tbuckley/cabot-search huggingface dataset:
Mediterranean Diet and Type 2 Diabetes Risk in the European Prospective Investigation Into Cancer and Nutrition (EPIC) Study
Journal: Diabetes Care (2011)

To study the association between adherence to the Mediterranean dietary pattern (MDP) and risk of developing type 2 diabetes, across European countries.We established a case-cohort study including 11,994 incident type 2 diabetic case subjects and a stratified subcohort of 15,798 participants selected from a total cohort of 340,234 participants with 3.99 million person-years of follow-up, from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The relative Mediterranean diet score (rMED) (score range 0-18) was used to assess adherence to MDP on the basis of reported consumption of nine dietary components characteristic of the Mediterranean diet. Cox proportional hazards regression, modified for the case-cohort design, was used to estimate the association between rMED and risk of type 2 diabetes, adjusting for confounders.The multiple adjusted hazard ratios of type 2 diabetes among individuals with medium (rMED 7-10 points) and high adherence to MDP (rMED 11-18 points) were 0.93 (95% CI 0.86-1.01) and 0.88 (0.79-0.97), respectively, compared with individuals with low adherence to MDP (0-6 points) (P for trend 0.013). The association between rMED and type 2 diabetes was attenuated in people <50 years of age, in obese participants, and when the alcohol, meat, and olive oil components were excluded from the score.In this large prospective study, adherence to the MDP, as defined by rMED, was associated with a small reduction in the risk of developing type 2 diabetes in this European population.
Detection of extrapulmonary lesions with integrated PET/CT in the staging of lung cancer
Authors: W. De Wever, Y. Vankan, S. Stroobants, J. Verschakelen
Journal: European Respiratory Journal (2007)

The aim of the present study was to assess retrospectively the additional value of positron emission tomography (PET)/computed tomography (CT) in the detection of unexpected extrapulmonary lesions in the staging of patients with a malignant pulmonary lesion in comparison with CT and PET used alone. A total of 217 patients with a pathologically proven lung tumour underwent PET/CT. CT, PET and PET/CT were evaluated in the detection of extrapulmonary lesions. These abnormalities were compared with the final diagnosis obtained from the medical records and statistical analysis was carried out. In total, 108 lesions were clinically detected. PET/CT showed a sensitivity, specificity, positive and negative predictive values and accuracy of 100, 81, 71, 100 and 87%, respectively, for the detection of extrapulmonary lesions and 92, 98, 89, 98 and 97%, respectively, for the detection of malignant extrapulmonary lesions. PET/CT was significantly better than CT and PET used alone. Conventional staging work-up has a poor sensitivity in detecting second primary cancers or unexpected metastases. The detection of malignant extrapulmonary lesions is necessary for correct tumour staging. By combining both metabolic and anatomical information, positron emission tomography/computed tomography is able to depict more unexpected extrapulmonary lesions than computed tomography and positron emission tomography used alone, and positron emission tomography/computed tomography provides more additional information of malignancy or benignancy of lesions detected with one of the two imaging modalities alone.
BMA warns government control over GP consortiums will be too powerful
Authors: A. O'Dowd
Journal: BMJ (2011)

Claims that doctors will have real control of the new commissioning consortiums to choose services for patients are fatally undermined by “overly restrictive and controlling” powers held by government, claim doctors’ leaders.

The BMA has raised concerns that under the planned reforms of the NHS, health secretary Andrew Lansley and the NHS Commissioning Board overseeing the GP consortiums will have too much control.

In a new briefing issued on 28 February, the BMA said some of the legislation in its current form went against government pledges to put doctors “in the driving seat” and could prevent them from delivering improvements to patient care.

The briefing A genuine devolution of power? has been timed to raise …
Preparation and evaluation of tamsulosin hydrochloride sustained-release pellets modified by two-layered membrane techniques
Authors: Jingmin Wang, Yinghua Sun, Bo Li, Rui Fan, Bing Li, Tengrui Yin, Ling Rong, Jin Sun
Journal: Asian Journal of Pharmaceutical Sciences (2014)

