tbuckley/cabot-search huggingface dataset:
Lung Cancer Screening: Ready for Prime Time?
Authors: J. Peres
Journal: JNCI Journal of the National Cancer Institute (2010)

ews from the National Lung Screening Trial (NLST) in November made headlines worldwide: A screening program had succeeded in cutting deaths from the world's most lethal cancer by 20%.In this randomized, controlled trial, 54,000 current or former heavy smokers aged 55 -74 years received either chest X-rays or low-dose helical computed tomography (CT) scans in an attempt to detect lung cancer early enough to reduce mortality.An estimated 222,520 cases of lung cancer will be diagnosed in the United States this year, and 157,399 people are expected to die of the disease -more than will die of breast, colon, and prostate cancer combined.The ramifi cations of a screening program that could make a dent in that number could hardly be overestimated."The fi nding is incredibly encouraging," said Claudine Isaacs, M.D., principal investigator of the NLST at Georgetown Lombardi Comprehensive Cancer Center, which enrolled 1,800 patients in the trial."It's very impressive, especially given a malignancy for which our treatments are not all that effective."Several previous trials comparing chest X-rays to no screening failed to reduce deaths from lung cancer, although they greatly increased the number of small tumors detected.(The NLST confi rmed that there is no benefi t to screening with chest X-rays.)More recent studies, such as the Early Lung Cancer Action Project (ELCAP), have suggested a benefi t to helical, or spiral, CT screening, which can detect much smaller tumors than can X-rays.But they were not controlled trials.This was the fi rst prospective, randomized trial of the screening method.
Assessing the risk of hypoxia in flight: the need for more rational guidelines
Authors: RK Coker, MR Partridge
Journal: European Respiratory Journal (2000)

This study aimed to test the hypothesis that advice currently given by respiratory physicians to potentially hypoxic patients planning air travel varies and is not evidence-based. A prospective observational study was performed, surveying respiratory physicians in England and Wales. Sixty-two per cent responded. Nearly two-thirds worked in district general hospitals, a quarter in university hospitals, and the rest in tertiary referral (specialist) centres or a combination thereof. Most provide advice routinely; most of the remainder do on request or if concerned. Assessments comprise spirometry, blood gas level measurement, oximetry, predictive equations and hypoxic challenge tests. Twenty-five per cent of physicians measuring blood gas levels recommend in-flight oxygen when arterial oxygen tension (Pa,O2) &lt;7.3 kPa, 50% when Pa,O2 is 7.3-8.0 kPa. Over two-thirds using spirometry recommend oxygen when the forced expiratory volume in one second &lt;40% of the predicted value. Half recommend oxygen when arterial oxygen saturation (Sa,O2) &lt;90%, 33% when Sa,O2 is 90-94%. Fewer than 10% of district hospital physicians (and none in other hospitals) use predictive equations. More than half of specialists but fewer than 10% of district hospital physicians perform hypoxic challenge tests. The risk of hypoxia at altitude is recognized by most respiratory physicians in England and Wales, but assessment methods and criteria for recommending oxygen vary widely. This suggests that most current advice is not evidence-based. Evidence-based guidelines are required.
Catheter Ablation of Cardiac Autonomic Nerves for Prevention of Vagal Atrial Fibrillation
Authors: Patrick Schauerte, Benjamin J. Scherlag, Jan Pitha, Michael A. Scherlag, Dwight Reynolds, Ralph Lazzara, Warren M. Jackman
Journal: Circulation (2000)

Vagal stimulation shortens the atrial effective refractory period (AERP) and maintains atrial fibrillation (AF). This study investigated whether the parasympathetic pathways that innervate the atria can be identified and ablated by use of transvenous catheter stimulation and radiofrequency current catheter ablation (RFCA) techniques.In 11 dogs, AERPs were determined at 7 atrial sites during bilateral cervical vagal nerve stimulation (VNS) and electrical stimulation of the third fat pad (20 Hz) in the right pulmonary artery (RPA). VNS shortened the AERP at all sites (from 123+/-4 to 39+/-4 ms, P<0.001) and increased the covariance of AERP (COV-AERP) (from 9+/-3% to 27+/-13%, P<0.001). RPA stimulation shortened the AERP at all sites from 123+/-4 to 66+/-13 ms (P<0.001) and increased the COV-AERP from 9+/-3% to 30+/-12% (P<0.001). In 7 dogs, transvascular RFCA of the parasympathetic pathways along the RPA was performed, and in 3 dogs, additional RFCA of parasympathetic fibers along the inferior (n=2) or superior (n=1) vena cava was performed. RFCA blunted the AERP shortening at all sites during VNS (114+/-4 ms after RFCA), abolished the increase of COV-AERP during VNS (12+/-7% after RFCA), and led to an increase of the baseline AERP (123+/-4 ms before versus 127+/-3 ms after RFCA, P=0.002). Before RFCA, AF could be induced and maintained as long as VNS was continued, whereas after RFCA, AF was no longer inducible during VNS.-Transvascular atrial parasympathetic nerve system modification by RFCA abolishes vagally mediated AF. This antifibrillatory procedure may provide a foundation for investigating the usefulness of neural ablation in chronic animal models of AF and eventually in patients with AF and high vagal tone.
Association of Intrauterine Exposure to Maternal Diabetes and Obesity With Type 2 Diabetes in Youth
Authors: Dana Dabelea, Elizabeth J. Mayer-Davis, Archana P. Lamichhane, Ralph B. D'Agostino, Angela D. Liese, Kendra S. Vehik, K.M. Venkat Narayan, Phillip Zeitler, Richard F. Hamman
Journal: Diabetes Care (2008)

