tbuckley/cabot-search huggingface dataset:
High Incidence of Poor Sulfoxidation in Patients with Primary Biliary Cirrhosis
Authors: Adesuwa B. Olomu, Christopher R. Vickers, Rosemary H. Waring, David Clements, Christopher Babbs, Thomas W. Warnes, Elwyn Elias
Journal: New England Journal of Medicine (1988)

An impaired sulfoxidation pathway has been implicated in the pathogenesis of chlorpromazine-induced hepatotoxicity. Since some patients with chronic chlorpromazine-induced cholestasis may have features of primary biliary cirrhosis, we studied the ability to sulfoxidate the amino acid analogue S-carboxymethyl-cysteine in 44 patients with primary biliary cirrhosis and in two control groups--one without liver disease and one with a variety of liver diseases other than primary biliary cirrhosis. Poor sulfoxidation was observed in 84 percent of the patients with primary biliary cirrhosis, as compared with 24 percent of patients with other liver diseases and 22 percent of normal controls (P less than 0.0005 for both comparisons). Poor sulfoxidation did not correlate with the degree of hyperbilirubinemia or histologic severity of liver disease in any of the groups studied. There was an inverse correlation with age only in the patients with primary biliary cirrhosis (r = -0.44, P less than 0.001). Liver transplantation was performed in six of the patients and improved sulfoxidation in five; in the four with primary biliary cirrhosis, sulfoxidation improved from poor to good or intermediate. We conclude that poor sulfoxidation is closely associated with primary biliary cirrhosis but not with the other liver diseases we studied.
High-Resolution DNA Copy Number Profiling of Malignant Peripheral Nerve Sheath Tumors Using Targeted Microarray-Based Comparative Genomic Hybridization
Authors: Kiran K. Mantripragada, Gillian Spurlock, Lan Kluwe, Nadia Chuzhanova, Rosalie E. Ferner, Ian M. Frayling, Jan P. Dumanski, Abhijit Guha, Victor Mautner, Meena Upadhyaya
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Neurofibromatosis type 1 (NF1) is an autosomal dominant condition that predisposes to benign and malignant tumors. The lifetime risk of a malignant peripheral nerve sheath tumor (MPNST) in NF1 is ∼10%. These tumors have a poor survival rate and their molecular basis remains unclear. We report the first comprehensive investigation of DNA copy number across multitude of genes in NF1 tumors using high-resolution array comparative genomic hybridization (CGH), with the aim to identify molecular signatures that delineate malignant from benign NF1 tumors. Experimental Design: We constructed an exon-level resolution microarray encompassing 57 selected genes and profiled DNA from 35 MPNSTs, 16 plexiform, and 8 dermal neurofibromas. Bioinformatic analysis was done on array CGH data to identify concurrent aberrations in malignant tumors. Results: The array CGH profiles of MPNSTs and neurofibromas were markedly different. A number of MPNST-specific alterations were identified, including amplifications of ITGB4, PDGFRA, MET, TP73, and HGF plus deletions in NF1, HMMR/RHAMM, MMP13, L1CAM2, p16INK4A/CDKN2A, and TP53. Copy number changes of HMMR/RHAMM, MMP13, p16INK4A/CDKN2A, and ITGB4 were observed in 46%, 43%, 39%, and 32%, respectively of the malignant tumors, implicating these genes in MPNST pathogenesis. Concomitant amplifications of HGF, MET, and PDGFRA genes were also revealed in MPNSTs, suggesting the putative role of p70S6K pathway in NF1 tumor progression. Conclusions: This study highlights the potential of array CGH in identifying novel diagnostic markers for MPNSTs.
Complications of Intrathoracic Surgery
Authors: Alan T. Marty
Journal: JAMA (1980)

Some complications occur mysteriously. And all too often, we explain them unscientifically or blame them on the patient's disease process. This book adds solid weight to more objective insights about such phenomena. It does so by first seeking experimental evidence. In regard to coronary ostial stenosis after aortic valve replacement, for instance, we find that merely controlling perfusion pressure does not prevent the problem. (Experimental arterial distension alone, created by oversized perfusion cannulas, more likely induces these obstructive lesions.) The book then emphasizes preventive measures, reviews the literature, and presents clinical results with various management techniques, including those that have proved unsuccessful. While previous books have focused on surgical complications, this is the first one to dwell on cardiothoracic surgery. Until now, any such text was doomed to outdate prematurely— largely because the cardiac surgical materials and techniques that created the problems were annually being modified. It has taken this
Cellular FLICE-Inhibitory Protein Down-regulation Contributes to Celecoxib-Induced Apoptosis in Human Lung Cancer Cells
Authors: Xiangguo Liu, Ping Yue, Axel H. Schönthal, Fadlo R. Khuri, Shi-Yong Sun
Journal: Cancer Research (2006)