The aim of the present study was to develop tamsulosin hydrochloride sustained-release pellets using two-layered membrane techniques. Centrifugal granulator and fluidized-bed coater were employed to prepare drug-loaded pellets and to employ two-layered membrane coating respectively. The prepared pellets were evaluated for physicochemical characterization, subjected to differential scanning calorimetry (DSC) and in vitro release of different pH. Different release models and scanning electron microscopy (SEM) were utilized to analyze the release mechanism of Harnual® and home-made pellets. By comparing the dissolution profiles, the ratio and coating weight gain of Eudragit® NE30D and Eudragit® L30D55 which constitute the inside membrane were identified as 18:1 and 10%–11%. The coating amount of outside membrane containing Eudragit® L30D55 was determined to be 0.8%. The similarity factors (f2) of home-made capsule and commercially available product (Harnual®) were above 50 in different dissolution media. DSC studies confirmed that drug and excipients had good compatibility and SEM photographs showed the similarities and differences of coating surface between Harnual® and self-made pellets before and after dissolution. According to Ritger-Peppas model, the two dosage form had different release mechanism.
Haemodynamic effects, safety, and pharmacokinetics of human stresscopin in heart failure with reduced ejection fraction†
Authors: Mihai Gheorghiade, Stephen J. Greene, Piotr Ponikowski, Aldo P. Maggioni, Jerzy Korewicki, Cezar Macarie, Marco Metra, Jacek Grzybowski, Serban‐Ion Bubenek‐Turconi, Waldemar Radziszewski, Allan Olson, Orlando F. Bueno, Atalanta Ghosh, Lawrence I. Deckelbaum, Lilian Y. Li, Ayan R. Patel, Andreas Koester, Marvin A. Konstam
Journal: European Journal of Heart Failure (2013)
Regulation of human immunoglobulin E synthesis in acute graft versus host disease.
Authors: J A Saryan, J Rappeport, D Y Leung, R Parkman, R S Geha
Journal: Journal of Clinical Investigation (1983)

Immunoglobulin (Ig) E synthesis was studied in vitro in eight patients who had received transplants of allogeneic bone marrow. Seven of these patients developed acute graft vs. host disease (GVHD) and elevated serum IgE levels, whereas the eighth did not. In vitro synthesis of IgE, but not of IgG, was elevated in cultures of lymphocytes obtained during acute GVHD (17,923 +/- 14,607 pg/10(6) cells) but not in cultures of lymphocytes obtained after resolution of the acute GVHD when the serum IgE had returned to normal (106 +/- 31 pg/10(6) cells). In contrast, lymphocytes from the patient with no acute GVHD, like normal lymphocytes, failed to synthesize IgE in vitro. The increased in vitro IgE synthesis in acute GVHD was suppressed by normal allogeneic lymphocytes and by autologous lymphocytes obtained after the resolution of the acute GVHD, but not by allogeneic lymphocytes obtained from patients undergoing acute GVHD. The deficiency in functional IgE-specific suppressor cells in acute GVHD occurred in the face of normal or increased percentages of circulating T8+ cells, which in normal subjects contain the IgE-specific suppressor cells. In two patients studied, there was evidence of activated IgE-specific, circulating helper T cells. T cells from these two patients, but not normal T cells, secreted spontaneously upon culture in vitro a factor that induced IgE, but not IgG, synthesis by normal B cells. Finally, a survey of 21 bone marrow transplant recipients revealed that acute GVHD was a necessary requirement for the development of elevated serum IgE levels in recipients of bone marrow transplants. These results suggest that acute GVHD is accompanied by an imbalance in IgE-specific immunoregulatory T cells consisting of activated helper T cells and deficient suppressor cells.
Impaired formation of beta-adrenergic receptor-nucleotide regulatory protein complexes in pseudohypoparathyroidism.
Authors: J A Heinsimer, A O Davies, R W Downs, M A Levine, A M Spiegel, M K Drezner, A De Lean, K A Wreggett, M G Caron, R J Lefkowitz
Journal: Journal of Clinical Investigation (1984)

