tbuckley/cabot-search huggingface dataset:
Respiratory symptoms in patients with treated hypothyroidism and inflammatory bowel disease
Authors: S S Birring
Journal: Thorax (2003)

Patients with idiopathic chronic cough and unexplained airflow obstruction in non-smokers have been shown to have an increased prevalence of hypothyroidism and other organ specific autoimmune disorders. Whether patients with hypothyroidism have an increased prevalence of respiratory symptoms is unknown.The prevalence of respiratory symptoms was assessed in 124 patients with treated hypothyroidism recruited from primary and secondary care, 64 outpatients with inflammatory bowel disease, and 1346 control adults recruited randomly from the electoral register in a case-control study. Respiratory symptoms and smoking history were assessed by a respiratory symptom questionnaire.After adjustment for age, sex and smoking, symptoms of breathlessness and sputum production were more prevalent in both patient populations than in controls (odds ratios for hypothyroidism and inflammatory bowel disease; breathlessness: 3.1 (95% CI 2.1 to 4.6) and 3.4 (95% CI 2.0 to 6.0), respectively; sputum production: 2.7 (95% CI 1.6 to 4.5) and 2.5 (95% CI 1.2 to 5.0), respectively). Cough during the day and night was significantly more prevalent in patients with hypothyroidism (1.8 (95% CI 1.2 to 2.9)) and approached significance in those with inflammatory bowel disease (1.8 (95% CI 1.0 to 3.4)). Wheeze and nocturnal cough were no more prevalent in either disease population than in controls.There is a significantly increased prevalence of respiratory symptoms in patients with hypothyroidism or inflammatory bowel disease compared with controls recruited from the general population. Further work is required to determine whether similar differences are seen in comparison with hospital based controls. These findings support the hypothesis that there is a link between autoimmune hypothyroidism and respiratory disease.
Collagen XXIII Expression Is Associated with Prostate Cancer Recurrence and Distant Metastases
Authors: Jacqueline Banyard, Lere Bao, Matthias D. Hofer, David Zurakowski, Kristin A. Spivey, Adam S. Feldman, Lloyd M. Hutchinson, Rainer Kuefer, Mark A. Rubin, Bruce R. Zetter
Journal: Clinical Cancer Research (2007)

Abstract Purpose: We had previously identified a new transmembrane collagen, type XXIII, in metastatic rat prostate carcinoma cells. The purpose of this study was to determine the expression of collagen XXIII in human prostate cancer and investigate its relationship with disease progression. Experimental Design: We investigated collagen XXIII expression in prostate cancer tissue and did a retrospective analysis of association with prostate-specific antigen (PSA)–defined disease recurrence. The presence of collagen XXIII in prostate cancer patient urine was also assessed before and after prostatectomy. Results: Collagen XXIII protein was detected at very low levels in benign prostate tissue and was significantly increased in prostate cancer. Distant metastases exhibited significantly higher collagen XXIII levels compared with either localized prostate cancer or regional (lymph node) metastases. Patients with high collagen XXIII levels had a 2.8-fold higher risk of PSA failure with median time to failure of 8.1 months, compared with low collagen XXIII patients with a median time to failure of 5 years. Multivariate Cox regression showed that the presence of collagen XXIII was significantly associated with time to PSA recurrence, independent of other clinical variables. Collagen XXIII was also detected in prostate cancer patient urine, with reduced levels after prostatectomy, indicating potential as a noninvasive fluid biomarker. Conclusions: We present the first report demonstrating increased collagen XXIII expression in prostate cancer tissue. We show that collagen XXIII level is a significant independent predictor of PSA-defined disease recurrence, suggesting a potential role as a molecular biomarker of prostate cancer progression and metastasis.
FOXP3 Expression and Overall Survival in Breast Cancer
Authors: Andrea Merlo, Patrizia Casalini, Maria Luisa Carcangiu, Chiara Malventano, Tiziana Triulzi, Sylvie Mènard, Elda Tagliabue, Andrea Balsari
Journal: Journal of Clinical Oncology (2009)

