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Biomedical subjects

C Schechter

Publications and source records attributed to C Schechter.

At least 19 recordsLinked to original sources

The cost-effectiveness of nCPAP treatment in patients with moderate-to-severe obstructive sleep apnoea.

The demand for diagnostic and therapeutic services for obstructive sleep apnoea syndrome (OSAS) showed marked growth during the 1990s. This paper analyses the long-term cost-effectiveness of nasal continuous positive airway pressure (nCPAP) treatment in comparison to conventional null treatment. A Markov model was used to represent the natural history of OSAS based upon published evidence. Utility values came from a survey of OSAS patients. Data on health costs were collected from hospitals in the Basque Country, Spain. The incremental cost-effectiveness ratio of nCPAP treatment is <6,000 Euros per quality-adjusted life year. On disaggregated analysis, nCPAP treatment accounts for 86% of incremental costs; 84% of incremental effectiveness is attributable to improved quality of life. Treatment of obstructive sleep apnoea syndrome with nasal continuous positive airway pressure has a cost-effectiveness that is in line with that of other commonly funded treatments such as antihypertensive drugs. The key clinical benefit of nasal continuous positive airway pressure treatment is improvement in the quality of life of patients with obstructive sleep apnoea syndrome. This benefit is also precisely the one for which the evidence base is strongest. The remaining uncertainties concerning the impact of nasal continuous positive airway pressure on long-term mortality have only a relatively small impact on the economics of treatment.

Adult↗

Outpatient treatment of deep venous thrombosis in diverse inner-city patients.

PURPOSE: We sought to describe the development and outcomes of a hospital-based program designed to provide safe and effective outpatient treatment to a diverse group of patients with acute deep venous thrombosis. METHODS: Patients enrolled in the program were usually discharged on the day of or the day after presentation. Low- molecular-weight heparin was administered for a minimum of 5 days and warfarin was given for a minimum of 3 months. The hospital provided low-molecular-weight heparin free of charge to patients. Patients received daily home nursing visits to monitor the prothrombin time, assess compliance, and detect complications. The inpatient and outpatient records of the first 89 consecutive patients enrolled in the program were reviewed. Patients were observed for a 3-month period after enrollment. RESULTS: The median length of stay was 1 day. Low-molecular-weight heparin was administered for a mean (+/- standard deviation [SD]) of 4.7 +/- 2.4 days at home. Recurrent thromboembolism was noted in 1 patient (1%), major bleeding in 2 patients (2%), and minor bleeding in 2 patients (2%). No patients died or developed thrombocytopenia. Assuming that patients would have been hospitalized for the duration of treatment with low-molecular-weight heparin, the program eliminated a mean of 4.7 days of hospitalization, with an estimated reduction of $1,645 in total health care costs per patient. CONCLUSION: This hospital-based program to provide outpatient treatment of deep venous thrombosis to a diverse group of inner-city patients achieved a low incidence of adverse events and substantial health care cost savings. Specific strategies, including providing low-molecular-weight heparin free of charge and daily home nursing visits, can be utilized to facilitate access to outpatient treatment and ensure high-quality care.

Adult↗

Atherosclerotic aortic component quantification by noninvasive magnetic resonance imaging: an in vivo study in rabbits.

OBJECTIVES: We sought to demonstrate the ability that noninvasive in vivo magnetic resonance imaging (MRI) has to quantify the different components within atherosclerotic plaque. BACKGROUND: Atherosclerotic plaque composition plays a critical role in both lesion stability and subsequent thrombogenicity. Noninvasive MRI is a promising tool for the characterization of plaque composition. METHOD: Thoracic and abdominal aortic atherosclerotic lesions were induced in rabbits (n = 5). Nine months later, MRI was performed in a 1.5T system. Fast spin-echo sequences (proton density-weighted and T2-weighted [T2W] images) were obtained (in-plane resolution: 350 x 350 microns, slice thickness: 3 mm). Magnetic resonance images were correlated with matched histopathological sections (n = 108). RESULTS: A significant correlation (p < 0.001) was observed for mean wall thickness and vessel wall area between MRI and histopathology (r = 0.87 and r = 0.85, respectively). The correlation was also present on subanalysis of the thoracic and upper part of the abdominal aorta, susceptible to respiratory motion artifacts. There was a significant correlation for plaque composition (p < 0.05) between MRI and histopathology for the analysis of lipidic (low signal on T2W, r = 0.81) and fibrous (high signal on T2W, r = 0.86) areas with Oil Red O staining. T2-weighted images showed greater contrast than proton density-weighted between these different components of the plaques as assessed by signal intensity ratio analysis with the mean difference in signal ratios of 0.47 (S.E. 0.012, adjusted for clustering of observations within lesions) being significantly different from 0 (t1 = 39.1, p = 0.016). CONCLUSIONS: In vivo noninvasive high resolution MRI accurately quantifies fibrotic and lipidic components of atherosclerosis in this model. This may permit the serial analysis of therapeutic strategies on atherosclerotic plaque stabilization.

