tbuckley/cabot-search huggingface dataset:
Serco Health's reply to article on lack of transparency in NHS commissioning
Authors: S. Colclough
Journal: BMJ (2014)

<h3>Abstract</h3> Periodontitis is an inflammatory disease which is characterized by progressive destruction of the periodontium and causes tooth loss in adults. Periodontitis is known to be associated with dysbiosis of the oral microflora, often linked to various diseases. However, the complexity of plaque microbial communities of periodontitis, and antibiotic resistance and enhanced virulence make this disease difficult to treat. Therefore, we used metagenomic shotgun sequencing in this study to investigate the etiology, antibiotic-resistant genes (ARGs) and virulence genes (VirGs) of periodontitis. We revealed a significant shift in the composition of oral microbiota as well as several functional pathways that were represented significantly more abundant in periodontitis patients than in controls. Additionally, we observed several positively selected ARGs and VirGs with the Ka/Ks ratio &gt; 1 by analyzing our data and a previous periodontitis dataset, indicating that ARGs and VirGs in oral microbiota may suffer from positive selection. Moreover, 5 of 12 positively selected ARGs and VirGs in periodontitis patients were found in the genomes of respiratory tract pathogens. Of note, 91.8% of the background VirGs with at least one non-synonymous single-nucleotide polymorphism for natural selection were also from respiratory tract pathogens. These observations suggest a potential association between periodontitis and respiratory infection at the gene level. Our study enriches the knowledge of pathogens and functional pathways as well as the positive selection of antibiotic resistance and pathogen virulence in periodontitis patients, and provides evidence from the gene level for an association between periodontitis and respiratory infection.
Role of Gamma Globulin for Immunoprophylaxis in Multiple Myeloma
Authors: Sydney E. Salmon, Bohumil A. Samal, Donald M. Hayes, Henry Hosley, Sherwood P. Miller, Albert Schilling
Journal: New England Journal of Medicine (1967)

BACTERIAL infection is one of the leading causes of morbidity and mortality in patients with multiple myeloma.1 , 2 Although most patients have large amounts of homogeneous myeloma immunoglobulin present in the serum or urine, these globulins appear to lack antibody function, and patients with myeloma often have impaired response to antigenic stimulation and reduced levels of normal immune globulins.3 , 4 Delayed hypersensitivity mechanisms are usually intact.5 These findings are qualitatively similar to defects in host defense observed in patients with primary agammaglobulinemia, in whom prophylactic gamma-globulin injections have proved to be of great value in reducing the frequency of serious infections.6 Because . . .
Causes of Hyperketonemia
Authors: Selden E. Spencer
Journal: JAMA (1979)

<h3>To the Editor.—</h3> The article by Schade and Eaton (241:2064, 1979) on the differential diagnosis and therapy for the hyperketonemic state<sup>1</sup>may have the unintended effect of lulling the reader into ignoring perhaps less common but equally serious and lethal causes of hyperketonemia and ketonuria. Isopropyl alcohol intoxication is associated with hyperketonemia and ketonuria<sup>1</sup>without glycosuria or acidosis. The experience of Ashkar and Miller<sup>2</sup>and Vermeulen<sup>3</sup>warns us that unraveling the cause of hyperketonemia in a diabetic alcoholic with access to isopropyl alcohol can be confusing and difficult. Also, mildly elevated serum ketone levels were reported in a case of cyanide poisoning.<sup>4</sup> The isopropyl alcohol intoxication would probably represent a fifth category of hyperketonemic causes. It is purely exogenous. The hyperketonemia of cyanide poisoning is neither well established nor clear in etiology, but may relate to severe lactic acidosis and stress.
SAFETY AND EFFECTIVENESS OF BALLOON AORTIC VALVULOPLASTY FOR SEVERE AORTIC STENOSIS IN THE CONTEMPORARY ERA
Authors: Anirudh Kumar, David Paniagua, Biswajit Kar, Anita Deswal, Mahboob Alam, Shuab Omer, Faisal Bakaeen, Todd Rosengart, Alvin Blaustein, Biykem Bozkurt, Hani Jneid, Michael E. DeBakey
Journal: Journal of the American College of Cardiology (2014)
Authors' reply to Moore
Authors: F. Lapi, L. Azoulay, S. Suissa
Journal: BMJ (2013)

We would like to respond to Moore’s thoughtful comments.1 2 

Firstly, we considered this important point in our analyses—we adjusted the models for the use of drugs related to the indications for non-steroidal anti-inflammatory drugs (NSAIDs). These included antibiotics (related to short term infections) and immunosuppressive agents (related to conditions associated with …
Reliability of Visual Field Results over Repeated Testing
Authors: Joanne Katz, Alfred Sommer, Kathe Witt
Journal: Ophthalmology (1991)

