tbuckley/cabot-search huggingface dataset:
Cardiovascular Disease and Diabetes
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2003)

This is the fourth in a series of articles covering the 2002 American Diabetes Association Annual Meeting, San Francisco, CA, 14–18 June 2002.

Peter Savage (Ellicott City, MD) discussed secular trends in cardiovascular disease (CVD) among patients with diabetes. Two-thirds to three-quarters of patients with diabetes will eventually die of CVD. Diabetes is becoming more important as a cause of CVD in the population because of its increasing prevalence, due to the high incidence in minority populations and the increasing obesity of the population. The “key question,” Savage stated, is whether persons with diabetes are different from those without diabetes in not enjoying the same decline in CVD that has been seen in the overall population over the past 50 years, presumably reflecting a variety of advances in the treatment of risk factors. In a study of time trends in mortality in U.S. adults between surveys in 1971–1975 and in 1982–1984, diabetic men had a decline of 13% in age-adjusted CVD mortality, while that for nondiabetic men was 36%, and diabetic women had an increase of 23%, while women without diabetes had a decline in CVD mortality of 27% (1). Although microvascular disease is relatively specific for diabetes, macrovascular disease appears as an acceleration of the illness seen in persons without diabetes. High LDL is a risk factor in those with and without diabetes, but persons with diabetes tend to have low HDL, high triglyceride, and abnormal LDL particle size. They have the hypertension of the insulin resistance syndrome, which becomes exacerbated with renal disease (and diabetic patients with renal disease have extraordinarily high rates of CVD). Diabetes is associated with coagulation abnormalities and inflammation, as well as hyperglycemia, glycation, and secondary effects on CVD risk factors. Insulin resistance and hyperinsulinemia are additional factors in persons with diabetes.

Savage pointed …
PTU-196 Small Bowel Capsule Endoscopy – a Retrospective Analysis of 348 Cases from Qeii and Lister Hospitals
Authors: J A Evans, S Beg, R Nathwani, K Samsheer, E Ebro, E Turnbull
Journal: Gut (2013)

<h3>Introduction</h3> Small bowel capsule endoscopy (SBCE) is a useful diagnostic tool for investigating iron deficiency anaemia (IDA) and suspected Crohn’s disease (CD)<sup>1,2</sup>, but its use is often limited to specialist teaching centres. We aim to establish whether SBCE is a useful tool when employed in a district general hospital (DGH) setting. <h3>Methods</h3> We retrospectively analysed the data of all SBCE carried out at QEII and Lister hospitals over 36 months since its introduction in 2009 using the GIVEN Pillcam SB 2 system. Patient demographics, indications, previous investigations, SBCE findings and how these altered management were reviewed. <h3>Results</h3> 348 studies were performed on 175 males and 173 females; the mean age was 54.3 years (range 17–86). 207/348 (59%) revealed some form of pathology. 7 studies were incomplete (2.01%). Patency capsules were used in those with suspected risk of stricturing pathology for 22/348 cases (6.32%). No cases required surgical retrieval of a capsule. The most common indication for SBCE was IDA = 185/348 studies (53.1%). The next most common indication was suspected CD = 141/348 (40.5%). All patients had undergone bi-directional endoscopy prior to SBCE. The commonest findings were; small bowel (SB) erosions/ulcers (65 cases) SB angiodysplasia (39 cases) CD (21 cases) SB ulcers (19) polypoidal masses (13 cases) and fresh blood (11 cases). 3 cases of lymphoma and one of Enterobius vermicularis were discovered. Where IDA was the indication, 65/185 studies (35.1%) had findings that led to an alteration in management. In studies for suspected CD, 44/141 (31.2%) had findings that led to an alteration in management. <h3>Conclusion</h3> For IDA the diagnostic yield of 35% is in keeping with previously published data, which shows that SBCE can identify a source of bleeding in 31- 76%1. For CD we identified abnormal pathology requiring further intervention in 31% of cases. It is debatable whether a small number of terminal ileal ulcers is sufficient to diagnose CD. If greater than 3 are seen, histological confirmation of CD is attempted via repeat endoscopy. 9 of the 348 patients had previously undergone a SBCE and the less invasive nature of SBCE lends itself to repeated use for small bowel CD surveillance. SBCE is a reliable, safe and useful tool in the setting of a DGH setting for identifying small bowel pathology and should not be restricted to specialist centres. <h3>Disclosure of Interest</h3> None Declared. <h3>References</h3> R Sidhu, D Sanders, A Morris, M McAlindon. Guidelines on small bowel enteroscopy and capsule endoscopy in adults. BSG Guidelines. Gut 2008; 57:125–136. SK Patel, P Mairs. A Review of Small Bowel Capsule Endoscopy Performed At Darent Valley Hospital Since Its Introduction in 2006. The Online Journal of Clinical Audits. 2011; Vol 3(3)
Stimulation and Suppression of the Mineralocorticoid Hormones in Normal Subjects and Adrenocortical Disorders*
Authors: C. E. KATER, E. G. BIGLIERI, N. BRUST, B. CHANG, J. HIRAI, I. IRONY
Journal: Endocrine Reviews (1989)

