tbuckley/cabot-search huggingface dataset:
Isolated right ventricular dysfunction in systemic sclerosis: latent pulmonary hypertension?
Authors: S. Huez, F. Roufosse, J-L. Vachiéry, A. Pavelescu, G. Derumeaux, J-C. Wautrecht, E. Cogan, R. Naeije
Journal: European Respiratory Journal (2007)

Right ventricular function is frequently abnormal in patients with systemic sclerosis, but whether this is related to pulmonary vascular complications of the disease is unclear. Standard echocardiography with tissue Doppler imaging was performed at rest and during exercise for the study of right ventricular function and pulmonary circulation in 25 consecutive systemic sclerosis patients and in 13 age-matched healthy controls. When compared with the controls, the patients had no difference in systolic right ventricular pressure gradient, but a decreased pulmonary flow acceleration time, and increased right ventricular free wall thickness and end-diastolic dimensions. At the tricuspid annulus, the E maximal velocity was decreased (8.9±4 versus 11.7±2.3 cm·s −1 ) and the isovolumic relaxation time corrected to RR interval was increased (6.5±2.9 versus 4.5±2.5%). The tissue Doppler imaging profile at the mitral annulus was similar in both groups. At exercise, 18 patients had a decreased maximum workload and cardiac output, no change in systolic right ventricular pressure gradient, but an increase in the slope of pulmonary artery pressure/flow relationships. These results suggest that patients with systemic sclerosis may present with latent pulmonary hypertension as a likely cause of right ventricular diastolic dysfunction, as revealed by stress echocardiography and tissue Doppler imaging.
Phase I/II study of neoadjuvant bevacizumab, erlotinib and 5-fluorouracil with concurrent external beam radiation therapy in locally advanced rectal cancer
Authors: L.S. Blaszkowsky, D.P. Ryan, J. Szymonifka, D.R. Borger, A.X. Zhu, J.W. Clark, E.L. Kwak, H.J. Mamon, J.N. Allen, E. Vasudev, P.C. Shellito, J.C. Cusack, D.L. Berger, T.S. Hong
Journal: Annals of Oncology (2013)
1078 HYPOCHOLESTEROLAEMIA IN CHRONIC HEPATITIS C GENOTYPE 3 INFECTION IS DUE TO BOTH REDUCED CHOLESTEROL PRODUCTION AND INCREASED LDL CLEARANCE
Authors: D. Sheridan, K. Bartlett, D. Felmlee, S.H. Bridge, G.L. Toms, G. Dubuc, S. Nabil, J. Davignon, D. Neely, M.F. Bassendine
Journal: Journal of Hepatology (2010)
Pheochromocytoma with Rupture of an Intracranial Aneurysm
Authors: Elizabeth F. Browne, John S. Meyer
Journal: New England Journal of Medicine (1952)

THE neurologic complications of pheochromocytoma have recently been emphasized by Apter and his associates,1 who reviewed the literature and described a clinical case of their own. Out of approximately 200 cases of pheochromocytoma collected from the literature up to 1950, they were able to find 28 cases with evident neurologic complications, and in 16 of these the nervous system was examined at autopsy. The most common complication was intracranial hemorrhage, which occurred in 11 cases; in 2 of these the hemorrhages were subarachnoid. The origin of the subarachnoid hemorrhage, which was found in only 1 of these cases, was a . . .
Surface Charge Regulation of Osteogenic Differentiation of Mesenchymal Stem Cell on Polarized Ferroelectric Crystal Substrate
Authors: Jianhua Li, Xiaoning Mou, Jichuan Qiu, Shu Wang, Dongzhou Wang, Dehui Sun, Weibo Guo, Deshuai Li, Anil Kumar, Xuebin Yang, Aixue Li, Hong Liu
Journal: Advanced Healthcare Materials (2015)

Polarized ferroelectric crystal lithium niobate wafers with different cuts are selected to offer differently charged surfaces. By induction of the mesenchymal stem cells differentiation into osteoblasts on different charged surfaces, the specific osteogenic-associated markers are assessed and the results illustrate that the positively charged wafer surface enhances rBMMSCs osteogenic differentiation. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Lessons from Whitehall
Authors: K. Calman
Journal: BMJ (1998)

I have been asked on several occasions recently if I have any advice for my successor. I find it difficult (and perhaps inappropriate) to give advice, and I would certainly not expect it to be taken. I have, however, learnt many lessons during the seven years I spent in Whitehall, and these might be worth sharing.

