tbuckley/cabot-search huggingface dataset:
Prognostic Factors in HIV-Related Diffuse Large-Cell Lymphoma: Before Versus After Highly Active Antiretroviral Therapy
Authors: Soon-Thye Lim, Roksana Karim, Anil Tulpule, Bharat N. Nathwani, Alexandra M. Levine
Journal: Journal of Clinical Oncology (2005)

Purpose To compare the prognostic factors for survival and the validity of the International Prognostic Index (IPI) in patients with HIV-related diffuse large-cell lymphoma (HIV-DLCL) treated with curative intent in the pre–highly active antiretroviral therapy (HAART) era versus the HAART era. Patients and Methods We retrospectively reviewed 192 patients with HIV-DLCL diagnosed from 1982 to 2003. Pre-HAART era included 120 patients who did not receive HAART, whereas the HAART era included 72 patients diagnosed after January 1997 who received HAART. Results There were no statistically significant differences in terms of either lymphoma or HIV-related characteristics in the two time periods. The complete response rate improved from 32% in the pre-HAART to 57% in the HAART era (P = .0006), and median survival time improved from 8.3 to 43.2 months (P = .0005). In groups with low-, low-intermediate–, and high-intermediate–risk IPI disease, 3-year overall survival rates were 20%, 22%, and 5% in the pre-HAART era and 64%, 64%, and 50% in the HAART era, respectively. On multivariate analysis, factors independently associated with decreased survival in both periods were increasing IPI scores and failure to attain complete remission, whereas CD4 less than 100 cells/μL predicted shorter survival in only the pre-HAART era. Conclusion Prognostic factors and overall survival of patients with HIV-DLCC have changed. Clinical outcomes in patients with HIV-DLCL are now approaching the outcomes of patients with de novo lymphoma.
Cisplatin benefit is predicted by immunohistochemical analysis of DNA repair proteins in squamous cell carcinoma but not adenocarcinoma: theranostic modeling by NSCLC constituent histological subclasses
Authors: W.E. Pierceall, K.A. Olaussen, V. Rousseau, E. Brambilla, K.M. Sprott, F. Andre, J.-P. Pignon, T. Le Chevalier, R. Pirker, C. Jiang, M. Filipits, Y. Chen, J.L. Kutok, D.T. Weaver, B.E. Ward, J.-C. Soria
Journal: Annals of Oncology (2012)
Combined sensory and motor deficit in primary neuropathic faecal incontinence.
Authors: J Rogers, M M Henry, J J Misiewicz
Journal: Gut (1988)

Eleven patients with idiopathic faecal incontinence (IFI) and nine normal controls were studied with techniques of mucosal electrosensitivity and rectal distention for the quantitative assessment of anal and rectal sensation and with manometric and electromyographic tests for the assessment of anorectal motor function. The tests of motor function showed pelvic floor motor neuropathy in the patients with IFI, compared with controls, anal canal resting and voluntary contraction pressures were significantly (p less than 0.05, p less than 0.002) lower, pudendal nerve terminal motor latency and external anal sphincter fibre density were significantly (p less than 0.05, p less than 0.05) raised. The results of mucosal electrosensitivity (MES) disclosed a sensory deficit in the anal canal in patients with IFI, compared with controls, MES threshold was significantly (p less than 0.002) higher. Sensory thresholds to rectal distension were similar in the two groups. This study shows that sensory deficit of the anal canal occurs in combination with the motor neuropathy of the anal canal musculature in primary neuropathic faecal incontinence.
Clinical Guide to Depression and Bipolar Disorder: Findings From the Collaborative Depression Studyedited by Martin B. Keller, M.D., CoryellWilliam H. M.D., EndicottJean Ph.D., MaserJack D. Ph.D., and SchettlerPamela J. Ph.D. Washington, DC, American Psychiatric Publishing, 2013, 234 pp., $58.00.
Authors: Steven L. Dubovsky
Journal: American Journal of Psychiatry (2014)
Thalamic and Prefrontal FDG Uptake in Never Medicated Patients With Schizophrenia
Authors: Douglas S. Lehrer, Bradley T. Christian, Joseph Mantil, Aaron C. Murray, Bradley R. Buchsbaum, Terrence R. Oakes, William Byne, Eileen M. Kemether, Monte S. Buchsbaum
Journal: American Journal of Psychiatry (2005)

