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Biomedical subjects

L Moore

Publications and source records attributed to L Moore.

At least 37 records · Page 2Linked to original sources

The use of hairless (IAF/HA-HO) guinea pigs for the determination of delayed-type hypersensitivity to tuberculin.

Guinea pigs are a classic animal model for studying delayed-type hypersensitivity (DTH) reactions. However, skin irritation due to hair removal can interfere with the evaluation of the modulation of these responses by various mediators. A DTH model using hairless (IAF/HA-HO) guinea pigs, sensitized with complete Freund's adjuvant and repeatedly skin tested with tuberculin, purified protein derivative, (PPD) has therefore been developed. At 10 weeks after sensitization, intradermal PPD elicited minimal erythema at 6 h, which increased over the next 18 h to a maximum at 24 h, and declined by 48 h. The response could be quantified by bioassay using graded doses of PPD. Reactions at 24 h were characterized by predominantly mononuclear cell deep and superficial dermal infiltrates. Dermal DTH in hairless guinea pigs is thus, grossly and histologically similar to that seen in Hartley guinea pigs.

Animals↗

Pseudomonas aeruginosa infection mimicking erythema annulare centrifugum.

A 3-year-old girl receiving chemotherapy for acute lymphocytic leukaemia developed a rapidly expanding red annular plaque on her thigh, initially without signs of systemic toxicity or local pain. Subsequently she developed Pseudomonas aeruginosa sepsis and purpura at the leading edge of the plaque. Skin biopsy showed an extensive necrotizing vasculitis with numerous Gram-negative bacilli in the blood vessel walls. In immunocompromised individuals, skin biopsy and culture of cutaneous lesions for bacteria and fungi should be considered even in the absence of signs of systemic toxicity or multiple lesions.

Child, Preschool↗

Nitric oxide synthase is absent in only a subset of cases of pyloric stenosis.

PURPOSE: The aim of this study was to study nitric oxide synthase (NOS) immunohistochemistry in the pyloric muscle and establish the role of nitric oxide in pyloric stenosis. METHODS: Pyloric muscle biopsy specimens were obtained from 20 patients with pyloric stenosis during pyloromyotomy. Ten control specimens without pyloric disease were obtained from autopsy performed less than 4 hours after death on age-matched babies who died of other causes. Tissues were fixed in 4% paraformaldehyde immediately. A monoclonal antibody against the neuronal form of NOS (bNOS) was used for immunohistochemistry. RESULTS: Immunohistochemistry showed activity of bNOS in the control specimens and some pyloric stenosis specimens. This shows that NOS is present in the pylorus in normal cases as well as in a few cases of pyloric stenosis. CONCLUSIONS: NOS deficiency leading to lack of locally available nitric oxide causes a failure of smooth muscle relaxation. This may account for the cause of pyloric stenosis in infants. However, this study shows that this is true probably only in a subset of cases. The etiology of pyloric stenosis may still be multifactorial. Further investigations are required regarding the etiology of pyloric stenosis. J Pediatr Surg 36:616-619.

Biopsy, Needle↗

Assessing service quality in paediatric audiology and early deaf education.

Quality monitoring and assurance is a key aspect of evidence-based service provision in health and education. Part I of the present paper summarizes the results from a survey in which performance of health-based paediatric audiology services in the UK was assessed against existing good practice guidelines (NDCS, 1994, 1996). The results of the survey indicated varied levels of provision, with guidelines commonly not followed. Part II of the paper reports the detailed development of two short questionnaires designed to provide scores (out of 100) reflecting aspects of service quality in paediatric audiology services and in early deaf education services. The results from the use of the two indices (the Paediatric Audiology Service Index (PASI) and the Deaf Education Early Service Index (DEESI)) are presented along with data from some component questions. Although some services are functioning close to guideline levels of service, the overall distribution of scores is such as to raise serious concerns about the variability of quality and the consequent inequity of provision for children with permanent hearing loss and their families in both health and education services.

Age Factors↗

Gas chromatography-mass spectrometry confirmation of Cozart RapiScan saliva methadone and opiates tests.

