tbuckley/cabot-search huggingface dataset:
Combined influences of Gm and HLA phenotypes upon multiple sclerosis susceptibility and severity.
Authors: J P Salier, R Sesboüé, C Martin-Mondière, M Daveau, P Cesaro, B Cavelier, A Coquerel, L Legrand, J M Goust, J D Degos
Journal: Journal of Clinical Investigation (1986)

In some Caucasian populations, multiple sclerosis (MS) susceptibility has been independently related to given alleles of HLA or Gm systems that respectively code for major histocompatibility complex class I and II antigens or immunoglobulin G heavy chains. Whether given combinations of alleles at both series of loci simultaneously influence MS susceptibility and/or severity was investigated by comparing 147 French MS patients and 226 geographically-matched healthy controls. The G2m(-23)/HLA-B35 phenotype and G1m(-1)/HLA-B7(-)/HLA-DR2 phenotype were respectively associated with significant protection against (relative risk = 0.05) and susceptibility to (relative risk = 4.3) MS. When considering MS severity, the presence of HLA-B7 antigen correlated with a more severe disease in Gm1/Gm3 heterozygous patients, but not in Gm3/Gm3 homozygous patients. Conversely, an HLA-B12-associated milder disease was restricted to Gm3/Gm3 homozygotes. These results demonstrate the combined influence on MS of genetic loci that are unlinked but immune response-associated. Combined Gm and HLA typing is very likely able to serve as a prognostic indicator in this disease.
Safe splenoportography: Objective confirmation is still needed
Authors: Flemming Burcharth
Journal: Hepatology (1988)

The records of 37 patients who had undergone splenoportography, including one group of 12 who were studied before 1976 and a second group of 25 who were studied after 1977, were reviewed. The primary difference was that in the second group, the tract in the spleen was occluded with absorbable gelatin sponge (Gelfoam) plugs as the needle was withdrawn. In addition, there were minor changes in technique, such as changes in the needle puncture angle and entry site. When the new technique was used, there was a significant decrease in the complications traditionally associated with splenoportography. This procedure is safe and deserves to be considered the procedure of choice in patients in whom precise anatomic information is needed preoperatively that cannot be obtained with noninvasive procedures such as ultrasound or magnetic resonance imaging.
Classic and Molecular Cytogenetic Analyses Reveal Chromosomal Gains and Losses Correlated with Survival in Head and Neck Cancer Patients
Authors: Nádia Aparecida Bérgamo, Luciana Caricati da Silva Veiga, Patricia Pintor dos Reis, Inês Nobuko Nishimoto, José Magrin, Luiz Paulo Kowalski, Jeremy A. Squire, Sílvia Regina Rogatto
Journal: Clinical Cancer Research (2005)

Genetic biomarkers of head and neck tumors could be useful for distinguishing among patients with similar clinical and histopathologic characteristics but having differential probabilities of survival. The purpose of this study was to investigate chromosomal alterations in head and neck carcinomas and to correlate the results with clinical and epidemiologic variables.Cytogenetic analysis of short-term cultures from 64 primary untreated head and neck squamous cell carcinomas was used to determine the overall pattern of chromosome aberrations. A representative subset of tumors was analyzed in detail by spectral karyotyping and/or confirmatory fluorescence in situ hybridization analysis.Recurrent losses of chromosomes Y (26 cases) and 19 (14 cases), and gains of chromosomes 22 (23 cases), 8 and 20 (11 cases each) were observed. The most frequent structural aberration was del(22)(q13.1) followed by rearrangements involving 6q and 12p. The presence of specific cytogenetic aberrations was found to correlate significantly with an unfavorable outcome. There was a significant association between survival and gains in chromosomes 10 (P = 0.008) and 20 (P = 0.002) and losses of chromosomes 15 (P = 0.005) and 22 (P = 0.021). Univariate analysis indicated that acquisition of monosomy 17 was a significant (P = 0.0012) factor for patients with a previous family history of cancer.The significant associations found in this study emphasize that alterations of distinct regions of the genome may be genetic biomarkers for a poor prognosis. Losses of chromosomes 17 and 22 can be associated with a family history of cancer.
Mechanical coupling between the hemithoraces in humans
Authors: B Johansen, P Giaever, F Aspestrand, A Kolbenstvedt
Journal: European Respiratory Journal (1996)

