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Biomedical subjects

J M Robbins

Publications and source records attributed to J M Robbins.

At least 19 recordsLinked to original sources
PubMed2001

Identification of Id4 as a regulator of BRCA1 expression by using a ribozyme-library-based inverse genomics approach.

Expression of the breast and ovarian cancer susceptibility gene BRCA1 is down-regulated in sporadic breast and ovarian cancer cases. Therefore, the identification of genes involved in the regulation of BRCA1 expression might lead to new insights into the pathogenesis and treatment of these tumors. In the present study, an "inverse genomics" approach based on a randomized ribozyme gene library was applied to identify cellular genes regulating BRCA1 expression. A ribozyme gene library with randomized target recognition sequences was introduced into human ovarian cancer-derived cells stably expressing a selectable marker [enhanced green fluorescence protein (EGFP)] under the control of the BRCA1 promoter. Cells in which BRCA1 expression was upregulated by particular ribozymes were selected through their concomitant increase in EGFP expression. The cellular target gene of one ribozyme was identified to be the dominant negative transcriptional regulator Id4. Modulation of Id4 expression resulted in inversely regulated expression of BRCA1. In addition, increase in Id4 expression was associated with the ability of cells to exhibit anchorage-independent growth, demonstrating the biological relevance of this gene. Our data suggest that Id4 is a crucial gene regulating BRCA1 expression and might therefore be important for the BRCA1 regulatory pathway involved in the pathogenesis of sporadic breast and ovarian cancer.

BRCA1 Protein↗
PubMed2001

Inpatient care for uncomplicated bronchiolitis: comparison with Milliman and Robertson guidelines.

CONTEXT: Bronchiolitis is the most common lower respiratory tract infection in infancy. A recent Centers for Disease Control and Prevention report confirmed that hospitalization rates for bronchiolitis have increased 2.4-fold from 1980 to 1996. Controversies exist about optimal treatment plans. Milliman and Robertson recommend ambulatory care management; in case of hospitalization, the recommended length of stay is 1 day. OBJECTIVES: To relate actual practice variation for infants admitted with uncomplicated bronchiolitis to Milliman and Robertson's recommendations. DESIGN: Prospective observational study. SETTING: General care wards of 8 pediatric hospitals of the Child Health Accountability Initiative during the winter of 1998-1999. PATIENTS: First-time admissions for uncomplicated bronchiolitis in patients not previously diagnosed as having asthma and who were younger than 1 year. MAIN OUTCOME MEASURES: Respiratory rate, monitored interventions, attainment of discharge criteria goals, and length of stay. RESULTS: Eight hundred forty-six patients were included in the final analysis: 85.7% were younger than 6 months, 48.5% were nonwhite, and 64.1% were Medicaid recipients or self-pay. On admission to the hospital, 18.3% of the infants had respiratory rates higher than higher than 80 breaths per minute, 53.8% received supplemental oxygen therapy, and 52.6% received intravenous fluids. These proportions decreased to 1.9%, 33.8%, and 20.3%, respectively, 1 day after admission, and to 0.7%, 20.1%, and 8.6%, respectively, 2 days after admission. The average length of stay was 2.8 days (SD, 2.3 days). CONCLUSIONS: Milliman and Robertson's recommendations do not correspond to practice patterns observed at the hospitals participating in this study; no hospital met the Milliman and Robertson recommended 1-day goal length of stay. Administration of monitored intervention persisted past the second day of hospitalization.

Ambulatory Care↗
PubMed2001

Improving estimates of caregiver time cost and family impact associated with birth defects.

BACKGROUND: Birth defects impose substantial costs on both families and society because of medical, developmental, and special education needs. Caring for children with birth defects also may influence caregiver time and impact the family. However, the economic cost of caregiver time and other impacts on the family has received far less attention than traditional healthcare costs. METHODS: This study reviews the literature on measuring caregiver time costs and family impact in an economic framework. The economic framework involves translating caregiver time or difficulties into appropriate units such as cost or quality adjusted life years (QALYs). RESULTS: Despite the potential important contribution of caregiver time costs to the total cost estimate of birth defects, few studies estimate caregiver time costs related specifically to birth defects. Only two studies provide estimates of these costs. Recent work has investigated the impact of chronic illness on caregivers in QALY terms, but birth defects have not been studied. Several issues need to be addressed in both the estimation of caregiver time costs and family impact to improve cost estimates. CONCLUSIONS: Improved estimates of caregiver time costs and impact on the family will assist policy makers in allocating resources for the prevention and treatment of birth defects. Future research should investigate the economic costs of caregiver time and family impact associated with caring for children with birth defects.

Caregivers↗
PubMed2001

Measuring outcomes of care for adolescents with emotional and behavioral problems.