Because neuroleptic treatment may cause long-lasting changes in brain structure and function, a group of patients with schizophrenia who had never been medicated was recruited to examine regional glucose metabolic rates in the frontal-striato-thalamic circuit.Twelve never medicated patients with schizophrenia (seven men, five women; mean age=29 years) and 13 normal volunteers (eight men and five women; mean age=28.5 years) underwent (18)F-fluorodeoxyglucose (FDG) positron emission tomography, and coregistered anatomical magnetic resonance imaging scans were also obtained. During FDG uptake, subjects performed a spatial attention task previously shown to activate the pulvinar region of the thalamus.Diminished regional glucose metabolism was found in the medial dorsal nucleus, posterior thalamus, and prefrontal cortex of patients with schizophrenia relative to normal volunteers, extending earlier results from studies of medicated and previously medicated patients.The finding of lower relative metabolic rates in the frontothalamic circuits of patients with schizophrenia is consistent with extended circuit deficits involving interactions of frontal executive areas with thalamic sensory and association processes.
TNF-α is critical for antitumor but not antiviral T cell immunity in mice
Authors: Thomas Calzascia, Marc Pellegrini, Håkan Hall, Laurent Sabbagh, Nobuyuki Ono, Alisha R. Elford, Tak W. Mak, Pamela S. Ohashi
Journal: Journal of Clinical Investigation (2007)

TNF-alpha antagonists are widely used in the treatment of inflammatory and autoimmune diseases, but their use is associated with reactivation of latent infections. This highlights the importance of TNF-alpha in immunity to certain pathogens and raises concerns that critical aspects of immune function are impaired in its absence. Unfortunately, the role of TNF-alpha in the regulation of T cell responses is clouded by a myriad of contradictory reports. Here, we show a role for TNF-alpha and its receptors, TNFR1 and TNFR2, specifically in antitumor immunity. TNF-alpha-deficient mice exhibited normal antiviral responses associated with strong inflammation. However, TNF-alpha/TNFR1-mediated signals on APCs and TNF-alpha/TNFR2 signals on T cells were critically required for effective priming, proliferation, and recruitment of tumor-specific T cells. Furthermore, in the absence of TNF-alpha signaling, tumor immune surveillance was severely abrogated. Finally, treatment with a CD40 agonist alone or in combination with TLR2 stimuli was able to rescue proliferation of TNF-alpha-deficient T cells. Therefore, TNF-alpha signaling may be required only for immune responses in conditions of limited immunostimulatory capacity, such as tumor surveillance. Importantly, these results suggest that prolonged continuous TNF-alpha blockade in patients may have long-term complications, including potential tumor development or progression.
Global histone H3 lysine 4 (H3K4) dimethylation is an important prognostic factor in lung cancer
Authors: Yuichiro Machida, Yoshimichi Ueda, Miyako Shimazaki, Motoyasu Sagawa, Tsutomu Sakuma
Journal: European Respiratory Journal (2012)

[Introduction]

Epigenetic modifications may contribute to the development and progression of cancer. This study seeks to elucidate the role of global histone modifications as a clinicopathological factor in lung cancer.

[Methods]A series of 92 surgical specimens from patients with lung cancer were utilized from the surgical files of Kanazawa Medical University Hospital between 2001 and 2008. The 92 tumor specimens were examined by immunohistochemistry. Dimethylated histone 3 lysine 4 (H3K4diMe), Acetylated histone 3 lysine 9 (H3K9Ac), acetylated histone 3 lysine 18 (H3K18Ac), trimethylated histone 3 lysine 27 (H3K27trime), himethylated histone 4 arginine 3 (H4R3diMe) was assessed in paraffin-embedded tumor samples. They were dichotomized into two categories as low expression and high expression. The association between staining intensity and clinicopathological factor was analyzed.

[Results]Lung cancers of various histologic subtypes showed that dimethylated histone 3 lysine 4 (H3K4diMe), acetylated histone 3 lysine 9 (H3K9Ac), acetylated histone 3 lysine 18 (H3K18Ac), trimethylated histone 3 lysine 27 (H3K27trime), dimethylated histone 4 arginine 3 (H4R3diMe) were high expressed in tumor cells of 40, 10, 9, 9, 10%. Expression of dimethylated histone 3 lysine 4 (H3K4diMe) correlated positively with recouurence (p=0.039) and stage (p=0.005) and cell differentiation (p=0.002). Univariate analysis showed that high expression of dimethylated histone 3 lysine 4 (H3K4diMe) correlated with recouurenc

[Conclusion]We hypothesize that expression of H3K4diMe may be considered as a significatnt factor for patients with lung cancer.
Jails, Microbes, and the Three-Foot Barrier
Authors: John D. Nelson
Journal: New England Journal of Medicine (1996)

