (p=.009) than non-picky eaters. Mothers of picky eaters compared to those of non-picky eaters used persuasion (p=.0001) and ranked their child's eating behaviors as more problematic (p=.0001). CONCLUSION: Toddlers perceived by their mothers as picky eaters had significantly lower dietary variety and diversity scores. Parents need information and strategies to increase the number of foods acceptable to their toddlers and to develop a sound feeding plan.

Body Height↗

Unwelcome customers? The epidemiology of removal from general practitioner lists in Sheffield.

BACKGROUND: The 1990 contract and the 1991 fundholding scheme encouraged speculation that general practitioners (GPs) may remove patients from their lists for financial reasons. Despite assertions that patient removals are increasing, little evidence exists on the number or trends in removals. AIM: To describe the epidemiology of removals by time, place, and person, and to determine whether removals have increased in recent years. METHOD: Descriptive analysis of routine data relating to all removals of Sheffield residents from GP lists during 1991-1996. RESULTS: Removal from a doctor's list was a rare event (2.4 per 1000 patients per year) that did not become more common over the period examined. Removal rates varied by age, sex, and practice, with relatively high rates among children, young women, and the over-75s. There was a significant tendency for higher removal rates in more deprived parts of the city. CONCLUSION: Removal rates have not increased in Sheffield. The reasons for the variation in rates by age, sex, and practice are unknown. The higher rates noted in the under-fives and young women are consistent with the possibility that the 1990 target payment scheme may have increased removal rates in these age groups.

Adolescent↗

Post-operative feeding strategies for infants with cleft lip.

UNLABELLED: Post-operative feeding techniques for infants following primary repair of cleft lip vary considerably. Recommendations range from immediate return to nipple feeding post-operatively to abstinence from nipple feeding for up to 6 weeks. Different surgeons prescribe different post-operative feeding protocols among and within centers. The purposes of this retrospective study (n = 42) were to: (1) identify the specific nonnipple feeding guidelines given to caregivers prior to surgery and the duration for those practices to be used in the post-operative period, (2) describe caregiver compliance, and (3) identify post-operative complications (e.g. dehiscence) related to type and duration of feeding strategies. Feeding guidelines included: nonnipple feeding for 6 weeks (n = 28, 67%), 3 weeks (n = 6, 14%), 2 weeks (n = 6, 14%), and unrestricted return to nipple (n = 2, 5%). Nearly all caregivers (n = 37, 88%) complied with recommendations. The others (n = 5, 12%) returned their infants to nipple feeding sooner than recommended (three in the nonnipple group for 6 weeks, and one each in the other two groups). No medical/surgical complications were related to feeding strategies. CONCLUSION: caregivers typically comply with post-operative feeding recommendations. However, the variability in those recommendations should be reduced with feeding made as easy as possible and not a jeopardy to wound healing.

Bottle Feeding↗

Purification of a fatty acid-stimulated protein-serine/threonine phosphatase from bovine brain and its identification as a homolog of protein phosphatase 5.

An arachidonic acid-stimulated Ser/Thr phosphatase activity was detected in soluble extracts prepared from rat pituitary clonal GH4C1 cells, rat or bovine brain, and bovine heart. The enzyme activity was purified to homogeneity from bovine brain as a monomer with a Mr of 63,000 and a specific activity of 32 nmol of Pi released per min/mg of protein when assayed in the presence of 10 microM phosphocasein in the absence of lipid. Arachidonic acid stimulated activity 4-14-fold, with half-maximal stimulation at 50-100 microM, when assayed in the presence of a variety of phosphosubstrates including casein, reduced carboxamidomethylated and maleylated lysozyme, myelin basic protein, and histone. Oleic acid, linoleic acid, and palmitoleic acid also stimulated activity; however, saturated fatty acids and alcohol or methyl ester derivatives of fatty acids did not significantly affect activity. The lipid-stimulated phosphatase was identified as the bovine equivalent of protein phosphatase 5 or a closely related homolog by sequence analysis of proteolytic fragments generated from the purified enzyme. When recombinant rat protein phosphatase 5 was expressed as a cleavable glutathione S-transferase fusion protein, the affinity-purified thrombin-cleaved enzyme exhibited a specific activity and sensitivity to arachidonic acid similar to those of the purified bovine brain enzyme. These results suggest that protein phosphatase 5 may be regulated in vivo by a lipid second messenger or another endogenous activator.

Amino Acid Sequence↗