Decreased activity of the guanine nucleotide regulatory protein (N) of the adenylate cyclase system is present in cell membranes of some patients with pseudohypoparathyrodism (PHP-Ia) whereas others have normal activity of N (PHP-Ib). Low N activity in PHP-Ia results in a decrease in hormone (H)-stimulatable adenylate cyclase in various tissues, which might be due to decreased ability to form an agonist-specific high affinity complex composed of H, receptor (R), and N. To test this hypothesis, we compared beta-adrenergic agonist-specific binding properties in erythrocyte membranes from five patients with PHP-Ia (N = 45% of control), five patients with PHP-Ib (N = 97%), and five control subjects. Competition curves that were generated by increasing concentrations of the beta-agonist isoproterenol competing with [125I]pindolol were shallow (slope factors less than 1) and were computer fit to a two-state model with corresponding high and low affinity for the agonist. The agonist competition curves from the PHP-Ia patients were shifted significantly (P less than 0.02) to the right as a result of a significant (P less than 0.01) decrease in the percent of beta-adrenergic receptors in the high affinity state from 64 +/- 22% in PHP-Ib and 56 +/- 5% in controls to 10 +/- 8% in PHP-Ia. The agonist competition curves were computer fit to a "ternary complex" model for the two-step reaction: H + R + N in equilibrium HR + N in equilibrium HRN. The modeling was consistent with a 60% decrease in the functional concentration of N, and was in good agreement with the biochemically determined decrease in erythrocyte N protein activity. These in vitro findings in erythrocytes taken together with the recent observations that in vivo isoproterenol-stimulated adenylate cyclase activity is decreased in patients with PHP (Carlson, H. E., and A. S. Brickman, 1983, J. Clin. Endocrinol. Metab. 56:1323-1326) are consistent with the notion that N is a bifunctional protein interacting with both R and the adenylate cyclase. It may be that in patients with PHP-Ia a single molecular and genetic defect accounts for both decreased HRN formation and decreased adenylate cyclase activity, whereas in PHP-Ib the biochemical lesion(s) appear not to affect HRN complex formation.
Functional characterization of natural telomerase mutations found in patients with hematologic disorders
Authors: Zhong-Tao Xin, Adam D. Beauchamp, Rodrigo T. Calado, Jennifer W. Bradford, Joshua A. Regal, Aarthi Shenoy, Yuying Liang, Peter M. Lansdorp, Neal S. Young, Hinh Ly
Journal: Blood (2006)
Assessment of Sample Frame Validity After Pilot Recruitment for a Population Based Study of Infant Food Allergy
Authors: N.J. Osborne, J.J. Koplin, L.C. Gurrin, M. Gibson, L. Thiele, L. Miles, K. Aurich, D. Hill, A. Lowe, M. Matheson, A. Ponsonby, M. Tang, S. Dharmage, M. Wake, K. Allen
Journal: Journal of Allergy and Clinical Immunology (2009)
Podocytes Are Nonhematopoietic Professional Antigen-Presenting Cells
Authors: Andreas Goldwich, Miriam Burkard, Martha Ölke, Christoph Daniel, Kerstin Amann, Christian Hugo, Christian Kurts, Alexander Steinkasserer, André Gessner
Journal: Journal of the American Society of Nephrology (2013)

Podocytes are essential to the structure and function of the glomerular filtration barrier; however, they also exhibit increased expression of MHC class II molecules under inflammatory conditions, and they remove Ig and immune complexes from the glomerular basement membrane (GBM). This finding suggests that podocytes may act as antigen-presenting cells, taking up and processing antigens to initiate specific T cell responses, similar to professional hematopoietic cells such as dendritic cells or macrophages. Here, MHC-antigen complexes expressed exclusively on podocytes of transgenic mice were sufficient to activate CD8+ T cells in vivo. In addition, deleting MHC class II exclusively on podocytes prevented the induction of experimental anti-GBM nephritis. Podocytes ingested soluble and particulate antigens, activated CD4+ T cells, and crosspresented exogenous antigen on MHC class I molecules to CD8+ T cells. In conclusion, podocytes participate in the antigen-specific activation of adaptive immune responses, providing a potential target for immunotherapies of inflammatory kidney diseases and transplant rejection.
Using Diffusion Imaging to Study Human Connectional Anatomy
Authors: Heidi Johansen-Berg, Matthew F.S. Rushworth
Journal: Annual Review of Neuroscience (2009)

Diffusion imaging can be used to estimate the routes taken by fiber pathways connecting different regions of the living brain. This approach has already supplied novel insights into in vivo human brain anatomy. For example, by detecting where connection patterns change, one can define anatomical borders between cortical regions or subcortical nuclei in the living human brain for the first time. Because diffusion tractography is a relatively new technique, however, it is important to assess its validity critically. We discuss the degree to which diffusion tractography meets the requirements of a technique to assess structural connectivity and how its results compare to those from the gold-standard tract tracing methods in nonhuman animals. We conclude that although tractography offers novel opportunities it also raises significant challenges to be addressed by further validation studies to define precisely the limitations and scope of this exciting new technique.
Is a Lymph Node Detected by the Dye-Guided Method a True Sentinel Node in Gastric Cancer?
Authors: Hirohisa Osaka, Masakazu Yashiro, Tetsuji Sawada, Kei Katsuragi, Kosei Hirakawa
Journal: Clinical Cancer Research (2004)