Purpose The transcription factor forkhead box P3 (FOXP3) up- or downregulates a large number of genes and has been recently reported to be expressed in tumor cells. We investigated the prognostic importance of FOXP3 expression in patients with breast cancer. Patients and Methods The expression patterns of FOXP3 were characterized by immunohistochemistry in primary breast carcinoma specimens from patients of the Milan 3 and 1 trials. Kaplan-Meier analysis and Cox proportional hazards regression modeling were used to assess the overall survival, distant metastasis-free survival, and local relapse cumulative incidence, according to the presence or absence of FOXP3 expression. Results FOXP3 expression in tumors was associated with worse overall survival probability and the risk increased with increasing FOXP3 immunostaining intensity. FOXP3 was also a strong prognostic factor for distant metastases-free survival but not for local recurrence risk. In multivariate analysis FOXP3 resulted an independent prognostic factor and the hazard ratio of FOXP3 expression and of lymph node positivity were similar. In the Milan 3 trial, the probability of 10-year survival in node-negative subgroup was 100% for FOXP3-negative and 82% for FOXP3-positive patients; in node-positive subgroup 82% for FOXP3-negative and 41% for FOXP3-positive patients. Even in the Milan 1 trial the lack of FOXP3 expression in node-positive subgroup was related to a significantly better prognosis than in FOXP3-positive patients (10-year survival probability, 89% v 59%). Conclusion The data identify FOXP3 expression as a new independent prognostic factor in breast carcinoma, which might help to improve the selection of patients for appropriate therapy.
Use of Conventional Radiation Therapy As Part of Breast-Conserving Treatment
Authors: Timothy J. Whelan
Journal: Journal of Clinical Oncology (2005)

Whole breast irradiation following breastconserving surgery is an integral part of breast-conserving therapy (BCT). Radiation therapy was introduced early in the development of breast-conserving surgery and techniques were based on the premise that limited surgery might leave microscopic residual disease in the breast. Early studies of mastectomy specimens demonstrated that microscopic disease could extend up to 2 to 4 cm beyond the primary site of the tumor within the breast tissue. Trials comparing mastectomy to BCT (breast-conserving surgery plus radiation) demonstrated equivalent survival confirming the effectiveness of this combined approach. Trials comparing breast-conserving surgery alone to breast-conserving surgery plus radiation confirmed a substantial decrease in the risk of local recurrence and the prevention of mastectomy with breast irradiation. Whole breast irradiation is normally delivered with two opposed tangential fields to encompass the breast, often including part of the underlying chest wall and the lower axilla. Beam modifying devices, usually lead wedges, are used to improve dose homogeneity. A dose of 45 to 50 Gy in 25 fractions (or daily doses) of 1.8 to 2 Gy, Monday to Friday for 5 weeks, is often used. Additional radiation limited to the site of the primary tumor, called boost irradiation, may be given using a variety of approaches to a dose of 10 to 16 Gy in five to eight fractions. This technique has been in existence since the early 1980s, with little changes until recently. Increasingly, centers now use computed tomography (CT) to plan radiation therapy which permits clearer definition of underlying lung and heart and avoidance of these critical structures. CT planning also permits for the correction of underlying lung density and optimization of compensation if necessary. Patient selection criteria for whole breast irradiation are based on the eligibility criteria of the original trials and include any patient with a primary tumor of less than 5 cm with clear margins of the excision following breast-conserving surgery. Absolute contraindications to breast irradiation include pregnancy and previous breast irradiation (including mantle irradiation for Hodgkin’s disease). Relative contraindications include scleroderma, systemic lupus erythematosis, severe cardiopulmonary disease, or the inability to lie supine, which would limit the ability to deliver radiotherapy. Breast irradiation is well tolerated. Common early toxicity includes fatigue, breast edema, and skin erythema and irritation, which can have a modest impact on quality of life. Mild to moderate longterm effects are relatively uncommon: 5% to 10% of patients may experience limited breast pain attributed to radiation therapy or adverse cosmetic outcome associated with breast fibrosis, scar retraction, and telangiectasia. Serious long-term adverse effects are relatively rare (less than 1%) and include radiation pneumonitis, VOLUME 23 d NUMBER 8 d MARCH 1
Quantitative analysis of regional systolic function with left ventricular aneurysm.
Authors: A C Nicolosi, H M Spotnitz
Journal: Circulation (1988)