#### Summary points

My purpose was, firstly, to argue (and sometimes to fight) for better health and health care in England, and, secondly, to ensure that professions, and in particular the medical profession, were both at the centre of the change process and up to the job. Such a vision cannot, and should not, be achieved alone; it requires the help of many colleagues in the colleges, the universities, the General Medical Council, the BMA, the wider medical profession, other professional groups, patients, and the public. Look how far we have come in seven years, though it has not been without its problems. The stories that could be told are many—of the battles fought, of the scars inflicted, and the achievements gained. Sometimes the job has felt lonely, often very exposed, but never without excitement and always great fun. It has been enormously enjoyable.

Much of the task is about leadership. For me, this means showing the way and this sometimes requires taking a difficult path, or even a new road, if the prize is to be won, …
THE TREATMENT OF VOMITING
Authors: BERNARD FANTUS
Journal: JAMA (1923)

Vomiting, one of our protective reflexes, not infrequently requires treatment because of uselessness, excess, or a tendency to self-perpetuation. <h3>USEFUL VOMITING</h3> Is there irritating material in the stomach? should be the first question in the treatment of vomiting. If there is, as in a case of drug or food poisoning, emesis should be encouraged by copious drinking of lukewarm water, unless a stomach tube is available. The use of this is preferable, as with it one can cleanse the stomach much more thoroughly. When offending food is vomited, the emesis requires no direct treatment. All that is necessary is to give the stomach rest for a few hours. We must, however, beware of falling into the facile error, so commonly committed by the laity, of incriminating whatever food has just previously been eaten, when, in reality, the vomiting frequently is symptomatic of some disease like cholelithiasis or appendicitis. Earmarks of
Clinical and Biochemical Interactions of Glucose-6-Phosphate Dehydrogenase Deficiency and Sickle-Cell Anemia
Authors: Sergio Piomelli, Carl A. Reindorf, Mohamed T. Arzanian, Laurence M. Corash
Journal: New England Journal of Medicine (1972)

Abstract The extremely young red-cell population in sickle-cell anemia invariably results in increased G-6-PD activity. This effect is more marked in persons who genotypically have the sex-linked Gd A- type of G-6-PD deficiency, and may even mask the phenotypic expression of the enzyme deficiency. Electrophoresis and family studies were used to determine the genotype in patients with sickle-cell anemia. Among 15 such patients five were Gd A- as compared with 11 of 102 randomly selected Afro-American controls (0.05   0.01). These findings showing a relative preponderance of the Gd A- type in patients with sickle-cell anemia support the Lewis hypothesis that the simultaneous inheritance of both defects may be clinically beneficial.
Transient Gene Expression by Nonintegrating Lentiviral Vectors
Authors: Sarah J. Nightingale, Roger P. Hollis, Karen A. Pepper, Denise Petersen, Xiao-Jin Yu, Catherine Yang, Ingrid Bahner, Donald B. Kohn
Journal: Molecular Therapy (2006)

Nonintegrating lentiviral (NIL) vectors were produced from HIV-1-based lentiviral vectors by introducing combinations of mutations made to disable the integrase protein itself and to alter the integrase recognition sequences (att) in the viral LTR. NIL vectors with these novel combinations of mutations were used to transduce the human T lymphoid cell line Jurkat and primary human CD34+ hematopoietic progenitor cells to assess their efficacy measured through transient expression of the enhanced green fluorescent protein (eGFP) reporter gene. The most disabled NIL vectors resulted in initial high levels of eGFP expression (∼90% of cells), but expression was transient, diminishing toward background (<0.5%) within less than 1 month. Southern blot analyses of transduced Jurkat cells confirmed the loss of detectable NIL vector sequence (linear form and one- and two-LTR circles) by 1 month. There were low residual levels of integration by NIL vectors (reduced approximately 104-fold compared to wild-type vectors), despite any combination of the engineered changes. Based upon analysis of the sequences of the DNA from the junctions of the vector LTR and cellular chromosomes, these rare integrated NIL vector sequences were not mediated by an integrase-driven mechanism due to reversion of the engineered mutations, but more likely were produced by background recombination events. The development of NIL vectors provides a novel tool for efficient transient gene expression in primary stem cells and hematopoietic and lymphoid cells.
Future Directions in the Study and Management of Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency
Authors: Deborah P. Merke, Stefan R. Bornstein, Nilo A. Avila, George P. Chrousos
Journal: Annals of Internal Medicine (2002)