Abstract The cyclooxygenase-2 (COX-2) inhibitor celecoxib is an approved drug in the clinic for colon cancer chemoprevention and has been tested for its chemopreventive and therapeutic efficacy in various clinical trials. Celecoxib induces apoptosis in a variety of human cancer cells including lung cancer cells. Our previous work has shown that celecoxib induces death receptor 5 expression, resulting in induction of apoptosis and enhancement of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–induced apoptosis in human lung cancer cells. In the current study, we further show that celecoxib down-regulated the expression of cellular FLICE-inhibitory protein (c-FLIP), a major negative regulator of the death receptor–mediated extrinsic apoptotic pathway, through a ubiquitin/proteasome–dependent mechanism independent of COX-2 in human lung cancer cells. Overexpression of c-FLIP, particularly FLIPL, inhibited not only celecoxib-induced apoptosis but also apoptosis induced by the combination of celecoxib and TRAIL. These results thus indicate that c-FLIP down-regulation also contributes to celecoxib-induced apoptosis and enhancement of TRAIL-induced apoptosis, which complements our previous finding that the extrinsic apoptotic pathway plays a critical role in celecoxib-induced apoptosis in human lung cancer cells. Collectively, we conclude that celecoxib induces apoptosis in human lung cancer cells through activation of the extrinsic apoptotic pathway, primarily by induction of death receptor 5 and down-regulation of c-FLIP. (Cancer Res 2006; 66(23): 11115-9)
Hidden Formaldehyde in E-Cigarette Aerosols
Authors: R Paul Jensen, Wentai Luo, James F Pankow, Robert M Strongin, David H Peyton
Journal: New England Journal of Medicine (2015)

This letter reports a chemical analysis of vapor from electronic cigarettes that shows high levels of formaldehyde, a known carcinogen. The authors project that the associated incremental lifetime risk of cancer could be higher than that from long-term smoking.
Pharmaceutical Industry Commission, Government Agencies Seek to Expedite New Addiction Therapy
Authors: Charles Marwick
Journal: JAMA (1991)

THE PHARMACEUTICAL industry has formed an eight-member Commission on Medicine for Treating Drug Dependence and Abuse to work with government agencies in expediting promising pharmacologic approaches to the treatment of addiction. It is chaired by Harry M. Meyer, Jr, MD, president, Medical Research Division, American Cyanamid Company, Wayne, NJ. Frederick K. Goodwin, MD, administrator, Alcohol, Drug Abuse, and Mental Health Administration, Rockville, Md, points to what he calls "a virtual explosion of knowledge" in the understanding of neurochemical mechanisms of behavior. What has been called the psychopharmacological revolution "permits us to target therapeutic compounds with ever-increasing specificity," he says. "We have advanced from relying on the observations of drug effects on a particular condition to a capacity to rationally design compounds that will redress the specific neurochemical deficiencies associated with illnesses such as addiction," Goodwin says. The commission's goals, as Goodwin sees them, are to discover possibly effective agents that
[385] LIVER FIBROSIS REVERSION STRATEGY USING ad-MMP8 AND ad-uPA ADENOVIRAL VECTORS
Authors: J.T. Garcia-Banuelos, F.J. Galvez-Gastelum, L. Ruiz-Corro, A. Segura, J. Gonzalez-Cuevas, J. Armendariz-Borunda
Journal: Journal of Hepatology (2007)
The role of ATP and purinergic-receptor- signalling in the pathogenesis of ALI/ARDS
Authors: Sanja Cicko, Korcan Ayata, Kristin Baudiss, Andreas Zech, Marco Idzko
Journal: European Respiratory Journal (2013)