OBJECTIVE—Limited data exist on the association between in utero exposure to maternal diabetes and obesity and type 2 diabetes in diverse youth. These associations were explored in African-American, Hispanic, and non-Hispanic white youth participating in the SEARCH Case-Control Study. RESEARCH DESIGN AND METHODS—A total of 79 youth with type 2 diabetes and 190 nondiabetic control youth aged 10–22 years attended a research visit. In utero exposures to maternal diabetes and obesity were recalled by biological mothers. RESULTS—Youth with type 2 diabetes were more likely to have been exposed to maternal diabetes or obesity in utero than were nondiabetic control youth (P &amp;lt; 0.0001 for each). After adjusting for offspring age, sex, and race/ethnicity, exposure to maternal diabetes (odds ratio [OR] 5.7 [95% CI 2.4–13.4]) and exposure to maternal obesity (2.8 [1.5–5.2]) were independently associated with type 2 diabetes. Adjustment for other perinatal and socioeconomic factors did not alter these associations. When offspring BMI was added, the OR for the association between in utero exposure to obesity and type 2 diabetes was attenuated toward the null (OR 1.1 [0.5–2.4]). Overall, 47.2% (95% CI 30.9–63.5) of type 2 diabetes in youth could be attributed to intrauterine exposure to maternal diabetes and obesity. CONCLUSIONS—Intrauterine exposures to maternal diabetes and obesity are strongly associated with type 2 diabetes in youth. Prevention efforts may need to target, in addition to childhood obesity, the increasing number of pregnancies complicated by obesity and diabetes.
Direct evidence for a stimulatory effect of hyperglycemia per se on peripheral glucose disposal in type II diabetes.
Authors: B Capaldo, D Santoro, G Riccardi, N Perrotti, L Saccà
Journal: Journal of Clinical Investigation (1986)

The effect of hyperglycemia per se on glucose uptake by muscle tissue was quantitated in six controls and six type II diabetics by the forearm technique, under conditions of insulin deficiency induced by somatostatin (SRIF) infusion (0.7 mg/h). Blood glucose concentration was clamped at its basal value during the first 60 min of SRIF infusion and then raised to approximately 200 mg/dl by a variable glucose infusion. Plasma insulin levels remained at or below 5 microU/ml during SRIF infusion, including the hyperglycemic period. No appreciable difference between controls and diabetics was present in the basal state as to forearm glucose metabolism. After 60 min of SRIF infusion and euglycemia, forearm glucose uptake fell consistently from 2.1 +/- 0.7 mg X liter-1 X min-1 to 1.0 +/- 0.6 (P less than 0.05) and from 1.7 +/- .2 to 0.4 +/- 0.3 (P less than 0.02) in the control and diabetic groups, respectively. The subsequent induction of hyperglycemia caused a marked increase in both the arterial-deep venous blood glucose difference (P less than 0.02-0.01) and forearm glucose uptake (P less than 0.01-0.005). However, the response in the diabetic group was significantly greater than that observed in controls. The incremental area of forearm glucose uptake was 276 +/- 31 mg X liter-1 X 90 min and 532 +/- 81 in the control and diabetic groups, respectively (P less than 0.02). In the basal state, the forearm released lactate and alanine both in controls and diabetic subjects at comparable rates. No increment was observed after hyperglycemia, despite the elevated rates of glucose uptake. It is concluded that (1) hyperglycemia per se stimulates forearm glucose disposal to a greater extent in type II diabetics than in normal subjects; and (2) the resulting increment of glucose disposal does not accelerate the forearm release of three carbon compounds. The data support the hypothesis that hyperglycemia per se may play a compensatory role for the defective glucose disposal in type II diabetes.
Covarion Shifts Cause a Long-Branch Attraction Artifact That Unites Microsporidia and Archaebacteria in EF-1α Phylogenies
Authors: Yuji Inagaki, Edward Susko, Naomi M. Fast, Andrew J. Roger
Journal: Molecular Biology and Evolution (2004)

