tbuckley/cabot-search huggingface dataset:
Hepatitis A and Non–A, Non–B Viral Hepatitis in São Paulo, Brazil: Epidemiological, Clinical, and Laboratory Comparisons in Hospitalized Patients
Authors: Raymond S. Koff, Claudio S. Pannuti, Marcelo L.G. Pereira, Bengt G. Hansson, Jules L. Dienstag, Amato V. NETO, Doris C. Wong, Robert H. Purcell
Journal: Hepatology (1982)

During a 33–month period, 295 patients with acute viral hepatitis were admitted to a state hospital for civil servants and their dependents in Sao Paulo, Brazil. Seventy–nine per cent (232) were HBsAg negative. To define the contribution of non–A, non–B viral hepatitis to hepatitis morbidity in this population, further serological studies were performed in 147 confirmed HBsAg–negative patients. One hundred and twelve (76%) were serologically classified as hepatitis A based on identification of IgM antibody to hepatitis A virus. Thirty patints (20%) without IgM antibody to hepatitis A virus, HBsAg, or anti–HBc were categorized as the non–A, non–B hepatitis group. The remaining five patients had probable hepatitis B (IgM antibody to hepatitis A virus negative, HBsAg negative, anti–HBs negative but anti–HBc positive). These data suggest that all three etiological forms of viral hepatitis are endemic in Sao Paulo. Epidemiological, clinical, and laboratory features were compared in the hepatitis A and non–A, non–B hepatitis groups. Patients with non–A, non–B hepatitis were significantly older than patients with hepatitis A (mean age ± S.D.: 30 ± 22 years vs. 9 ± 9 years, p &lt; 0.001). Contact with hepatitis or jaundice was recognized in 26 (23%) of 112 hepatitis A patients and 3 (10%) of 30 non–A, non–B patients, a difference which was not statistically significant. Parenteral exposures were identified in 13 (43%) of 30 patients with non–A, non–B hepatitis and 23 (21%) of the 112 hepatitis A patients. Blood transfusion in the 2 months preceding onset of illness was reported in 5 (17%) of the 30 non–A, non–B patients and in none of the hepatitis A group (p &lt; 0.001). Although prodromal symptoms and fever were more common in patients with hepatitis A, neither these nor other clinical features appeared to be distinguishing characteristics. Similarly, mean peak SGPT levels, peak SGPT levels of &gt; 1,000 HJ/per liter, and the mean duration of SGPT elevations for each group were not significantly different. Mean peak serum bilirubin levels were slightly higher in the non–A, non–B group than in the hepatitis A group (7.6 ± 8.0 mg per dl vs. 5.1 ± 2.7, p &lt; 0.01) and peak bilirubin levels &gt; 10 mg per dl were found in 27% of the non–A, non–B group and 5% of the hepatitis A group (p &lt; 0.001). Whether the higher bilirubin levels reflect an agent–related phenomenon or an older population of affected patients is uncertain.
Should Elderly Non–Small-Cell Lung Cancer Patients Be Offered Elderly-Specific Trials? Results of a Pooled Analysis From the North Central Cancer Treatment Group
Authors: Aminah Jatoi, Shauna Hillman, Philip Stella, Erin Green, Alex Adjei, Suresh Nair, Edith Perez, Bipinkur Amin, Steven E. Schild, Rene Castillo, James R. Jett
Journal: Journal of Clinical Oncology (2005)