The object of this study was to determine the sensitivity and specificity of the Cozart RapiScan onsite saliva test for methadone and opiates versus laboratory-based enzyme immunoassay (EIA) and gas chromatography-mass spectrometry (GC-MS) confirmation. Fifty saliva specimens were obtained from 28 volunteers among persons entering a substance abuse clinic. Specimens were tested onsite using the Cozart RapiScan Saliva test and Cozart RapiScan Reader. Specimens were retested by Cozart Microplate EIA assays on receipt at the laboratory and then frozen for later confirmation by GC-MS. For GC-MS, deuterated internal standards were added to specimen aliquots which were extracted using solid-phase columns at pH 6 and eluted with dichloromethane/isopropanol/ammonia (80:19:2). The dry residues were derivatized with PFOH and PFPA and dried, and the reconstituted extract was injected and quantitated by GC-MS. The Cozart RapiScan Methadone Saliva Assay was found to have a sensitivity and specificity of 100% +/- 12% versus GC-MS (2-ng/mL cutoff) and a sensitivity of 100% +/- 11% and a specificity of 95% +/- 2.4% versus the Microplate EIA for methadone (30-ng/mL cutoff). The Cozart RapiScan Saliva Opiate test had a sensitivity of 100% +/- 12% and a specificity of 92% +/- 3.2% versus GC-MS (2-ng/mL cutoff) and a sensitivity of 96% +/- 2.2% and specificity of 95% +/- 2.4% versus the Microplate EIA for opiates (30-ng/mL cutoff).

Gas Chromatography-Mass Spectrometry↗

School smoking policies and smoking prevalence among adolescents: multilevel analysis of cross-sectional data from Wales.

OBJECTIVE: To examine the association between school smoking policies and smoking prevalence among pupils. DESIGN: Multilevel analysis of cross-sectional data from surveys of schools and pupils. SETTING: 55 secondary schools in Wales. SUBJECTS: 55 teachers and 1375 pupils in year 11 (aged 15-16). MAIN OUTCOME MEASURES: Self-reported smoking behaviour. RESULTS: The prevalence of daily smoking in schools with a written policy on smoking for pupils, teachers, and other adults, with no pupils or teachers allowed to smoke anywhere on the school premises, was 9.5% (95% confidence interval (CI) 6.1% to 12.9%). In schools with no policy on pupils' or teachers' smoking, 30.1% (95% CI 23.6% to 36.6%) of pupils reported daily smoking. In schools with an intermediate level of smoking policy, 21.0% (95% CI 17.8% to 24.2%) smoked every day. School smoking policy was associated with school level variation in daily smoking (p = 0.002). In multilevel analysis, after adjusting for pupils' sex, parents' and best friends' smoking status, parental expectations, and alienation from school, there was less unexplained school level variation, but school smoking policy remained significant (p = 0.041). The association of smoking policy with weekly smoking was weaker than for daily smoking, and not significant after adjustment for pupil level variables. Both daily and weekly smoking prevalence were lower in schools where pupils' smoking restrictions were always enforced. Enforcement of teacher smoking restrictions was not significantly associated with pupils' smoking. CONCLUSIONS: This study demonstrates an association between policy strength, policy enforcement, and the prevalence of smoking among pupils, after having adjusted for pupil level characteristics. These findings suggest that the wider introduction of comprehensive school smoking policies may help reduce teenage smoking.

Adolescent↗

Provision of emergency contraception in general practice and confidentiality for the under 16's: results of a postal survey by general practitioners in Avon.

OBJECTIVE: To describe the provision of emergency contraception and confidentiality for the under 16's by general practitioners (GPs) in Avon, in order to inform the development of a health promotion intervention in schools in Avon. DESIGN: Confidential postal questionnaire survey. SETTING: All principals in general practice in Avon Health Authority, South West England. SUBJECTS: Five hundred and eighty general practice principals were sent the questionnaire. RESULTS: Four hundred and eighty-six (84%) principals in general practice responded to the questionnaire. Only three (0.6%) GPs did not provide hormonal emergency contraception. Nearly half (232, 47.7%) would fit the intrauterine device (IUD) as emergency contraception. Fitting an IUD was associated with female gender of the GP (OR = 2.34, 95% CI 1.53-3.71), and whether the GP had a family planning qualification (OR = 4.55, 95% CI 2.41-8.60). Three hundred and fifty-two (72%) respondents would provide emergency contraception on a Sunday if requested to do so by a 14-year-old who reported having had unprotected sex the night before. Practice nurses in 26 (5%) of the respondent's practices were available to provide advice and tablets for patients requesting hormonal emergency contraception. However, 74 (21%) respondents employed a family planning trained practice nurse who was not involved in any way in the provision of emergency contraception. Practice nurses remain an under used resource in this area. CONCLUSION: Our findings suggest that most GPs provide hormonal emergency contraception. Only eight (1.6%) of respondents would need to ask for parental consent prior to providing hormonal emergency contraception to a 14-year old-girl. Young people need to be informed of GPs widespread adherence to current confidentiality guidelines.