In summary, maneuvers that affect the RAS stimulate or suppress solely aldosterone and 18-OHB and have little, if any, effect on DOC, 18-OHDOC, B, or cortisol. The magnitude of aldosterone response seems to be of equal magnitude for all stimulatory or suppressive maneuvers as used in the present protocols. Although primarily originating in the ZG, some secretion of 18-OHB from the ZF is evident by its disproportionate responses (in relation to aldosterone) to maneuvers challenging ACTH. The prompt and marked increases the 18-OHDOC and B after ACTH make them the most sensitive "markers" of the ZF steroid activity. The application of those maneuvers and MCH measurements to adrenal disorders should help to further characterize their pathophysiology.
Phase I study of carboplatin, doxorubicin and weekly paclitaxel in patients with advanced ovarian carcinoma
Authors: V. Hess, M.W. Verrill, C.C. Bomphray, M.M. Vaughan, M. Allen, M.E. Gore
Journal: Annals of Oncology (2003)

Doxorubicin is an active compound in epithelial ovarian cancer (EOC), but adding it to carboplatin-paclitaxel causes toxicity. Toxicity can be reduced by weekly administration. We examined the tolerability of weekly paclitaxel in combination with carboplatin and doxorubicin.Chemotherapy naïve patients with EOC were treated with doxorubicin (50 mg/m(2) day 1), carboplatin (AUC 6 day 1) and paclitaxel (days 1, 8, 15, 21), 28-day cycle. Three patients were treated at each paclitaxel dose level, starting at 60, 75 and 90 mg/m(2)/week. If more than two patients in a cohort experienced dose-limiting toxicity (DLT) three more patients were treated at the dose level below.Twelve patients with advanced EOC received a median of six cycles (range 2-6) of the three-drug combination. DLT occurred at dose level 3: prolonged grade 4 febrile neutropenia, 1 patient; grade 3 peripheral neuropathy, 1 patient. All six patients treated at dose level 2 experienced short-lived grade 4 neutropenia, which led to dose modifications resulting in an actual delivered dose of paclitaxel of 64 mg/m(2)/week. Eight out of 12 patients had measurable disease on CT scan: four obtained a partial remission; three had stable disease.The combination of carboplatin, doxorubicin and paclitaxel in patients with EOC is active and its main toxicity is myelosuppression. Dose intensity of paclitaxel can be maintained in a three-drug combination through weekly administration (65 mg/m(2)).
Reconstructing Population Histories from Single Nucleotide Polymorphism Data
Authors: J. Siren, P. Marttinen, J. Corander
Journal: Molecular Biology and Evolution (2010)