On the binding of an old book on the shelf in my office is imprinted “Common Contagious Diseases — Stimson.”1 Fifty years ago, when it was published, medical and nonmedical people alike could have told you, without even checking the table of contents, what those diseases were: diphtheria, scarlet fever, measles, rubella, whooping cough, mumps, chickenpox, smallpox, meningococcal meningitis, and poliomyelitis. Now the phrase “common contagious diseases” is obsolete and no longer appears in textbooks about infectious diseases, let alone as the title of a book. Smallpox is gone, and poliomyelitis will soon disappear from the planet. Diphtheria, measles, rubella, . . .
The Natural History of Hepatitis C Virus Infection
Authors: David L. Thomas, Jacquie Astemborski, Rudra M. Rai, Frank A. Anania, Melody Schaeffer, Noya Galai, Karen Nolt, Kenrad E. Nelson, Steffanie A. Strathdee, Lisette Johnson, Oliver Laeyendecker, John Boitnott, Lucy E. Wilson, David Vlahov
Journal: JAMA (2000)

Hepatitis C virus (HCV) infection may resolve (viral clearance), persist without complications, or cause end-stage liver disease (ESLD). The frequency and determinants of these outcomes are poorly understood.To assess the incidence and determinants of viral clearance and ESLD among persons who acquired HCV infection from injection drug use.Community-based prospective cohort study with enrollment in 1988-1989 and a median follow-up of 8.8 years.A total of 1667 persons aged 17 years or older with a history of injection drug use and an HCV antibody-positive test result during follow-up.Viral clearance was assessed in a subset of 919 patients and defined as failure to detect HCV RNA in at least 2 consecutive samples collected 5 or more months apart. End-stage liver disease was assessed at semiannual visits and by review of medical records and death certificates and defined by the presence of ascites, esophageal varices, or hepatic encephalopathy, or when ESLD was stated as a cause of death.Viral clearance was observed in 90 persons who were compared with 722 with persistent viremia, while the viremia of 107 was not resolved. Viral clearance occurred more often in nonblacks (adjusted odds ratio [OR], 5.15; 95% confidence interval [CI], 2.60-10.17) and those not infected with human immunodeficiency virus (HIV) (adjusted OR, 2.19; 95% CI, 1.26-3.47). Forty cases of ESLD were observed throughout follow-up (incidence, 3.1 per 1000 person-years). In a multivariate model, risk of ESLD was higher for persons aged 38 years or older at enrollment (adjusted relative incidence, 3.67; 95% CI, 1.96-6.88) and who reported ingestion of more than 260 g of alcohol per week (adjusted relative incidence, 3.60; 95% CI, 1.73-7.52). Of 210 patients without ESLD randomly selected for biopsy, only 2 had cirrhosis.Our results indicate that although HCV infection can be self-limited or associated with ESLD, the majority of adults have persistent viremia without clinically demonstrable liver disease. Further research is needed to explain the less frequent clearance of HCV infection among black persons and to improve utilization of treatment for those infected in the context of injection drug use. JAMA. 2000;284:450-456
Social anxiety disorder
Authors: F. R Schneier
Journal: BMJ (2003)

Is common, underdiagnosed, impairing, and treatable 

The hallmark of social anxiety disorder is extreme and persistent fear of embarrassment and humiliation.1 People with this condition (which is also known as social phobia) often avoid participating in social and public activities, such as public speaking, social gatherings, or meetings. Whereas normative social anxiety may serve to focus attention and prevent inappropriate behaviour, the intense symptoms of social anxiety disorder, by definition, interfere with functioning or cause marked distress.

Differentiation of social anxiety disorder from other phobic disorders was first validated by its characteristic age of onset in the mid-teens and greater ratio of men to women.2 Although once believed to be uncommon, social anxiety disorder was found to be the third most prevalent psychiatric disorder in the US national comorbidity survey,3 and most studies in Europe and North America have found a 7-12% lifetime prevalence in the community and higher rates in primary care samples.4

Despite increasing recognition of social anxiety disorder as common, impairing, yet treatable, it often remains undiagnosed.4 …
The biphasic flow volume loop - A case report of post-tuberculosis left main bronchus (LMB) stricture
Authors: Adeline Teh, Carmen Tan, Chuen Peng Lee, Jessica Pau, Christopher Seet, Wee See Yap
Journal: European Respiratory Journal (2013)

