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C Wells

Publications and source records attributed to C Wells.

At least 19 recordsLinked to original sources

Impact of a national external quality assessment scheme for breast pathology in the UK.

BACKGROUND: This article presents the results and observed effects of the UK National Health Service Breast Screening Programme (NHSBSP) external quality assurance scheme in breast histopathology. AIMS/METHODS: The major objectives were to monitor and improve the consistency of diagnoses made by pathologists and the quality of prognostic information in pathology reports. The scheme is based on a twice yearly circulation of 12 cases to over 600 registered participants. The level of agreement was generally measured using kappa statistics. RESULTS: Four main situations were encountered with respect to diagnostic consistency, namely: (1) where consistency is naturally very high-this included diagnosing in situ and invasive carcinomas (and certain distinctive subtypes) and uncomplicated benign lesions; (2) where the level of consistency was low but could be improved by making guidelines more detailed and explicit-this included histological grading; (3) where consistency could be improved but only by changing the system of classification-this included classification of ductal carcinoma in situ; and (4) where no improvement in consistency could be achieved-this included diagnosing atypical hyperplasia and reporting vascular invasion. Size measurements were more consistent for invasive than in situ carcinomas. Even in cases where there is a high level of agreement on tumour size, a few widely outlying measurements were encountered, for which no explanation is readily forthcoming. CONCLUSIONS: These results broadly confirm the robustness of the systems of breast disease diagnosis and classification adopted by the NHSBSP, and also identify areas where improvement or new approaches are required.

Breast Neoplasms↗

The NHS breast screening programme (pathology) EQA: experience in recent years relating to issues involved in individual performance appraisal.

BACKGROUND: The original role of the National Health Service breast screening programme (pathology) external quality assessment (EQA) scheme was educational; it aimed to raise standards, reinforce use of common terminology, and assess the consistency of pathology reporting of breast disease in the UK. AIMS/METHODS: To examine the performance (scores) of pathologists participating in the scheme in recent years. The scheme has evolved to help identify poor performers, reliant upon setting an acceptable cutpoint. Therefore, the effects of different cutpoint strategies were evaluated and implications discussed. RESULTS/CONCLUSIONS: Pathologists who joined the scheme improved over time, particularly those who did less well initially. There was no obvious association between performance and the number of breast cancer cases reported each year. This is not unexpected because the EQA does not measure expertise, but was established to demonstrate a common level of performance (conformity to consensus) for routine cases, rather than the ability to diagnose unusual/difficult cases. A new method of establishing cutpoints using interquartile ranges is proposed. The findings also suggest that EQA can alter a pathologist's practice: those who leave the scheme (for whatever reason) have, on average, marginally lower scores. Consequently, with the cutpoint methodology currently used (which is common to several EQA schemes) there is the potential for the cutpoint to drift upwards. In future, individuals previously deemed competent could subsequently be erroneously labelled as poor performers. Due consideration should be given to this issue with future development of schemes.

Breast Neoplasms↗

Antisense transcription in the mammalian transcriptome.

Antisense transcription (transcription from the opposite strand to a protein-coding or sense strand) has been ascribed roles in gene regulation involving degradation of the corresponding sense transcripts (RNA interference), as well as gene silencing at the chromatin level. Global transcriptome analysis provides evidence that a large proportion of the genome can produce transcripts from both strands, and that antisense transcripts commonly link neighboring "genes" in complex loci into chains of linked transcriptional units. Expression profiling reveals frequent concordant regulation of sense/antisense pairs. We present experimental evidence that perturbation of an antisense RNA can alter the expression of sense messenger RNAs, suggesting that antisense transcription contributes to control of transcriptional outputs in mammals.

Animals↗

The transcriptional landscape of the mammalian genome.

This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.

3' Untranslated Regions↗

Improved sensitivity of sputum smear microscopy after processing specimens with C18-carboxypropylbetaine to detect acid-fast bacilli: a study of United States-bound immigrants from Vietnam.

The goal of this study was to evaluate the effect of the specimen-processing method that uses the detergent C18-carboxypropylbetaine (CB-18) on the sensitivity of acid-fast bacillus (AFB) staining. Vietnamese immigrants with abnormal chest radiographs provided up to three sputum specimens, which were examined for acid-fast bacilli by use of direct auramine and Ziehl-Neelsen staining. The remaining sputum was split; half was cultured, and the other half was incubated with CB-18 for 24 h, centrifuged, and examined for AFB by both staining methods. CB-18 processing improved the sensitivity of AFB staining by 20 to 30% (only differences in auramine sensitivity were statistically significant) but reduced specificity by approximately 20% (P < 0.05). These findings have direct utility for overseas migrant tuberculosis screening programs, for which maximizing test sensitivity is a major objective.