Unilateral airway occlusion permits measurement of single lung function. Since the results suggest that the occluded lung influences the mobility of the contralateral hemithorax, we wanted to test this hypothesis. In eight healthy subjects, we measured, using computed tomography, lung parenchymal area and inner rib cage parasagittal and transverse diameters at three different levels and at maximal inspiration and expiration. These measurements were made without and during balloon occlusion of one mainstem bronchus at residual volume (RV) and at total lung capacity (TLC). Unilateral occlusion at RV reduced the ipsilateral diameters in maximal inspiration, but the increase during inspiration was still 39-50% of that without occlusion. The inspiratory increase in contralateral diameters was reduced to 64-80% of the increase without occlusion. Occlusion at TLC reduced the expiratory decrease in ipsilateral diameters to 37-57% of that without occlusion. The expiratory decrease on the contralateral side was reduced to 56-70% of that without occlusion. Due to accompanying mediastinal shifts the parenchymal areas of the occluded lung barely changed. In contrast, the contralateral area was 86-97% of that without occlusion. We conclude that the movement of the two hemithoraces are, at least partially, interdependent. The occluded hemithorax prevents full expansion/compression of the nonoccluded contralateral side, whilst its own mobility appears to be increased by the presence of this nonoccluded side. Potential negative effects are outweighed by the physiological benefit of the coupling, as this mechanism could secure ventilation to a chest half without own movement.
Efficacy of rehabilitation (lengthening) exercises, platelet-rich plasma injections, and other conservative interventions in acute hamstring injuries: an updated systematic review and meta-analysis
Authors: Haiko IMFL Pas, Gustaaf Reurink, Johannes L Tol, Adam Weir, Marinus Winters, Maarten H Moen
Journal: British Journal of Sports Medicine (2015)

Background Our 2012 review on therapeutic interventions for acute hamstring injuries found a lack of high-quality studies. The publication of new studies warranted an update. Objectives To update and reanalyse the efficacy of conservative treatments for hamstring injury. Data sources PubMed, EMBASE, Web of Science, Cochrane library, CINAHL and SPORTDiscus were searched till mid-February 2015. Study eligibility criteria Randomised controlled trials (RCTs) on the effect of conservative interventions versus a control group or other intervention for hamstring injuries (HI) were included. Data analysis The search results were screened independently by two authors. Risk of bias assessment was performed using a modified Downs and Black scale with a maximum score of 28. Meta-analysis was performed, where possible. Main results 10 RCTs (526 participants), including 6 new RCTs, were identified. Two RCTs were of good/excellent quality, the rest were fair or poor (median Downs and Black score 16 (IQR 9)). Meta-analysis of two studies on rehabilitation (lengthening) exercises showed a significantly reduced time to return to play (HR 3.22 (95% CI 2.17 to 4.77), p&lt;0.0001) but no difference in risk of re-injury. Meta-analysis of three studies investigating platelet-rich plasma (PRP) showed no effect when compared to control (HR 1.03 (95% CI 0.87 to 1.22), p=0.73). Limited evidence was found that progressive agility and trunk stability training may reduce re-injury rates. Conclusions Meta-analysis showed superior efficacy for rehabilitation exercises. PRP injection had no effect on acute hamstring injury. Limited evidence was found that agility and trunk stabilisation may reduce re-injury rates. The limitations identified in the majority of RCTs should improve the design of new hamstring RCTs.
Relationship between GSTP1 Ile105Val polymorphism and docetaxel-induced peripheral neuropathy: clinical evidence of a role of oxidative stress in taxane toxicity
Authors: O. Mir, J. Alexandre, A. Tran, J.-P. Durand, G. Pons, J.-M. Treluyer, F. Goldwasser
Journal: Annals of Oncology (2009)
Selective Inhibition of Growth of <i>Tuberous Sclerosis Complex 2</i>–Null Cells by Atorvastatin Is Associated with Impaired Rheb and Rho GTPase Function and Reduced mTOR/S6 Kinase Activity
Authors: Geraldine A. Finlay, Amy J. Malhowski, Yingling Liu, Barry L. Fanburg, David J. Kwiatkowski, Deniz Toksoz
Journal: Cancer Research (2007)