Congenital adrenal hyperplasia describes a group of inherited autosomal recessive disorders characterized by an enzymatic defect in cortisol biosynthesis, compensatory increases in corticotropin secretion, and adrenocortical hyperplasia. 21-Hydroxylase deficiency is responsible for more than 95% of cases and is one of the most common known autosomal recessive disorders. The classic or severe type presents in the newborn period or early childhood with virilization and adrenal insufficiency, with or without salt loss; the mild or nonclassic form presents in late childhood or early adulthood with mild hyperandrogenism and is an important cause of masculinization and infertility in women. This wide range of phenotypic expression is mostly explained by genetic variation, although genotype-phenotype discrepancies have been described. Reproductive, metabolic, and other comorbid conditions, including risk for tumors, are currently under investigation in both forms of the disease. A high proportion of patients with adrenal incidentalomas may be homozygous or heterozygous for 21-hydroxylase deficiency. Women with congenital adrenal hyperplasia often develop the polycystic ovary syndrome. Ectopic adrenal rest tissue is often found in the testes of men with congenital adrenal hyperplasia; characteristic clinical and radiologic findings help differentiate this tissue from other tumors. Levels of corticotropin-releasing hormone are elevated in patients with depression and anxiety and are expected to be elevated in patients with congenital adrenal hyperplasia; it is unknown whether patients with 21-hydroxylase deficiency have an increased incidence of these psychiatric disorders. Abnormalities in both the structure and function of the adrenal medulla have been shown in patients with classic congenital adrenal hyperplasia, and the degree of adrenomedullary impairment may be a biomarker of disease severity. The 21-hydroxylase-deficient mouse has provided a useful model with which to examine disease mechanisms and test new therapeutic interventions in classic disease, including gene therapy. Treatment of this condition is intended to reduce excessive corticotropin secretion and replace both glucocorticoids and mineralocorticoids. However, clinical management is often complicated by inadequately treated hyperandrogenism, iatrogenic hypercortisolism, or both. New treatment approaches currently under investigation include combination therapy to block androgen action and inhibit estrogen production, and bilateral adrenalectomy in the most severely affected patients. Other approaches, which are in a preclinical stage of investigation, include treatment with a corticotropin-releasing hormone antagonist and gene therapy.
Free radical mediation of the effects of acidosis on calcium transport by cardiac sarcoplasmic reticulum in whole heart homogenates
Authors: M L HESS, E OKABE, P. ASH, H A KONTOS
Journal: Cardiovascular Research (1984)

Generation of oxygen free radicals by xanthine acting on xanthine oxidase as a substrate significantly depressed calcium transport by sarcoplasmic reticulum in canine whole heart homogenates at 37°C. At pH 7.0, this effect was completely inhibited by the addition of superoxide dismutase (SOD), a scavenger of the superoxide anion radical. At pH 6.4, SOD (5 to 20 μg·ml−1) was ineffective but catalase (20 μg·ml−1 was able to inhibit the effects of the xanthine-xanthine oxidase system. SOD + catalase (20 μg·ml−1) and SOD + mannitol, a scavenger of the hydroxyl free radical, inhibited the effects of the xanthine-xanthine oxidase system at pH 6.4. Preincubation at pH 6.4, in the absence of an exogenous free radical generating system, depressed calcium transport. This depression was more severe the longer the duration of incubation. However, return of the pH to 7.0 after preincubation at pH 6.4 partially restored calcium uptake velocity. The degree of reversibility was decreased the longer the period of incubation at pH 6.4. SOD reversed the effects of incubation at pH 6.4 for 5 min, but not those for incubations of 10 and 15 min. Mannitol alone was ineffective. The combinations of SOD and mannitol significantly reversed the effects of pH 6.4 up to 15 min. These results demonstrate that both exogenously generated and endogenously generated free oxygen radicals are capable of depressing calcium transport by cardiac sarcoplasmic reticulum in the whole heart homogenate in the presence of endogenous scavenging systems. Our results also demonstrate that acidosis depresses calcium transport by two mechanisms, one which is readily reversible and independent of the generation of free radicals, and a second mechanism which is a consequence of the generation of free radicals. The generation of superoxide anion radical by whole heart homogenate during acidosis was confirmed by demonstrating SOD reversible reduction of ferrocytochrome c at pH 6.4 but not at pH 7.0.
Letter: An unnecessary risk to children.
Authors: J S Anderson
Journal: BMJ (1976)