To answer the question, "should elderly non-small-cell lung cancer patients be offered elderly-specific trials?"The North Central Cancer Treatment Group (NCCTG) performed a pooled analysis of elderly patients who participated in elderly-specific trials (required age > or = 65 years) and age-unspecified trials (required age > or = 18 years). Between 1998 and 2000, all NCCTG non-small-cell lung cancer (NSCLC) patients with incurable cancer, age > or = 65 years, and receiving first-line chemotherapy were included. A total of 118 elderly patients participated in elderly-specific trials, and 108, in age-unspecified trials. Demographics and outcomes were compared based on trial type.The median age of elderly patients in elderly-specific trials was greater: median (range): 73 years (65 to 87) and 70 years (65 to 85), respectively (P < .001), as was the percentage older than 80 years: 17% and 3%, respectively (P = .0008). Median survival times were 232 and 302 days, respectively (P = .08). After adjustment for baseline age, Eastern Cooperative Oncology Group performance score, cancer stage, and body mass index, this survival difference was not statistically significant (hazard ratio = 1.25; P = .16). Grade 3 or worse nonhematologic adverse event rates were greater in age-unspecified trials (81% v 57%, respectively; P < .001), as were grade 3 or worse hematologic events (68% v 10%, respectively; P < .001).Elderly patients in NSCLC elderly-specific trials suffered lower rates of severe adverse events with no statistically significant differences in survival. It seems that elderly-specific trials are providing quality care and helping to define optimal cancer therapy in the elderly, particularly among the "oldest of the old."
Potential Antiatherogenic Mechanisms of Ascorbate (Vitamin C) and α-Tocopherol (Vitamin E)
Authors: Anitra C. Carr, Ben-Zhan Zhu, Balz Frei
Journal: Circulation Research (2000)

The premise that oxidative stress, among several other factors, plays an important role in atherogenesis implies that the development and progression of atherosclerosis can be inhibited by antioxidants. In this minireview we discuss several mechanisms by which the antioxidants ascorbate (vitamin C) and alpha-tocopherol (vitamin E) may protect against atherosclerosis. These mechanisms include inhibition of LDL oxidation and inhibition of leukocyte adhesion to the endothelium and vascular endothelial dysfunction. Overall, ascorbate appears to be more effective than alpha-tocopherol in mitigating these pathophysiological processes, most likely as a result of its abilities to effectively scavenge a wide range of reactive oxygen and nitrogen species and to regenerate alpha-tocopherol, and possibly tetrahydrobiopterin, from its radical species. In contrast, alpha-tocopherol can act either as an antioxidant or a pro-oxidant to inhibit or facilitate, respectively, lipid peroxidation in LDL. However, this pro-oxidant activity of alpha-tocopherol is prevented by ascorbate acting as a coantioxidant. Therefore, an optimum vitamin C intake or body status may help protect against atherosclerosis and its clinical sequelae, whereas vitamin E may only be effective in combination with vitamin C.
Mechanical and morphological properties of arterial resistance vessels in young and old spontaneously hypertensive rats.
Authors: D M Warshaw, M J Mulvany, W Halpern
Journal: Circulation Research (1979)

We studied alterations in structural and mechanical properties of mesenteric arterial resistance vessels from young (6-week) and old (50-week) spontaneously hypertensive (SHR)and matched normotensive Wistar-Kyoto (WKY) rats. Emphasis was placed upon relating the active tension capabilities of these vessels to their smooth muscle cell content. Cylindrical segments, 0.7 mm long with internal diameters of 150 micrometer, were mounted in a myograph capable of recording circumferential vessel wall tension and dimensions. Comparisons of vessel morphology and mechanics were performed at a normalized internal circumference, L1,where active tension (delta T1) is near maximum. Arterial wall and medial hypertrophy were observed in young and old SHR. Since the percent smooth muscle cells within the media for SHR was similar to that of WKY, both increased smooth muscle cell and connective tissue content account for the medial hypertrophy. These differences in SHR vessels were reflected directly in their passive and active mechanical properties. Fully relaxed vessels from SHR were less compliant, and upon activation at L1 (high potassium depolarization), delta T1 was not different for young SHR and WKY, but values for old SHR were 35% greater (P less than 0.05) than for WKY. When relating the active force generation of the vessel to the actual smooth muscle cell area, values for smooth muscle cell stress (force/area) were similar for SHR and WKY at both ages. In addition, similarities were observed for active dynamic mechanical measurements of Young's modulus and half response time. Genetic hypertension in rats therefore appears to be associated with the development of increased vessel contractility determined by a greater number of smooth muscle cells which possess contractile properties similar to those of normotensive vessels.
Platelet glycoprotein V binds to collagen and participates in platelet adhesion and aggregation
Authors: Sylvie Moog, Pierre Mangin, Nadège Lenain, Catherine Strassel, Catherine Ravanat, Simone Schuhler, Monique Freund, Martine Santer, Mark Kahn, Bernhard Nieswandt, Christian Gachet, Jean-Pierre Cazenave, François Lanza
Journal: Blood (2001)
Insulin-like Growth Factor Receptor Inhibitors: Baby or the Bathwater?
Authors: D. Yee
Journal: JNCI Journal of the National Cancer Institute (2012)