Abstract Inactivating mutations in the tuberous sclerosis complex 2 (TSC2) gene, which encodes tuberin, result in the development of TSC and lymphangioleiomyomatosis (LAM). The tumor suppressor effect of tuberin lies in its GTPase-activating protein activity toward Ras homologue enriched in brain (Rheb), a Ras GTPase superfamily member. The statins, 3-hydroxy-3-methylglutaryl CoA reductase inhibitors, have pleiotropic effects which may involve interference with the isoprenylation of Ras and Rho GTPases. We show that atorvastatin selectively inhibits the proliferation of Tsc2−/− mouse embryo fibroblasts and ELT-3 smooth muscle cells in response to serum and estrogen, and under serum-free conditions. The isoprenoids farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP) significantly reverse atorvastatin-induced inhibition of Tsc2−/− cell growth, suggesting that atorvastatin dually targets a farnesylated protein, such as Rheb, and a geranylgeranylated protein, such as Rho, both of which have elevated activity in Tsc2−/− cells. Atorvastatin reduced Rheb isoprenylation, GTP loading, and membrane localization. Atorvastatin also inhibited the constitutive phosphorylation of mammalian target of rapamycin, S6 kinase, and S6 found in Tsc2−/− cells in an FPP-reversible manner and attenuated the high levels of phosphorylated S6 in Tsc2-heterozygous mice. Atorvastatin, but not rapamycin, attenuated the increased levels of activated RhoA in Tsc2−/− cells, and this was reversed by GGPP. These results suggest that atorvastatin may inhibit both rapamycin-sensitive and rapamycin-insensitive mechanisms of tuberin-null cell growth, likely via Rheb and Rho inhibition, respectively. Atorvastatin may have potential therapeutic benefit in TSC syndromes, including LAM. [Cancer Res 2007;67(20):9878–86]
Surgeon Influence on Use of Needle Biopsy in Patients With Breast Cancer: A National Medicare Study
Authors: Jan M. Eberth, Ying Xu, Grace L. Smith, Yu Shen, Jing Jiang, Thomas A. Buchholz, Kelly K. Hunt, Dalliah M. Black, Sharon H. Giordano, Gary J. Whitman, Wei Yang, Chan Shen, Linda Elting, Benjamin D. Smith
Journal: Journal of Clinical Oncology (2014)

Use of needle biopsy is a proposed quality measure in the diagnosis and treatment of breast cancer, yet prior literature documents underuse. Nationally, little is known regarding the contribution of a patient's surgeon to needle biopsy use, and knowledge regarding downstream impact of needle biopsy on breast cancer care is incomplete.Using 2003 to 2007 nationwide Medicare data from 89,712 patients with breast cancer and 12,405 surgeons, logistic regression evaluated the following three outcomes: surgeon consultation before versus after biopsy, use of needle biopsy (yes or no), and number of surgeries for cancer treatment. Multilevel analyses were adjusted for physician, patient, and structural covariates.Needle biopsy was used in 68.4% (n = 61,353) of all patients and only 53.7% of patients seen by a surgeon before biopsy (n = 32,953/61,312). Patient factors associated with surgeon consultation before biopsy included Medicaid coverage, rural residence, residence more than 8.1 miles from a radiologic facility performing needle biopsy, and no mammogram within 60 days before consultation. Among patients with surgeon consultation before biopsy, surgeon factors such as absence of board certification, training outside the United States, low case volume, earlier decade of medical school graduation, and lack of specialization in surgical oncology were negatively correlated with receipt of needle biopsy. Risk of multiple cancer surgeries was 33.7% for patients undergoing needle biopsy compared with 69.6% for those who did not (adjusted relative risk, 2.08; P < .001).Needle biopsy is underused in the United States, resulting in a negative impact on breast cancer diagnosis and treatment. Surgeon-level interventions may improve needle biopsy rates and, accordingly, quality of care.
Evaluation of Adverse Events Experienced by Older Patients Participating in Studies of Molecularly Targeted Agents Alone or in Combination
Authors: Carol A. Townsley, Gregory R. Pond, Amit M. Oza, Hal W. Hirte, Eric Winquist, Glenwood Goss, Pamela Degendorfer, Malcolm J. Moore, Lillian L. Siu
Journal: Clinical Cancer Research (2006)

