BRCA: the breast, ovarian, and other cancer genes.
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BRCA2 Protein↗
Biomedical subjects
J Boyd
Publications and source records attributed to J Boyd.
Telomerase activity in sex cord-stromal tumors of the ovary.
OBJECTIVE: Telomerase is a ribonucleoprotein that protects chromosomes from degradation and end-to-end fusions by maintaining telomere length. Studies have shown that telomerase is present in 95% of gynecologic malignancies and in 88% of epithelial ovarian carcinomas but undetectable in benign tissue. The aim of this investigation was to determine whether telomerase is present in sex cord-stromal tumors and whether telomerase activity is indicative of patient outcomes. METHODS: Forty-five consecutive sex cord-stromal ovarian tumors were analyzed by using reverse transcription-polymerase chain reaction for expression of human telomerase, human telomerase reverse transcriptase, and telomerase activity. RESULTS: Of the 29 patients with malignant cell types (granulosa cell, Sertoli-Leydig cell, and steroid cell tumors), 21 of the 28 patients (75%) available for follow-up had recurrence, with a mean follow-up of 86 months (95% CI, 36-157 months). The telomerase repeat amplification protocol assay had a sensitivity of 74% and specificity of 94% for malignancy. Patients with telomerase-positive tumors had a mean disease-free interval of 66.5 months; for those with telomerase-negative tumors the interval was 90 months. In addition, patients with telomerase-positive tumors were more likely to be dead from disease or alive with disease than those without telomerase activity, and they showed trends toward requiring a larger number of surgical procedures for the treatment of their disease. However, these trends were not statistically significant. CONCLUSION: Although activation of telomerase is clearly an important step in carcinogenesis, it is unlikely to be helpful in the clinical management of sex cord-stromal tumors of the ovary.
DNA-Binding Proteins↗
Gender and survival: a population-based study of 201,114 men and women following a first acute myocardial infarction.
OBJECTIVES: We tested the hypotheses that the effect of gender on short-term case fatality following a first admission for acute myocardial infarction (AMI) varies with age, and that this effect is offset by differences in the proportion of men and women who survive to reach hospital. BACKGROUND: Evidence is conflicting regarding the effect of gender on prognosis after AMI. METHODS: All 201,114 first AMIs between 1986 and 1995 were studied. Both 30-day and 1-year case fatality were analyzed for the 117,749 patients hospitalized and for all first AMIs, including deaths before hospitalization. The effect of gender and its interaction with age on survival was examined using multivariate modeling. RESULTS: Gender-based differences in survival varied according to age in hospitalized patients, with younger women having higher 30-day case fatality than men (e.g., <55 years, women 6.5% vs. 4.8% men, p < 0.0001). When deaths from first AMI before hospitalization were included in 30-day case fatality, women were less likely to die (adjusted odds ratio 0.9, confidence interval 0.89 to 0.93). Gender was not an independent predictor of one-year survival (p = 0.16). CONCLUSIONS: Female gender increases the probability of surviving to reach hospital, and this outweighs the excess risk of death occurring in younger women following hospitalization. Overall, men have a higher 30-day case fatality than women. Women do not fare worse than men after AMI when age and other factors are taken into account. However, men are more likely to die before hospitalization.
Age Factors↗
Solution structure of the LDL receptor EGF-AB pair: a paradigm for the assembly of tandem calcium binding EGF domains.
BACKGROUND: From the observed structure and sequence of a pair of calcium binding (cb) epidermal growth factor-like (EGF) domains from human fibrillin-1, we proposed that many tandem cbEGF domains adopt a conserved relative conformation. The low-density lipoprotein receptor (LDLR), which is functionally unrelated to fibrillin-1, contains a single pair of EGF domains that was chosen for study in the validation of this hypothesis. The LDLR is the protein that is defective in familial hypercholesterolaemia, a common genetic disorder that predisposes individuals to cardiovascular complications and premature death. RESULTS: Here, we present the solution structure of the first two EGF domains from the LDL receptor, determined using conventional NMR restraints and residual dipolar couplings. The cbEGF domains have an elongated, rod-like arrangement, as predicted. The new structure allows a detailed assessment of the consequences of mutations associated with familial hypercholesterolaemia to be made. CONCLUSIONS: The validation of the conserved arrangement of EGF domains in functionally distinct proteins has important implications for structural genomics, since multiple tandem cbEGF pairs have been identified in many essential proteins that are implicated in human disease. Our results provide the means to use homology modeling to probe structure-function relationships in this diverse family of proteins and may hold the potential for the design of novel diagnostics and therapies in the future.