The success of targeted therapies for cancer is undisputed; strong preclinical evidence has resulted in the approval of several new agents for cancer treatment. The type I insulin-like growth factor receptor (IGF1R) appeared to be one of these promising new targets. Substantial population and preclinical data have all pointed toward this pathway as an important regulator of tumor cell biology. Although early results from clinical trials that targeted the IGF1R showed some evidence of response, larger randomized phase III trials have not shown clear clinical benefit of targeting this pathway in combination with conventional strategies. These disappointing results have resulted in the discontinuation of several anti-IGF1R programs. However, the conduct of these trials has brought to the forefront several important factors that need to be considered in the conduct of future clinical trials. The need to develop biomarkers, a clearer understanding of insulin receptor function, and defining rational combination regimens all require further consideration. In this commentary, the current state of IGF1R inhibitors in cancer therapy is reviewed.
Cyclooxygenase 1 is required for pH control at the mouse gastric surface
Authors: H K Baumgartner
Journal: Gut (2004)

<b>Background:</b> Endogenous cyclooxygenase (COX) activity is required to maintain a relatively alkaline surface pH at the gastric luminal surface. <b>Aims:</b> The purpose of this study was to determine which COX isoform, COX-1 or COX-2, is responsible for regulating the protective surface pH gradient and to test if COX inhibitors also had non-COX mediated effects in vivo. <b>Methods:</b> Immunofluorescence and western blot analysis showed constitutive expression of both COX isoforms in the normal mouse stomach. We used in vivo confocal microscopy to measure pH near the mucosal surface of anaesthetised COX-1 (−/−), COX-2 (−/−), or wild-type mice of the same genetic background. <b>Results:</b> When the gastric mucosal surface was exposed and superfused (0.2 ml/min) with a weakly buffered saline solution (pH 3) containing the pH indicator Cl-NERF, the pH directly at the gastric surface and thickness of the pH gradient were similar in wild-type and COX-2 (−/−) mice, but COX-1 (−/−) mice had a significantly thinner pH gradient. Addition of indomethacin had minimal effects on the residual surface pH gradient in COX-1 (−/−) mice, suggesting no role for COX-2 in surface pH regulation. Whole stomach perfusion studies demonstrated diminished net alkali secretion in COX-1 (−/−) mice, and application of SC-560 or rofecoxib to wild-type mice and mutant mice confirmed that only COX-1 inhibition reduced alkali secretion. <b>Conclusion:</b> COX-1 is the dominant isoform regulating the normal thickness of the protective surface pH gradient in mouse stomach.
Extended <i>RAS</i> Gene Mutation Testing in Metastatic Colorectal Carcinoma to Predict Response to Anti–Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015
Authors: Carmen J. Allegra, R. Bryan Rumble, Stanley R. Hamilton, Pamela B. Mangu, Nancy Roach, Alexander Hantel, Richard L. Schilsky
Journal: Journal of Clinical Oncology (2015)

Purpose An American Society of Clinical Oncology Provisional Clinical Opinion (PCO) offers timely clinical direction after publication or presentation of potentially practice-changing data from major studies. This PCO update addresses the utility of extended RAS gene mutation testing in patients with metastatic colorectal cancer (mCRC) to detect resistance to anti–epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) therapy. Clinical Context Recent results from phase II and III clinical trials in mCRC demonstrate that patients whose tumors harbor RAS mutations in exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146) are unlikely to benefit from therapy with MoAbs directed against EGFR, when used as monotherapy or combined with chemotherapy. Recent Data In addition to the evidence reviewed in the original PCO, 11 systematic reviews with meta-analyses, two retrospective analyses, and two health technology assessments based on a systematic review were obtained. These evaluated the outcomes for patients with mCRC with no mutation detected or presence of mutation in additional exons in KRAS and NRAS. PCO All patients with mCRC who are candidates for anti-EGFR antibody therapy should have their tumor tested in a Clinical Laboratory Improvement Amendments–certified laboratory for mutations in both KRAS and NRAS exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146). The weight of current evidence indicates that anti-EGFR MoAb therapy should only be considered for treatment of patients whose tumor is determined to not have mutations detected after such extended RAS testing.
International Union of Pharmacology. LXV. The Pharmacology and Classification of the Nuclear Receptor Superfamily: Glucocorticoid, Mineralocorticoid, Progesterone, and Androgen Receptors
Authors: Nick Z. Lu, Suzanne E. Wardell, Kerry L. Burnstein, Donald Defranco, Peter J. Fuller, Vincent Giguere, Richard B. Hochberg, Lorraine McKay, Jack-Michel Renoir, Nancy L. Weigel, Elizabeth M. Wilson, Donald P. McDonnell, John A. Cidlowski
Journal: Pharmacological Reviews (2006)