Fifty-one normal subjects, 337 with ocular hypertension, and 55 patients with glaucoma underwent C-30-2 testing on the Humphrey Field Analyzer on at least three occasions over a 6-year period. The time between tests was approximately 1 year. Using the manufacturer's standard for a reliable field (false-positive and false-negative rates, <33%; fixation losses, <20%), no trends in the proportion of reliable fields or the component indices were observed over time. Four percent of normal subjects, 9% of those with ocular hypertension, and 8% of patients with glaucoma were unable to meet the reliability standard every time they were tested. This repeated lack of reliability was due almost exclusively to fixation losses. However, patients with glaucoma were more likely to have repeatedly high false-negative responses than those with ocular hypertension or normal subjects, providing further evidence that false-negative responses are more indicative of glaucoma than of patient reliability.
Prevalence of pulmonary hypertension in hereditary spherocytosis
Authors: Shelley E. Crary, Claudio Ramaciotti, George R. Buchanan
Journal: American Journal of Hematology (2011)

Vascular complications, including pulmonary hypertension (PH), have been reported to occur following splenectomy for various disorders,including hereditary spherocytosis (HS). We performed a prospective cross-sectional study of 36 adults with HS (78% with prior splenectomy)utilizing echocardiography to estimate tricuspid regurgitant jet velocity (TRV) as well as measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) to screen for PH. No participant with HS hada significantly elevated TRV or NT-proBNP level, despite a median 25-year interval since splenectomy (95% confidence interval for point prevalence 0, 0.097). Although our study was limited by a small sample size, it appears that persons with HS, following splenectomy, appear unlikely to be at significantly increased risk of developing PH to the degree reported for thalassemia and sickle cell disease
Adaptive immune responses triggered by oxidative stress contribute to hepatic inflammation in NASH
Authors: Salvatore Sutti, Aastha Jindal, Irene Locatelli, Marco Vacchiano, Luca Gigliotti, Cristina Bozzola, Emanuele Albano
Journal: Hepatology (2013)

Previous studies have shown that human nonalcoholic steatohepatitis (NASH) is often associated with the presence of circulating antibodies against protein adducted by lipid peroxidation products. Here we used the methionine-choline deficient (MCD) model of NASH to characterize the possible involvement of adaptive immunity in NASH. In mice fed up to 8 weeks with the MCD diet the extension of liver injury and lobular inflammation paralleled the development of immunoglobulin G (IgG) against malonyldialdehyde (MDA) and 4-hydroxynonenal (4-HNE)-derived antigens as well as with the hepatic recruitment of CD4(+) and CD8(+) T-lymphocytes responsive to the same antigens. Moreover, in these animals the individual IgG reactivity against MDA-adducts positively correlated with transaminase release and hepatic tumor necrosis factor alpha (TNF-α) expression. To substantiate the role of immune responses triggered by oxidative stress in the progression of NASH, mice were immunized with MDA-adducted bovine serum albumin (MDA-BSA) before feeding the MCD diet. MDA-BSA immunization did not affect control mice livers, but further stimulated transaminase release, lobular inflammation, and the hepatic expression of proinflammatory cytokine in MCD-fed mice. The increased severity of NASH in immunized MCD-fed mice involved liver recruitment and the T helper (Th)-1 activation of CD4(+) T cells that, in turn, further stimulated macrophage M1 responses. Moreover, hepatic fibrosis was also evident in these animals in relation with an IL-15-mediated increase of natural killer T-cells (NKT) and the up-regulation in liver production of osteopontin by NKT cells and hepatic macrophages. These results indicate that oxidative stress can contribute to the progression of NASH by stimulating both humoral and cellular immune responses, pointing to the possible role of adaptive immunity in the pathogenesis of the disease.
Local Controlled Intramyocardial Delivery of Platelet-Derived Growth Factor Improves Postinfarction Ventricular Function Without Pulmonary Toxicity
Authors: Patrick C.H. Hsieh, Catherine MacGillivray, Joseph Gannon;, Francisco U. Cruz, Richard T. Lee
Journal: Circulation (2006)