Adolescent↗

Blind trials of an onsite saliva drug test for marijuana and opiates.

The objective of these clinical trials was to calculate the performance, limit of detection, specificity and sensitivity of a novel, semi-quantitative immunoassay for drugs of abuse in saliva and to determine operator bias when measured blind by four different operators. The test is based on lateral flow gold particle technology coupled with digital photography to provide a semi-quantitative end point. The performance of the test was compared with that of enzyme immunoassays and GC/MS methods. Volunteers consumed marijuana or codeine and their saliva was collected 0.25 to 24 h later with the Cozart RapiScan collection device. The sensitivity and specificity of the opiate test were both 100%+/-10.4% for codeine for 9 h after dosing. The cutoff of the marijuana test at 10 ng/mL THCA was too high to detect marijuana use for more than a few hours after smoking. There was no operator bias because the results were presented in written form either as "positive" or "negative" for each of the five drug classes on the screen of the hand-held reader.

Cannabinoids↗

Managing atypical squamous cells of undetermined significance in Papanicolaou smears.

OBJECTIVE: To assess strategies using repeated conventional Pap smear and human papillomavirus (HPV) DNA testing, alone or in combination, for identifying women with concomitant cervical intraepithelial neoplasia 2 and 3 (CIN 2/3) in women with atypical squamous cells of undetermined significance (ASCUS) in their Pap smears. STUDY DESIGN: A total of 360 women cytologically diagnosed with ASCUS were referred for colposcopy and underwent a repeat Pap smear, a biopsy when necessary and HPV testing using three different modes of detection of high-oncogenic-risk HPV types: 1, first-generation Hybrid Capture test (HC-1) (Digene Diagnostics, Gaithersburg, Maryland); 2, second-generation Hybrid Capture test (HC-2); and 3, polymerase chain reaction (PCR). RESULTS: Nineteen patients (5.3%) had histologic CIN 2/3. The sensitivity and specificity of the repeat Pap smear alone for the detection of CIN 2/3 were 73.7% and 62.9%, respectively, when referring all women with a repeat Pap smear using an ASCUS-positive threshold. The proportion of women referred for colposcopy was 39.0%. When HPV testing for high risk was used for identification of women with histologic CIN 2/3, sensitivity and specificity were, respectively, 68.4% and 85.9% for HC-1, 89.5% and 73.9% for HC-2 and 89.5% and 59.0% for PCR. The rate of referral for colposcopy of these three modes of HPV testing was 16.9%, 29.4% and 44.0%, respectively. The sensitivity and specificity for identification of women with concomitant CIN 2/3 using a combination of repeat cytology showing a low grade squamous intraepithelial lesion or high grade squamous intraepithelial lesion and/or a test positive for high-oncogenic-risk HPV group were, respectively, 94.7% and 73.2% when used in combination with HC-2. The referral rate of women for colposcopy of this combined strategy was 30.4%. CONCLUSION: As compared to the strategy using abnormal repeat Pap smear alone, those using high-risk HPV testing with Hybrid Capture showed statistically significantly higher specificities and lower proportions of women with ASCUS referred for colposcopy. In particular, a promising strategy would be to refer for colposcopy only women with repeat Pap smears showing squamous intraepithelial lesion and/or those positive for high-risk HPV detected by Hybrid Capture testing.

Adolescent↗

Chromosome 9 deletions and recurrence of superficial bladder cancer: identification of four regions of prognostic interest.

