tbuckley/cabot-search huggingface dataset:
Patterns of quantitative sensation testing of hypoesthesia and hyperalgesia are predictive of diabetic polyneuropathy: a study of three cohorts. Nerve growth factor study group.
Authors: P J Dyck, P J Dyck, T S Larson, P C O'Brien, J A Velosa
Journal: Diabetes Care (2000)

To test quantitative sensation testing (QST) patterns of hypoesthesia and hyperalgesia as indicators of diabetic polyneuropathy (DPN) and its severityWe used Computer-Assisted Sensory Examination IV; characterized the QST results of the foot of each patient in three diabetic cohorts (approximately 1,500 patients) as hyperesthetic (< or = 2.5th percentile), low-normal (2.5th-50th percentiles), high-normal (50th-97.5th percentiles), or hypoesthetic (> or = 97.5th percentile); and tested associations with symptoms, impairments, and test abnormalities.Overall neuropathic impairment was most severe in the pancreas-renal transplant and nerve growth factor cohorts, but it was much less severe in the population-based Rochester Diabetic Neuropathy Study (RDNS) cohort. The frequency distribution of sensory abnormalities mirrored this difference. When the QST spectra of diabetic cohorts were compared with those of the control subject cohort for vibration and cooling sensations, the only abnormality observed was hypoesthesia, which was expressed as an increased number of subjects with values at or above the 97.5th percentile or by an increased percentage of cases with high-normal values. Symptoms and impairments of DPN were significantly more frequent in the subjects with values at or above the 97.5th percentile than in the subjects whose values were between the 50th and 97.5th percentiles. For heat pain (HP) sensation thresholds (intermediate pain severity [HP:5], pain threshold [HP:0.5], and pain-stimulus response slope [HP:5-0.5]), an increased frequency of both hypoalgesia and hyperalgesia was observed (especially in the RDNS cohort). Steeper pain-stimulus response slopes were significantly associated with sensory symptoms, including severity of pain.1) Decreased vibratory sensation (hypoesthesia) appears to be characteristic of mild DPN, whereas panmodality hypoesthesia is characteristic of severe DPN. 2) A shift of vibratory and cold detection thresholds (and also of attributes of nerve conduction and a measure of autonomic dysfunction) from low-normal (2.5th-50th percentiles) to high-normal (50th-97.5th percentiles) appears to precede overt expression of DPN and to thereby provide evidence of subclinical abnormality 3) Heat stimulus-induced hyperesthesia (low thresholds) occurs especially in mild DPN, and, because it correlates with DPN symptoms and impairments, it must be attributed to hyperalgesia rather than to supersensitivity Therefore, hypoalgesia or hyperalgesia may be an indicator of early DPN.
Progressive development of a Th1-type hepatic cytokine profile in rats with experimental cholangitis
Authors: Kartika Tjandra, Keith A. Sharkey, Mark G. Swain
Journal: Hepatology (2000)

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are presumed autoimmune chronic cholestatic liver diseases characterized by cholangitis and progressive loss of bile ducts. Cytokines have been postulated to be involved in the progression of these diseases, but their role is poorly defined. Our objectives were to characterize a rat model of cholangitis and to determine Type 1/Type 2 (Th1/Th2) cytokine profile shifts in this model. Cholangitis was induced in Sprague-Dawley rats (200 to 225 g) by low-dose oral administration of the biliary toxin α-naphthylisothiocyanate (ANIT) (1 g/kg powdered rat chow ad libitum ) for 4, 7, and 14 days. Cholestasis was observed in ANIT-treated animals. Liver histology of ANIT-treated rats showed hepatic inflammation centered on damaged bile ducts, significant bile duct proliferation, and progressive fibrosis. Immunohistochemistry showed enhanced staining of hepatic major histocompatibility complex (MHC) II, CD4, and CD8 in portal areas of ANIT-treated animals. In addition, the hepatic cytokine profile became increasingly Th1 in nature with progressive ANIT treatment. In summary, experimental cholangitis biochemically and histologically mimics human chronic cholangitis and furthermore, is associated with a progressive shift to a more Th1-dominant hepatic cytokine profile. Therefore, this model may be useful for examining the role of cytokines in the progression of chronic cholangitic diseases.
Cholinesterase Inhibitors and Hospitalization for Bradycardia: A Population-Based Study
Authors: Laura Y. Park-Wyllie, Muhammad M. Mamdani, Ping Li, Sudeep S. Gill, Andreas Laupacis, David N. Juurlink
Journal: PLoS Medicine (2009)