Left ventricular aneurysm (LVA) remains a poorly understood entity, often resulting in congestive failure that is not consistently improved by standard resection with linear closure. Although other surgical approaches have been proposed, current methods to assess their effect on left ventricular function are not adequate. The purpose of the present study was to quantitatively define regional systolic function in patients with LVA and to assess acute changes in regional function after standard repair. Seven patients underwent resection of an anteroapical LVA. Intraoperative two-dimensional echocardiography was performed off cardiopulmonary bypass immediately before and after resection. In all patients, short-axis views at the papillary muscle (apex) level showed anteroseptal paradox and distorted geometry, whereas at the mitral valve (base), symmetric wall motion and geometry were preserved. Videotaped echo images were divided into octants by a floating axis fitted to internal landmarks. Myocardial area and midwall perimeter were obtained for each octant, and wall thickness was calculated at end diastole (ED), isovolumetric systole (IS), and end systole (ES). Wall thickening (delta t) for each segment was calculated as the percent increase in thickness from ED and averaged for all seven patients. At the apex level before resection, isovolumetric thinning occurred in the aneurysm as well as bordering segments, with delta t ranging from -17 +/- 5% (+/- SEM) in the anteroseptal segment to 12 +/- 6% posterolaterally (p less than 0.05). The isovolumetric bulge was followed by late-systolic thickening, however, with delta t ranging from 13 +/- 7% to 27 +/- 8% (NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Fate of intercellular junctions in isolated adult rat cardiac cells.
Authors: F Mazet, B A Wittenberg, D C Spray
Journal: Circulation Research (1985)

Freeze fracture and thin section techniques have revealed morphological changes in gap junctions and intercalated discs of adult rat myocytes following enzymatic dissociation. Cell separation leaves behind small vesicular remnants of formerly adjacent cells connected to the intact cell by gap junctions; in contrast, desmosomes cleave at the region of intercellular contact. Apparently, the next step in gap junction breakdown is internalization of the remnants. In thin section, lanthanum penetration reveals that the cleft of some apparently internalized gap junctions is in contact with the sarcolemma, while that of others is not. In freeze fracture replicas, cytoplasmic gap junctions frequently possess hexagonally packed domains of E-face pits separated by smooth regions that may correspond to separations of membranes of internalized junctions found in thin section. Study of material maintained overnight at 37 degrees C showed no surface junctional remnants; topologies of cytoplasmic gap junctions were generally complex, and concentric membrane vesicles were common. These observations suggest that enzymatic dissociation initiates a progressive, defined sequence of junctional internalization that begins with attached cell remnants and may have as the last determinable step the separation into single membranes inside the intact cell.
Abnormal fMRI Response of the Dorsolateral Prefrontal Cortex in Cognitively Intact Siblings of Patients With Schizophrenia
Authors: Joseph H Callicott, Michael F Egan, Venkata S Mattay, Alessandro Bertolino, Ashley D Bone, Beth Verchinksi, Daniel R Weinberger
Journal: American Journal of Psychiatry (2003)

The identification of neurobiological intermediate phenotypes may hasten the search for susceptibility genes in complex psychiatric disorders such as schizophrenia. Earlier family studies have suggested that deficits in executive cognition and working memory may be related to genetic susceptibility for schizophrenia, but the biological basis for this behavioral phenotype has not been identified.The authors used functional magnetic resonance imaging (fMRI) during performance of the N-back working memory task to assess working memory-related cortical physiology in nonschizophrenic, cognitively intact siblings of patients with schizophrenia. They compared 23 unaffected siblings of schizophrenic patients to 18 matched comparison subjects. As a planned replication, they studied another 25 unaffected siblings and 15 comparison subjects.In both cohorts, there were no group differences in working memory performance. Nevertheless, both groups of siblings showed an exaggerated physiological response in the right dorsolateral prefrontal cortex that was qualitatively similar to results of earlier fMRI studies of patients with schizophrenia.These fMRI data provide direct evidence of a primary physiological abnormality in dorsolateral prefrontal cortex function in individuals at greater genetic risk for schizophrenia, even in the absence of a manifest cognitive abnormality. This exaggerated fMRI response implicates inefficient processing of memory information at the level of intrinsic prefrontal circuitry, similar to earlier findings in patients with schizophrenia. These data predict that inheritance of alleles that contribute to inefficient prefrontal information processing will increase risk for schizophrenia.
Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease
Authors: B Sido, V Hack, A Hochlehnert, H Lipps, C Herfarth, W Droge
Journal: Gut (1998)

