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Biomedical subjects

B D Wright

Publications and source records attributed to B D Wright.

At least 19 recordsLinked to original sources

Overexpression of HER2/neu in solid tumours: an immunohistochemical survey.

AIMS: Using a standardized immunohistochemical assay we have evaluated 575 primary neoplasms of different histogenesis to determine the incidence of HER2 overexpression in some of the most common categories of human solid neoplasms. This study addresses the variable incidence of HER2 overexpression previously published for some tumour types. METHODS AND RESULTS: The immunohistochemical staining was performed on paraffin sections of surgical specimens and a well-defined scoring system based upon numbers of HER2 receptors expressed on the cell surface was applied. Overexpression of HER2 as defined as a HER2 score of equal or greater than 2 was seen in breast cancer (22%), pulmonary adenocarcinoma (28%), colorectal adenocarcinomas (17%), pulmonary squamous (11%) and gastric adenocarcinomas (11%). As expected, the proportion of cases with a HER2 score of 3 was highest in breast cancer. Contrary to published results prostate and pancreas adenocarcinomas showed a very low incidence of HER2 overexpression. CONCLUSIONS: Overexpression of HER2 is detected immunohistochemically in a proportion of epithelial neoplasms of diverse histogenesis in addition to ductal breast cancer. The standardized format of the assay will allow comparative analyses of studies performed at different institutions.

Female↗

FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family.

Bronchoalveolar lavage fluid from mice with experimentally induced allergic pulmonary inflammation contains a novel 9.4 kDa cysteine-rich secreted protein, FIZZ1 (found in inflammatory zone). Murine (m) FIZZ1 is the founding member of a new gene family including two other murine genes expressed, respectively, in intestinal crypt epithelium and white adipose tissue, and two related human genes. In control mice, FIZZ1 mRNA and protein expression occur at low levels in a subset of bronchial epithelial cells and in non-neuronal cells adjacent to neurovascular bundles in the peribronchial stroma, and in the wall of the large and small bowel. During allergic pulmonary inflammation, mFIZZ1 expression markedly increases in hypertrophic, hyperplastic bronchial epithelium and appears in type II alveolar pneumocytes. In vitro, recombinant mFIZZ1 inhibits the nerve growth factor (NGF)-mediated survival of rat embryonic day 14 dorsal root ganglion (DRG) neurons and NGF-induced CGRP gene expression in adult rat DRG neurons. In vivo, FIZZ1 may modulate the function of neurons innervating the bronchial tree, thereby altering the local tissue response to allergic pulmonary inflammation.

Amino Acid Sequence↗

A new look at the Western Ontario and McMaster Universities Osteoarthritis Index using Rasch analysis.

OBJECTIVE: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a valid and widely used instrument for the assessment of osteoarthritis patients. We examined whether applying Rasch analysis, a new item-response theory, supports its metric properties. METHODS: The metric properties were examined in a cohort of patients with osteoarthritis of the hip or knee. In an exploratory approach, a validated German version of the WOMAC was analyzed using Rasch analysis for its unidimensionality and construct definition. RESULTS: One hundred fifty-eight patients were included in the study. The 3 WOMAC domains--pain, stiffness, and physical function--were unidimensional when examined separately. In an analysis including all items, the stiffness items did not fit the model. This indicates that they are distinct from the pain and function items. Item difficulty analyses revealed redundancy between corresponding pain and function items addressing the same task (e.g., "pain while standing upright" and "difficulty while standing"). CONCLUSION: Applying Rasch analysis to the 3 WOMAC domains confirms their unidimensionality. However, the pain and function items seem to represent the same construct. Thus, it may be possible to simplify these domains to avoid redundancy. The impact of reducing items must nevertheless be examined.

Activities of Daily Living↗

VEGF is required for growth and survival in neonatal mice.

We employed two independent approaches to inactivate the angiogenic protein VEGF in newborn mice: inducible, Cre-loxP- mediated gene targeting, or administration of mFlt(1-3)-IgG, a soluble VEGF receptor chimeric protein. Partial inhibition of VEGF achieved by inducible gene targeting resulted in increased mortality, stunted body growth and impaired organ development, most notably of the liver. Administration of mFlt(1-3)-IgG, which achieves a higher degree of VEGF inhibition, resulted in nearly complete growth arrest and lethality. Ultrastructural analysis documented alterations in endothelial and other cell types. Histological and biochemical changes consistent with liver and renal failure were observed. Endothelial cells isolated from the liver of mFlt(1-3)-IgG-treated neonates demonstrated an increased apoptotic index, indicating that VEGF is required not only for proliferation but also for survival of endothelial cells. However, such treatment resulted in less significant alterations as the animal matured, and the dependence on VEGF was eventually lost some time after the fourth postnatal week. Administration of mFlt(1-3)-IgG to juvenile mice failed to induce apoptosis in liver endothelial cells. Thus, VEGF is essential for growth and survival in early postnatal life. However, in the fully developed animal, VEGF is likely to be involved primarily in active angiogenesis processes such as corpus luteum development.