OBJECTIVES: To validate the prototype Adolescent Treatment Outcomes Module (ATOM), examine its sensitivity to clinical change, and determine its feasibility for administration in routine clinical settings. METHOD: A sample of 67 adolescents, aged 11 through 18, was selected from new patients at two inpatient and two outpatient mental health programs. Adolescents and parents completed the ATOM and validating instruments at intake, 1 week postintake, and again at 6 months. RESULTS: Nine self-report symptoms predicted positive diagnoses of oppositional defiant, conduct, anxiety, and depressive disorders on the basis of structured diagnoses, with sensitivities of 0.7 to 0.8. Test-retest correlations for outcome scales were largely excellent (>0.70). Scales that measured functioning at home, in school, and in the community were moderately correlated in the expected direction with global functioning. Decreases in symptom severity and functional impairment were generally associated with decreases in validating instruments. Administration time averaged 25 minutes for adolescents and 28 minutes for parents. CONCLUSIONS: Both parents and adolescents readily completed the ATOM. Module scales demonstrated excellent reliability and good to fair concurrent validity. The ATOM was able to detect change and its absence.

Activities of Daily Living↗
PubMed2001

Socioeconomic status and type 2 diabetes in African American and non-Hispanic white women and men: evidence from the Third National Health and Nutrition Examination Survey.

OBJECTIVES: This study examined the associations of poverty income ratio (PIR), education, and occupational status with type 2 diabetes prevalence among African American and non-Hispanic White (White) women and men aged 40 to 74 years. METHODS: We analyzed cross-sectional data from the Third National Health and Nutrition Examination Survey, controlling for age and examination-related variables. RESULTS: Among African American women, there was a strong, graded association between PIR and diabetes, which remained significant after other risk factors were adjusted for. All 3 variables were significantly associated with diabetes among White women. Among White men, only PIR was significantly associated with diabetes. Controlling for risk factors substantially attenuated these associations among White women. There were no significant associations for African American men. CONCLUSIONS: Socioeconomic status is associated with type 2 diabetes prevalence among women, but not consistently among men. Diabetes prevalence is more strongly associated with PIR than with education or occupational status. These associations are largely independent of other risk factors, especially among African American women. Economic resources should be addressed in efforts to explain and reverse the increasing prevalence of diabetes in the United States.

Adult↗
PubMed2000

A novel functional genomics approach identifies mTERT as a suppressor of fibroblast transformation.

As a tool for functional genomics, a hairpin ribozyme gene library with randomized target recognition sequences was constructed in a retroviral vector. This library has the potential to target and cleave any possible RNA substrate. Mouse fibroblasts transduced with this ribozyme gene vector library were selected in a focus formation assay to isolate in vivo functional ribozymes that promote cell transformation in tissue culture. After two successive rounds of selection by focus formation assay, a transforming ribozyme (Rz007) was identified. The sequence of this ribozyme was used to identify the putative target genes responsible for the transformation. A candidate gene target for Rz007 encodes telomerase reverse transcriptase (mTERT). Both mRNA level and enzymatic activity of mTERT were down-regulated in Rz007-transformed cells. Furthermore, newly designed ribozymes, recognizing other potential ribozyme cleavage sites unique to the mTERT mRNA, also cause cell transformation, thus validating the role of mTERT in suppressing the transformation phenotype. These surprising results suggest that the commonly accepted role of telomerase in maintaining cellular immortalization is more complicated than previously thought. These studies also demonstrate the utility of this novel 'reverse' functional genomics approach, enabling the targeted discovery of genes, whether previously known or not, that are involved in any selectable phenotype.

3T3 Cells↗
PubMed2000

Toward a level playing field: predictive factors for the outcomes of mental health treatment for adolescents.

OBJECTIVE: To understand better the effectiveness of routine treatment for emotional and behavioral problems experienced by adolescents, methods are needed to control for between-provider differences in the distribution of factors that adversely affect treatment success. Such methods are necessary to fairly compare providers' outcomes and to aid clinicians in identifying adolescents for whom routine care may need to be altered. As a preliminary step toward developing a model to adjust treatment outcomes to account for predictive factors, findings from studies of treated samples of adolescents were reviewed to identify the factors that influence the likelihood of treatment success for this population. METHOD: Medline and PSYCInfo databases were searched for studies of treated adolescents that reported the association between expert-nominated predictive factors and outcomes. Thirty-four studies met inclusion criteria. RESULTS: Significant predictors identified in these studies include diagnosis, baseline severity of symptoms and functional impairment, family dysfunction, and previous treatment. Several expert-nominated factors have not been adequately studied in treated samples. CONCLUSIONS: Much basic work is needed before a convincing body of empirical evidence can explain predictive factors for adolescent mental health treatment outcomes. Future efforts should determine a reduced set of predictive factors that can be measured with minimal burden to providers.