Reactive oxygen species contribute to tissue injury in inflammatory bowel disease (IBD). The tripeptide glutathione (GSH) is the most important intracellular antioxidant.To investigate constituent amino acid plasma levels and the GSH redox status in different compartments in IBD with emphasis on intestinal GSH synthesis in Crohn's disease.Precursor amino acid levels were analysed in plasma and intestinal mucosa. Reduced (rGSH) and oxidised glutathione (GSSG) were determined enzymatically in peripheral blood mononuclear cells (PBMC), red blood cells (RBC), muscle, and in non-inflamed and inflamed ileum mucosa. Mucosal enzyme activity of gamma-glutamylcysteine synthetase (gamma GCS) and gamma-glutamyl transferase (gamma GT) was analysed. Blood of healthy subjects and normal mucosa from a bowel segment resected for tumor growth were used as controls.Abnormally low plasma cysteine and cystine levels were associated with inflammation in IBD (p < 10(-4)). Decreased rGSH levels were demonstrated in non-inflamed mucosa (p < 0.01) and inflamed mucosa (p = 10(-6)) in patients with IBD, while GSSG increased with inflammation (p = 0.007) compared with controls. Enzyme activity of gamma GCS was reduced in non-inflamed mucosa (p < 0.01) and, along with gamma GT, in inflamed mucosa (p < 10(-4)). The GSH content was unchanged in PBMC, RBC, and muscle.Decreased activity of key enzymes involved in GSH synthesis accompanied by a decreased availability of cyst(e)ine for GSH synthesis contribute to mucosal GSH deficiency in IBD. As the impaired mucosal antioxidative capacity may further promote oxidative damage, GSH deficiency might be a target for therapeutic intervention in IBD.
Diabetes Quality Improvement in Department of Veterans Affairs Ambulatory Care Clinics
Authors: Gayle E. Reiber, David Au, Mary McDonell, Stephan D. Fihn
Journal: Diabetes Care (2004)

OBJECTIVE— To conduct a group-randomized clinical trial to determine whether regular feedback to primary care providers of synthesized information on patients’ health, function, and satisfaction would demonstrate improved outcomes for their patients with diabetes. RESEARCH DESIGN AND METHODS—Patients in General Internal Medicine Clinics Department of Veterans Affairs (VA) Medical Centers were randomized into seven intervention or control firms. Patient self-reported information was collected by mail on general health, diabetes, and up to five other chronic conditions. Patients with diabetes received the Seattle Diabetes Questionnaire, the 36-item Medical Outcomes Study short form (SF-36), and a validated patient satisfaction questionnaire at regular intervals. Data from self-report, clinical, pharmacy, and laboratory sources were synthesized into patient-specific feedback reports that intervention providers received before patients’ visits. RESULTS—The timely delivery to primary care providers of state-of-the-art patient-feedback reports that identified patient issues and areas for improvement did not result in significant improvements in patient outcomes between the intervention and control firms. CONCLUSIONS—Outcomes in diabetic patients whose providers received synthesized patient data before visits were no better than in those receiving care from control firms. Future studies may benefit from substantial involvement in patients discussing, problem solving, and goal setting in addition to use of timely synthesized patient data.
The Cost-Effectiveness of Birth-Cohort Screening for Hepatitis C Antibody in U.S. Primary Care Settings
Authors: David B Rein, Bryce D Smith, John S Wittenborn, Sarah B Lesesne, Laura D Wagner, Douglas W Roblin, Nita Patel, John W Ward, Cindy M Weinbaum
Journal: Annals of Internal Medicine (2012)

