tbuckley/cabot-search huggingface dataset:
Treating Multidrug-Resistant Tuberculosis: Compliance and Side Effects
Authors: J. Rush Pierce
Journal: JAMA (1994)

To the Editor.  —For the initial treatment of tuberculosis (TB), Mahmoudi and Iseman 1 recommend a four-drug regimen that includes ethambutol. The Centers for Disease Control and Prevention (CDC) have recently and similarly recommended that initial TB treatment consist of four drugs including either ethambutol or streptomycin. 2 These revised recommendations for initial treatment have been made in an attempt to control multidrug-resistant TB, with the assumption that the drugs are relatively safe.  Ethambutol's major toxic effect is retrobulbar optic neuritis, which is said to occur infrequently. At daily dosages of 25 mg/kg, the published incidence of ethambutol-associated optic neuritis (EAON) is 5%; for daily dosages of 15 mg/kg, the incidence is less than 1%. 3   We provide state-funded TB treatment for persons in 26 Texas Panhandle counties and use ethambutol infrequently. We reviewed records of our patients who had received ethambutol during the previous 24 months. Patients with human
The summary of diabetes self-care activities measure: results from 7 studies and a revised scale.
Authors: D J Toobert, S E Hampson, R E Glasgow
Journal: Diabetes Care (2000)

OBJECTIVE: To review reliability, validity, and normative data from 7 different studies, involving a total of 1,988 people with diabetes, and provide a revised version of the Summary of Diabetes Self-Care Activities (SDSCA) measure. RESEARCH DESIGN AND METHODS: The SDSCA measure is a brief self-report questionnaire of diabetes self-management that includes items assessing the following aspects of the diabetes regimen: general diet, specific diet, exercise, blood-glucose testing, foot care, and smoking. Normative data (means and SD), inter-item and test-retest reliability, correlations between the SDSCA subscales and a range of criterion measures, and sensitivity to change scores are presented for the 7 different studies (5 randomized interventions and 2 observational studies). RESULTS: Participants were typically older patients, having type 2 diabetes for a number of years, with a slight preponderance of women. The average inter-item correlations within scales were high (mean = 0.47), with the exception of specific diet; test-retest correlations were moderate (mean = 0.40). Correlations with other measures of diet and exercise generally supported the validity of the SDSCA subscales (mean = 0.23). CONCLUSIONS: There are numerous benefits from standardization of measures across studies. The SDSCA questionnaire is a brief yet reliable and valid self-report measure of diabetes self-management that is useful both for research and practice. The revised version and its scoring are presented, and the inclusion of this measure in studies of diabetes self-management is recommended when appropriate.
Randomized Clinical Trials With Biomarkers: Design Issues
Authors: B. Freidlin, L. M. McShane, E. L. Korn
Journal: JNCI Journal of the National Cancer Institute (2010)

Clinical biomarker tests that aid in making treatment decisions will play an important role in achieving personalized medicine for cancer patients. Definitive evaluation of the clinical utility of these biomarkers requires conducting large randomized clinical trials (RCTs). Efficient RCT design is therefore crucial for timely introduction of these medical advances into clinical practice, and a variety of designs have been proposed for this purpose. To guide design and interpretation of RCTs evaluating biomarkers, we present an in-depth comparison of advantages and disadvantages of the commonly used designs. Key aspects of the discussion include efficiency comparisons and special interim monitoring issues that arise because of the complexity of these RCTs. Important ongoing and completed trials are used as examples. We conclude that, in most settings, randomized biomarker-stratified designs (ie, designs that use the biomarker to guide analysis but not treatment assignment) should be used to obtain a rigorous assessment of biomarker clinical utility.
Fossil Calibration of Molecular Clocks and the Divergence Times of Geminate Species Pairs Separated by the Isthmus of Panama
Authors: Peter B. Marko
Journal: Molecular Biology and Evolution (2002)