Microsporidia branch at the base of eukaryotic phylogenies inferred from translation elongation factor 1alpha (EF-1alpha) sequences. Because these parasitic eukaryotes are fungi (or close relatives of fungi), it is widely accepted that fast-evolving microsporidian sequences are artifactually "attracted" to the long branch leading to the archaebacterial (outgroup) sequences ("long-branch attraction," or "LBA"). However, no previous studies have explicitly determined the reason(s) why the artifactual allegiance of microsporidia and archaebacteria ("M + A") is recovered by all phylogenetic methods, including maximum likelihood, a method that is supposed to be resistant to classical LBA. Here we show that the M + A affinity can be attributed to those alignment sites associated with large differences in evolutionary site rates between the eukaryotic and archaebacterial subtrees. Therefore, failure to model the significant evolutionary rate distribution differences (covarion shifts) between the ingroup and outgroup sequences is apparently responsible for the artifactual basal position of microsporidia in phylogenetic analyses of EF-1alpha sequences. Currently, no evolutionary model that accounts for discrete changes in the site rate distribution on particular branches is available for either protein or nucleotide level phylogenetic analysis, so the same artifacts may affect many other "deep" phylogenies. Furthermore, given the relative similarity of the site rate patterns of microsporidian and archaebacterial EF-1alpha proteins ("parallel site rate variation"), we suggest that the microsporidian orthologs may have lost some eukaryotic EF-1alpha-specific nontranslational functions, exemplifying the extreme degree of reduction in this parasitic lineage.
Academic Performance of Psychiatrists Compared to Other Specialists Before, During, and After Medical School
Authors: Frederick S. Sierles, Michael J. Vergare, Mohammadreza Hojat, Joseph S. Gonnella
Journal: American Journal of Psychiatry (2004)

This study was designed to compare psychiatrists with other physicians on measures of academic performance before, during, and after medical school.More than three decades of data for graduates of Jefferson Medical College (N=5,701) were analyzed. Those who pursued psychiatry were compared to physicians in seven other specialties on 18 performance measures. Analysis of covariance was used to control for gender effect.Compared to other physicians, psychiatrists scored higher on measures of verbal ability and general information before medical school and on evaluations of knowledge and skills in behavioral sciences during medical school, but they scored lower on United States Medical Licensing Examinations step 3.The results generally confirmed the authors' expectations about psychiatrists' academic performance. More attention should be paid to the general medical education of psychiatrists.
Prostaglandin synthesis by bovine mesenteric arteries and veins.
Authors: D A Terragno, K Crowshaw, N A Terragno, J C McGiff
Journal: Circulation Research (1975)

Prostaglandins (PG) were synthesized at similar rates by bovine mesenteric arteries and veins; viz., ca. 200 ng/g wet weight after one hour of incubation. After synthesis, PGE and PGF compounds were released from slices of arteries and veins into the incubating medium; PG were not detected in the walls of these blood vessels. Arachidonic acid, the precursor to PGE-2 and PGF-2-alpha, did not affect PG synthesis, whereas meclofenamate, an aspirin-like agent, decreased synthesis in arteries and veins by 90%. The PG biosynthetic capacity of these blood vessels is high, as indicated by greater than 20% conversion of (1-14C)-arachidonic acid to radiolabeled PG. Under control conditions in both arteries and veins, synthesis of PGE-2 exceeded that of PGF-2-alpha twofold. Bradykinin selectively increased the synthesis of a PGE-like substance in arteries and of a PGE-like substance in veins.
Colorectal cancers soon after colonoscopy: a pooled multicohort analysis
Authors: Douglas J Robertson, David A Lieberman, Sidney J Winawer, Dennis J Ahnen, John A Baron, Arthur Schatzkin, Amanda J Cross, Ann G Zauber, Timothy R Church, Peter Lance, E Robert Greenberg, María Elena Martínez
Journal: Gut (2013)