Abstract Background: The tolerability of molecularly targeted agents in older patients has not been specifically examined. Adverse event data from clinical trials in the Princess Margaret Hospital Phase II Consortium database were analyzed to address this question. Methods: The Consortium database collects trial information on all patients treated with either a molecularly targeted agent alone or in combination since 2001. The frequency of adverse events was determined and analyzed by two different age groups, &amp;lt;65 years and ≥65 years. Toxicity indices (TI) and frequencies of dose-limiting toxicities (DLT), based on adverse events of all causalities (TIALL and DLTALL), and on adverse events that were at least possibly related to the molecularly targeted agent (TIMTA and DLTMTA), were calculated for both age groups. Results: Four hundred and one patients who received 1,252 treatment cycles were analyzed from 19 different studies. Baseline performance status was similar between both age groups, but fewer older patients have had multiple prior regimens of chemotherapy or prior radiation therapy. A comparison of the proportions of younger and older patients experiencing DLTALL and DLTMTA showed similar results. The TIMTA values were comparable between the two age groups in both single agent (3.25 versus 3.00, for &amp;lt;65 versus ≥65 years) and multi-agent (3.65 versus 3.00, for &amp;lt;65 versus ≥65 years) trials. Conclusions: Older patients seem to tolerate molecularly targeted therapies either alone or in combination with chemotherapy as well as younger patients. Age alone should not be a barrier in the administration of targeted agents.
Cerebral Salt Wasting Versus SIADH
Authors: Richard H. Sterns, Stephen M. Silver
Journal: Journal of the American Society of Nephrology (2008)

The term cerebral salt wasting (CSW) was introduced before the syndrome of inappropriate antidiuretic hormone secretion was described in 1957. Subsequently, CSW virtually vanished, only to reappear a quarter century later in the neurosurgical literature. A valid diagnosis of CSW requires evidence of inappropriate urinary salt losses and reduced "effective arterial blood volume." With no gold standard, the reported measures of volume depletion do not stand scrutiny. We cannot tell the difference between CSW and the syndrome of inappropriate antidiuretic hormone secretion. Furthermore, the distinction does not make a difference; regardless of volume status, hyponatremia complicating intracranial disease should be treated with hypertonic saline.
An Address on the Surgical Treatment of Abscess of the Lung and Empyema
Authors: T. P. Teale
Journal: BMJ (1888)

large cavity between the baoe of the lung and the diaphragm whech communicated with the hepatic abscess through the open- ing in the diaphragm.Relief from the second operation was but transitory, and he died at the end of two weeks from the secoRnor operation.CASAC D.-Nnr.P., a patient of Mr. Carter, of Chapel Allerton, in the course of an illness began to expectorate fetid pus.TheLe was dulness about the base of the right lung.A large collectioJo of most offensive pus was found by incision between the ril)s and drainage was established.There was not the relief expectedR and he sank at the end of a week.At the postMtumortem,examinatioir the abscess was found to have buinowed behind the liver, and in the posterior mediastinum, and recovery under any circumstances of treatment seemed to have been out of the q,aestion.To these cases of my own I may without impropriety add twvo others whinh have been related to me by medical friends, both of whirh re.overed.NCar.R. N. Hartley, of Leeds, gives me partiHulars of the following case: A female, aged 27, suffered from acute pleui o- pneumonia, followed by very slow HonvalesoenHe, with an tuneven temperature, dulness at the base of the left lunga, pain eitla orthopncea, arod then sudden expectoration of offensive pNrs.'unlture with a trooar between the seventh and eiglith ribs juDt in front of the angle, disEovered pus.Guided by the cannnied Mne inieed and extposed the lungcrontinued the incision throigli the lung until he reaPhed and iet out about a quart of stinkiing pus.The cavity was drained.In three days all ur(rent sym- ptoms had gone and the patient Could lie dowI.The patient made a 910W but uininterrupted recovery.Dr. Davies, of Swainton, tells me the following case: Afarmer, aged 21, i July, 1885,, uffered from left pneumonia, and Rdas laid up the followingnwinter, expettorating pus.In the spring of 1886 the left lung was well, when the right, lung fell ainiss, wvitli expectoration of pus, often in great quiantities, even a quart at a time.ThiA Jontinued until June, 1887, when the expLptoratior betame horriblo fetid.In March, 18S8, he berame worse and seemed to be sifking.On April rst
Androstenedione Is the Preferred Androgen Source in Hormone Refractory Prostate Cancer—Letter
Authors: Nima Sharifi, Richard J. Auchus
Journal: Clinical Cancer Research (2014)