Amino Acid Sequence↗
Strategic planning for ICCD clubhouse implementation: development of the Clubhouse Research and Evaluation Screening Survey (CRESS). International Center for Clubhouse Development.
The Clubhouse Research and Evaluation Screening Survey (CRESS) is a brief instrument designed to predict clubhouse readiness for certification assessment and, hence, performance in regard to expected model outcomes. The development of CRESS provides a practical example of the methodological challenges involved in creating a brief and valid screening instrument. Developed over a period of 5 years, CRESS is grounded in a series of workgroups, surveys, and pilot studies conducted by Fountain House and the International Center for Clubhouse Development (ICCD) in New York City. CRESS is shown to have criterion-oriented validity for the measurement of ICCD clubhouse model-related performance, as well as demonstrated ease in administration to a national sample of mental health programs.
Certification↗
Psychopathology and young people with Down's syndrome: childhood predictors and adult outcome of disorder.
There is a scarcity of follow-up studies into adult life of psychiatric disorder in young people with intellectual disability. The key aims of the present study were: (1) to determine the outcome of psychopathology present in childhood in individuals with Down's syndrome (DS); and (2) to look at childhood predictors of adult psychiatric disorder. Fifty-two young people with DS were identified from a sample of 193 subjects examined in childhood and adolescence for psychiatric and behaviour disorder. These young adults were interviewed for the presence of psychiatric disorder. No significant relationship was found between childhood mental disorder and psychiatric disorder in adult life for those individuals with DS. Early childhood factors of psychiatric disorder, challenging behaviour and family environment, except social background, did not predict adult psychopathology in young people with DS. Childhood disorder in individuals with DS has a good early prognosis with little evidence of continuity of the disorder into adult life.
Adolescent↗
Inspired gas temperature during mechanical ventilation: effects of environmental temperature and airway temperature probe position.
OBJECTIVES: To determine the inspired gas temperature during mechanical ventilation with: (i) five different humidicrib temperatures; (ii) two airway temperature probe (ATP) positions; and (iii) four ATP adaptors. METHODOLOGY: An observational study in the Neonatal Intensive Care Laboratory, Westmead Hospital. The inspired gas temperature was measured at the proximal end of the endotracheal tube (ETT) during conventional mechanical ventilation using a Tele-thermometer. Inspired gas temperature measurements were made with: (i) the humidicrib temperature set at 30.8. 32.9, 35.2, 36.2. or 37.2 degrees C; (ii) the ATP either (A) positioned inside the humidicrib at the distal end of the inspiratory tubing or (B) positioned outside the humidicrib 50 cm proximal to the ETT, with the inspired gas temperatures set at 36.5 and 39.0 degrees C, respectively; and (iii) the measurements repeated with four different ATP adaptors at each humidicrib temperature and each ATP position. RESULTS: With the ATP inside the humidicrib, there were no significant differences between set and actual inspired gas temperature. However, with the ATP outside the humidicrib, there were significant decreases in inspired gas temperature at each humidicrib temperature. For instance, with the ATP outside the humidicrib and set at 39.0 degrees C, the inspired gas temperature decreased to 34.7+/-0.2 degrees C at a humidicrib temperature of 30.8 degrees C and to 37.7+/-0.2 degrees C at a humidicrib temperature of 37.2 degrees C. The type of ATP adaptor also had a significant effect on inspired gas temperature. CONCLUSIONS: With the ATP placed outside the humidicrib and with variations of humidicrib temperature, infants are likely to have inspired gas temperatures that are significantly different to the desired temperature. Certain ATP adaptors cause these variations in inspired gas temperature to be more pronounced. Extreme care must be used to avoid suboptimal inspired gas temperatures with these environmental variations and the ATP positioned outside the humidicrib.