Abstract Purpose: A sentinel node is defined as the initial lymph node, to which cancer cells metastasize from a primary tumor. Recently, sentinel node navigation surgery has been done using the dye-guided method. However, no study has shown that a lymph node detected by the dye-guided method is the true sentinel node from the viewpoint of micrometastasis. Micrometastases of lymph nodes, in which no metastasis was found by H&amp;E staining, were examined to establish whether a lymph node detected by the dye-guided method is the true sentinel node. Experimental Design: Isosulfan blue was injected endoscopically as the dye-guided method at a submucosal lesion of early gastric cancer. Total 345 lymph nodes, including 150 blue-dyed lymph nodes and 195 nondyed lymph nodes were collected from 57 patients and each was quartered. Two quarters were examined histologically by H&amp;E staining and cytokeratin staining. The other specimens were used for quantitative reverse transcription-PCR of CEA and CK20 mRNAs. Results: Lymph node disease was not found in any of 345 lymph nodes from the 57 patients by routine H&amp;E staining. By contrast, either CEA or CK20 mRNA expression was detected in 21 of 345 lymph nodes obtained from the 10 (18%) of 57 patients by quantitative reverse transcription-PCR. Eight of the 21 micrometastasis-positive lymph nodes were confirmed to be positive for cytokeratin staining. Although micrometastasis of nondyed lymph nodes was found in three cases, these were included in the 10 cases with micrometastasis of blue-dyed nodes, such that there was no patient who only had micrometastasis in nondyed nodes. Six of 10 cases were micrometastasis-positive in a single node; all six were blue-dyed nodes. Conclusion: A lymph node detected by the dye-guided method should be a true sentinel node to which cancer cells metastasize initially.
Clinical Evaluation of Alternative-Site Glucose Measurements in Patients After Major Cardiac Surgery
Authors: Martin Ellmerer, Martin Haluzik, Jan Blaha, Jaromir Kremen, Stepan Svacina, Wolfgang Toller, Julia Mader, Lukas Schaupp, Johannes Plank, Thomas Pieber
Journal: Diabetes Care (2006)

OBJECTIVE—Tight glycemic control improves outcome in critically ill patients but requires frequent glucose measurements. Subcutaneous adipose tissue (SAT) has been characterized as promising for glucose monitoring in diabetes, but it remains unknown whether it can also be used as an alternative site in critically ill patients. The present study was performed to clinically evaluate the relation of glucose in SAT compared with arterial blood in patients after major cardiac surgery. RESEARCH DESIGN AND METHODS—Forty critically ill patients were investigated at two clinical centers after major cardiac surgery. Arterial blood and SAT microdialysis samples were taken in hourly intervals for a period of up to 48 h. The glucose concentration in dialysate was calibrated using a two-step approach, first using the ionic reference technique to calculate the SAT glucose concentration (SATg) and second using a one-point calibration procedure to obtain a glucose profile comparable to SAT-derived blood glucose (BgSAT). Clinical validation of the data was performed by introducing data analysis based on an insulin titration algorithm. RESULTS—Correlation between dialysate glucose and blood glucose (median 0.80 [interquartile range 0.68–0.88]) was significantly improved using the ionic reference calibration technique (SATg vs.blood glucose 0.90 [0.83–0.94]; P &amp;lt; 0.001). Clinical evaluation of the data indicated that 96.1% of glucose readings from SAT would allow acceptable treatment according to a well-established insulin titration protocol. CONCLUSIONS—The results indicate good correlation between SATg and blood glucose in patients after major cardiac surgery. Clinical evaluation of the data suggests that with minor limitations, glucose from SAT can be used to establish tight glycemic control in this patient group.
<i>Staphylococcus aureus</i> golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity
Authors: George Y. Liu, Anthony Essex, John T. Buchanan, Vivekanand Datta, Hal M. Hoffman, John F. Bastian, Joshua Fierer, Victor Nizet
Journal: The Journal of Experimental Medicine (2005)