Background— Local delivery methods can target therapies to specific tissues and potentially avoid toxicity to other organs. Platelet-derived growth factor can protect the myocardium, but it also plays an important role in promoting pulmonary hypertension. It is not known whether local myocardial delivery of platelet-derived growth factor during myocardial infarction (MI) can lead to sustained cardiac benefit without causing pulmonary hypertension. Methods and Results— We performed a randomized and blinded experiment of 127 rats that survived experimental MI or sham surgery. We delivered platelet-derived growth factor (PDGF)-BB with self-assembling peptide nanofibers (NFs) to provide controlled release within the myocardium. There were 6 groups with n≥20 in each group: sham, sham+NF, sham+NF/PDGF, MI, MI+NF, and MI+NF/PDGF. Serial echocardiography from 1 day to 3 months showed significant improvement of ventricular fractional shortening, end-systolic dimension, and end-diastolic dimension with local PDGF delivery ( P &lt;0.05 for MI+NF/PDGF versus MI or MI+NF). Catheterization at 4 months revealed improved ventricular function in the controlled delivery group (left ventricular end-diastolic pressure, cardiac index, +dP/dt, −dP/dt, and time constant of exponential decay all P &lt;0.05 for MI+NF/P versus MI or MI+NF). Infarcted myocardial volume was reduced by NF/PDGF therapy (34.0±13.3% in MI, 28.9±12.9% in MI+NF, and 12.0±5.8% in MI+NF/PDGF; P &lt;0.001). There was no evidence of pulmonary toxicity from the therapy, with no differences in right ventricular end-systolic pressure, right ventricular dP/dt, bromodeoxyuridine staining, or pulmonary artery medial wall thickness. Conclusions— Intramyocardial delivery of PDGF by self-assembling peptide NFs leads to long-term improvement in cardiac performance after experimental infarction without apparent pulmonary toxicity. Local myocardial protection may allow prevention of heart failure without systemic toxicity.
Intussusception after Appendicectomy
Authors: T. Bliss
Journal: BMJ (1944)

MEDICAL JOJRNALBut in conformity with Shrubsall I saw malignant disease in 2 red-haired patients only.It should be of va.ue further to study the incidence of red hair in pulmonary tuberculosis, rheumatic fever, acute tonsillitis, purpura simplex, and epilepsy. BLEEDINGThe contributor to the Journal stated that he had no know- ledge of any work on red hair and excessive bleeding.There is, however, evidence that rheumatic fever is associated with unusual (if not excessive) tendency to bleed.The tendency of rheumatic persons to nose-bleeding is discussed by Levine, Andren, and Homans (1930).Coburn (1933) found post- mortem evidence that rheumatic fever was associated with diffuse haemorrhagic changes.I (Davis, 1941, 1943) have given evidence of a special association between purpura simplex anid rheumatism.I do not vet know whether this assocIation is stronger in red-haired rheumatic subjects.Although many clinicians will have seen purpura in tuberculosis the association is re'atively rare (Davis, 1943).It might also be worth while investigating th:s association in red-haired tuberculous patients.De-air's of a Ser-ies of 100 Red-haired Patientts (Diseases in which Red Hair was seenz in miior-e thani 3 Patients) Ttl Cases with Percentage of Dis ase Totases Red HTaital 100 Red-haired Dis ase Cases Red Hair ~~~Patients Pulmonary tuberculosis .. 296 23 (7 8%) 23 Rheumatic fever (past or present) 248 5 (r0',) 15 Acute tonsillitis .162 12(7 4<.i)
Aquatic models for the study of renal transport function and pollutant toxicity.
Authors: D S Miller
Journal: Environmental Health Perspectives (1987)

Studies of renal cell transport mechanisms and their impairment by xenobiotics are often limited by technical difficulties related to renal tubule complexity. Problems include the juxtaposition of multiple tubule segments with different transport functions and severely limited access to the tubular lumen. Some limitations can be overcome by the careful selection of an appropriate aquatic experimental system. Two aquatic models for the vertebrate proximal segment are discussed here. The first is the kidney from certain marine flounder, which offers the following advantages: long-term viability, little tissue of nonproximal origin, and easy tubule isolation. Data are presented to demonstrate how studies with flounder kidney can be used to elucidate cellular mechanisms whereby different classes of toxic pollutants may interact. Results from these experiments indicate that the excretion of certain anionic xenobiotics can be delayed by other anionic xenobiotics that compete for secretory transport sites and by compounds that disrupt cellular ion gradients and energy metabolism needed to drive transport. The second system is the crustacean urinary bladder, a simple, flatsheet epithelium. Bladder morphology and transport physiology closely resemble those of vertebrate proximal segment. Electron micrographs show a brush border membrane at the luminal surface, numerous mitochondria, and an infolded serosal membrane, while in vivo and in vitro transport studies show reabsorption of NaCl, nutrients and water and secretion of organic cations; organic anions are secreted in bladders from some species and reabsorbed in others. Moreover, since bladders can be mounted as flat sheets in flux chambers, studies with this tissue avoid the problems of complex renal tubule geometry and tissue heterogeneity that limit transport studies in proximal tubule.
New sweet potato could help combat blindness in Africa
Authors: C. Wallerstein
Journal: BMJ (2000)

A new variety of sweet potato selected by scientists in Peru could help to prevent millions of cases of blindness and disease among children in Africa.