Calibration of nucleotide sequence divergence rates provides an important method by which to test many hypotheses of evolution. In the absence of an adequate fossil record, geological events, rather than the first appearances of sister taxa in the geological record, are often used to calibrate molecular clocks. The formation of the Isthmus of Panama, which isolated the tropical western Atlantic and eastern Pacific oceans, is one such event that is frequently used to infer rates of nucleotide sequence divergence. Isthmian calibrations assume that morphologically similar "geminate" species living now on either side of the isthmus were isolated geographically by the latest stages of seaway closure 3.1-3.5 MYA. Here, I have applied calibration dates from the fossil record to cytochrome c oxidase-1 (CO1) and nuclear histone-3 (H3) divergences among six pairs of geminates in the Arcidae to test this hypothesis. Analysis of CO1 first and third positions yield geminate divergences that predate final seaway closure, and on the basis of CO1 first positions, times for all six geminates are significantly greater than 3.5 Myr. H3 sequences produce much more recent geminate divergences, some that are younger than 3.1 Myr. But H3-derived estimates for all arcid geminates are not significantly different from both 0 and 15 Myr. According to CO1, one of the two most divergent pairs, Arca mutabilis and A. imbricata, split more than 30 MYA. This date is compatible with the fossil record, which indicates that these species were morphologically distinct at least 16-21 MYA. Across all CO1 nucleotide sites, divergence rates for arcids are slower than the rates reported for other taxa on the basis of isthmian calibrations, with the exception of rates determined from the least divergent species pair in larger surveys of multiple transisthmian pairs. Rate differences between arcids and some taxa may be real, but these data suggest that divergence rates can be greatly overestimated when dates corresponding to final closure of the Central American Seaway are used to calibrate the molecular clocks of marine organisms.
Enterocyte function in progressive systemic sclerosis as estimated by the deconjugation of pteroyltriglutamate to folic acid.
Authors: L Hendel, J Hendel, I Joergensen
Journal: Gut (1987)

As a measure of enterocyte function, the deconjugation of pteroyl-L-glutamyl-gamma-L-glutamyl-gamma-L-glutamic acid to folic acid and subsequent active absorption was measured in 19 patients with progressive systemic sclerosis and compared with 14 controls. The absorption step of folic acid was identical in the two groups, while deconjugation of pteroyl-L-glutamyl-gamma-L-glutamyl-gamma-L-glutamic acid was significantly decreased in the patients with progressive systemic sclerosis. This observation suggests a primary epithelial defect of the small intestine in patients with progressive systemic sclerosis.
MicroRNA Expression Ratio Is Predictive of Head and Neck Squamous Cell Carcinoma
Authors: Michele Avissar, Brock C. Christensen, Karl T. Kelsey, Carmen J. Marsit
Journal: Clinical Cancer Research (2009)

The involvement of microRNAs in cancer and their potential as biomarkers of diagnosis and prognosis are becoming increasingly appreciated. We sought to identify microRNAs altered in head and neck squamous cell carcinoma (HNSCC) and to determine whether microRNA expression is predictive of disease. RNA isolated from fresh-frozen primary tumors, fresh-frozen nondiseased head and neck epithelial tissues, and HNSCC cell lines was profiled for the expression of 662 microRNAs by microarray. The microRNAs that were both differentially expressed on the array and by quantitative reverse transcription-PCR were subsequently validated by quantitative reverse transcription-PCR using a total of 99 HNSCC samples and 14 normal epithelia. A marked difference in microRNA expression pattern was observed between tumors and cell lines. Eighteen microRNAs were significantly altered in their expression between normal tissues and tumors. Four of these microRNAs were validated in the larger sample series, and each showed significant differential expression (P < 0.0001). Furthermore, an expression ratio of miR-221:miR-375 showed a high sensitivity (0.92) and specificity (0.93) for disease prediction. These data suggest that cultured tumor cell lines are inappropriate for microRNA biomarker identification and that the pattern of microRNA expression in primary head and neck tissues is reflective of disease status, with certain microRNAs exhibiting strong predictive potential. These results indicate that miR-221 and miR-375 should be evaluated further as diagnostic biomarkers because they may hold utility in defining broadly responsive prevention and treatment strategies for HNSCC.
The diagnosis and management of aortic dissection
Authors: Sri G Thrumurthy, Alan Karthikesalingam, Benjamin O Patterson, Peter J E Holt, Matt M Thompson
Journal: BMJ (2011)

#### Summary points

Aortic dissection is caused by an intimal and medial tear in the aorta with propagation of a false lumen within the aortic media. It is part of the “acute aortic syndrome”—an umbrella term for aortic dissection, intramural haematoma, and symptomatic aortic ulcer (table⇓).1 Acute dissection is the most common aortic emergency, with an annual incidence of 3-4 per 100 000 in the United Kingdom and United States, which exceeds that of ruptured aneurysm.2 w1 w2 The prognosis is grave, with 20% preadmission mortality and 30% in-hospital mortality.2

View this table:

European Society of Cardiologists’ classification of acute aortic syndrome 



The best treatment depends on the anatomical and temporal classification of the disease. Aortic dissection is therefore categorised according to the site of the entry tear and the time between the onset of symptoms and diagnosis. A dissection is considered “acute” when the diagnosis is made within 14 days of onset, and thereafter it is termed “chronic.” The location of the entry tear plays a key role in treatment and outcome, and it is classified by being in the ascending aorta (Stanford type A dissection) or distal to …
Glycemia and Corrected QT Interval Prolongation in Young Type 1 Diabetic Patients
Authors: Bert Suys, Sara Heuten, Daniel De Wolf, Marc Verherstraeten, Lieve Op de Beeck, Dirk Matthys, Christiaan Vrints, Raoul Rooman
Journal: Diabetes Care (2006)

The relationship between a prolonged QT interval and an increased risk of sudden death has been extensively explored in familial long QT syndrome, sudden infant death, and ischemic heart disease (1–3). Several recent studies also describe the relation between corrected QT interval (QTc) prolongation, diabetes complications, and an increased mortality in adults (4,5). We recently described QTc prolongation and a larger QT dispersion in a cohort of children and adolescents with type 1 diabetes (6). The influence of changes in glycemia on the length of the QT or QTc remains a controversial issue. Experimental hypoglycemia and, just recently, spontaneous clinical episodes of hypoglycemia proved to lead to QTc lengthening (7–9). There is some evidence that prolonged cardiac repolarization contributes to sudden death associated with nocturnal hypoglycemia in young people with diabetes (10–13). On the other hand, a relation between hyperglycemia and abnormal cardiac repolarization has also been described (14). We therefore simultaneously recorded QT and QTc values using 24-h Holter registration and glucose levels with a continuous glucose monitoring system in children and adolescents with type 1 diabetes.

Nine children and adolescents with stable type 1 diabetes (five males and four females aged 9–19 years) were prospectively recruited from the patient population that regularly attends the Diabetes Clinic for …
Correlation between functional asymmetry of professional soccer players and sprint
Authors: I Sannicandro, A Piccinno, R A Rosa, S De Pascalis
Journal: British Journal of Sports Medicine (2011)

Background The functional asymmetry (FA) of the soccer player lower limb is often analyzed to reduce the risk of injury. In football have been described power asymmetries (Samadi et al ., 2009; Bittencourt et al ., 2008; Rahnama et al ., 2005), differences in plantar pressure (Wong et al ., 2007), asymmetries in vertical jump (Impellizzeri et al ., 2007), differences in the ground reaction forces during the landing between dominant and non-dominant limb (Sannicandro, 2008). The FA, however, besides being a significant element of risk of injury, can affect the performance of the soccer player. Objective The study aims to analyze the relationships between asymmetry of the strength of the lower limb and sprint in professional footballers. Design Descriptive research (a correlation study which investigates the relationship between variables). Setting Soccer Elite Division, at the end of off season conditioning. Participants 25 soccer players (26.1 ± 2.9 year, 179.8 ± 3.6 cm, 77.9 ± 2.5 kg). Assessment of risk factors The assessment of explosive strength was performed through monopodalic jump, in literature defined as hop test and sprint test on 10 m and 20 m through photocells (TTSport, San Marino). Main outcome measurements FA was calculated between the two limbs as follows (jump dominant-limb – jump non-dominant limb)/jump dominant-limb * 100 (Yamamoto, 1993; Impellizzeri et al ., 2007). This value was correlated with the results (sec) obtained in the 10 m sprint and 20 m sprint. Results The analysis of the correlation between FA and sprint 10 m and 20 m sprint between FA and showed values equal respectively to r=0.702 (p&lt;0.001) and r=0.215 (ns). Conclusion The results would suggest that the FA in the lower limb explosive strength affects the performance of short sprints, but not those of the longer sprint. In the 20 m sprint, other factors, such as cyclic speed and intermuscular coordination, could be of greater importance.
DAP12/TREM2 Deficiency Results in Impaired Osteoclast Differentiation and Osteoporotic Features
Authors: Juha Paloneva, Jami Mandelin, Anna Kiialainen, Tom Böhling, Johannes Prudlo, Panu Hakola, Matti Haltia, Yrjö T. Konttinen, Leena Peltonen
Journal: The Journal of Experimental Medicine (2003)