Environment, Controlled↗
Inspired gas humidity during mechanical ventilation: effects of humidification chamber, airway temperature probe position and environmental conditions.
OBJECTIVES: To determine the inspired gas humidity during mechanical ventilation with: (i) four different humidification chambers; (ii) two airway temperature probe (ATP) positions; (iii) five different humidicrib temperatures; and (iv) insulating the inspiratory limb with bubble wrap. METHODOLOGY: An observational study in the Neonatal Laboratory and Neonatal Intensive Care Unit, Westmead Hospital. The humidity of the inspired gas was measured at the proximal end of the endotracheal tube (ETT) during mechanical ventilation. Inspired humidity measurements were made with four different humidification chambers (Fisher & Paykel (F&P Healthcare Pty Ltd, Auckland, New Zealand) auto refill MR290. F&P manual refill MR310, Suruga (Suruga Inc. Humidifiers, Vincent Medical, Dongguan, China) manual refill MI-20 and MI-10F) with the humidity control (relative humidity setting) set at - 2. Measurements were made with the ATP positioned either; (A) at the distal end of the inspiratory tube inside the humidicrib or (B) outside the humidicrib 50 cm proximal to the ETT. The inspired gas temperatures were set at 36.5 degrees C and at 39.0 degrees C, respectively. For each of the different humidification chambers and ATP positions, inspired humidity measurements were made with the humidicrib temperature set at 30.8, 32.9, 35.2, 36.2, or 37.2 degrees C. Two further sets of measurements were made, one with the inspiratory limb insulated with bubble wrap and the second set without bubble wrap. RESULTS: There were significant differences in inspired humidity with the four humidification chambers at both ATP positions at all humidicrib temperatures. Both Suruga humidification chambers produced significantly higher inspired gas humidities under most conditions. Positioning the ATP outside the humidicrib produced significantly higher inspired gas humidities than with the ATP inside the humidicrib. Insulating the inspiratory tubing with bubble wrap also significantly improved the inspired gas humidity. CONCLUSIONS: Significant differences in inspired gas humidity were found with the humidification chambers tested. The position of the ATP and the set temperature had a significant impact on the absolute humidity of the inspired gas. In general, higher inspired gas humidities were obtained with the ATP outside the humidicrib. However, condensation of water close to the ETT appeared at low humidicrib temperatures (< 36.2 degrees C) with the ATP outside the humidicrib and extreme care should be taken that particulate water does not enter the lungs under these conditions.
Environment, Controlled↗
Segmental mandibular reconstruction by microincremental automatic distraction osteogenesis: an animal study.
We investigated the reconstruction of a surgically created critical size mandibular defect in sheep using a newly developed automatic distraction device. The device has an implantable component, which is fixed to the mandible to allow the transfer of the transport disc across the created defect, and an external component which is mounted on the activation pump and secured away from the site of bone distraction. Compression of the bellows in the external component causes fluid to be forced through the connecting tube into the distraction component. Distraction at a rate of 1 mm over 24 h was achieved in six sheep. New bone generated at the site of the created defects both anterior (compression side) and posterior (tension side) to the transport disc and had similar radiodensity to the adjacent mandibular bone eight weeks after the completion of distraction.
Angiography↗
A refined solution structure of hen lysozyme determined using residual dipolar coupling data.
A high resolution NMR structure of hen lysozyme has been determined using 209 residual 1H-15N dipolar coupling restraints from measurements made in two different dilute liquid crystalline phases (bicelles) in conjunction with a data set of 1632 NOE distance restraints, 110 torsion angle restraints, and 60 hydrogen bond restraints. The ensemble of 50 low-energy calculated structures has an average backbone RMSD of 0.50+/-0.13A to the mean structure and of 1.49+/-0.10A to the crystal structure of hen lysozyme. To assess the importance of the dipolar coupling data in the structure determination, the final structures are compared with an ensemble calculated using an identical protocol but excluding the dipolar coupling restraints. The comparison shows that structures calculated with the dipolar coupling data are more similar to the crystal structure than those calculated without, and have better stereochemical quality. The structures also show improved quality factors when compared with additional dipolar coupling data that were not included in the structure calculations, with orientation-dependent 15N chemical shift changes measured in the bicelle solutions, and with T1/T2 values obtained from 15N relaxation measurements. Analysis of the ensemble of NMR structures and comparisons with crystal structures, 15N relaxation data, and molecular dynamics simulations of hen lysozyme provides a detailed description of the solution structure of this protein and insights into its dynamical behavior.