Adult↗

High prevalence of drug-resistant tuberculosis, Republic of Lithuania, 2002.

BACKGROUND: Nations of the former Soviet Union have the world's highest reported levels of resistance to anti-tuberculosis drugs. We conducted the first national survey of anti-tuberculosis drug resistance in the Republic of Lithuania. METHODS: We tested Mycobacterium tuberculosis isolates from all incident culture-positive pulmonary TB patients registered in 2002. New patients were those treated for <1 month with any first-line anti-tuberculosis drug (isoniazid [INH], rifampin [RMP], ethambutol, or streptomycin); previously treated patients were those treated for > or =1 month. RESULTS: Of 1163 isolates, 475 (41%) were resistant to at least one first-line drug, and 263 (23%) were resistant to at least INH and RMP (MDR); this included 76/818 (9.3%) from new patients and 187/345 (54%) from previously treated patients. Of 52 MDR isolates randomly selected for extended testing at an international reference laboratory, 27 (51%, 95%CI 38-66) had resistance to pyrazinamide, 21 (40%, 95%CI 27-55) to kanamycin, and 9 (17%, 95%CI 8-30) to ofloxacin. CONCLUSIONS: The prevalence of MDR-TB in Lithuania is among the world's highest. Among MDR-TB isolates, aminoglycoside and fluoroquinolone resistance were common. To combat drug-resistant TB, Lithuania has implemented the WHO global TB control strategy (DOTS), and is developing an MDR-TB treatment program (DOTS-Plus).

Adolescent↗

Improved tuberculosis case detection through public-private partnership and laboratory-based surveillance, Kannur District, Kerala, India, 2001-2002.

BACKGROUND: Efforts to intensify global tuberculosis (TB) control are limited by difficulties in coordinating with private doctors. More than half of Indian TB patients may initially consult a private provider, but many are neither diagnosed accurately nor treated effectively. We established and evaluated a public-private partnership based on surveillance of TB detected in private laboratories and use of standardised directly observed treatment regimens. METHODS: In one district, the governmental TB control programme offered training in microscopy to all large private sector laboratories, and educated private physicians on the importance of microscopy for TB diagnosis. We reviewed records from participating private laboratories and all publicly diagnosed patients. RESULTS: Of 2328 pulmonary TB patients registered from July 2001 to December 2002, 404 (17%) were detected in the private sector. The annual new AFB-positive case notification rate increased by 21%, from 27.8/100,000 in 2000 to 33.5/100,000 in 2002. Surveillance at private laboratories found an additional 260 nonregistered AFB-positive patients. CONCLUSIONS: This public-private partnership substantially increased TB case detection and established a sustainable framework for private sector involvement in TB control. In the setting of a strong public sector programme, the combination of active surveillance of private laboratories along with physician sensitisation is a promising approach to improve TB case detection.

Humans↗

Histological quality of polyps resected using the cold versus hot biopsy technique.

BACKGROUND AND STUDY AIMS: The monopolar hot biopsy technique is a widespread method of removing and cauterizing small colonic polyps. Due to the insulated cups of the biopsy forceps, it also allows adequate histological interpretation of the resected specimen. In our experience, polyps removed using the monopolar hot biopsy technique have been less histologically interpretable in comparison with polyps removed using cold biopsy forceps. The aim of this study was to assess and compare the diagnostic quality of polyps obtained using the hot biopsy and cold biopsy techniques. PATIENTS AND METHODS: This was a prospective study of consecutive patients undergoing colonoscopy with removal of polyps using either hot biopsy or cold biopsy techniques. One experienced endoscopist using the same techniques carried out the biopsies. An experienced gastrointestinal pathologist, blinded to the technique used, evaluated the specimens for diameter, artifacts, cautery damage, tissue fragmentation, and general histological and diagnostic quality. Statistical analysis was carried out using the chi-squared test, Fisher's exact test, and Student's t-test. RESULTS: Forty-three consecutive patients (84 % men; mean age 63.8 +/- 15 years) underwent 88 biopsies (45 hot biopsies and 43 cold biopsies). There were no statistically significant differences between the two study groups with regard to demographic data, indications for colonoscopy, endoscopic findings, or polyp size. Cautery damage, architectural distortion, and tissue fragmentation occurred more frequently in polyps resected using the hot biopsy technique ( P < 0.001). CONCLUSIONS: The quality of the specimens removed by cold biopsy was generally better than when using hot biopsy technique. Histological evaluation is more difficult in polyps resected with the hot biopsy technique in comparison with the cold biopsy technique. When the nature of polyps affects the patient's management, a biopsy may be obtained before polyp coagulation.