The glucocorticoid receptor (GR[1][1]), mineralocorticoid receptor (MR), progesterone receptor (PR), and androgen receptor (AR) are classic members of the nuclear receptor superfamily, composing subfamily 3C. Members of this subfamily are among those receptors that were cloned the earliest, with the
Progression From Newly Acquired Impaired Fasting Glucose to Type 2 Diabetes
Authors: Gregory A. Nichols, Teresa A. Hillier, Jonathan B. Brown
Journal: Diabetes Care (2007)

n response to our report on progression from impaired fasting glucose to diabetes (1), Dinneen and Rizza (2) note that they had previously demonstrated a clear gradation of risk of progression to diabetes among nondiabetic individuals with baseline fasting plasma glucose (FPG) Ͻ100 mg/dl (3).They express interest in knowing whether this observation can be replicated in our data.Unfortunately, the study in question did not include individuals with normal fasting glucose.However, in a related study previously reported in Diabetes Care (4), we identified over 28,000 health plan members with baseline FPG under 100 mg/dl on whom such analyses are possible.We are currently preparing a manuscript that will fully address this important issue and are therefore precluded from reporting that data here.Nevertheless, we concur with Dinneen and Rizza (2) that the relative risk of diabetes likely increases with rising fasting glucose even at apparently normal FPG levels.
Arterial pH and PaCO2 (at presentation or pre NIV) are poor predictors of death or length of stay (LOS) in patients receiving non invasive ventilation (NIV) for acute type 2 respiratory failure (T2RF)
Authors: Sarah Davies, Adeel Sahal, Manish Pagaria, Joyutpal Das
Journal: European Respiratory Journal (2014)

Introduction

Patients with decompensated T2RF and arterial pH <7.26 are thought to have worse outcomes and there is debate over treatment in a level 2 setting. This study at a District General Hospital aimed to identify if pH, PaCO2 or level 2 care has significant correlation to LOS or mortality.

Method

Retrospective analysis of patients requiring NIV over 12 months(November 2012-13), and the relationship between admission and pre-NIV pH and PaCO2 to mortality and LOS.

Results

185 patients identified (89 male, 96 female). Overall mortality was 44.3%. There was no statistically significant difference between mean pre-NIV pH (7.25, SD0.10 vs 7.20,SD0.11 ) or admission pH(7.29,SD0.13 vs 7.30,SD0.12) in survival group compared to deceased group. Similarly, no significant difference was seen in pre-NIV PaCO2(10.97,SD3.72 vs 10.24,SD3.60) or admission PaCO2(9.76,SD4.08 vs 9.24,SD3.90) in the two groups. Analysis with spearman's rank correlation co-efficient showed no correlation between LOS with pre-NIV pH, pre-NIV PaCO2, admission pH or admission PaCO2. Median LOS was 11 days.

41.6% (77 patients) were level 2 with a mortality of 42.25%, ward patient mortality was higher 46.15% (p0.61) but not statistically significant. Mean pre-NIV pH for HDU patients was 7.22,SD0.12, compared with 7.26,SD0.70 for ward. Median LOS was 11 days for HDU and 10 days for ward.