weakness in any other muscle groups.Two separate Tensilon tests (10 mg edrophonium chloride) wvith saline control were performed in a double-blind manner.After the first injection of edrophonium chloride the ptosis improved greatly, and two days later with the second test the im- provement was less marked.After the Tensilon tests all therapy was stopped and the patient referred to the late Professor Andrew Wilson, who suggested that this myasthenic syndrome might be related to the practolol.Electromyography revealed no abnormality, nor did it six months later, when the patient had been off all therapy.Investigations including ESR, haemoglobin, blood urea and electrolytes, thyroid function tests, and x-rays of the mediastinum revealed no abnormality.The myasthenic symptoms have not recurred following the second dose of edrophonium chloride, but because the patient's blood pressure rose after stopping the practolol he was restarted on spironolactone 100 mg daily and bendrofluazide 5 mg daily.
Exuberated Numbers of Tumor-Specific T Cells Result in Tumor Escape
Authors: Ofir Goldberger, Ilan Volovitz, Arthur Machlenkin, Ezra Vadai, Esther Tzehoval, Lea Eisenbach
Journal: Cancer Research (2008)

Abstract Cytotoxic T cells (CTL) play a major role in tumor rejection. Expansion of CTLs, either by immunization or adoptive transfer, is a prominent goal in current immunotherapy. The antigen-specific nature of these expansion processes inevitably initiates a clonotypic attack on the tumor. By injecting an Ovalbumin-expressing melanoma into OT-I mice, in which &amp;gt;90% of CTLs recognize an Ovalbumin peptide, we show that an increased number of tumor-specific CTLs causes emergence of escape variants. We show that these escape variants are a result of antigen silencing via a yet undetermined epigenetic mechanism, which occurs frequently and is spontaneously reversible. We further show that an increase in the time of tumor onset in OT-I compared with C57BL/6J is a result of immune selection. [Cancer Res 2008;68(9):3450–7]
Neointimal Smooth Muscle Cells Display a Proinflammatory Phenotype Resulting in Increased Leukocyte Recruitment Mediated by P-Selectin and Chemokines
Authors: Ute Zeiffer, Andreas Schober, Michael Lietz, Elisa A. Liehn, Wolfgang Erl, Neil Emans, Zhong-qun Yan, Christian Weber
Journal: Circulation Research (2004)

Leukocyte recruitment is crucial for the response to vascular injury in spontaneous and accelerated atherosclerosis. Whereas the mechanisms of leukocyte adhesion to endothelium or matrix-bound platelets have been characterized, less is known about the proadhesive role of smooth muscle cells (SMCs) exposed after endothelial denudation. In laminar flow assays, neointimal rat SMCs (niSMCs) supported a 2.5-fold higher arrest of monocytes and “memory” T lymphocytes than medial SMCs, which was dependent on both P-selectin and VLA-4, as demonstrated by blocking antibodies. The increase in monocyte arrest on niSMCs was triggered by the CXC chemokine GRO-α and fractalkine, whereas “memory” T cell arrest was mediated by stromal cell–derived factor (SDF)-1α. This functional phenotype was paralleled by a constitutively increased mRNA and surface expression of P-selectin and of relevant chemokines in niSMCs, as assessed by real-time PCR and flow cytometry. The increased expression of P-selectin in niSMCs versus medial SMCs was associated with enhanced NF-κB activity, as revealed by immunofluorescence staining for nuclear p65 in vitro. Inhibition of NF-κB by adenoviral IκBα in niSMCs resulted in a marked reduction of increased leukocyte arrest in flow. Furthermore, P-selectin expression by niSMCs in vivo was confirmed in a hypercholesterolemic mouse model of vascular injury by double immunofluorescence and by RT-PCR after laser microdissection. In conclusion, we have identified a NF-κB–mediated proinflammatory phenotype of niSMCs that is characterized by increased P-selectin and chemokine expression and thereby effectively supports leukocyte recruitment.
766 DEVELOPMENT OF A HYPERGLYCOSYLATEDIFN ALFAC0N1 (CIFN): TOWARDS BIMONTHLY OR MONTHLY DOSING FOR ANTIVIRAL THERAPIES IN DISEASES SUCH AS CHRONIC HEPATITIS C
Authors: J. Hong, J.S. Taylor, J.G. Julander, Q. Zhang, A.D. Stoycheva, H. Tan, C.V. Moy, S. Chanda, J.A. Symons, L.N. Beigelman, L.M. Blatt
Journal: Journal of Hepatology (2011)
Commissioning board looks for funding formula that will reduce health inequalities
Authors: G. Iacobucci
Journal: BMJ (2012)

The NHS Commissioning Board has rejected the use of a new funding formula for allocating health service funding in England for 2013-14, owing to fears that it may be “inconsistent” with its aim of reducing health inequalities.