Animals↗

Organization and functional analysis of the mouse transporter associated with antigen processing 2 promoter.

In accordance with the key role of MHC class I molecules in the adaptive immune response against viruses, they are expressed by most cells, and their expression can be enhanced by cytokines. The assembly and cell surface expression of class I complexes depend on a continuous peptide supply. The peptides are generated mainly by the proteasome and are transported to the endoplasmic reticulum by a peptide transport pump consisting of two subunits, TAP1 and TAP2. The proteasome low molecular weight polypeptide (2 and 7), as well as TAP (1 and 2) genes, are coordinately regulated and are induced by IFNs. Despite this coordinate regulation, examination of tumors shows that these genes can be discordantly down-regulated. In pursuing a molecular explanation for these observations, we have characterized the mouse TAP2 promoter region and 5'-flanking sequence. We show that the 5' untranslated regions of TAP2 genes have a characteristic genomic organization that is conserved in both the mouse and the human. The mouse TAP2 promoter belongs to a class of promoters that lack TATA boxes but contain a MED1 (multiple start site element downstream) sequence. Accordingly, transcription is initiated from multiple sites within a 100-nucleotide window. An IFN regulatory factor 1 (IRF1)/IRF2 binding site is located in this region and is involved in both basal and IRF1-induced TAP2 promoter activity. The implication of the extensive differences found among the promoters of class I heavy chain, low molecular weight polypeptide, and TAP genes, all encoding proteins involved in Ag presentation, is discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Contingency valuation and preferences of health states associated with side effects of antipsychotic medications in schizophrenia.

The purpose of this study was to investigate the construct validity and the test-retest reliability of the willingness to pay (WTP) method for estimating health state preferences associated with side effects of antipsychotic medication. Ninety-six schizophrenia patients on antipsychotics were asked (1) how much they would be willing to pay to get rid of side effects with 100 percent probability, (2) a standard gamble (SG) question measuring utilities of patient's health state associated with side effects, and (3) their WTP to get rid of side effects based on the utility found with SG. Patients were divided into three groups based on severity of side effects. There was a significant difference between side effect severity groups for (1) the utility associated with side effects (Kruskal-Wallis [K-W] chi-square = 8.48, p = 0.014), and (2) their WTP to get rid of side effects with either 100 percent probability (K-W chi-square = 14.32,p = 0.001) or based on the utility associated with side effects (K-W chi-square = 5.96, p = 0.051). There was a significant correlation between utility and the WTP based on utility (Spearman r = -0.42, p = 0.003). Because of a wide variation in side effects at the 1-month interval, we were unable to assess the test-retest reliability of SG and WTP. Our results suggest that WTP has some construct validity in valuating and measuring preferences of health states associated with side effects of antipsychotics in schizophrenia.

Adult↗

Human cytomegalovirus protein US2 interferes with the expression of human HFE, a nonclassical class I major histocompatibility complex molecule that regulates iron homeostasis.

HFE is a nonclassical class I major histocompatibility complex (MHC) molecule that is mutated in the autosomal recessive iron overload disease hereditary hemochromatosis. There is evidence linking HFE with reduced iron uptake by the transferrin receptor (TfR). Using a panel of HFE and TfR monoclonal antibodies to examine human HFE (hHFE)-expressing cell lines, we demonstrate the expression of stable and fully glycosylated TfR-free and TfR-associated hHFE/beta2m complexes. We show that both the stability and assembly of hHFE complexes can be modified by the human cytomegalovirus (HCMV) viral protein US2, known to interfere with the expression of classical class I MHC molecules. HCMV US2, but not US11, targets HFE molecules for degradation by the proteasome. Whether this interference with the regulation of iron metabolism by a viral protein is a means of potentiating viral replication remains to be determined. The reduced expression of classical class I MHC and HFE complexes provides the virus with an efficient tool for altering cellular metabolism and escaping certain immune responses.

Amino Acid Sequence↗

Predictors of follow-up of atypical and ASCUS papanicolaou tests in a high-risk population.