Animals↗
Magnetic resonance imaging as the primary imaging modality in children presenting with acute non-traumatic hip pain.
The role of magnetic resonance imaging (MRI) in children presenting with acute non-traumatic hip pain was evaluated prospectively. Hip MRI was performed in addition to standard investigations (arthrosonography +/- hip radiographs) in 50 children presenting to the accident and emergency department of a paediatric hospital. MRI was performed on an open 0.23T system and comprised gradient echo T1 weighted coronal, fast spin echo T2 weighted coronal and inversion recovery spin echo (IRSE) axial sequences. Diagnostic quality MRI examinations were obtained in 94% of children. The IRSE sequence was the most reliable at determining underlying disorder (p<0.002). Interobserver agreement on the MRI examinations was very good with unweighted kappa value of 0.89, 95% confidence intervals 0.79, 0.99. Sensitivity of MRI was 0.79 (0.68, 0.90, specificity 1.00 (0.89, 1.00), accuracy 0.81 (0.70, 0.92), PPV 1.00 (0.89, 1), NPV 0.36 (0.25, 0.47). Sensitivity of standard imaging was 0.70 (0.54-0.86), specificity 0.57 (0.41, 0.73), accuracy 0.72 (0.56, 0.88), PPV 0.91 (0.75, 1.00), NPV 0.24 (0.08, 0.40). MRI correctly identified all seven children with serious underlying disorder whereas conventional imaging correctly diagnosed only two. Pelvic musculoskeletal infection was associated with the combination of marked alteration in signal in tissues adjacent to a symptomatic hip and an erythrocyte sedimentation rate of >20 mm 1st h (p<0.0001). In conclusion, MRI is a practical, well accepted and accurate non-invasive imaging technique in children presenting with acute non-traumatic hip pain. Combined with inflammatory markers MRI can be used to determine those children who require aggressive management. Where it is available, MRI is the imaging modality of choice in this condition.
Adolescent↗
The ICCD benchmarks for clubhouses: a practical approach to quality improvement in psychiatric rehabilitation.
OBJECTIVE: The study evaluated whether the average performance of clubhouses certified by the International Center for Clubhouse Development (ICCD) should be considered valid benchmarks for clubhouse programs. METHODS: A representative sample of clubhouses more than three years old that were based on the Fountain House model participated in a 1998 mail survey. To verify that ICCD certification is a valid indicator of program quality for use in setting benchmark performance rates, 71 certified and 48 noncertified programs were compared on a variety of organizational variables. RESULTS: Even though certified and noncertified clubhouses were similar in organizational structure and resources, findings from a logistic regression analysis confirmed that certified clubhouses provided a wider array of rehabilitation services and achieved higher rates of employment. CONCLUSIONS: The findings suggest that ICCD certification is a valid indicator of program quality. The ICCD has therefore proposed that the average performance of certified U.S. clubhouses in specific domains be adopted as benchmarks for organizational performance. When tailored for programs in particular regions and with specific levels of funding, the ICCD benchmarks for clubhouse performance set fair and reasonable expectations for clubhouse programs and for the design of performance contracts between departments of mental health and ICCD clubhouses.
Benchmarking↗
Electronic health summaries--building on the foundation of Scottish Record Linkage system.
Developing electronic patient records is currently a priority for Health Services, so that the clinician treating the patient has all the relevant information available on the desktop. However, as with paper records, there is the danger of information overload, with key information being missed. It is now recognized that electronic health summaries of patient events will be needed. This paper describes the Scottish Record Linkage system, which has been routinely used over the last 10 years to build event histories for patients in the NHS in Scotland. Probability matching has been used to identify records belonging to an individual since a unique patient identification number has not been in general use. We present examples of use of this rich information resource, either for clinical decision making, evidence based medicine, or population needs assessment, and investigate how the system may be developed in a data-warehousing environment to populate electronic health summaries for the five million residents of Scotland.