Golden color imparted by carotenoid pigments is the eponymous feature of the human pathogen Staphylococcus aureus. Here we demonstrate a role of this hallmark phenotype in virulence. Compared with the wild-type (WT) bacterium, a S. aureus mutant with disrupted carotenoid biosynthesis is more susceptible to oxidant killing, has impaired neutrophil survival, and is less pathogenic in a mouse subcutaneous abscess model. The survival advantage of WT S. aureus over the carotenoid-deficient mutant is lost upon inhibition of neutrophil oxidative burst or in human or murine nicotinamide adenine dinucleotide phosphate oxidase–deficient hosts. Conversely, heterologous expression of the S. aureus carotenoid in the nonpigmented Streptococcus pyogenes confers enhanced oxidant and neutrophil resistance and increased animal virulence. Blocking S. aureus carotenogenesis increases oxidant sensitivity and decreases whole-blood survival, suggesting a novel target for antibiotic therapy.
Exhaled hydrogen sulfide in patients with chronic airway inflammatory disease
Authors: Yahong Chen, Xinmao Wang, Wanzhen Yao, Chaoshu Tang
Journal: European Respiratory Journal (2011)

Background:  Chronic obstructive pulmonary disease (COPD) and asthma are two common chronic airway inflammatory diseases. Recent studies showed that endogenous hydrogen sulfide (H 2 S) might be the third signaling gasotransmitter playing a important role in inflammation.   Objective:  To investigate whether exhaled H 2 S level is related to airway inflammation in COPD and asthma.   Methods:  Clinical data, inflammatory cell in induced sputum, plasma level of TNF-α, IL-8 and LTB4, exhaled and plasma H 2 S level were studied in 41 patients with AECOPD, 36 with stable COPD, 50 with acute exacerbation of asthma, 24 with stable asthma, and 11 healthy subjects.   Results:  Exhaled H 2 S level were lower by 20.63% and 37.81%, respectively, in patients with stable COPD and AECOPD than healthy controls ( P  2 S level was decreased by 21.64% in patients with AECOPD than stable COPD patients ( P  2 S was positively correlated with the percentage of predicted inspiratory capacity ( r =0.321,  P =0.026), negatively correlated with plasma H 2 S levels ( r =-0.384,  P =0.021) and SGRQ activity score (r=-0.226,  P =0.05). Exhaled H 2 S levels were decreased by 29.5% and 31.4%, respectively, in patients with stable and acute exacerbation of asthma than healthy controls (all  P  2 S levels than non-smokers ( P  2 S in asthma was negatively correlated with plasma LTB4 ( r =-0.627,  P =0.05).   Conclusions:  Exhaled hydrogen sulfide was decreased in patients with COPD and asthma. Its alteration in level may be connected with airway inflammation.  The study is funded by NSFC (No. 30871127), NCET (No. 985-2-082-113), and Chinese Medical Association CRD Grant (No. 08020370115).
Treatment of Recurrent Genital Herpes Simplex Infections With Oral Acyclovir
Authors: Richard C. Reichman
Journal: JAMA (1984)

Two hundred fifty patients were entered into a multicenter trial to evaluate the efficacy and toxicity of orally administered acyclovir for treatment of recurrent genital herpes. The study consisted of part A, in which patients entered the study within 48 hours of the onset of lesions, and part B, in which patients self-initiated therapy as soon as possible after the onset of a recurrent episode. In both parts, patients received either acyclovir (200 mg) or placebo, five times daily for five days. In both parts, the duration of virus shedding and the time to crusting and healing of lesions were shorter among acyclovir recipients than among placebo recipients. In part B, fewer acyclovir recipients formed new lesions during the study medication period than did placebo recipients. When parts A and B were compared directly, the duration of virus shedding and the times required for crusting and healing of lesions were significantly shorter among acyclovir recipients in part B than among acyclovir recipients in part A. No significant differences in the duration of itching and pain or in the times of subsequent recurrence were noted between acyclovir and placebo groups in either part A or part B. No significant toxic or adverse reactions were seen in acyclovir recipients. Oral acyclovir shortens the duration of virus shedding and the duration of lesions in patients with recurrent genital herpes. These effects are more pronounced when therapy is self-initiated by patients early in the course of a recurrent episode. (<i>JAMA</i>1984;251:2103-2107)