OBJECTIVE: Our goals were to assess adherence to the National Cancer Institute clinical practice guideline for the management of atypical squamous cells of uncertain significance (ASCUS) Papanicolaou (Pap) test results in a community at high risk of cervical cancer. We also hoped to identify predictors of adherence to the guideline. STUDY DESIGN: We used an historical cohort and collected data by chart abstraction. POPULATION: Our study included women receiving care in 7 urban community health centers who had an initial ASCUS or atypical Pap test result in 1996. We excluded women with a history of cervical dysplasia or human immunodeficiency virus infection, yielding a final sample of 387 women. OUTCOMES: measured The outcome measured was the level of adherence to the guideline, defined as falling within 1 of 3 mutually exclusive categories (complete, moderate, or low). RESULTS: Care providers recommended colposcopy after an initial atypical Pap test result in 12% of cases and repeat cytology in 67%. Failure to document a plan for management was found in 19% of cases. Complete adherence was achieved for 27% of subjects, moderate adherence for 28%, and low adherence for 45%. The factors associated with complete versus moderate or low adherence included site of care, description of the abnormality (ASCUS vs atypia), availability of on-site colposcopy, and discussing the plan at a visit. CONCLUSIONS: Adherence with the National Cancer Institute clinical practice guideline in this setting was disappointing and varied substantially by site. Factors amenable to change that may improve follow-up include good communication of results with patients and providing colposcopy at the site of primary care.

Cohort Studies↗

Genetic testing: a physician's perspective.

Progress in DNA diagnostics has been extremely rapid. We sought to determine attitudes, awareness, and knowledge of genetic testing by physicians affiliated with the Mount Sinai Medical Center. We surveyed 363 physicians within whose fields genetic testing for various diseases and disorders exist. Physicians' awareness of and opinions regarding testing, attitudes toward counseling, knowledge of the field, and interest in further education were assessed. Three hundred forty-one (341) physicians were determined to be eligible for the study and, of these, 89 (26%) returned completed surveys. Of the respondents, 71% rated their knowledge of genetics and genetic testing as "fair" to "poor"; only 37% read articles concerning genetic testing on a regular basis. Physician awareness of currently available testing produced a bell-shaped distribution. Knowledge regarding Mendelian genetics yielded a bimodal distribution, and knowledge reflecting an understanding of the mechanics behind genetic testing produced a bell-like curve, skewed to the right. Those who identified themselves as practicing within an "academic" setting scored significantly higher on the Mendelian genetics and testing mechanics sections than those practicing in a "private" setting. Ninety-eight percent (98%) of the physicians said they would refer their patients to a genetic counselor. Although 91% of the respondents were aware of the existence of genetic counseling services, only 71% were aware of the services available at major New York medical centers. Of those aware of counseling services, 53% had referred a patient to them, and 83% of those who referred were "mostly" to "very" satisfied with the counseling. Ninety-five percent (95%) of the physicians believed that the doctor, among others, has the responsibility to counsel patients about genetic testing, yet only 51% felt that they had the time. No statistically significant preference was found concerning the methods for gaining further education or information about genetic testing. Further education for physicians is required in order for them to accurately convey the risks and benefits of genetic testing to their patients. Furthermore, awareness of the counseling services available within the New York area needs to be heightened in order to provide physicians and patients with the specific services they desire. The most efficient and effective methods for providing information and for heightening awareness need to be determined through additional research.

Clinical Competence↗

An integrated program for evidence-based medicine in medical school.

To provide optimal care for their patients, clinicians must be able to locate and interpret the most current literature. Teaching the necessary skills to medical students is essential, if we wish to train clinicians to be able to keep up with the expansion of biomedical knowledge for their entire working lives. In this paper, we describe our school's four-year curriculum in evidence-based medicine and the performance of three senior classes on the summative evaluation exercise devised to measure the program's success.

Curriculum↗

Carpal tunnel syndrome and workers' compensation among an occupational clinic population in New York State.

BACKGROUND: This study evaluated the experience in the New York State workers' compensation (WC) system of 135 patients with work-related carpal tunnel syndrome diagnosed at an academic occupational medicine clinic between 1991-1994. METHODS: Worker's Compensation Board (WCB) records were reviewed to ascertain: (1) the proportion of WC claims that were not initially accepted (i.e., that were challenged) by the WC insurer, (2) the proportion of challenged claims ultimately decided in the claimant's favor, (3) the length of the period between case filing and claim adjudication, and (4) risk factors for claim challenge. RESULTS: Seventy-nine percent of the claims were not initially accepted by the WC insurer (challenged/no response). Of the 81 challenged/no response cases adjudicated (ruled on) at the time of the study, 96.3% were accepted as work-related. Mean time from claim initiation to adjudication was 429 days (range 58-1,617). Mean time from physician request for any treatment and WCB authorization was 226 days (range 0-1,296). Mean time from physician request for surgery authorization and WCB authorization was 318 days (range 7-595). Claims filed by non-whites, low-wage workers, and union members were significantly more likely than others to be challenged. CONCLUSIONS: Patients with work-related carpal tunnel syndrome face frequent claim challenge by WC insurers in NY State, with attendant prolonged delays in adjudication and treatment authorization. Likelihood of claim rejection was strongly related to ethnicity and socio-economic status.