In a previous study, loss of heterozygosity (LOH) of 28 chromosome 9 microsatellite markers was assessed on 139 Ta/T1 bladder tumors. LOH at one or more loci was detected in 67 tumors, 62 presenting subchromosomal deletions. One hundred and thirty-three of these patients have now been followed for up to 8 years. The purpose of the present study was to evaluate the potential biological significance of chromosome 9 deletions in superficial bladder tumors at initial diagnosis. High grade was associated with LOH (P=0.004). Large tumors carried more frequently 9p deletions (P=0.022). Female patients had more chromosome 9q LOH than male patients did (P=0.010). Chromosome 9 LOH at all loci was associated with an elevated risk of recurrence but four regions were associated with a particularly high risk of recurrence. Multivariate analysis taking into account grade, stage, size and number of tumors showed that tumors deleted in the regions 9ptr-p22, 9q22.3, 9q33, and 9q34 recurred significantly more rapidly than those without deletions (Recurrence rate ratio=2.32, 2.53, 2.52 and 2.43 respectively). Log-rank statistics comparing Kaplan-Meier survival curves for the same chromosomal regions confirmed the correlation (P=0.0002, 0.010, 0.002 and 0.009 respectively). Only four patients progressed to muscle-invasive disease. They all had extensive deletions on 9q but none had deletions at 9ptr-p22. This study suggests a link between chromosome 9 anomalies and recurrence of superficial bladder cancer.

Aged↗

Detection of human herpes virus 6 DNA in fetal hydrops.

Human herpes virus 6 (HHV6) DNA was detected in two of eight fetuses with hydrops and none of ten non-hydropic dead fetuses. Both cases with HHV6 DNA had chromosomal abnormalities. Positive results were confirmed with a second PCR specific for an alternate region of the HHV6 genome. Restriction endonuclease analysis confirmed that the viral DNA was representative of HHV6 type A.

DNA, Viral↗

Tumorigenic pathways in low-stage bladder cancer based on p53, MDM2 and p21 phenotypes.

Our aim was to determine whether the pattern of expression of the interrelated proteins p53, MDM2 and p21 could shed light on the etiopathogenic mechanisms of superficial bladder tumors. Protein expression was detected by immunohistochemistry (IHC) using monoclonal antibodies (MAbs) Pab 1801 for p53, IF2 for MDM2 and EA10 for p21 on 269 newly diagnosed bladder tumors (214 pTa and 55 pT1; 93 grade I, 145 grade 2 and 31 grade 3). While no p21 immunoreactivity was found in normal urothelium, 85% of tumors were strongly p21-positive. MDM2 was overexpressed in 44% of tumors, almost all being also positive for p21. p53 was overexpressed in 20% of cases: 66% of p53-positive tumors were also MDM2 positive, compared with only 38% of p53-negative tumors. p53 mutations were studied by direct DNA sequencing in a subset of 24 high-grade tumors. Both MDM2 and p21 were less frequently expressed in p53 mutated tumors compared with tumors with a wild-type gene. Distinct phenotypes were correlated with the frequency of poorly differentiated (grade 3) tumors. The most common phenotypes were p21+/MDM2-/p53- and p21+/MDM2+/p53- observed in 38% and 29% of tumors, respectively. Grade 3 tumors were found in 4% and 8% of these 2 groups, in contrast with 30% frequency in p21+/p53+ tumors (p = 0.002) regardless of their MDM2 phenotype. Four of the 5 (80%) tumors that were p53-positive but negative for p21 were grade 3. Our data suggest that several tumorigenic pathways for superficial bladder tumors can be reflected by the expression pattern of these 3 proteins.

Aged↗

Lifetime occupational physical activity and incidental prostate cancer (Canada).

OBJECTIVES: The objective of this study was to assess the risk of incidental prostate cancer associated with occupational physical activity in a population of patients treated for benign prostatic hyperplasia (BPH) by transurethral resection of the prostate (TURP). METHODS: This case-control study was conducted in men aged 45 and over referred for TURP to relieve the symptoms of BPH in one of the eight hospitals of the Quebec City area between October 1990 and December 1992. Cases (n = 64) were all men incidentally diagnosed with prostate cancer and controls were the 546 patients with solely a histological diagnosis of BPH. At the time of their interview, the patients completed a diet history questionnaire and a general questionnaire including a lifetime occupational history. Physical activity was estimated for each job according to data from the US Department of Labor. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) of incidental prostate cancer associated with occupational physical activity while adjusting for confounders. RESULTS: A positive association was observed between "ever having a job with sedentary/light work" and incidental prostate cancer (OR = 1.9; 95% CI = 1.1-3.3). ORs for prostate cancer associated with 0%, 1-49%, and > or =50% of life spent in jobs with sedentary/light work were 1.0, 1.6 (95% CI = 0.8-3.1), and 2.5 (95% CI = 1.2-5.2), respectively (p-value for trend = 0.01). Occupational physical activity in the job held during the longest period was inversely associated with prostate cancer: ORs were 1.0, 0.5 (95% CI = 0.2-1.2), 0.4 (95% CI = 0.2-0.9) and 0.2 (95% CI = 0.1-0.7) for sedentary, light, moderate, and high/very high levels, respectively (p-value for trend = 0.008). CONCLUSIONS: The results of this study suggest that physical activity at work could have a beneficial effect on the occurrence of prostate cancer.