Age Factors↗

Mapping variables.

This paper describes Mapping Variables, the principal technique for planning and constructing a test or rating instrument. A variable map is also useful for interpreting results. Modest reference is made to the history of mapping leading to its importance in psychometrics. Several maps are given to show the importance and value of mapping a variable by person and item data. The need for a critical appraisal of maps is also stressed.

Maps as Topic↗

Rasch measurement for reducing the items of the Nottingham Health Profile.

The present study aimed to develop a short form of the Spanish version of the Nottingham Health Profile (NHP) by means of Rasch analysis. Data from several Spanish studies that included the NHP since 1987 were collected in a common database. Forty-five different studies were included, covering a total of 9,419 subjects both from the general population and with different clinical pathologies. The overall questionnaire (38 items) was simultaneously analyzed using the dichotomous response model. Parameter estimates, model-data fit and separation statistics were computed. The items of the NHP were additionally regrouped into two different scales: Physical (19 items) and Psychological (19 items). Separated Physical and Psychological parameter estimates were produced using the simultaneous item calibrations as anchor values. Misfitting items were deleted, resulting in a 22 item final short form (NHP22)-11 Physical and 11 Psychological-. The evaluation of the item hierarchies confirmed the construct validity of the new questionnaire. To demonstrate the invariance of the NHP22 item calibrations, Rasch analyses were performed separately for each study included in the sample and for several sociodemographic and health status variables. Results confirmed the validity of using the NHP22 item calibrations to measure different groups of people categorized by gender, clinical and health status.

Health Status Indicators↗

Relationships between disability measures and nursing effort during medical rehabilitation for patients with traumatic brain and spinal cord injury.

OBJECTIVE: The increasing use of disability measures requires that the validity of these instruments be adequately demonstrated. This study sought to evaluate the concurrent validity of one disability measure, the Functional Independence Measure (FIMSM) using minutes of care reported by nursing staff. STUDY DESIGN: Correlational, cohort design. SETTING: Eight inpatient medical rehabilitation hospitals that subscribe to the Uniform Data System for Medical Rehabilitation. PATIENTS OR OTHER PARTICIPANTS: 129 patients with traumatic brain injury (TBI) and 53 patients with traumatic spinal cord injury (SCI). INTERVENTIONS: Routine rehabilitation care. MAIN OUTCOME MEASURES: Patient-nurse contact times were recorded with a stop watch for a 24-hour period during the first and last weeks of inpatient rehabilitation. The FIM was also completed during the first and last weeks of rehabilitation. RESULTS: Contact times declined from the first to last weeks of rehabilitation, concurrent with improving scores on motor and cognitive measures derived from the FIM. Statistically significant correlations between contact times and FIM measures were observed for medication dispensing, treatment provision, and teaching/activities of daily living at admission and discharge. Smaller and usually nonsignificant correlations were observed in activities that did not involve direct patient contact. Contact times increased exponentially as disability increased. CONCLUSIONS: These results support the construct validity of the FIM by demonstrating strong relationships (r values in the range of .40 to .60) between burden of care and a measure of disability.

Adult↗

Improving detection of violence among pregnant adolescents.

PURPOSE: The purpose of this study was to determine whether a systematic assessment protocol could increase reporting of violence among pregnant adolescents compared with a routine prenatal assessment. This study also sought to examine issues related to violence assessment among maternity care coordinators. METHODS: The Maternity Care Coordination (MCC) program in a health department prenatal clinic in North Carolina routinely screened all clients for violence at their first visit. This assessment was not standardized. In 1994, the MCC program implemented a systematic violence assessment protocol for all adolescents (n = 117). The protocol assessed violence at three points during pregnancy by asking one direct question: "Have you been hit, slapped, kicked, or hurt during this pregnancy?" To examine the effectiveness of the system, we retrospectively reviewed the 1993 MCC records in which the coordinators routinely screened clients for violence (n = 129). To examine issues related to screening, we conducted in-depth interviews with the maternity care coordinators. RESULTS: The routine pre-intervention assessment indicated that 5.4% of adolescents 12-19 years of age reported prenatal violence. The systematic assessment protocol resulted in a significant increase in reported violence from 5.4% to 16.2% (odds ratio = 2.9, 95% confidence interval = 1.6, 5.6, adjusted for race). Maternity care coordinators identified five factors related to increased reporting using the standardized protocol: (a) written protocol and data collection form; (b) asking direct, specific questions; (c) not labeling the victim; (d) not naming the perpetrator; and (e) conducting multiple assessments. CONCLUSIONS: Multiple, direct, systematic assessments throughout prenatal care resulted in increased reporting of prenatal violence among adolescents compared to single, routine, nonstructured assessments.