Aged↗

Managing chronic headaches in the clinic.

Chronic daily headache (CDH), which is often linked to a history of migraine, tension-type headache and the abuse of headache medications, and cluster headache are the best known of the chronic headaches. These headaches may not be well recognised or well treated in primary care. This article outlines the development of management algorithms for these headache subtypes, designed for use by the primary care physician with an interest in headache. Principles of care for chronic headaches include implementation of screening procedures, differential diagnosis, tailoring of management to the individual's needs, proactive follow-up and a team approach to care. These principles can be customised to the headache subtype by the selection of appropriate therapies. The optimal treatments for CDH include physical therapy to the neck if there is any stiffness there, withdrawal of abused medications and treatment of any subsequent withdrawal symptoms and headache prophylaxis, together with the provision of acute medications as rescue therapy. Optimal treatments for cluster headache include short- and long-term prophylaxis to prevent the headaches developing and acute medications for use as rescue. If treatment is ineffective, alternative medications can be provided at follow-up, with the possibility of referral for refractory patients.

Adolescent↗

Risk factors for death during tuberculosis treatment in Orel, Russia.

SETTING AND METHODS: In Orel, high tuberculosis (TB) case fatality rates have persisted despite successful implementation of the World Health Organization (WHO) global TB control strategy. We conducted a case control study to identify risk factors for mortality among Orel TB patients reported from October 1999 through June 2001. Cases were patients who died within 8 months of treatment initiation. We analyzed data abstracted from medical records using conditional logistic regression. RESULTS: Over the 21-month period, 63/1069 (5.9%) TB patients overall and 45/521 (8.6%) sputum smear-positive patients died during treatment. Compared to 192 controls, independent risk factors for death for both smear-positive and smear-negative patients included unemployment (adjusted odds ratio [AOR] 4.9, 95% confidence interval [CI] 1.9-12.9), homelessness (AOR 9.5, 95% CI 1.3-70.9), congestive heart failure (AOR 5.4, 95% CI 1.9-15.9), chronic lung disease (AOR 2.4, 95% CI 1.1-5.4), cancer (AOR 7.2, 95% CI 1.2-45.0), bilateral disease on chest X-ray (AOR 6.3, 95% CI 2.3-17.1), and hyperbilirubinemia (AOR 5.2, 95% CI 1.1-25.3). Among deaths, the median time from treatment initiation to death was 35 days. CONCLUSIONS: The diagnosis and treatment of TB in suspects with the observed comorbidities and risk factors should be aggressively pursued. The association of unemployment and homelessness with mortality suggests a contribution of poverty to death during TB treatment.

Adolescent↗

Metastases to the breast revisited: radiological-histopathological correlation.

Metastases to the breast from extramammary tumours are infrequent. The main challenge in diagnosis is differentiating them from primary breast cancer. Radiologically this can be difficult as there are no specific imaging characteristics for metastases to the breast. Cytopathological evaluation, as well as full radiological assessment, is vital to avoid unnecessary surgery. Sources of primary tumours include a wide variety of cancers. In this pictorial review we illustrate a number of the commonest sources of primary tumours including lymphoma, lung, ovarian and cervical carcinoma, intestinal carcinoid and rare cases of Ewing's sarcoma and malignant pigmented melanocytic schwannoma (low-grade malignant melanoma).

Adult↗

High-resolution backscatter electron imaging of colloidal gold in LVSEM.

High-resolution backscatter electron (BSE) imaging of colloidal gold can be accomplished at low voltage using in-lens or below-the-lens FESEMs equipped with either Autrata-modified yttrium aluminium garnet (YAG) scintillators doped with cerium, or with BSE to secondary electron (SE) conversion plates. The threshold for BSE detection of colloidal gold was 1.8 keV for the YAG detector, and the BSE/SE conversion was sensitive down to 1 keV. Gold particles (6, 12 and 18 nm) have an atomic number of 79 and were clearly distinguished at 500,000x by materials contrast and easily discriminated from cell surfaces coated with platinum with an atomic number of 78. BSE imaging was relatively insensitive to charging, and build up of carbon contamination on the specimen was transparent to the higher energy BSE.

Electrons↗

Impact of the growing HIV-1 epidemic on multidrug-resistant tuberculosis control in Latvia.