Conclusion

Pre-NIV pH and PaCO2 in patients with T2RF are not reliable predictors of mortality or LOS. This review indicates that appropriate patients with T2RF should be treated with NIV regardless of severity of the arterial pH and PaCO2.
Effect of Antidepressant Medication Use on Emotional Information Processing in Major Depression
Authors: Tony T. Wells, Elise M. Clerkin, Alissa J. Ellis, Christopher G. Beevers
Journal: American Journal of Psychiatry (2013)

Acute administration of antidepressant medication increases emotional information processing for positive information in both depressed and healthy persons. This effect is likely relevant to the therapeutic actions of these medications, but it has not been studied in patients with major depressive disorder taking antidepressants as typically prescribed in the community.The authors used eye tracking to examine the effects of antidepressant medication on selective attention for emotional stimuli in a sample of 47 patients with major depressive disorder (21 medicated and 26 unmedicated) and 47 matched comparison subjects without depression. Participants completed a passive-viewing eye-tracking task assessing selective attention for positive, dysphoric, threatening, and neutral stimuli in addition to providing medication information and self-report measures of depression and anxiety severity.Depressed participants currently taking antidepressants and nondepressed comparison subjects demonstrated greater total gaze duration and more fixations for positive stimuli compared with unmedicated depressed participants. Depressed participants on medication also had fewer fixations for dysphoric stimuli compared with depressed participants not on medication.Antidepressants, as prescribed in the community to patients with depression, appear to modify emotional information processing in the absence of differences in depression severity. These results are consistent with previous work and indicate a robust effect for antidepressants on positive information processing. They also provide further evidence for modification of information processing as a potential mechanism of action for antidepressant medication.
Neutrophil degranulation mediates severe lung damage triggered by streptococcal M1 protein
Authors: O. Soehnlein, S. Oehmcke, None X, A. G. Rothfuchs, R. Frithiof, N. van Rooijen, M. Mörgelin, H. Herwald, L. Lindbom
Journal: European Respiratory Journal (2008)

Streptococcus pyogenes of the M1 serotype can cause streptococcal toxic shock syndrome commonly associated with acute lung injury. The aim of the present study was to investigate the role of neutrophils and their secretion products in M1 protein-induced lung damage. The degranulation of neutrophils by M1 protein was studied in whole blood using marker analysis for individual granule subsets. In mice, M1 protein was injected intravenously and the lung damage was assessed by histology, electron microscopy, cell count in bronchoalveolar lavage fluid and analysis of lung vascular permeability. Comparisons were made in mice with intact white blood count, neutropenic mice and neutropenic mice injected with the secretion of activated neutrophils. In whole blood, M1 protein forms complexes with fibrinogen that bind to β 2 -integrins on the neutrophil surface, resulting in degranulation of all four subsets of neutrophil granules. Intravenous injection of M1 protein into mice induced neutrophil accumulation in the lung, increase in vascular permeability and acute lung damage. Depletion of neutrophils from the circulation completely abrogated lung injury and vascular leakage. Interestingly, the lung damage was restored by injecting neutrophil secretion. The present data suggest that neutrophil granule proteins are directly responsible for lung damage induced by the streptococcal M1 protein.
Treatment of perioral dermatitis with topical pimecrolimus
Authors: Marina Rodríguez-Martín, Miguel Sáez-Rodríguez, Ana Carnerero-Rodríguez, Fernando Rodríguez-García, Roberto Cabrera de Paz, Miriam Sidro-Sarto, Francisco Guimerá, Rosalba Sánchez, Marta García-Bustínduy, Antonio Noda-Cabrera
Journal: Journal of the American Academy of Dermatology (2007)
The kick with the stick
Authors: A Exadaktylos, S Eggli, H Zimmermann
Journal: British Journal of Sports Medicine (2001)

To investigate the incidence and type of severe microscooter related injuries in adults.Data were collected between January and September 2000 from the University Hospital Berne, the only referral centre for major trauma in that city, using the software package Qualicare, which connects clinical data with categorised keywords, allowing the immediate localisation of patient groups with defined diagnosis or other clinical information.Only 0.2% of the patients treated had suffered a microscooter accident. There were five head injuries: three facial lacerations, one fractured mandible, and one cerebral concussion. One patient showed clinical signs of a cervical whiplash injury without radiological findings. There were also two cases of finger laceration and two of muscular contusions of the lower extremities.Although only a small proportion of the trauma cases were the result of riding microscooters, a system of injury surveillance should be started. Furthermore, protective gear should be worn particularly when microscooters are ridden in the street.