Adolescent↗

Assessing for violence during pregnancy using a systematic approach.

OBJECTIVES: The purpose of this study was to determine whether a systematic, multiple assessment protocol could increase reporting of prenatal violence compared with a one-time routine assessment. METHOD: In 1994, the Maternity Care Coordination (MCC) program in a health department prenatal clinic in North Carolina implemented a concise, systematic assessment protocol on all 384 women who enrolled in the program from April 1994 to April 1995. The protocol assessed for violence at three times during pregnancy using the direct question, "Have you been hit, slapped, kicked, or hurt during this pregnancy?" To determine the effectiveness of the system, we retrospectively examined the 1991-1993 MCC records (n = 1056) in which the care coordinators routinely screened all clients for violence at their first visit only. RESULTS: Compared with the routine assessment approach, the new systematic assessment protocol increased reporting of prenatal violence at the initial prenatal visit from 6.3% to 10.9% (relative risk = 1.7, 95% confidence interval = 1.2, 2.5), and the multiple assessments increased reporting of prenatal violence to 14.1% (relative risk = 2.2, 95% confidence interval = 1.6, 3.1). CONCLUSIONS: Our study suggests that a concise and systematic screening technique using direct questions combined with multiple assessments increased reporting of prenatal violence compared with a single routine assessment.

Confidence Intervals↗

FIM measurement properties and Rasch model details.

To summarize, we take issue with the criticisms of Dickson & Köhler for two main reasons: 1. Rasch analysis provides a model from which to approach the analysis of the FIM, an ordinal scale, as an interval scale. The existence of examples of items or individuals which do not fit the model does not disprove the overall efficacy of the model; and 2. the principal components analysis of FIM motor items as presented by Dickson & Köhler tends to undermine rather than support their argument. Their own analyses produce a single major factor explaining between 58.5 and 67.1% of the variance, depending upon the sample, with secondary factors explaining much less variance. Finally, analysis of item response, or latent trait, is a powerful method for understanding the meaning of a measure. However, it presumes that item scores are accurate. Another concern is that Dickson & Köhler do not address the issue of reliability of scoring the FIM items on which they report, a critical point in comparing results. The Uniform Data System for Medical Rehabilitation (UDSMRSM) expends extensive effort in the training of clinicians of subscribing facilities to score items accurately. This is followed up with a credentialing process. Phase 1 involves the testing of individual clinicians who are submitting data to determine if they have achieved mastery over the use of the FIM instrument. Phase 2 involves examining the data for outlying values. When Dickson & Köhler investigate more carefully the application of the Rasch model to their FIM data, they will discover that the results presented in their paper support rather than contradict their application of the Rasch model! This paper is typical of supposed refutations of Rasch model applications. Dickson & Köhler will find that idiosyncrasies in their data and misunderstandings of the Rasch model are the only basis for a claim to have disproven the relevance of the model to FIM data. The Rasch model is a mathematical theorem (like Pythagoras') and so cannot be disproven by empirical data once it has been deduced on theoretical grounds. Sometimes empirical data are not suitable for construction of a measure. When this happens, the routine fit statistics indicate the unsuitable segments of the data. Most FIM data do conform closely enough to the Rasch model to support generalizable linear measures. Science can advance!

Activities of Daily Living↗

Effect of MgSO4 on heart rate monitoring in the preterm fetus.

OBJECTIVE: To evaluate in a controlled, blind fashion, using both subjective and objective criteria, whether MgSO4 is associated with clinically significant changes in fetal heart rate monitoring. STUDY DESIGN: Fetal heart rate tracings were prospectively collected before and after MgSO4 loading in 50 preterm labor patients. Three obstetricians, blind to treatment status, graded the tracings using both subjective and objective criteria. RESULTS: The baseline fetal heart rate declined slightly after therapy. Subjective, but not objective, evaluation demonstrated a greater likelihood of decreased variability after MgSO4 loading. There was no difference in periodic changes after MgSO4 loading. Multiple regression analysis showed a greater likelihood of decreased variability at earlier gestational ages but no relationship to the serum magnesium level. CONCLUSION: Magnesium sulfate tocolysis is associated with a subjective decrease in fetal heart rate variability in the preterm fetus.