Latvia, a country with levels of multidrug-resistant (MDR) TB among the highest in the world, experienced a 58-fold increase in HIV seroprevalence among all persons tested in the country from 1996 through 2001. In addition, HIV seroprevalence among TB cases increased from 0.4% to 1.4%, and among MDR-TB cases from 0% to 5.6% from 1998 through 2001, potentially compromising gains made to date in controlling the country's MDR-TB epidemic. The following will be critical to the future of MDR-TB control in Latvia: containing HIV transmission in the country, particularly among injection drug users who comprised 72% of all HIV cases reported in the country by the end of 2001, as well as 81% of all MDR-TB cases co-infected with HIV; expanding capabilities to more rapidly detect and successfully treat patients with MDR-TB; developing mutual TB control strategies between the National TB and AIDS programs; and continuing to improve institutional infection control measures, particularly in hospitals and prisons where an increasing number of persons infected with HIV come into contact with persons with active MDR-TB.

Communicable Disease Control↗

Encouraging outcomes in the first year of a TB control demonstration program: Orel Oblast, Russia.

SETTING: Orel, Russia. OBJECTIVE: To evaluate outcomes of tuberculosis (TB) patients treated in the first year of a TB control demonstration project using a revised strategy of directly observed treatment, short-course (DOTS). Standard methods recommended by World Health Organization (WHO) were adapted to include mycobacterial cultures. DESIGN: Retrospective cohort analysis of TB patients diagnosed between October 1999 and September 2000. RESULTS: Among 749 TB patients, 65% had bacteriologic confirmation of pulmonary TB, 31% were diagnosed clinically, and 4% had extra-pulmonary TB. Most (92%) had no previous TB treatment, but 8% were identified as retreatment cases. Of all patients, 41% had new sputum smear-positive TB. No patients were HIV-infected. Multidrug-resistant (MDR) TB levels were 3% among new and 17% among retreatment patients. Among new smear-positive patients, treatment success was 79% (72% cure, 7% completion); remaining outcomes were 8% failure, 3% default, 8% death, and 1% transfer. Success rates for new culture-positive and clinically diagnosed patients were 81% and 91%, respectively. CONCLUSION: Despite historical differences, successful implementation of the revised TB strategy in Russia is possible. Treatment success rates were high, suggesting WHO targets of 85% cure for smear-positive patients is attainable. Obstacles include drug resistance and elevated death rates among smear-positive patients.

Adolescent↗

Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs.

Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.

Alternative Splicing↗

Application of pressurized liquid extraction technology to pharmaceutical solid dosage form analysis.

The technique of pressurized liquid extraction has been evaluated for the extraction of active ingredients from pharmaceutical dosage forms using montelukast sodium oral chewable tablets as a model. The extraction method was optimized for the number of extraction cycles, extraction time, extraction solvent composition and temperature. Samples were extracted using two cycles of water for 2 min with a cell temperature of 40 degrees C and a pressure of 1.0 x 10(4) kPa, to disintegrate the tablet, followed by three cycles of methanol for 3 min at 70 degrees C and 1.0 x 10(4) kPa, to solubilize montelukast sodium. The method demonstrated an extraction efficiency of 98.2% of label claim and an RSD of 1.3% (n=10), as compared to 97.6% and an RSD of 0.9% obtained using a validated mechanical extraction method.

Chromatography, Liquid↗

Telomerase activity and Bcl-2 expression in human breast cancer.

AIMS: Telomerase is a ribonucleoprotein that synthesizes telomeres and plays an important role in cellular immortalization. Bcl-2 gene encodes for a mitochondrial protein thought to prevent apoptosis of normal cells. We previously reported telomerase activity in 74% of human invasive breast cancers and detected a significant association between telomerase activity and prognostic parameters such as nodal status, tumour size and cellular proliferation. We hypothesized that telomerase reactivation in human breast cancer was associated with increased immunohistochemical expression of Bcl-2. METHODS: Bcl-2 immunohistochemical expression was determined in 25 infiltrating breast carcinomas with known telomerase activity (17 telomerase-positive and 8 telomerase-negative). The percentage of strongly and moderately stained tumour cells for Bcl-2 was determined by a breast pathologist who was blinded to telomerase data. Fisher's exact test was used to examine the association between telomerase activity and Bcl-2 expression. RESULTS: The median percentage of strongly stained tumour cells was 50% for telomerase-positive tumours (range, 0--100%) and 45% for telomerase-negative tumours (range, 0--100%). Twelve (70%) of 17 telomerase-positive tumours expressed strong or moderate Bcl-2 staining in >50% of tumour cells compared with six (75%) of eight telomerase-negative tumours (P=1.0). CONCLUSION: Telomerase reactivation seems to be independent of Bcl-2 protein expression in human breast cancer.

Adult↗