Carpal Tunnel Syndrome↗

Is immobilization associated with an abnormal lipoprotein profile? Observations from a diverse cohort.

OBJECTIVE: The potential effects of ethnicity, gender, and adiposity on the serum lipid profile in persons with spinal cord injury (SCI) were determined. SUBJECTS: Subjects with SCI were recruited during their annual physical examination from Rancho Los Amigos Medical Center, Downey, California. Sedentary able-bodied controls were Bridge and Tunnel Officers of the Triboro Bridge and Tunnel Authority of the New York City metropolitan area. METHODS: Serum lipid profiles were investigated in 320 subjects with SCI and compared to those obtained from 303 relatively sedentary able-bodied controls. Serum lipid studies were obtained in the fasting state. Data were collected between 1993 and 1996. All lipid determinations were performed by the same commercial laboratory. MAIN OUTCOME MEASURES: The dependent variables were the values from the lipid profile analysis. The independent variables consisted of study group, gender, ethnic group, age, duration of injury, and anthropometric measurements. RESULTS: The serum high-density lipoprotein cholesterol (HDL-c) level was reduced in the SCI compared with the control group (mean+/-SEM) (42+/-0.79 vs 47+/-0.67 mg/dl, P<0.0005). The serum HDL-c level was significantly lower in males with SCI than males in the control group (39+/-0.83 vs 45+/-0.70 mg/dl, P<0.0001), but not for females (51+/-1.54 vs 54 1.52 mg/dl, n.s.). Within the subgroups for whites and Latinos, HDL-c values were also lower in subjects with SCI than in controls (whites: 41+/-1.02 vs 46+/-0.86 mg/dl, P<0.0001; Latinos: 37+/-1.53 vs 42+/-1.59 mg/dl, P<0.05), but not for African Americans (49+/-1.56 vs 51+/-1.27 mg/dl, n.s.). African Americans had higher HDL-c values than whites or Latinos (SCI: 49+/-1.56 vs 41+/-1.02 or 37+/-1.53 mg/dl, P< 0.0001; controls: 51+/-1.27 vs 46+/-0.86 mg/dl, P<0.01 or 42+/-1.59 mg/dl, P<0.0005). In persons with SCI, the serum HDL-c values were inversely related to body mass index and estimated per cent body fat (r=0.27, P<0.0001). CONCLUSION: In white and Latino males, but not in females or African Americans, immobilization from SCI appears to be associated with lower HDL-c values than in controls.

Adult↗

MHC class I heavy chain mRNA must exceed a threshold level for the reconstitution of cell surface expression of class I MHC complexes in cells transformed by the highly oncogenic adenovirus 12.

In primary embryonal fibroblasts from transgenic mice expressing H-2(b) genes and a miniature swine class I transgene (PD1), transformation with adenovirus 12 results in suppression of assembly and cell surface expression of all class I complexes. Cell surface expression of PD1 can be recovered by transfecting the cells with peptide transporter genes. However, reconstitution of the H-2Kb gene expression requires, in addition, a 2-fold increase in the steady state level of the H-2Kb mRNA that can be attained by treatment of the cells with interferons or by transfecting them with the H-2Kb gene. A detailed analyses of the biogenesis of class I molecules has revealed the steady state expression of free class I heavy chains that are not converted into conformed complexes even when peptide transporter genes are overexpressed. The fact that class I complex assembly seems to be highly inefficient in certain cell lines might be a major in vivo obstacle for the elimination of transformed or virus-infected cells by cytotoxic T lymphocytes, especially in view of the fact that the level of class I gene transcription is often down-regulated in cancer cells and/or that assembly of class I major histocompatibility complexes can be subverted by virus-encoded proteins.

Adenoviridae↗

Prenatal genetic carrier testing using triple disease screening.