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), Nasu-Hakola disease, is a globally distributed recessively inherited disease. PLOSL is characterized by cystic bone lesions, osteoporotic features, and loss of white matter in the brain leading to spontaneous bone fractures and profound presenile dementia. We have earlier characterized the molecular genetic background of PLOSL by identifying mutations in two genes, DAP12 and TREM2. DAP12 is a transmembrane adaptor protein that associates with the cell surface receptor TREM2. The DAP12–TREM2 complex is involved in the maturation of dendritic cells. To test a hypothesis that osteoclasts would be the cell type responsible for the bone pathogenesis in PLOSL, we analyzed the differentiation of peripheral blood mononuclear cells isolated from DAP12- and TREM2-deficient PLOSL patients into osteoclasts. Here we show that loss of function mutations in DAP12 and TREM2 result in an inefficient and delayed differentiation of osteoclasts with a remarkably reduced bone resorption capability in vitro. These results indicate an important role for DAP12–TREM2 signaling complex in the differentiation and function of osteoclasts.
Inhibition of nitric oxide production. Mechanisms of vascular albumin leakage.
Authors: I Kurose, P Kubes, R Wolf, D C Anderson, J Paulson, M Miyasaka, D N Granger
Journal: Circulation Research (1993)

The mechanisms by which nitric oxide modulates microvascular albumin exchange were investigated by monitoring leukocyte-endothelial cell adhesion and fluorescein isothiocyanate-albumin leakage in rat mesenteric venules exposed to NG-nitro-L-arginine methyl ester (L-NAME). L-NAME elicited an initial rapid increase followed by a slower rate of albumin accumulation in the interstitial space. The initial phase of albumin leakage preceded the L-NAME-induced leukocyte adherence and emigration, whereas the magnitude of the albumin leakage observed in the later phase of L-NAME exposure was highly correlated with the number of adherent and emigrated leukocytes in the same segment of venule. Monoclonal antibodies (MAbs) directed against adhesion molecules CD11/CD18, ICAM-1, or P-selectin, but not a nonbinding MAb, attenuated the albumin leakage induced by L-NAME. WEB2086, a platelet activating factor antagonist, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-br-cGMP) reduced the leukocyte adherence and emigration as well as the increased albumin leakage. Only 8-br-cGMP and the P-selectin MAb attenuated the platelet-leukocyte aggregation elicited by L-NAME. Phalloidin, which promotes endothelial junctional integrity, inhibited both the early and late phases of albumin leakage. Overall, these findings suggest that the increased albumin leakage observed in postcapillary venules after inhibition of nitric oxide production involves a mechanism that includes a role for cGMP, platelet activating factor, leukocyte-endothelial cell adhesion, and the endothelial cell cytoskeleton.
Plasma Growth Differentiation Factor-15 Independently Predicts All-Cause and Cardiovascular Mortality As Well As Deterioration of Kidney Function in Type 1 Diabetic Patients With Nephropathy
Authors: Maria Lajer, Anders Jorsal, Lise Tarnow, Hans-Henrik Parving, Peter Rossing
Journal: Diabetes Care (2010)

Growth deferentiation factor-15 (GDF-15) is involved in inflammation and apoptosis. Expression is induced in the heart in response to ischemia and in atherosclerotic plaques. The aim of this study was to investigate GDF-15 levels in relation to all-cause mortality, cardiovascular mortality and morbidity, decline in glomerular filtration rate (GFR), and progression toward end-stage renal disease (ESRD).The study was a prospective observational follow-up study including 451 type 1 diabetic patients with diabetic nephropathy (274 men, aged 42.1 +/- 0.5 years [means +/- SD], diabetes duration 28.3 +/- 8.9 years, GFR 76 +/- 33 ml/min/1.73 m(2)) and a control group of 440 patients with longstanding type 1 diabetes and persistent normoalbuminuria (232 men, aged 45.4 +/- 11.5 years, duration of diabetes 27.7 +/- 10.1 years). The patients were followed for 8.1 (0.0-12.9) years (median [range]).Among normoalbuminuric patients, GDF-15 above the median predicted an adjusted (age, systolic blood pressure [sBP], and estimated GFR) increased risk of all-cause mortality (hazard ratio [HR] 3.6 [95% CI 1.3-10.3]; P = 0.014). Among patients with diabetic nephropathy, higher (fourth quartile) versus lower (first quartile) GDF-15 levels predict all-cause mortality (covariate-adjusted [sex, age, smoking, blood pressure, A1C, cholesterol, GFR, N-terminal prohormone B-type natriuretic peptide, antihypertensive treatment, and previous cardiovascular events]; HR 4.86 [95% CI 1.37-17.30]) as well as fatal and nonfatal cardiovascular events (adjusted HR 5.59 [1.23-25.43] and 3.55 [1.08-11.64], respectively). In addition, higher GDF-15 levels predict faster decline in GFR (P < 0.001) but not development of ESRD.Higher levels of GDF-15 are a predictor of all-cause and cardiovascular mortality and morbidity in patients with diabetic nephropathy. Furthermore, higher levels of GDF-15 are associated with faster deterioration of kidney function.
Intranasal administration of recombinant human cartilage glycoprotein-39 as a treatment for rheumatoid arthritis: a phase II, multicentre, double-blind, randomised, placebo-controlled, parallel-group, dose-finding trial
Authors: R. B. M. Landewe, J. G. A. Houbiers, F. Van den Bosch, J. in't Hout, P. C. P. M. Verschueren, J. H. Meijerink, F. H. J. van den Hoogen, B. A. Masek, G. A. W. Bruyn, J. M. G. W. Wouters, A. E. Voskuyl, J. M. van Laar, J. J. W. Bijlsma, D. M. F. M. van der Heijde, F. C. Breedveld, L. B. A. van de Putte, A. M. M. Miltenburg, F. de Keyser
Journal: Annals of the Rheumatic Diseases (2009)