Background: This study examined the role of extracellular ATP in recruiting inflammatory cells to the lung after induction of injury with lipopolysaccharide (LPS). Extracellular ATP serves as a danger signal to alert the immune system of tissue damage by acting on P2X or P2Y receptors. Acute lung injury (ALI) is characterized by rapid alveolar injury inflammation, cytokine induction, neutrophils accumulation and vascular leakage leading to lung oedema. Here we show that endogenous pulmonary ATP levels are increased in a mouse model of acute lung injury (ALI). ATP neutralization or specific/unspecific P2R-blockade markedly reduced LPS-induced lung injury.  Aims: Investigate if extracellular ATP plays a role in the LPS mediated inflammation  Methods and Results: To address this hypothesis, we used a murine model of LPS-induced ALI. These studies revealed that intrapulmonary application of ATP/ADP hydrolyzing enzyme apyrase or specific/unspecific P2R-Antagonists prior (prophylactic) or 24 hours after (therapeutic) LPS instillation decreased neutrophil trafficking into the lungs, pro-inflammatory cytokines levels in bronchoalveolar lavage fluid.  Conclusion: Finally we can show that apyrase or antagonists can reduce and prevent LPS induced lung inflammation. This is a projection of a new therapeutical form, what can fully develop.
Dinucleotide repeat polymorphism of matrix metalloproteinase-9 gene is associated with diabetic nephropathy
Authors: Shiro Maeda, Masakazu Haneda, Baoliang Guo, Daisuke Koya, Kazuyuki Hayashi, Toshiro Sugimoto, Keiji Isshiki, Hitoshi Yasuda, Atsunori Kashiwagi, Ryuichi Kikkawa
Journal: Kidney International (2001)
Central Airways Behave More Stiffly during Forced Expiration in Patients with Asthma
Authors: HEIN J. L. BRACKEL, OLE F. PEDERSEN, PAUL G. H. MULDER, SHELLEY E. OVERBEEK, KAREL F. KERREBIJN, JAN M. BOGAARD
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Chronic inflammation and extracellular remodeling of the airway wall characterize asthma. The purpose of this study was to examine whether these features cause a change in airway mechanical properties. We examined 14 healthy and 10 young adults with long-lasting asthma, the latter treated with inhaled bronchodilators and corticosteroids. To obtain area-versus-transmural pressure (A–Ptm) curves during forced expiration (Pedersen, O. F., et al. J. Appl. Physiol. 1982;52:357–369), we used an esophageal balloon and a Pitot static probe positioned at five locations between the right lower lobe and midtrachea. Cross-sectional area (A), airway compliance (Caw = dA/dPtm), and specific airway compliance (sCaw = Caw/A) were obtained from the A–Ptm curves. Results showed that: (1) A was larger in males than in females; (2) Caw and sCaw decreased with a more downstream position; and (3) Caw and sCaw were significantly lower in the patients with asthma, with the differences between the asthmatic patients and the healthy subjects becoming smaller toward the trachea. The lower Caw and sCaw in the patients with long-lasting asthma support the concept that chronic inflammation and remodeling of the airway wall may result in stiffer dynamic elastic properties of the asthmatic airway.
Lump in the Stomach
Authors: Imre M. Sandor
Journal: JAMA (1973)

<h3>To the Editor.—</h3> Over the years, I have encountered several patients with the presenting complaint of "lump in the stomach." All of these patients were young males and all of them vacillated for several months before seeking advice. They were very concerned, tense, and obviously foremost in their minds was the possibility of cancer. The objective finding was that of a normal palpable xiphoid process. I wonder how frequent this phenomenon might be in other physicians' experience? If the condition is unnamed, the term "xiphoidophobia" might be appropriate.
Role of imbalance of eicosanoid pathways and staphylococcal superantigens in chronic rhinosinusitis
Authors: R. Pezato, M. Świerczyńska‐Krępa, E. Niżankowska‐Mogilnicka, L. Derycke, C. Bachert, C. A. Pérez‐Novo
Journal: Allergy (2012)

Abstract Chronic rhinosinusitis ( CRS ) is a multifactorial disease of the upper airways with a high prevalence (approximately 11%) in the general population. Different immune and inflammatory mechanisms are involved in its pathogenesis. Alterations in the arachidonic acid pathway (leading to an imbalanced production of eicosanoids) have been linked to the pathophysiology of different diseases especially nasal polyposis, asthma, and aspirin‐exacerbated respiratory disease. Furthermore, viral and bacterial infections have been identified as important factors amplifying the pro‐inflammatory reactions in these pathologies. This review summarizes the impact of an imbalance in the eicosanoid pathway and the effect of S taphylococcus aureus enterotoxins on the regulation of the pro‐inflammatory network in CRS and their translation into disease severity.
The Capsids of HIV-1 and HIV-2 Determine Immune Detection of the Viral cDNA by the Innate Sensor cGAS in Dendritic Cells
Authors: Xavier Lahaye, Takeshi Satoh, Matteo Gentili, Silvia Cerboni, Cécile Conrad, Ilse Hurbain, Ahmed El Marjou, Christine Lacabaratz, Jean-Daniel Lelièvre, Nicolas Manel
Journal: Immunity (2013)
A Noninvasive System for Monitoring Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors with Plasma DNA
Authors: Tomomi Nakamura, Naoko Sueoka-Aragane, Kentaro Iwanaga, Akemi Sato, Kazutoshi Komiya, Tomonori Abe, Norio Ureshino, Shinichiro Hayashi, Toshiya Hosomi, Mitsuharu Hirai, Eisaburo Sueoka, Shinya Kimura
Journal: Journal of Thoracic Oncology (2011)
The safety of intravenous dipyridamole thallium myocardial perfusion imaging. Intravenous Dipyridamole Thallium Imaging Study Group.
Authors: A Ranhosky, J Kempthorne-Rawson
Journal: Circulation (1990)