Background: In the United States, hepatitis C virus (HCV) infection is most prevalent among adults born from 1945 through 1965, and approximately 50% to 75% of infected adults are unaware of their infection. Objective: To estimate the cost-effectiveness of birth-cohort screening. Design: Cost-effectiveness simulation. Data Sources: National Health and Nutrition Examination Survey, U.S. Census, Medicare reimbursement schedule, and published sources. Target Population: Adults born from 1945 through 1965 with 1 or more visits to a primary care provider annually. Time Horizon: Lifetime. Perspective: Societal, health care. Intervention: One-time antibody test of 1945–1965 birth cohort. Outcome Measures: Numbers of cases that were identified and treated and that achieved a sustained viral response; liver disease and death from HCV; medical and productivity costs; quality-adjusted life-years (QALYs); incremental cost-effectiveness ratio (ICER). Results of Base-Case Analysis: Compared with the status quo, birth-cohort screening identified 808 580 additional cases of chronic HCV infection at a screening cost of $2874 per case identified. Assuming that birth-cohort screening was followed by pegylated interferon and ribavirin (PEG-IFN+R) for treated patients, screening increased QALYs by 348 800 and costs by $5.5 billion, for an ICER of $15 700 per QALY gained. Assuming that birth-cohort screening was followed by direct-acting antiviral plus PEG-IFN+R treatment for treated patients, screening increased QALYs by 532 200 and costs by $19.0 billion, for an ICER of $35 700 per QALY saved. Results of Sensitivity Analysis: The ICER of birth-cohort screening was most sensitive to sustained viral response of antiviral therapy, the cost of therapy, the discount rate, and the QALY losses assigned to disease states. Limitation: Empirical data on screening and direct-acting antiviral treatment in real-world clinical settings are scarce. Conclusion: Birth-cohort screening for HCV in primary care settings was cost-effective. Primary Funding Source: Division of Viral Hepatitis, Centers for Disease Control and Prevention.
Diabetes is a risk factor for tuberculosis in the Inuit population of Greenland: Table 1–
Authors: Stine Byberg, Bolette Soborg, Mikael Andersson, Peter Bjerregaard, Marit E. Jørgensen
Journal: European Respiratory Journal (2012)

To the Editors:

Diabetes is a known risk factor for tuberculosis (TB), and studies across populations and geographic regions suggest substantial increased risks of developing TB ranging from 1.16 to 7.83 with co-existing diabetes [1]. It is suggested that the risk is due to latent TB infections being activated by the hyperglycemia associated with diabetes. The evolving epidemiology of concurrent diabetes and TB in settings where both diseases are frequent is therefore looked upon with special concern. The prevalence of diabetes among the Greenland Inuit is high (10%) and increasing [2]. Meanwhile, the TB incidence remains high with an estimated 180 cases per 100,000 suggesting ongoing TB transmission [3]. The aim of this study was to quantify the effect of diabetes on TB development among the Greenland Inuit.

We conducted a retrospective cohort study. Study participants comprised ethnic Inuit who participated in two previously conducted cross-sectional studies where diabetes status were assessed; Inuit Health in Transition Study (IHIT) [4] and the Greenland Population Study (B99) [2]. All study participants in IHIT and B99 were randomly selected from the Civil Registration System (CRS) in order to represent the entire Greenlandic population. The CRS provides all citizens of Greenland with a unique identification number at birth, facilitating tracing of persons through all public registries. The CRS identifier enabled follow-up of study participants in the National TB register. The study was approved by the Ethics Review of Greenland.

Participants not previously diagnosed with diabetes (98%) underwent a standard oral glucose tolerance test (OGTT). Participants were categorised with diabetes if previously diagnosed with diabetes or if fasting and 2-h blood glucose levels were ≥7 mmol·L−1 and ≥11.1 mmol·L−1, respectively. …