Autoantigen-specific immunotherapy by mucosal tolerance induction via the intranasal route is an attractive therapeutic option for the treatment of autoimmune diseases, including rheumatoid arthritis (RA). Human cartilage glycoprotein-39 (HC gp-39) has been identified as a potential key autoantigen in RA. Based on animal studies, intranasal administration of the autoantigen is hypothesised to induce immunological tolerance in patients with RA and to ameliorate disease activity. In a phase I/IIA clinical trial in patients with RA, intranasal application of HC gp-39 was safe and well tolerated.To investigate the efficacy of intranasally administered fully human, recombinant HC gp-39 (Org 39141) by a large clinical study.In a 13-week multicentre, double-blind, randomised, placebo-controlled, parallel-group, dose-finding, proof-of-concept trial, patients with RA (disease-modifying antirheumatic drug (DMARD) naive or after washout of DMARD treatment) were randomised to receive either intranasal applications of placebo or HC gp-39 in doses of 30, 150, 300 or 600 microg, once a week. The primary efficacy variable was the 28 joint count Disease Activity Score (DAS28).During the treatment period the DAS28 decreased similarly for all treatment groups-including placebo-indicating lack of efficacy of intranasal HC gp-39 treatment in the current setting. Safety variables were similar for all study groups.It was concluded that with the treatment protocol used (dose levels and frequency of dosing), intranasal treatment with Org 39141 was safe but did not result in more clinical improvement than in placebo-treated patients.
Divergent patterns of matrix metalloproteinase activity during wound healing in ileum and colon of rats.
Authors: W F Seifert, T Wobbes, T Hendriks
Journal: Gut (1996)

BACKGROUND: Uncontrolled and increased extracellular matrix degradation during early anastomotic repair in the intestine may reduce wound strength increasing the risk of anastomotic dehiscence. AIMS: To characterise the metalloproteinases present in intact and anastomosed ileum and colon to study their role in matrix degradation after surgery. SUBJECTS: Tissue extracts of uninjured, and of anastomosed rat ileum and colon at postoperative days 1, 2, 3, 7, and 90, were used. METHODS: Metalloproteinases were identified by gelatin and casein zymography. Aminophenylmercuric acetate (APMA) treatment was used to activate latent metalloproteinases. RESULTS: Both uninjured ileum and colon contained a 60 and 67 kDa activity, but a 54 and 72 kDa gelatinase was present in ileum only, and a 51 kDa activity in colon only. APMA treatment converted the 60 kDa protease to 54 and 51 kDa forms and the 72 kDa protease to the 67 kDa form. These gelatinases may correspond to latent and active forms of MMP 1 and MMP 2, respectively. Additional metalloproteinases were observed after anastomotic construction. Both ileum and colon contained 95 and 230 kDa gelatinases, which were converted to 83 and 76 kDa forms by APMA. They may be the latent and active forms of MMP 9, respectively. Gelatinolytic activities of 25 and 28 kDa were only found in anastomosed ileum. Caseinolytic activities were only found in ileum extracts and those were most prominent at day 1, 2, and 3 after surgery. CONCLUSIONS: The metalloproteinase pattern in ileum and colon differ considerably suggesting that matrix degradation after anastomotic construction may also vary.
Standardisation of spirometry
Authors: M. R. Miller, J. Hankinson, V. Brusasco, F. Burgos, R. Casaburi, A. Coates, R. Crapo, P. Enright, C. P. M. van der Grinten, P. Gustafsson, R. Jensen, D. C. Johnson, N. MacIntyre, R. McKay, D. Navajas, O. F. Pedersen, R. Pellegrino, G. Viegi, J. Wanger
Journal: European Respiratory Journal (2005)