Clinical data on 3,911 patients were collected from 64 individual investigators to evaluate the safety of intravenous dipyridamole-thallium imaging as an alternative to exercise thallium imaging for the evaluation of coronary artery disease. There were two deaths because of myocardial infarctions, two nonfatal myocardial infarctions, and six cases of acute bronchospasm. Chest pain occurred in 770 patients (19.7%). Headache and dizziness were reported by 476 patients (12.2%) and 460 patients (11.8%), respectively. ST-T changes on the electrocardiogram were seen in 292 patients (7.5%). Use of parenteral aminophylline to treat adverse events associated with intravenous dipyridamole brought complete relief of symptoms in 439 of 454 patients (96.7%). There is a potential for increased risk for serious ischemic events in patients with a history of unstable angina who are administered intravenous dipyridamole. In patients with acutely unstable angina (i.e., continuing chest pain) or in the acute phase of myocardial infarction, use of intravenous dipyridamole in thallium scintigraphy should be avoided. There is also an increased risk for bronchospasm in patients with a history of asthma; acute bronchospasm can be relieved immediately by administration of aminophylline. These results demonstrate that intravenous dipyridamole-thallium scintigraphy is a relatively safe, noninvasive technique for the evaluation of coronary artery disease.
Rx of Bladder Cancer: Complex and Controversial
Authors: M. Bagshaw, W. L. Caldwell, H. Grabstald, M. Wizenberg
Journal: CA A Cancer Journal for Clinicians (1973)

Rxof BladderCancer: ComplexandControversialComplex decisions regarding the choice of treatment for the patient with bladder cancer may pose many often controversial questions.On what criteria is this choice best made?What is the role of combined preoperative irradiation and surgery?How are the complications of high dose irradiation best managed and prevented?Is chemotherapy of value in the treatment of bladder cancer?In the following series of questions and answers, these and other practical questions are discussed by some outstanding specialists in the field, including:
Glucocorticoid-remediable Aldosteronism in a Large Kindred: Clinical Spectrum and Diagnosis Using a Characteristic Biochemical Phenotype
Authors: Glenn M. Rich, Stanley Ulick, Sandra Cook, Jennifer Z. Wang, Richard P. Lifton, Robert G. Dluhy
Journal: Annals of Internal Medicine (1992)

▪ Objective: To define the clinical spectrum of glucocorticoid-remediable aldosteronism (GRA) in a large kindred. ▪ Design: Screening all at-risk relatives of a proband for GRA using a specific biochemical phenotype and collecting of medical histories of kindred members from five generations. ▪ Setting: Outpatient General Clinical Research Centers and patients' homes. ▪ Measurements: Screening was done while patients were on a self-selected diet and included blood pressure determinations; serum potassium and plasma renin activity and aldosterone measurements; and 24-hour urinary tetrahydroaldosterone, 18-oxotetrahydrocortisol, and 18-hydroxycortisol measurements. ▪ Results: Diagnosis of GRA was established on the basis of a previously described specific biochemical abnormality, overproduction of the cortisol C-18 oxidation products (18-oxotetrahydrocortisol and 18-hydroxycortisol) in urine and their ratio relative to tetrahydroaldosterone. Glucocorticoid-remediable aldosteronism was diagnosed in 11 additional patients spanning three generations; this group included the youngest patient (3 months old) ever diagnosed with GRA. Complete penetrance of the biochemical abnormality is likely, with 11 of 18 at-risk patients displaying the phenotype. All patients with GRA had elevated blood pressure. Affected adult patients had been diagnosed as hypertensive before reaching 21 years of age (n = 7 mean, 16.1 ± 3.4 years). All affected patients were normokalemic (4.3 ± 0.3 mmol/L). ▪ Conclusion: Hypertension is a characteristic feature of GRA. Elevated blood pressure in this kindred developed at an early age and often was severe. Because a normal potassium level does not exclude the diagnosis of GRA, the disorder may be underdiagnosed. The value of a specific cortisol C-18 oxidation phenotype in the diagnosis of GRA has been confirmed.
A Vital Rationalist: Selected Writings From Georges Canguilhem
Authors: David Michael Levin
Journal: JAMA (1994)