Gascoigne et al. described the biphasic spirogram as a clue to unilateral narrowing of a mainstem bronchus in 1990. Sporadic case reports, have emerged since, in patients with endobronchial neoplasms with this characteristic pattern of flow volume loop. We present a case of LMB obstruction secondary to post-tuberculosis stricture with this biphasic spirogram. Miss L is a 38-year-old Chinese lady with a medical history of pulmonary tuberculosis in 2003. This was complicated by bronchiectasis and LMB stricture. She was referred to our institution in 2012. High resolution thoracic CT revealed an asymmetrical smaller calibre of left main bronchus, with short segment of tight stenosis immediately proximal to its bifurcation. Flexible bronchoscopy revealed a stenotic web at distal LMB, 3cm below main carina (Figure 1). Initial flow volume loop (Figure 2) was suggestive of a unilateral bronchial obstruction. She underwent rigid bronchoscopy and Nd-YAG laser resection of webbed stricture at distal LMB (Figure 1). Flow volume loop and flexible bronchoscopy post-procedure (Figure 2) showed improvement in LMB obstruction.
Estrogen Plus Progestin and the Risk of Peripheral Arterial Disease
Authors: Judith Hsia, Michael H. Criqui, Rebecca J. Rodabough, Robert D. Langer, Helaine E. Resnick, Lawrence S. Phillips, Matthew Allison, Denise E. Bonds, Kamal Masaki, Panagiota Caralis, Jane M. Kotchen
Journal: Circulation (2004)

Observational studies have reported less frequent carotid atherosclerosis in healthy women taking postmenopausal hormone therapy. Estrogen with progestin did not reduce peripheral arterial events among women with preexisting coronary heart disease. This analysis evaluates clinical peripheral arterial disease among generally healthy women in the Women's Health Initiative randomized trial of estrogen plus progestin.The Estrogen Plus Progestin trial assigned 16 608 postmenopausal women, mean age 63.3+/-7.1 years, to daily conjugated estrogens (0.625 mg) with medroxyprogesterone acetate (2.5 mg) or placebo and documented health outcomes over an average of 5.6 years of follow-up. Hospitalization for peripheral arterial disease was infrequent, with annualized rates of 0.08%, 0.06%, and 0.02% for carotid disease, lower extremity arterial disease, and abdominal aortic aneurysm, respectively. The incidence of peripheral arterial events did not differ between treatment groups (hazard ratio [HR] 0.89, 95% confidence interval 0.63, 1.25). The risk was slightly greater among women assigned to active estrogen with progestin in years 1 (HR 1.33) and 2 (HR 1.27), and was slightly lower in later years (HR 0.85 and 0.87 in years 5 and > or =6). Among adherent participants, the hazard ratio for peripheral arterial events was 1.23 (95% confidence interval 0.79, 1.91) over the 5.6 years of follow up. Subgroup analysis identified no significant interactions between estrogen with progestin and baseline characteristics with regard to peripheral arterial disease risk.Among generally healthy postmenopausal women, conjugated estrogens with progestin did not confer protection against peripheral arterial disease.
Synthesis and release of B-lymphocyte stimulator from myeloid cells
Authors: Bernardetta Nardelli, Ornella Belvedere, Viktor Roschke, Paul A. Moore, Henrik S. Olsen, Thi Sau Migone, Svetlana Sosnovtseva, Jeffrey A. Carrell, Ping Feng, Judith G. Giri, David M. Hilbert
Journal: Blood (2001)
Pathogenetic Loop Between Diabetes and Cell Senescence
Authors: Roberto Testa, Antonio Ceriello
Journal: Diabetes Care (2007)

Cell senescence has recently been postulated as an important cause/consequence of type 2 diabetes and its complications. Cellular senescence is defined as a limited ability of human cells to divide, and it becomes evident through phenotypic changes in morphology, gene expression, and function (1). It has long been known that genomic instability, a hallmark of premature aging disorders such as in the Werner syndrome, is associated with type 2 diabetes (2), and, recently, great attention has been paid to the potential impact of vascular cellular senescence on diabetes by means of the study on endothelial progenitor cells (EPCs). EPCs were discovered in 1997. They are derived from bone marrow and are mobilized to the peripheral circulation in response to different stimuli. Defined as circulating immature cells that contribute to vascular homeostasis and compensatory angiogenesis (3), EPCs are able to regenerate injured endothelium, accelerate re-endothelization, and limit the formation of atherosclerotic lesions. Their identification has prompted an explosion of interest regarding their role in the pathogenesis of micro- and macrovascular diseases. Different studies have demonstrated that EPCs are …
Integrin αvβ6 critically regulates hepatic progenitor cell function and promotes ductular reaction, fibrosis, and tumorigenesis
Authors: Zhen‐Wei Peng, Naoki Ikenaga, Susan B. Liu, Deanna Y. Sverdlov, Kahini A. Vaid, Richa Dixit, Paul H. Weinreb, Shelia Violette, Dean Sheppard, Detlef Schuppan, Yury Popov
Journal: Hepatology (2015)