<h3>Objective</h3> Some individuals are diagnosed with colorectal cancer (CRC) despite recent colonoscopy. We examined individuals under colonoscopic surveillance for colonic adenomas to assess possible reasons for diagnosing cancer after a recent colonoscopy with complete removal of any identified polyps. <h3>Design</h3> Primary data were pooled from eight large (&gt;800 patients) North American studies in which participants with adenoma(s) had a baseline colonoscopy (with intent to remove all visualised lesions) and were followed with subsequent colonoscopy. We used an algorithm based on the time from previous colonoscopy and the presence, size and histology of adenomas detected at prior exam to assign interval cancers as likely being new, missed, incompletely resected (while previously an adenoma) or due to failed biopsy detection. <h3>Results</h3> 9167 participants (mean age 62) were included in the analyses, with a median follow-up of 47.2 months. Invasive cancer was diagnosed in 58 patients (0.6%) during follow-up (1.71 per 1000 person-years follow-up). Most cancers (78%) were early stage (I or II); however, 9 (16%) resulted in death from CRC. We classified 30 cancers (52%) as probable missed lesions, 11 (19%) as possibly related to incomplete resection of an earlier, non-invasive lesion and 14 (24%) as probable new lesions. The cancer diagnosis may have been delayed in three cases (5%) because of failed biopsy detection. <h3>Conclusions</h3> Despite recent colonoscopy with intent to remove all neoplasia, CRC will occasionally be diagnosed. These cancers primarily seem to represent lesions that were missed or incompletely removed at the prior colonoscopy and might be avoided by increased emphasis on identifying and completely removing all neoplastic lesions at colonoscopy.
Chronic Pain States: Pharmacological Strategies to Restore Diminished Inhibitory Spinal Pain Control
Authors: Hanns Ulrich Zeilhofer, Dietmar Benke, Gonzalo E. Yevenes
Journal: The Annual Review of Pharmacology and Toxicology (2011)

Potentially noxious stimuli are sensed by specialized nerve cells named nociceptors, which convey nociceptive signals from peripheral tissues to the central nervous system. The spinal dorsal horn and the trigeminal nucleus serve as first relay stations for incoming nociceptive signals. At these sites, nociceptor terminals contact a local neuronal network consisting of excitatory and inhibitory interneurons as well as of projection neurons. Blockade of neuronal inhibition in this network causes an increased sensitivity to noxious stimuli (hyperalgesia), painful sensations occurring after activation of non-nociceptive fibers (allodynia), and spontaneous pain felt in the absence of any sensory stimulation. It thus mimics the major characteristics of chronic pain states. Diminished inhibitory pain control in the spinal dorsal horn occurs naturally, e.g., through changes in the function of inhibitory neurotransmitter receptors or through altered chloride homeo-stasis in the course of inflammation or nerve damage. This review summarizes our current knowledge about endogenous mechanisms leading to diminished spinal pain control and discusses possible ways that could restore proper inhibition through facilitation of fast inhibitory neurotransmission.
Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity
Authors: Yiqi Guo, Magali Audry, Michael Ciancanelli, Laia Alsina, Joana Azevedo, Melina Herman, Esperanza Anguiano, Vanessa Sancho-Shimizu, Lazaro Lorenzo, Elodie Pauwels, Paul Bastard Philippe, Rebeca Pérez de Diego, Annabelle Cardon, Guillaume Vogt, Capucine Picard, Zafitsara Zo Andrianirina, Flore Rozenberg, Pierre Lebon, Sabine Plancoulaine, Marc Tardieu, Valérie Doireau, Emmanuelle Jouanguy, Damien Chaussabel, Frederic Geissmann, Laurent Abel, Jean-Laurent Casanova, Shen-Ying Zhang
Journal: The Journal of Experimental Medicine (2011)

Autosomal dominant TLR3 deficiency has been identified as a genetic etiology of childhood herpes simplex virus 1 (HSV-1) encephalitis (HSE). This defect is partial, as it results in impaired, but not abolished induction of IFN-β and -λ in fibroblasts in response to TLR3 stimulation. The apparently normal resistance of these patients to other infections, viral illnesses in particular, may thus result from residual TLR3 responses. We report here an autosomal recessive form of complete TLR3 deficiency in a young man who developed HSE in childhood but remained normally resistant to other infections. This patient is compound heterozygous for two loss-of-function TLR3 alleles, resulting in an absence of response to TLR3 activation by polyinosinic-polycytidylic acid (poly(I:C)) and related agonists in his fibroblasts. Moreover, upon infection of the patient’s fibroblasts with HSV-1, the impairment of IFN-β and -λ production resulted in high levels of viral replication and cell death. In contrast, the patient’s peripheral blood mononuclear cells responded normally to poly(I:C) and to all viruses tested, including HSV-1. Consistently, various TLR3-deficient leukocytes from the patient, including CD14+ and/or CD16+ monocytes, plasmacytoid dendritic cells, and in vitro derived monocyte-derived macrophages, responded normally to both poly(I:C) and HSV-1, with the induction of antiviral IFN production. These findings identify a new genetic etiology for childhood HSE, indicating that TLR3-mediated immunity is essential for protective immunity to HSV-1 in the central nervous system (CNS) during primary infection in childhood, in at least some patients. They also indicate that human TLR3 is largely redundant for responses to double-stranded RNA and HSV-1 in various leukocytes, probably accounting for the redundancy of TLR3 for host defense against viruses, including HSV-1, outside the CNS.
Polycystic Liver Disease: A Study of Cyst Fluid Constituents
Authors: Marcel Patterson, Juan C. Gonzalez-Vitale, Charles J. Fagan
Journal: Hepatology (1982)