Drug Monitoring↗

Impact of the loop electrosurgical excision procedure on future fertility.

OBJECTIVE: The loop electrosurgical excision procedure (LEEP) is a popular and effective method of conservatively treating premalignant lesions of the cervix in reproductive-age women. While the safety and effectiveness of LEEP has been documented, few data have been collected on the long-term effect of LEEP of the cervix on subsequent fertility. The purpose of this study was to determine that effect. STUDY DESIGN: A retrospective, cohort study with chart review and telephone or mail-in survey. One hundred fifty-eight women seen in the colposcopy clinic at New Hanover Regional Medical Center for abnormal cervical cytologic smears from January 1991 through December 1992 were surveyed concerning their reproductive history since undergoing colposcopy. The study group consisted of 79 women who had been treated with LEEP after demonstrating abnormalities on colposcopically directed cervical biopsy. The control group consisted of 79 women who underwent colposcopy and cervical biopsy without subsequent LEEP of the cervix. RESULTS: One hundred eleven women responded to the survey. In this study group, 11 of the 12 women who desired pregnancy actually became pregnant in the in interval between treatment and completion of the survey. All 17 patients in the control group who desired pregnancy became pregnant. CONCLUSION: In our patient population there appeared to be no significant detrimental effect of LEEP on future fertility. These preliminary findings are reassuring, however, due to the small sample size, the study lacked sufficient power for us to draw definitive conclusions.

Adult↗

Rasch analysis of Visual Analog Scale measurements before and after treatment of Patellofemoral Pain Syndrome in women.

The Visual Analog Scale (VAS) can be used to record subjectively experienced pain in different situations (items). By a mathematical method, the Rasch analysis, the original VAS recordings can be converted to an interval scale. Forty women with Patellofemoral Pain Syndrome (PFPS) reported their pain on the VAS from 12 different situations (items) before and after 12 weeks of rehabilitation. The items recorded pain during the last 3 months, during provocation tests, and during activities such as walking up stairs, jumping and strength testing. It was concluded that the items used for the patients with PFPS were hierarchically ordered in a statistically equivalent manner before and after rehabilitation. Subjectively reported pain after 12 weeks of rehabilitation was significantly alleviated for 23 (58%) of the 40 patients, compared with before rehabilitation. The patients with PFPS did not use the VAS as a linear scale over the full range. Rasch analysis of recordings made with the VAS gave a more detailed pain assessment.

Adolescent↗

Factors affecting number of prenatal care visits during second pregnancy among adolescents having rapid repeat births.

PURPOSE: To examine factors associated with the number of prenatal care visits during second pregnancy for adolescents having a short interval between pregnancies. METHODS: The sample includes all adolescents aged 13 to 17 years whose first pregnancy resulted in a birth at a regional medical center in southeastern North Carolina from January 1983 to December 1989 and who had a repeat pregnancy within 24 months which resulted in a birth. We abstracted data from medical records and birth certificates. We fit a negative binomial regression model to determine the effects of various factors on the number of prenatal care visits during second pregnancy. RESULTS: The number of prenatal care visits during the first pregnancy, poor first birth outcome, interval between first and second pregnancy, and care provided by health department staff during first pregnancy were all positively associated with number of prenatal care visits during second pregnancy when controlling for gestation age of second birth. Other independent variables in the model included maternal age, education, black race, and being unmarried at the time of second birth. CONCLUSIONS: Because prenatal care is important for healthy mothers and babies, adolescents should be encouraged to seek prenatal care early in the first pregnancy. This could be an important time to implement interventions aimed at increasing prenatal care utilization in this and subsequent pregnancies.

Adolescent↗

The structure and stability of the Functional Independence Measure.

The Functional Independence Measure (FIM) records the severity of disability of rehabilitation patients. The necessarily curvilinear relationship between the finite range of recorded FIM raw scores and the conceptually infinite range of additive disability measures is resolved through Rasch analysis. The analysis of admission and discharge FIM ratings of 14,799 patients shows that the 18 FIM items define two statistically and clinically different indicators. Thirteen items define disability in motor functions. Five items define disability in cognitive functions. Additive measures for each indicator have the same characteristics at admission and discharge, so that these measures can be used to assess change in patient status.

Activities of Daily Living↗