Population genetics encompasses a strong theoretical and applied research tradition on the multiple demographic processes that shape genetic variation present within a species. When several distinct populations exist in the current generation, it is often natural to consider the pattern of their divergence from a single ancestral population in terms of a binary tree structure. Inference about such population histories based on molecular data has been an intensive research topic in the recent years. The most common approach uses coalescent theory to model genealogies of individuals sampled from the current populations. Such methods are able to compare several different evolutionary scenarios and to estimate demographic parameters. However, their major limitation is the enormous computational complexity associated with the indirect modeling of the demographies, which limits the application to small data sets. Here, we propose a novel Bayesian method for inferring population histories from unlinked single nucleotide polymorphisms, which is applicable also to data sets harboring large numbers of individuals from distinct populations. We use an approximation to the neutral Wright–Fisher diffusion to model random fluctuations in allele frequencies. The population histories are modeled as binary rooted trees that represent the historical order of divergence of the different populations. A combination of analytical, numerical, and Monte Carlo integration techniques are utilized for the inferences. A particularly important feature of our approach is that it provides intuitive measures of statistical uncertainty related with the estimates computed, which may be entirely lacking for the alternative methods in this context. The potential of our approach is illustrated by analyses of both simulated and real data sets.
Seasonal variation in suppressor T cell subsets and non‐specific suppressor cell function in hay fever sufferers
Authors: A. G. Fennerty, K. P. Jones, R. Fifield, B. H. Davies
Journal: Allergy (1989)

The helper/suppressor T cell ratio, as defined by monoclonal antibodies, was significantly higher in hay fever sufferers compared with controls ( P &lt; 0.05), but only during or shortly after the pollen season. This was due to a reduction in the suppressor subset, which returned to control values in the winter. There was no significant difference in the non‐specific concanavalin A‐induced suppressor cell function compared with controls. The mean summer value was significantly lower than the winter value ( P &lt; 0.05), but we cannot be sure that this was not the result of changes in laboratory conditions. No relationship was found between T cell subsets or suppressor cell function and total or specific IgE levels, or between T cell subsets and suppressor cell function. Our findings suggest that in hay fever, reduction in suppressor cell numbers and function is a secondary phenomenon.
Once bitten, twice shy
Authors: B D Fox, S Morgenstern, A Grubstein, S Pitlik, M R Kramer
Journal: Thorax (2009)

A 46-year-old man of Ethiopian origin was admitted to hospital in 2008 for investigation of cough, increasing dyspnoea and weight loss over several weeks. He was known to be HIV positive. He had a history of several opportunistic infections, including Cryptosporidium diarrhoea, tuberculosis, Mycobacterium avium complex and Pseudomonas pneumonia. He had also been treated in 2005 for visceral leishmaniasis with liposomal amphotericin. His prescribed medication included trimethoprim–suxamethoxazole, clarithromycin, efarinez, lamivudine, zidovudine and folic acid. His compliance with highly active antiretroviral therapy (HAART) was known to be poor.

On physical examination he was afebrile. Aside from moderate tachypnoea (24 respirations/min), his vital signs were normal. General examination showed cachexia and marked parotid swelling. The abdomen was non-tender with hepatosplenomegaly. Cardiac/respiratory examination was …
Hospital Case Volume and Outcomes among Patients Hospitalized with Severe Sepsis
Authors: Allan J. Walkey, Renda Soylemez Wiener
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Processes of care are potential determinants of outcomes in patients with severe sepsis. Whether hospitals with more experience caring for patients with severe sepsis also have improved outcomes is unclear.To determine associations between hospital severe sepsis caseload and outcomes.We analyzed data from U.S. academic hospitals provided through University HealthSystem Consortium. We used University HealthSystem Consortium's sepsis mortality model (c-statistic, 0.826) for risk adjustment. Validated International Classification of Disease, 9th Edition, Clinical Modification algorithms were used to identify hospital severe sepsis case volume. Associations between risk-adjusted severe sepsis case volume and mortality, length of stay, and costs were analyzed using spline regression and analysis of covariance.We identified 56,997 patients with severe sepsis admitted to 124 U.S. academic hospitals during 2011. Hospitals admitted 460 ± 216 patients with severe sepsis, with median length of stay 12.5 days (interquartile range, 11.1-14.2), median direct costs $26,304 (interquartile range, $21,900-$32,090), and average hospital mortality 25.6 ± 5.3%. Higher severe sepsis case volume was associated with lower unadjusted severe sepsis mortality (R2 = 0.10, P = 0.01) and risk-adjusted severe sepsis mortality (R2 = 0.21, P < 0.001). After further adjustment for geographic region, number of beds, and long-term acute care referrals, hospitals in the highest severe sepsis case volume quartile had an absolute 7% (95% confidence interval, 2.4-11.6%) lower hospital mortality than hospitals in the lowest quartile. We did not identify associations between case volume and resource use.Academic hospitals with higher severe sepsis case volume have lower severe sepsis hospital mortality without higher costs.
Formulation of dual modality nanoparticles to enhance tobramycin efficacy in cystic fibrosis
Authors: Jill Deacon, Sharif Abdelghany, Stuart Elborn, Adrien Kissenpfennig, Clifford Taggart, Christopher Scott
Journal: European Respiratory Journal (2013)