CONTEXT: Rapid progress in gene discovery has dramatically increased diagnostic capabilities for carrier screening and prenatal testing for genetic diseases. However, simultaneous prenatal carrier screening for prevalent genetic disease has not been evaluated, and patient acceptance and attitudes toward this testing strategy remain undefined. OBJECTIVE: To evaluate an educational, counseling, and carrier testing program for 3 genetic disorders: Tay-Sachs disease (TSD), type 1 Gaucher disease (GD), and cystic fibrosis (CF) that differ in detectability, severity, and availability of therapy. DESIGN: Potential participants received education and genetic counseling, gave informed consent, chose screening tests, and completed pre-education and posteducation questionnaires that assessed knowledge, attitudes toward genetic testing, and disease testing preferences. SETTING: Medical genetics referral center. PATIENTS: Volunteer sample of 2824 Ashkenazi Jewish individuals enrolled as couples who were referred for TSD testing. INTERVENTION: Genetic counseling, education, and if chosen, genetic testing for any or all 3 disorders. MAIN OUTCOME MEASURE: Acceptance of screening for each of the 3 disorders. Secondary outcomes include attitudes toward genetic testing and reproductive considerations. RESULTS: Of the 2824 individuals tested for TSD, 97% and 95% also chose testing for CF and GD, respectively. The frequency of detected carriers was 1:21 for TSD, 1 :25 for CF, and 1:18 for GD. Twenty-one carriercoupleswere identified, counseled, and all postconception couples opted for prenatal diagnosis. Pre-education and posteducation questionnaires revealed that patients initially knew little about the diseases, but acquired disease information and increased knowledge of genetic concepts. Education and genetic counseling increased understanding and retention of genetic concepts and disease-related information, and minimized test-related anxiety. Although individuals sought screening for all 3 diseases, reproductive attitudes and decisions varied directly with disease severity and treatability. CONCLUSIONS: These findings emphasize the importance of genetic counseling for prenatal carrier testing and may improve understanding, acceptance, and informed decision making for prenatal carrier screening for multiple genetic diseases.

Adult↗

Synthesis and turnover of beta2-microglobulin in Ad12-transformed cells defective in assembly and transport of class I major histocompatibility complex molecules.

In primary embryonal fibroblasts from transgenic mice expressing H-2 genes and a miniature swine class I transgene (PD1), transformation with the highly oncogenic Ad12 results in a reduction in peptide transporter and proteasome-associated (LMP2 and LMP7) gene expression, and suppression in transport and cell surface expression of all class I antigens. The selective suppression in transport of H-2 (but not of PD1) molecules in cells reconstituted for the expression of peptide transporter and LMP genes implied that an additional factor(s) is involved in the assembly of class I complexes. Here we show that the beta2m, H-2Db, and H-2Kb genes are transcribed and translated in Ad12-transformed cells. However, unlike normal and E1Ad5-transformed cells, in which beta2m is either secreted unbound or bound to class I heavy chains, in Ad12-transformed cells significant amounts of beta2m are retained in the cell bound to the membrane, but free of class I heavy chains. This abnormal turnover of beta2m in the Ad12-transformed cells suggests the existence of a novel beta2m-binding molecule(s) that sequesters beta2m, and this process may provide a mechanism by which transformation with Ad12 may subvert class I complex formation.

Adenoviruses, Human↗

Thermodilution cardiac output measurement during simultaneous volume infusion through the venous infusion port of the pulmonary artery catheter.

OBJECTIVE: To determine the effect on thermodilution cardiac output (TDCO) measurements of continuous volume infusion through the right atrial venous infusion port of the pulmonary artery catheter. DESIGN: Prospective, blinded, randomly allocated crossover. SETTING: Surgical intensive care unit in a university hospital. PARTICIPANTS: Forty-nine hemodynamically stable patients between the ages of 43 and 84 in the intensive care unit and with a pulmonary artery catheter in place. INTERVENTIONS: Each patient received two room-temperature infusions (250 or 500 mL/hr) of 5% dextrose. Consecutive TDCO measurements were taken during each infusion and during a control period (no infusion). The sequence of infusion rates and control period was randomly determined. At both infusion rates, most patients exhibited a decrease in TDCO measurement of between 0.1 and 3.0 L/min. Although some patients exhibited an increase in measured TDCO, this increase was primarily between 0.1 and 0.5 L/min. MEASUREMENTS AND MAIN RESULTS: The mean TDCO measurements at infusion rates of 0, 250, and 500 mL/hr were 6.77, 6.49, and 6.47 L/min, respectively. Measured TDCO decreased on volume infusion by 0.3 +/- 0.13 L/min (mean +/- SD, p < 0.02). CONCLUSION: Rapid continuous infusion of fluid through the venous infusion port of the pulmonary artery catheter significantly limits the accuracy of simultaneous TDCO measurements. Optimally, TDCO measurements should be avoided during rapid volume infusion.

Adult↗