The formula, recommended by the Advisory Committee on Resource Allocation (ACRA), would radically alter the current funding system by using age rather than income of local general practice populations as the primary determinant for NHS spending.

In a statement published alongside its planning guidance for 2013-14,1 the board said that it had opted not to bring in the formula for 2013-14 and would instead give each clinical commissioning group a 2.3% uplift under the current formula, to offer the new organisations “stability in their first year.”

The board said that …
Nut, Corn, and Popcorn Consumption and the Incidence of Diverticular Disease
Authors: Lisa L. Strate, Yan L. Liu, Sapna Syngal, Walid H. Aldoori, Edward L. Giovannucci
Journal: JAMA (2008)

IVERTICULAR DISEASE IS A COMmon and costly digestive disorder in Western countries.2][3] Complications, including diverticulitis and diverticular bleeding, occur in an estimated 10% to 35% of persons with diverticulosis. 4,5Treatment of these complications frequently necessitates hospitalization and invasive procedures, including surgery.At least $2.4 billion in direct health care costs and 3400 deaths are attributed to diverticular disease in the United States each year, 6,7 and the medical and economic impact of this disorder is likely to increase substantially as the population ages.Historically, physicians have advised individuals with diverticular disease to avoid nuts, seeds, popcorn, corn, and other high-residue foods. 5,8,91][12] Stool may lodge within a diverticulum, obstruct the neck, or abrade the mucosa and precipitate inflammation or bleeding. 1,13uts, seeds, popcorn, and corn are presumed to be particularly likely to abrade the mucosa or to lodge within small diverticula. 5However, the biological mechanisms responsible for diverticu-lar complications remain poorly understood.Aside from luminal trauma, potential inciting factors include elevated colonic pressures, compromised colon wall integrity, and altered bacterial flora. 1 4 -2 0 To our knowledge, there is no evidence to support consumption of nuts, corn, popcorn, or seeds as a risk factor.Compelling evidence suggests that nuts are an important part of a healthy diet.Nuts are high in protein, unsaturated fats, fiber, vitamins, minerals, and other micronutrients.A diet high in nuts may protect against many com-mon diseases, including cardiovascular disease, diabetes, cancer of the colon and prostate, and cholelithiasis.
Perception of bronchoconstriction in asthma patients measured during histamine challenge test
Authors: ID Bijl-Hofland, HT Folgering, H van den Hoogen, SG Cloosterman, C Van Weel, JM Donkers, CP van Schayck
Journal: European Respiratory Journal (1999)

This study investigated two aspects of the perception of bronchoconstriction ("sensitivity" and "absolute perceptual magnitude") in asthmatic patients and identified which clinical characteristics are related to these two aspects of perception of bronchoconstriction. The perception of histamine induced bronchoconstriction was measured in 128 asthmatic patients. Subjects quantified their breathlessness on a Visual Analogue Scale (VAS) before forced expiratory volume in one second (FEV1 was measured after each inhalation of histamine. The perceptive "sensitivity" for changes in FEV1 was analysed by the "VAS percentage fall in FEV1" slope. The "absolute perceptual magnitude" was determined by the VAS value at a 20% fall in FEV1. Spearman correlations were used for analysis between the two aspects of perception and asthma symptoms, peak flow variability, bronchial responsiveness and FEV1 % predicted. Patients with a low "sensitivity" for changes in FEV1 were more likely to show a frequent peak flow variability (Rs=-0.21; p<0.05), a high bronchial responsiveness (Rs= 0.37; p<0.001) and a low baseline FEV1 % pred (Rs=0.22; p<0.05). Patient's "absolute perceptual magnitude" correlated positively with symptoms during daily life (significant correlations varied 0.21-0.32) but not with the lung function parameters. The severity of asthma reflected by a low lung function and a high bronchial responsiveness, is associated with a low "sensitivity" for changes in forced expiratory volume in one second. A patient's "absolute perceptual magnitude" is positively related with asthma symptoms during daily life.