Introduction  Cystic fibrosis (CF) patients aberrantly produce viscous mucus in their lungs, which acts as a penetrative barrier to antibiotic delivery and provides an ideal environment for bacterial colonisation.  Aims and Objectives  The aim is to develop a nanoparticle drug delivery system combining widely used CF therapeutics for an enhanced antibiotic effect. Tobramycin is an aminoglycoside antibiotic and the mucolytic DNase thins viscous secretions. For this study, it was hypothesised that alginate/chitosan nanoparticles (NPs) loaded with tobramycin and functionalised with DNase would enhance penetration of tobramycin to the site of infection within the mucus.  Methods  Tobramycin loaded alginate/chitosan NPs were formulated by ionotropic gelation and conjugated with DNase on their surface. NP formulation was optimised and CF sputum samples were tested with NPs to establish bactericidal effects against  Pseudomonas aeruginosa .  Results  NPs formed at around 500 nm and were loaded with tobramycin 89µg/mg polymer and DNase 19µg/mg polymer. Activity of both modalities was confirmed against  in vitro c ultures of  P. aeruginosa  and by cleavage of DNA (plasmid and CF sputum samples). Treatment of CF sputum with DNase-tobramycin NPs resulted in reduced viscosity and increased bacterial killing in these samples.  Conclusion  These novel alginate/chitosan NPs combining DNase and tobramycin are an effective antibacterial treatment in CF sputum. The incorporation of two widely used therapeutics into a single formulation provides promise in the future treatment regimen of CF patients.
Chipper: discovering transcription-factor targets from chromatin immunoprecipitation microarrays using variance stabilization.
Authors: Francis D Gibbons, Markus Proft, Kevin Struhl, Frederick P Roth
Journal: Genome biology (2005)

Chromatin immunoprecipitation combined with microarray technology (Chip2) allows genome-wide determination of protein-DNA binding sites. The current standard method for analyzing Chip2 data requires additional control experiments that are subject to systematic error. We developed methods to assess significance using variance stabilization, learning error-model parameters without external control experiments. The method was validated experimentally, shows greater sensitivity than the current standard method, and incorporates false-discovery rate analysis. The corresponding software ('Chipper') is freely available. The method described here should help reveal an organism's transcription-regulatory 'wiring diagram'.
Exercise for anxiety disorders: systematic review
Authors: Kaushadh Jayakody, Shalmini Gunadasa, Christian Hosker
Journal: British Journal of Sports Medicine (2013)

Background Anxiety disorders are commonly treated with antidepressants and psychological treatments. Some patients may prefer alternative approaches such as exercise. Objective To investigate the treatment effects of exercise compared with other treatments for anxiety disorders. Data sources Randomised controlled trials (RCTs) of exercise interventions for anxiety disorders were identified by searching six online databases (July 2011). A number of journals were also hand searched. Main results Eight RCTs were included. For panic disorder: exercise appears to reduce anxiety symptoms but it is less effective than antidepressant medication (1 RCT); exercise combined with antidepressant medication improves the Clinical Global Impression outcomes (1 RCT, p&lt;0.05); exercise combined with occupational therapy and lifestyle changes reduces Beck Anxiety Inventory outcomes (1 RCT, p=0.0002). For social phobias, added benefits of exercise when combined with group cognitive behavioural therapy (CBT) were shown (p&lt;0.05). There was no significant difference between aerobic and anaerobic exercise groups (1 RCT, p&gt;0.1) with both seeming to reduce anxiety symptoms (1 RCT, p&lt;0.001). It remains unclear as to which type of exercise; moderate to hard or very light to light, is more effective in anxiety reduction (2 RCTs). Conclusions Exercise seems to be effective as an adjunctive treatment for anxiety disorders but it is less effective compared with antidepressant treatment. Both aerobic and non-aerobic exercise seems to reduce anxiety symptoms. Social phobics may benefit from exercise when combined with group CBT. Further well-conducted RCTs are needed.
The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials
Authors: Panagiotis D. Kottaridis, Rosemary E. Gale, Marion E. Frew, Georgina Harrison, Stephen E. Langabeer, Andrea A. Belton, Helen Walker, Keith Wheatley, David T. Bowen, Alan K. Burnett, Anthony H. Goldstone, David C. Linch
Journal: Blood (2001)
T cell replacing factor substitutes for an I-J+ idiotype-specific T helper cell.
Authors: S Jayaraman, J E Swierkosz, C J Bellone
Journal: The Journal of Experimental Medicine (1982)