A simple deficiency of vitamin A is the leading cause of childhood blindness in developing countries, where around 251million children are vitamin A deficient, 10 million have xerophthalmia, or “dry eye,” 500000 are irreversibly blinded, and three million die of vitamin A deficiency-related illnesses.

The new bright orange sweet potato, known as …
Normalization of Plasma Insulin Profiles in Diabetic Subjects with Programmed Insulin Delivery
Authors: David S Schade, R Philip Eaton, William Spencer
Journal: Diabetes Care (1980)

Normalization of plasma glucose concentration with subcutaneous injections of insulin has been difficult. With intravenous insulin delivery, normalization of plasma glucose concentration in adult-onset diabetic patients has been achieved when their plasma insulin concentration was normalized. In juvenile-onset diabetic subjects totally lacking endogenous insulin, the effect of normalization of the plasma insulin concentration has not yet been reported. In the present studies, the plasma insulin profile was normalized in four brittle, insulin-dependent diabetic subjects throughout three meals (breakfast, lunch, and supper). Plasma free insulin concentration was assayed after precipitation of endogenous insulin antibodies with polyethylene glycol. Acute meal-related increases in plasma free insulin concentration were achieved with a programmable intravenous insulin delivery system. When plasma insulin profiles were normalized in insulin-dependent diabetic subjects lacking endogenous insulin secretion, an improvement in meal-related glucose excursions was observed. However, complete normalization of plasma glucose concentration was not achieved, suggesting that factors other than plasma insulin concentration modulate carbohydrate homeostasis in brittle diabetes. These factors may include portal vein hypoinsulinemia during peripheral vein insulin infusion, stress hormone concentrations, and tissue insulin resistance.
Impaired Insulin Sensitivity, Insulin Secretion, and Glucose Effectiveness Predict Future Development of Impaired Glucose Tolerance and Type 2 Diabetes in Pre-Diabetic African Americans
Authors: Kwame Osei, Scott Rhinesmith, Trudy Gaillard, Dara Schuster
Journal: Diabetes Care (2004)

OBJECTIVE—We examined the determinants of impaired glucose tolerance (IGT) and type 2 diabetes in first-degree relatives of African-American type 2 diabetic patients over 5–8 years (median 6). RESEARCH DESIGN AND METHODS—A total of 81 healthy subjects (age 41.5 ± 4.8 years; BMI 31.3 ± 3.6 kg/m2) participated in the study. Each subject underwent an oral glucose tolerance test (OGTT) and a frequently sampled intravenous glucose tolerance test at baseline. Insulin sensitivity index (Si) and glucose effectiveness index (Sg) were determined by the minimal model method. Homeostasis model assessment (HOMA) was used to estimate insulin resistance (HOMA-IR) and β-cell function (HOMA-%B). A total of 18 subjects progressed to either IGT or type 2 diabetes (progressors), whereas 19 subjects maintained normal glucose tolerance (nonprogressors). RESULTS—Comparing the progressors and nonprogressors, mean fasting serum glucose levels (95 ± 8 vs. 80 ± 14 mg/dl, P &amp;lt; 0.01) and 2-h serum glucose levels (149 ± 27 vs. 100 ± 60 mg/dl, P &amp;lt; 0.01) as well as 2-h serum insulin levels (117 ± 81 vs. 72 ± 87 μU/ml, P &amp;lt; 0.01) during OGTT were higher at baseline. Mean acute first-phase insulin secretion (205 ± 217 vs. 305 ± 230 μU/ml), HOMA-%B (148 ± 60 vs. 346 ± 372, P &amp;lt; 01), Si (1.61 ± 1.13 vs. 2.48 ± 1.25 × 10−4 · min−1 [μU/ml]−1), and Sg (1.48 ± 0.61 vs. 2.30 ± 0.97 × 10−2 · min−1) were lower in the progressors than in the nonprogressors at baseline. Mean HOMA-IR (3.31 ± 1.64 vs. 2.36 ± 1.64) was significantly greater in the progressors than the nonprogressors. At the time of diagnosis of glucose intolerance (IGT + diabetes), HOMA-%B (101 ± 48 vs. 148 ± 60, P &amp;lt; 0.001) and HOMA-IR (5.44 ± 2.55 vs. 3.31 ± 1.64, P &amp;lt; 0.003) deteriorated in the progressors versus baseline. CONCLUSIONS—We conclude that nondiabetic, first-degree relatives of African-American type 2 diabetic patients who progressed to IGT and type 2 diabetes manifest triple defects (decreased insulin secretion, insulin action, and glucose effectiveness) that antecede the disease.
Cardiovascular adverse effects during itraconazole therapy
Authors: S-L. Fung, C-H. Chau, W-W. Yew
Journal: European Respiratory Journal (2008)