Aged↗

PCR-based detection of the polymorphism at codon 136 in the ovine prion protein gene.

In many breeds of sheep, a polymorphism at codon 136 of the prion protein gene has been shown to be strongly associated with the risk of developing scrapie. A single-step procedure for detecting this allelic variation is described here. When performed on a series of animals, the test was in complete agreement with their genotypes as had been previously determined by sequencing. The test is potentially easier and quicker to perform than any of the variety of methods that are currently used for this purpose.

Animals↗

P53 point mutations in initial superficial bladder cancer occur only in tumors from current or recent cigarette smokers.

Sequencing of p53 exons 5-8 was carried out on 51 initial superficial bladder tumors selected on the basis of high grade and/or p53 overexpression (immunohistochemistry without antigen retrieval). Fourteen point mutations in 13 tumors and one 21 bp deletion in another tumor were identified. In addition, a germ-line mutation corresponding to a previously described polymorphism was detected in exon 6, in two tumors. Mostly G-->A transitions (10) were found. Only three occurred at CpG sites, suggesting a major role for exogenous carcinogens in bladder tumorigenesis. Immunostaining for p53 and MDM2, using antigen retrieval, was carried out on the same tumors. A correlation was found between the percentage of p53-positive cells and the presence of p53 mutations (P = 0.005). No correlation was found between overexpression of p53 and MDM2 in this selected cohort of mostly high grade tumors. The presence of p53 mutations was also analyzed as a function of the smoking habits of the patients. A significant association was found between the presence of p53 point mutations and the number of years of smoking (P = 0.043). All patients with tumors carrying missense or nonsense p53 mutations had smoked for >/=30 years and if former smokers, had stopped for </=5 years. However, no correlation was found between the presence of p53 point mutations and the number of cigarettes smoked. The deletion mutation was the only one present in a tumor from a non-smoker. The data suggest that duration of exposure to carcinogens is the most critical factor in p53 mutagenesis in bladder cancer.

Genes, p53↗

A yeast taf17 mutant requires the Swi6 transcriptional activator for viability and shows defects in cell cycle-regulated transcription.

In Saccharomyces cerevisiae, the Swi6 protein is a component of two transcription factors, SBF and MBF, that promote expression of a large group of genes in the late G1 phase of the cell cycle. Although SBF is required for cell viability, SWI6 is not an essential gene. We performed a synthetic lethal screen to identify genes required for viability in the absence of SWI6 and identified 10 complementation groups of swi6-dependent lethal mutants, designated SLM1 through SLM10. We were most interested in mutants showing a cell cycle arrest phenotype; both slm7-1 swi6Delta and slm8-1 swi6Delta double mutants accumulated as large, unbudded cells with increased 1N DNA content and showed a temperature-sensitive growth arrest in the presence of Swi6. Analysis of the transcript levels of cell cycle-regulated genes in slm7-1 SWI6 mutant strains at the permissive temperature revealed defects in regulation of a subset of cyclin-encoding genes. Complementation and allelism tests showed that SLM7 is allelic with the TAF17 gene, which encodes a histone-like component of the general transcription factor TFIID and the SAGA histone acetyltransferase complex. Sequencing showed that the slm7-1 allele of TAF17 is predicted to encode a version of Taf17 that is truncated within a highly conserved region. The cell cycle and transcriptional defects caused by taf17(slm7-1) are consistent with the role of TAF(II)s as modulators of transcriptional activation and may reflect a role for TAF17 in regulating activation by SBF and MBF.

Amino Acid Sequence↗