Cyst fluid from a patient with polycystic liver disease was obtained by needle aspiration using ultrasound guidance. The constituents of the fluid resembled the "bile salt-independent" fraction of human bile and supports the hypothesis that such cysts are lined by a functioning, secretory bile duct epithelium.
Increased Expression of Transforming Growth Factor- β 1 in Small Airway Epithelium from Tobacco Smokers and Patients with Chronic Obstructive Pulmonary Disease (COPD)
Authors: HAJIME TAKIZAWA, MITSURU TANAKA, KAZUTAKA TAKAMI, TAKAYUKI OHTOSHI, KOJI ITO, MASARU SATOH, YASUMASA OKADA, FUMIHIRO YAMASAWA, KAZUHIKO NAKAHARA, AKIRA UMEDA
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Tobacco smoke is believed to cause small airway disease and then chronic obstructive pulmonary disease (COPD), but the molecular mechanisms by which small airway obstruction occurs remain unknown. To study the gene expression levels of transforming growth factor (TGF)-beta1, a potent fibrogenic factor, in small airway epithelium from smokers and patients with COPD, we harvested highly pure samples of epithelial cells from small airways under direct vision by using an ultrathin bronchofiberscope BF-2.7T (outer diameter 2.7 mm with a biopsy channel of 0.8 mm in diameter). The expression levels of TGF-beta1 were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). The mRNA levels of TGF-beta1 corrected by beta-actin transcripts were significantly higher in the smoking group and patients with COPD than those in nonsmokers (p < 0.01). Furthermore, among smokers and patients with COPD, TGF-beta1 mRNA levels correlated positively with the extent of smoking history (pack-years) and the degree of small airway obstruction as assessed by measurements of flow-volume curves. Immunocytochemistry of the cells demonstrated more intense stainings for TGF-beta1 in samples from smokers and patients with COPD than from nonsmokers. Spontaneously released immunoreactive TGF-beta1 levels from cultured epithelial cells were more elevated in subjects with a history of smoking and patients with COPD than in nonsmokers. Our study showed a close link between smoking and expression of TGF-beta1 in small airways. Our results also suggested that small airway epithelial cells might be involved in obstructive changes found in smokers and patients with COPD.
Measurement of FEF25-75% and FEF75% does not contribute to clinical decision making
Authors: Philip H. Quanjer, Daniel J. Weiner, Jeffrey J. Pretto, Danny J. Brazzale, Piotr W. Boros
Journal: European Respiratory Journal (2013)

The aim of this study was to determine the added value of measuring the forced expiratory flow at 25–75% of forced vital capacity (FVC) (FEF 25–75% ) and flow when 75% of FVC has been exhaled (FEF 75% ) over and above the measurement of the forced expiratory volume in 1 s (FEV 1 ), FVC and FEV 1 /FVC ratio. We used spirometric measurements of FEV 1 , FVC and FEF 25–75% from 11 654 white males and 11 113 white females, aged 3–94 years, routinely tested in the pulmonary function laboratories of four tertiary hospitals. FEF 75% was available in 8254 males and 7407 females. Predicted values and lower limits of normal, defined as the fifth percentile, were calculated for FEV 1 , FVC, FEV 1 /FVC ratio, FEF 25–75% and FEF 75% using prediction equations from the Global Lung Function Initiative. There was very little discordance in classifying test results. FEF 25–75% and FEF 75% were below the normal range in only 2.75% and 1.29% of cases, respectively, whereas FEV 1 , FVC and FEV 1 /FVC ratio were within normal limits. Airways obstruction went undetected by FEF 25–75% in 2.9% of cases and by FEF 75% in 12.3% of cases. Maximum mid-expiratory flow and flow towards the end of the forced expiratory manoeuvre do not contribute usefully to clinical decision making over and above information from FEV 1 , FVC and FEV 1 /FVC ratio.