Georges Canguilhem, born in 1904, is still not as well known outside France as his most illustrious student, Michel Foucault, yet he is without doubt one of France's two most important philosophers of science (the other is Gaston Bachelard, his teacher). His contributions, in particular, to the history and theory of medicine and biology are equalled only, perhaps, by those of Henry Sigerist. This book is a carefully edited selection of texts, mostly drawn from<i>The Normal and the Pathological</i>(1950, 1966),<i>La Connaissance de la Vie</i>(1952),<i>La Formation du Concept de Reflexe aux XVIIe et XVIIIe Siècles</i>(1955),<i>Études d'Histoire et de Philosophie des Sciences</i>(1968), and<i>Ideology and Rationality in the History of the Life Sciences</i>(1977); but it also includes a number of other writings, important journal studies translated here for the first time. Part 1 of the book takes up questions of methodology relevant to
Points: Needs and opportunities in rehabilitation
Authors: R S Ramaiah
Journal: BMJ (1985)

reiterated my comment' on the treatment of cysticercosis with metriphonate and by means of radioimmunotherapy.Some other advances should be mentioned.In addition to praziquantel2-4 the anthelmninthic flubendazole has recently been used in the management of neurocysticercosis, with apparent success.5 Injection of quinine sulphate in distilled water into subcutaneous cysticerci has also been reported to destroy the bladderworms, thus obviating the need for their surgical excision.6
Attitudes towards screening for lung cancer among smokers and their non-smoking counterparts
Authors: G. A Silvestri, P. J Nietert, J. Zoller, C. Carter, D. Bradford
Journal: Thorax (2006)

<b>Background:</b> There has been resurgence of interest in lung cancer screening using low-dose computed tomography. The implications of directing a screening programme at smokers has been little explored. <b>Methods:</b> A nationwide telephone survey was conducted. Demographics, certain clinical characteristics and attitudes about screening for lung cancer were ascertained. Responses of current, former and never smokers were compared. <b>Results:</b> 2001 people from the US were interviewed. Smokers were significantly (p&lt;0.05) more likely than never smokers to be male, non-white, less educated, and to report poor health status or having had cancer, and less likely to be able to identify a usual source of healthcare. Compared with never smokers, current smokers were less likely to believe that early detection would result in a good chance of survival (p&lt;0.05). Smokers were less likely to be willing to consider computed tomography screening for lung cancer (71.2% (current smokers) <i>v</i> 87.6% (never smokers) odds ratio (OR) 0.48; 95% confidence interval (CI) 0.32 to 0.71). More never smokers as opposed to current smokers believed that the risk of disease (88% <i>v</i> 56%) and the accuracy of the test (92% <i>v</i> 71%) were important determinants in deciding whether to be screened (p&lt;0.05). Only half of the current smokers would opt for surgery for a screen-diagnosed cancer. <b>Conclusion:</b> The findings suggest that there may be substantial obstacles to the successful implementation of a mass-screening programme for lung cancer that will target cigarette smokers.
A Feasibility Study of Postoperative Adjuvant Therapy of Carboplatin and Weekly Paclitaxel for Completely Resected Non-small Cell Lung Cancer
Authors: Yoshinori Yamashita, Kazuhiko Kataoka, Teruyoshi Ishida, Motoki Matsuura, Noritomo Seno, Hidenori Mukaida, Eiji Miyahara, Yoshihiro Miyata, Riki Okita, Katsuhiko Shimizu, Masanobu Watari, Tsuneo Okumichi, Morihito Okada
Journal: Journal of Thoracic Oncology (2008)
The History of Middlesex North District Medical Society 1844–1944
Authors: Archibald R. Gardner
Journal: New England Journal of Medicine (1945)

CONDENSATION of time and space is one of the important characteristics of this civilization, and, as this is the centennial anniversary of our local society, an attempt will be made to condense one hundred years of its growth within the short time allotted. The great historian Livy complained of the scant records of the early history of Rome, but that was not my difficulty in this case. My problem was to select from the abundance of records some topics that might be of interest to you. Most of us like people better than dates, which is indeed an essential trait . . .