Adolescent↗
PubMed2000

Agreement between older subjects and proxy informants on history of surgery and childbirth.

OBJECTIVES: To assess the agreement between proxy informants' reports of history of surgery and childbirth and older index subjects' own recall. DESIGN: Interrater reliability study. SETTING: An outpatient family medicine clinic and a provincial electoral district in Montreal, Canada. PARTICIPANTS: Eighty-two subjects aged 65 years and older without cognitive impairment, identified from clinic and community settings, and each index subject's proxy respondent. MEASUREMENTS: Identical questionnaires were administered to index subjects and proxies. RESULTS: Proxies failed to report 39% of non-childbirth surgeries reported by index subjects, but failed to report only 10% of childbirths. Female proxies were significantly less likely than male proxies to underreport non-childbirth surgeries after controlling for age of index subject and interval since surgery. Longer interval since surgery was significantly associated with greater underreporting, whereas age of the index subject and relationship between proxy and index subject were not. Agreement between proxies and index subjects on date of surgery was much higher for childbirths than for non-childbirth surgeries. CONCLUSIONS: Our findings suggest that proxy respondents can provide reliable information on older women's history of childbirth but that use of proxy respondents for history of non-childbirth surgeries may result in substantial underreporting.

Age Factors↗
PubMed2000

Excess type 2 diabetes in African-American women and men aged 40-74 and socioeconomic status: evidence from the Third National Health and Nutrition Examination Survey.

OBJECTIVE: To examine whether socioeconomic status (SES) explains differences in the prevalence of type 2 diabetes between African-American and non-Hispanic white women and men. DESIGN: Cross sectional study of diabetes prevalence, SES, and other risk factors ascertained by physical examination and interview. SETTING: Interviews were conducted in subjects' homes; physical examinations were conducted in mobile examination centres. PARTICIPANTS: 961 African-American women, 1641 non-Hispanic white women, 839 African-American men and 1537 non-Hispanic white men, aged 40 to 74 years, examined in the Third National Health and Nutrition Examination Survey (NHANES III), a representative sample of the non-institutionalised civilian population of the United States, 1988-1994. MAIN RESULTS: Among women, African-American race/ethnicity was associated with an age adjusted odds ratio of 1.76 (95% confidence intervals 1.21, 2.57), which was reduced to 1.42 (95% confidence intervals 0.95, 2.13) when poverty income ratio was controlled. Controlling for education or occupational status had minimal effects on this association. When other risk factors were controlled, race/ethnicity was not significantly associated with type 2 diabetes prevalence. Among men, the age adjusted odds ratio associated with African-American race/ethnicity was 1.43 (95% confidence intervals 1.03, 1.99). Controlling for SES variables only modestly affected the odds ratio for African/American race/ethnicity among men, while adjusting for other risk factors increased the racial/ethnic differences. CONCLUSIONS: Economic disadvantage may explain much of the excess prevalence of type 2 diabetes among African-American women, but not among men.

Adult↗
PubMed2000

Recognizing, treating, and preventing common foot problems.

The incidence, prevalence, and severity of foot conditions increase with age. Teaching patients simple preventive techniques is crucial. Recognition, treatment, and prevention of common foot complaints--i.e., toenail problems, infections, corns and calluses, injuries, flat feet, bunions, arthritis of the toes, and toe and joint deformities--are reviewed.

Adult↗
PubMed1999

Response to health insurance by previously uninsured rural children.

OBJECTIVE: To examine the healthcare utilization and costs of previously uninsured rural children. DATA SOURCES/STUDY SETTING: Four years of claims data from a school-based health insurance program located in the Mississippi Delta. All children who were not Medicaid-eligible or were uninsured, were eligible for limited benefits under the program. The 1987 National Medical Expenditure Survey (NMES) was used to compare utilization of services. STUDY DESIGN: The study represents a natural experiment in the provision of insurance benefits to a previously uninsured population. Premiums for the claims cost were set with little or no information on expected use of services. Claims from the insurer were used to form a panel data set. Mixed model logistic and linear regressions were estimated to determine the response to insurance for several categories of health services. PRINCIPAL FINDINGS: The use of services increased over time and approached the level of utilization in the NMES. Conditional medical expenditures also increased over time. Actuarial estimates of claims cost greatly exceeded actual claims cost. The provision of a limited medical, dental, and optical benefit package cost approximately $20-$24 per member per month in claims paid. CONCLUSIONS: An important uncertainty in providing health insurance to previously uninsured populations is whether a pent-up demand exists for health services. Evidence of a pent-up demand for medical services was not supported in this study of rural school-age children. States considering partnerships with private insurers to implement the State Children's Health Insurance Program could lower premium costs by assembling basic data on previously uninsured children.