Fankhauser and colleagues recently report on pathways of androgen metabolism and dihydrotestosterone (DHT) synthesis in prostate cancer ([1][1]). Two possibilities for the fate of the adrenal steroid androstenedione in peripheral tissues are conversion to testosterone or 5α-reduction to 5α-
Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials
Authors: Lui G Franciosi, Zuzana Diamant, Katharine H Banner, Rob Zuiker, Nicoletta Morelli, Ingrid M C Kamerling, Marieke L de Kam, Jacobus Burggraaf, Adam F Cohen, Mario Cazzola, Luigino Calzetta, Dave Singh, Domenico Spina, Michael J A Walker, Clive P Page
Journal: The Lancet Respiratory Medicine (2013)
Nitric oxide, the biological mediator of the decade: fact or fiction?
Authors: S Singh, TW Evans
Journal: European Respiratory Journal (1997)

Nitric oxide (NO), an atmospheric gas and free radical, is also an important biological mediator in animals and humans. Its enzymatic synthesis by constitutive (c) and inducible (i) isoforms of NO synthase (NOS) and its reactions with other biological molecules such as reactive oxygen species are well characterized. NO modulates pulmonary and systemic vascular tone through its vasodilator property. It has antithrombotic functions and mediates some consequences of the innate and acute inflammatory responses; cytokines and bacterial toxins induce widespread expression of iNOS associated with microvascular and haemodynamic changes in sepsis. Within the lungs, a diminution of NO production is implicated in pathological states associated with pulmonary hypertension, such as acute respiratory distress syndrome: inhaled NO is a selective pulmonary vasodilator and can improve ventilation-perfusion mismatch. However, it may have deleterious effects through modulating hypoxic pulmonary vasoconstriction. Inhibitors of NOS may be of benefit in inotrope-refractory septic shock, but toxicity of newly developed selective iNOS inhibitors have prevented clinical trials of efficacy. An expanding literature on the origins and measurement of NO in exhaled breath implicates NO as a potentially useful marker of disease activity in respiratory tract inflammation in the future. This report reviews some aspects of research into the clinical importance of nitric oxide.
Simplification of antiviral hepatitis C virus therapy to support expanded access in resource-limited settings
Authors: Nathan Ford, Tracy Swan, Peter Beyer, Gottfried Hirnschall, Philippa Easterbrook, Stefan Wiktor
Journal: Journal of Hepatology (2014)

Currently, access to treatment for HCV is limited, with treatment rates lowest in the more resource-limited countries, including those countries with the highest prevalence. The use of oral DAAs has the potential to provide treatment at scale by offering opportunities to simplify drug regimens, laboratory requirements, and service delivery models. Key desirable characteristics of future HCV treatment regimens include high efficacy, tolerability, pan-genotype activity, short treatment duration, oral therapy, affordability, and availability as fixed-dose combination. Using such a regimen, HCV treatment delivery could be greatly simplified. Treatment could be initiated following confirmation of the presence of viraemia, with an initial assessment of the stage of liver disease. A combination DAA therapy that is safe and effective across genotypes could remove the need for genotyping and intermediary viral load assessments for response-guided therapy and reduce the need for adverse event monitoring. Simpler, safer, shorter therapy will also facilitate simplified service delivery, including task shifting, decentralization, and integration of treatment and care. The opportunity to scale up HCV treatment using such delivery approaches will depend on efforts needed to guarantee that the new DAAs are affordable in low-income settings. This will require the engagement of all stakeholders, ranging from the companies developing these new treatments, WHO and other international organizations, including procurement and funding mechanisms, governments and civil society.
Relation between changes in blood flow of the contralateral coronary artery and the angiographic extent and function of recruitable collateral vessels arising from this artery during balloon coronary occlusion
Authors: Michael K. Kyriakidis, Panaghiotis N. Petropoulakis, Costas A. Tentolouris, Stelios A. Marakas, Athanassios G. Antonopoulos, Costas V. Kourouclis, Pavlos K. Toutouzas
Journal: Journal of the American College of Cardiology (1994)