Decision Making↗
Analysis of fibroblast growth factor receptor 3 S249C mutation in cervical carcinoma.
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Adenocarcinoma↗
Evidence of improving prognosis in heart failure: trends in case fatality in 66 547 patients hospitalized between 1986 and 1995.
BACKGROUND: Contemporary survival in unselected patients with heart failure and the population impact of newer therapies have not been widely studied. Therefore, we have documented case-fatality rates (CFRs) over a recent 10-year period. METHODS AND RESULTS: In Scotland, all hospitalizations and deaths are captured on a single database. We have studied case fatality in all patients admitted with a principal diagnosis of heart failure from 1986 to 1995. A total of 66 547 patients (47% male) were studied. Median age was 72 years in men and 78 years in women. Crude CFRs at 30 days and at 1, 5, and 10 years were 19.9%, 44.5%, 76.5%, and 87.6%, respectively. Median survival was 1.47 years in men and 1.39 years in women (2.47 and 2. 36 years, respectively, in those surviving 30 days). Age had a powerful effect on survival, and sex, comorbidity, and deprivation had modest effects. One-year CF was 24.2% in those aged <55 years and 58.1% in those aged >84 years. After adjustment, 30-day CFRs fell between 1986 and 1995, by 26% (95% CI 15 to 35, P<0.0001) in men and 17% (95% CI 6 to 26, P<0.0001) in women. Longer term CFRs fell by 18% (95% CI 13 to 24, P<0.0001) in men and 15% (95% CI 10 to 20, P<0.0001) in women. Median survival increased from 1.23 to 1. 64 years. CONCLUSIONS: Heart failure CF is much higher in the general population than in clinical trials, especially in the elderly. Although survival has increased significantly over the last decade, there is still much room for improvement.
Aged↗
Absence of premalignant histologic, molecular, or cell biologic alterations in prophylactic oophorectomy specimens from BRCA1 heterozygotes.
BACKGROUND: The high mortality associated with ovarian carcinoma is largely a reflection of the inability to diagnose the disease at an early stage; the identification of a histologic lesion or molecular marker associated early stages of transformation would represent an important advance in understanding the natural history of this cancer. The existence of individuals with germline mutations in the ovarian and breast carcinoma susceptibility gene BRCA1 represents a unique opportunity to search for such premalignant alterations in ovarian tissues that are at unusually high risk for tumorigenesis. In this study, the authors addressed the hypothesis that pathologically normal ovaries removed from BRCA1 heterozygotes are likely to display premalignant histologic, molecular, and/or cell biologic alterations that may provide insight into early stages of ovarian tumorigenesis. METHODS: Ovarian tissues from 18 BRCA1 heterozygotes and from 20 age-matched controls were examined in a blinded fashion for histologic evidence of surface epithelial pseudostratification, epithelial inclusion cysts, deep cortical invaginations of surface epithelium, increased stromal cell activity, and surface papillomatosis. Immunohistochemical analyses for expression of BRCA1, p53, and ERBB-2 and quantitation of cell proliferation (Ki-67 expression) and apoptosis (TUNEL assay), were also performed on all specimens. RESULTS: Although histologic alterations were observed, there was no difference in frequency between cases and controls. Analysis of BRCA1 expression revealed ubiquitous nuclear immunoreactivity in the surface epithelial cells of all ovaries. Similarly, no evidence was found of p53 overexpression in any ovarian tissue or of a difference in ERBB-2 expression between cases and controls. Finally, no differences were observed in epithelial cell proliferation or apoptosis. CONCLUSIONS: Clinically, normal ovaries from BRCA1 heterozygotes do not show evidence of premalignant alterations in histology, molecular markers, cell proliferation, or apoptosis, indicating that such changes are likely rare.
Adult↗
Ten year audit of secondary prevention in coronary bypass patients.
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Anticholesteremic Agents↗