An in vitro system for the study of idiotype (Id) expression on antitrimethylamino hapten antibody-producing cells and its regulation by two classes of helper T cells is described. These cells are distinguished in four ways: one requires a hapten-carrier bridge and gives a good response that is low in Id; it does not bind to Id-coated dishes and is not affected by anti-I-J plus complement. The other requires antigen but not a hapten-carrier bridge, is bound by Id-coated dishes and is killed by anti-I-J and complement. The Id-specific cell appears to be antigen specific and acts via a soluble factor(s).
Untouched GMP-Ready Purified Engineered Immune Cells to Treat Cancer
Authors: Trudy Straetemans, Cordula Gründer, Sabine Heijhuurs, Samantha Hol, Ineke Slaper-Cortenbach, Halvard Bönig, Zsolt Sebestyen, Jürgen Kuball
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Engineering T cells with receptors to redirect the immune system against cancer has most recently been described as a scientific breakthrough. However, a main challenge remains the GMP-grade purification of immune cells selectively expressing the introduced receptor in order to reduce potential side effects due to poorly or nonengineered cells. Experimental Design: In order to test a novel purification strategy, we took advantage of a model γδT cell receptor (TCR), naturally interfering with endogenous TCR expression and designed the optimal retroviral expression cassette to achieve maximal interference with endogenous TCR chains. Following retroviral transduction, nonengineered and poorly engineered immune cells characterized by a high endogenous αβTCR expression were efficiently depleted with GMP-grade anti-αβTCR beads. Next, the engineered immune cells were validated for TCR expression, function against a panel of tumor cell lines and primary tumors and potential allo-reactivity. Engineered immune cells were further validated in two humanized mouse tumor models. Results: The untouched enrichment of engineered immune cells translated into highly purified receptor-engineered cells with strong antitumor reactivity both in vitro and in vivo. Importantly, this approach eliminated residual allo-reactivity of engineered immune cells. Our data demonstrate that even with long-term suboptimal interference with endogenous TCR chains such as in resting cells, allo-reactivity remained absent and tumor control preserved. Conclusions: We present a novel enrichment method for the production of untouched engineered immune cells, ready to be translated into a GMP-grade method and potentially applicable to all receptor-modified cells even if interference with endogenous TCR chains is far from complete. Clin Cancer Res; 21(17); 3957–68. ©2015 AACR.
Brief Communication: Severe Hepatotoxicity of Telithromycin: Three Case Reports and Literature Review
Authors: Kimberly D. Clay
Journal: Annals of Internal Medicine (2006)

Background: Telithromycin is a ketolide antibiotic approved by the U.S. Food and Drug Administration for acute bacterial infections causing sinusitis, bronchitis, and community-acquired pneumonia. Objective: To describe 3 cases of severe hepatotoxicity in patients receiving telithromycin. Design: Case reports. Setting: A tertiary care medical center. Patients: 3 previously healthy patients who had recently taken telithromycin and took no other prescription medications. Measurements: Serologic, histologic, and liver function tests. Results: Within a few days of receiving telithromycin, the patients presented with acute hepatitis. All had jaundice and markedly abnormal results on liver function tests. Results of viral serologic tests were negative. One patient spontaneously recovered, 1 required orthotopic liver transplantation, and 1 died. Histologic examination in the latter 2 patients showed massive hepatic necrosis. Limitations: Two patients had some history of alcohol use. The frequency of severe telithromycin-related hepatotoxicity cannot be established with case reports. Conclusions: Telithromycin can cause severe hepatotoxicity. Caution is advised in prescribing this drug pending additional postmarketing surveillance data.