Arkansas↗
PubMed1998

A number-needed-to-treat analysis of the use of respiratory syncytial virus immune globulin to prevent hospitalization.

OBJECTIVES: To estimate how many infants in selected high-risk subgroups would require treatment with respiratory syncytial virus immune globulin (RSV-IG) to avoid 1 hospital admission and to determine whether this is economically justified. DESIGN: Cost-benefit analysis. Data from 3 randomized controlled trials of RSV-IG are used to estimate the number needed to treat to prevent 1 hospital admission for respiratory syncytial virus infection. The threshold number needed to treat is computed according to a formula incorporating costs and benefits of RSV-IG prophylaxis. Estimates of the willingness to pay were obtained from a sample of 39 health care providers (35 physicians and 4 nurses). MAIN OUTCOME MEASURES: The number needed to treat to prevent 1 hospital admission for respiratory syncytial virus infection. The threshold number needed to treat that would balance costs with benefits. RESULTS: More than 16 (95% confidence interval, 12.5-23.8) infants would need to be treated with RSV-IG to avoid 1 hospital admission for respiratory syncytial virus infection, ranging from 63 for premature infants without chronic lung disease to 12 (confidence interval, 6.3-100.0) for infants with bronchopulmonary dysplasia. A sensitivity analysis of the costs and values of hospital admission for respiratory syncytial virus infection and RSV-IG treatment resulted in a weak recommendation against the treatment of infants with bronchopulmonary dysplasia and strong recommendations that the costs and risks of RSV-IG treatment outweigh the benefits for the combined sample of infants and premature infants without lung disease. CONCLUSIONS: The number-needed-to-treat procedures offer a method to assess evidence of treatment effects and decision rules for whether to accept treatment recommendations. Under plausible assumptions, treatment with RSV-IG is not recommended for infants without lung disease. Institutions can examine cost and benefit assumptions that best fit their own practice setting.

Cost Savings↗
PubMed1997

MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily.

Macrophages play a key role in both normal and pathological processes involving immune and inflammatory responses, to a large extent through their capacity to secrete a wide range of biologically active molecules. To identify some of these as yet not characterized molecules, we have used a subtraction cloning approach designed to identify genes expressed in association with macrophage activation. One of these genes, designated macrophage inhibitory cytokine 1 (MIC-1), encodes a protein that bears the structural characteristics of a transforming growth factor beta (TGF-beta) superfamily cytokine. Although it belongs to this superfamily, it has no strong homology to existing families, indicating that it is a divergent member that may represent the first of a new family within this grouping. Expression of MIC-1 mRNA in monocytoid cells is up-regulated by a variety of stimuli associated with activation, including interleukin 1beta, tumor necrosis factor alpha (TNF-alpha), interleukin 2, and macrophage colony-stimulating factor but not interferon gamma, or lipopolysaccharide (LPS). Its expression is also increased by TGF-beta. Expression of MIC-1 in CHO cells results in the proteolytic cleavage of the propeptide and secretion of a cysteine-rich dimeric protein of Mr 25 kDa. Purified recombinant MIC-1 is able to inhibit lipopolysaccharide -induced macrophage TNF-alpha production, suggesting that MIC-1 acts in macrophages as an autocrine regulatory molecule. Its production in response to secreted proinflammatory cytokines and TGF-beta may serve to limit the later phases of macrophage activation.

Amino Acid Sequence↗
PubMed1997

Molecular cloning and expression of a chloride ion channel of cell nuclei.

Ion channels are known to be present on the plasma membrane of virtually all cells and have been found on the membranes of various intracellular organelles. However, until recently they were believed not to occur at the nuclear membrane. In this study we describe the molecular cloning and characterization of a nuclear ion channel protein, designated nuclear chloride channel-27 (NCC27), from the human myelomonocytic cell line, U937. NCC27 is a novel chloride ion channel protein that was found to localize principally to the cell nucleus. Its only known homologue is a bovine chloride ion channel protein (p64) believed to localize to internal organelles. NCC27 therefore represents the first human member of a new class of organellar chloride ion channel proteins.

Amino Acid Sequence↗
PubMed1997

Latent variable models of functional somatic distress.

Latent variable models of functional somatic symptoms were estimated for a sample of 686 family medicine patients. Symptom items from the NIMH Diagnostic Interview Schedule were selected to approximate diagnoses of fibromyalgia syndrome (FMS), chronic fatigue syndrome (CFS), and irritable bowel syndrome (IBS). Confirmatory factor analysis demonstrated that hypothesized latent variables of somatic depression, somatic anxiety, FM-like, CF-like, and IB-like syndromes fit the observed covariations better than models hypothesizing fewer latent variables. Results offer tentative confirmation of functional somatic syndromes as discrete entities and suggest that relaxing the diagnostic criteria for somatization may identify individuals with distress limited to a single functional system.

Adult↗