Integrin αvβ6 is rapidly up‐regulated on cells of epithelial lineage during tissue injury, where one of its primary functions is activation of latent transforming growth factor beta 1 (TGFβ1). In human liver cirrhosis, αvβ6 is overexpressed by cells comprising the ductular reaction, and its inhibition suppresses experimental biliary fibrosis in rodents. Here, we show that αvβ6 is expressed on the actively proliferating subset of hepatic progenitor cells and is required for their progenitor function in vivo and in vitro through integrin αvβ6‐dependent TGFβ1 activation. Freshly isolated αvβ6 + liver cells demonstrate clonogenic potential and differentiate into cholangiocytes and functional hepatocytes in vitro , whereas colony formation by epithelial cell adhesion molecule‐positive progenitor cells is blocked by αvβ6‐neutralizing antibody and in integrin beta 6‐deficient cells. Inhibition of progenitors by anti‐αvβ6 antibody is recapitulated by TGFβ1 neutralization and rescued by addition of bioactive TGFβ1. Genetic disruption or selective targeting of αvβ6 with 3G9 antibody potently inhibits progenitor cell responses in mouse models of chronic biliary injury and protects from liver fibrosis and tumorigenesis, two conditions clinically associated with exacerbated ductular reaction. Conclusion: These results suggest that αvβ6 is a promising target for chronic fibrotic liver diseases and associated cancers. (H epatology 2016;63:217–232)
Integrative “Omic” Analysis of Experimental Bacteremia Identifies a Metabolic Signature That Distinguishes Human Sepsis from Systemic Inflammatory Response Syndromes
Authors: Raymond J. Langley, Jennifer L. Tipper, Shannon Bruse, Rebecca M. Baron, Ephraim L. Tsalik, James Huntley, Angela J. Rogers, Richard J. Jaramillo, Denise O'Donnell, William M. Mega, Mignon Keaton, Elizabeth Kensicki, Lee Gazourian, Laura E. Fredenburgh, Anthony F. Massaro, Ronny M. Otero, Vance G. Fowler, Emanuel P. Rivers, Chris W. Woods, Stephen F. Kingsmore, Mohan L. Sopori, Mark A. Perrella, Augustine M. K. Choi, Kevin S. Harrod
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Sepsis is a leading cause of morbidity and mortality. Currently, early diagnosis and the progression of the disease are difficult to make. The integration of metabolomic and transcriptomic data in a primate model of sepsis may provide a novel molecular signature of clinical sepsis.
Clinics in neurology and neurosurgery–extradural and subdural haematoma
Authors: G Davis, D W Marion, P Le Roux, E R Laws, P McCrory
Journal: British Journal of Sports Medicine (2008)

Although concussion is the most common type of brain injury seen in athletes, there is always the possibility that head impact may cause a more severe structural brain injury. This is a complication that is feared by all sports physicians and others involved in athletic care.

Acute subdural haematoma (ASDH) results from traumatic laceration to the brain, from bleeding from the cortical vessels into the subdural space or from acceleration–deceleration injury to the head that causes tearing of the bridging veins, resulting in clot formation in the subdural space between the arachnoid and dural meningeal layers. A subdural haematoma is often associated with some underlying parenchymal (brain) injury, including diffuse axonal injury. In contrast, extradural haematoma usually results from a skull fracture causing damage to a meningeal artery, which is situated between the dura and the skull. Classically, there is no significant parenchymal injury in extradural haematoma.

Subdural and extradural haematomas are distinct clinical entities that share some common elements in sports medicine yet also have certain individual peculiarities that are important in return-to-sports decision making.

A 31-year-old professional boxer has won all 26 fights he has contested. He sustained a small subdural haematoma in a fight he won (fig 1). There was mild mass effect from the subdural haematoma, and it was observed with serial CT scans, without the requirement for surgical drainage. Spontaneous resolution of the subdural collection was noted on a repeat CT scan at 6 weeks. It is now 1 year later, and he has a normal neurological examination and formal neuropsychological testing is normal. The result of his brain MRI scan is also normal (including magnetic resonance venogram (MRV) and magnetic resonance angiogram (MRA) sequences).



Figure 1 
Case 1: axial CT brain scan showing a 1 cm-thick right subdural haematoma (arrow) with underlying cerebral swelling.



What are …