To the Editors: 

Itraconazole has been widely used in the treatment of fungal disease including chronic necrotising pulmonary aspergillosis (CNPA) 1, 2. Its use has been associated with occasional reports of adverse cardiovascular events including congestive heart failure 3, hypertension (HT) 4, premature ventricular contractions 5 and even ventricular fibrillation 6. However, these adverse effects have been considered to be uncommon, if not rare, occurrences. From September, 1992 to April, 2001, the US Food and Drug Administration received only 59 reports of potential cases of congestive heart failure with the administration of itraconazole 3. Despite the recommendation …
Endoscopic versus Open Vein-Graft Harvesting in Coronary-Artery Bypass Surgery
Authors: Renato D. Lopes, Gail E. Hafley, Keith B. Allen, T. Bruce Ferguson, Eric D. Peterson, Robert A. Harrington, Rajendra H. Mehta, C. Michael Gibson, Michael J. Mack, Nicholas T. Kouchoukos, Robert M. Califf, John H. Alexander
Journal: New England Journal of Medicine (2009)

Vein-graft harvesting with the use of endoscopy (endoscopic harvesting) is a technique that is widely used to reduce postoperative wound complications after coronary-artery bypass grafting (CABG), but the long-term effects on the rate of vein-graft failure and on clinical outcomes are unknown.
Abstract 5232: Salivary proteome as an <i>in vivo</i> model to study breast cancer progression.
Authors: Charles F. Streckfus
Journal: Cancer Research (2013)

Abstract Background: To date, because of the complexity and heterogeneity of breast cancer, no individual model recapitulates all aspects of this disease. Since both the mammary and salivary glands are exocrine glands and that the literature has shown cross-talk between the two glands, we hypothesize that, secondary to breast cancer, the malignancy's rapid growth alters the proteomic content of the tissue microenvironment and that these changes may manifest in up or down regulation of salivary protein concentrations, which can be used as a sentinel body fluid for breast cancer modeling. Verification that salivary proteomic content can be used to model breast cancer progression employing HER2 biology would provide strong support for immediate translational testing in clinical trial settings that would further be accelerated with the use of saliva-based testing as one of the most easily accessible body fluids. Objective: The objective of this study was to compare the salivary protein profiles of pooled saliva specimens from individuals diagnosed with ductal carcinoma of the breast with and without HER2/neu overexpression as a potential alternate to current HER2/neu assessment methodologies. Methods: Pooled (n=10 subjects/pooled specimen) stimulated whole saliva specimens from women were analyzed. One pooled specimen was from healthy women, another was from women diagnosed with Stage IIa (T2N0M0) invasive ductal carcinoma (IDC) without positive HER2/neu receptor status. A third pooled specimen was from women diagnosed with Stage IIa (T2N0M0) IDC with a positive HER2/neu receptor status. Isotopically tagging proteins in the tumor groups and comparing them to the healthy control group measured differential expression of proteins. Experimentally, saliva from each of the pooled samples was trypsinized and the peptide digests labeled with the appropriate iTRAQ reagent. Labeled peptides from each of the digests were combined and analyzed by reverse phase (C18) capillary chromatography on an LC-MS/MS mass spectrometer equipped with an LC-Packings HPLC. Results: The results of the analyses yielded approximately 174 differentially expressed proteins in the saliva specimens. There were 20 proteins unique to HER2/neu positive receptor status and 28 proteins that were unique to HER2/neu negative status. Conclusions: The study suggests that saliva is a fluid suffused with solubilized by-products of oncogenic expression and that these proteins may be differently expressed in the presence of HER2/neu positive receptor status. It also provides support to the novel idea of using salivary secretions to study breast cancer progression Citation Format: Charles F. Streckfus. Salivary proteome as an in vivo model to study breast cancer progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5232. doi:10.1158/1538-7445.AM2013-5232