Cholinesterase inhibitors are commonly used to treat dementia. These drugs enhance the effects of acetylcholine, and reports suggest they may precipitate bradycardia in some patients. We aimed to examine the association between use of cholinesterase inhibitors and hospitalization for bradycardia.We examined the health care records of more than 1.4 million older adults using a case-time-control design, allowing each individual to serve as his or her own control. Case patients were residents of Ontario, Canada, aged 67 y or older hospitalized for bradycardia between January 1, 2003 and March 31, 2008. Control patients (3:1) were not hospitalized for bradycardia, and were matched to the corresponding case on age, sex, and a disease risk index. All patients had received cholinesterase inhibitor therapy in the 9 mo preceding the index hospitalization. We identified 1,009 community-dwelling older persons hospitalized for bradycardia within 9 mo of using a cholinesterase inhibitor. Of these, 161 cases informed the matched analysis of discordant pairs. Of these, 17 (11%) required a pacemaker during hospitalization, and six (4%) died prior to discharge. After adjusting for temporal changes in drug utilization, hospitalization for bradycardia was associated with recent initiation of a cholinesterase inhibitor (adjusted odds ratio [OR] 2.13, 95% confidence interval [CI] 1.29-3.51). The risk was similar among individuals with pre-existing cardiac disease (adjusted OR 2.25, 95% CI 1.18-4.28) and those receiving negative chronotropic drugs (adjusted OR 2.34, 95% CI 1.16-4.71). We found no such association when we replicated the analysis using proton pump inhibitors as a neutral exposure. Despite hospitalization for bradycardia, more than half of the patients (78 of 138 cases [57%]) who survived to discharge subsequently resumed cholinesterase inhibitor therapy.Among older patients, initiation of cholinesterase inhibitor therapy was associated with a more than doubling of the risk of hospitalization for bradycardia. Resumption of therapy following discharge was common, suggesting that the cardiovascular toxicity of cholinesterase inhibitors is underappreciated by clinicians.
Swaddling and congenital dislocation of the hip.
Authors: M A Smith
Journal: BMJ (1978)

sort of figure that surgical results must be balanced.While late surgery in a younger person must take account of the risks of rebleeding in the very long term,3 this is obviously not so in the elderly, whose mean expectation of life is in any case limited.It is not valid to compare the treatment of an aneurysmal subarachnoid haemorrhage with that of a fractured hip, an intestinal obstruction, or a dissecting aneurysm in an old person.Patients with the latter conditions will die if left untreated.Most patients with a ruptured aneurysm who survive the first haemorrhage and the next few weeks will recover to resume a normal life without any surgical treatment.
Abstract A13: Hypoxia-inducible factor-1 (HIF-1) in myeloid cells promotes angiogenesis by regulating VEGF and S100A8 production
Authors: G-One Ahn, Young-Eun Kim, Beom-Ju Hong, Seoyeon Bok, Chan-Ju Lee, Hak Jae Kim, Il Han Kim, Jun Seita, Irving Weissman, J Martin Brown
Journal: Cancer Research (2015)

Abstract Myeloid cells (cells that give rise to monocytes and macrophages) are a critical component in the solid tumor microenvironment, promoting angiogenesis and tumor recurrence to therapies. Recent literature have extensively demonstrated that hypoxia-inducible factor (HIF) is a key transcription factor in myeloid cells in responding to hypoxic stimuli including solid tumors and inflammation by secreting various cytokines and growth factors. Although a number of studies have reported that hypoxia exposure to primary macrophages induces HIF-1 activation and subsequent vascular endothelial growth factor (VEGF) production, there had been no mouse model to demonstrate this phenomenon. To better understand the role of transcriptional activation of HIF in pathological macrophages, we have created a new strain of myeloid-specific knockout (KO) mice targeting HIF pathways using hS100A8 as the myeloid promoter. S100A8 is an intracellular calcium binding protein and its expression has been heavily detected in pathological macrophages of many diseases including solid tumors, inflammatory bowel disease, obesity, and rheumatoid arthritis. Upon generating mice deficient for von Hippel Lindau (pVHL) tumor suppressor, the negative regulator of HIF, in myeloid cells, we observed erythema and increased VEGF expression in the bone marrow lysate. Moreover, these mice exhibited an enhanced angiogenesis in the subcutanouesly implanted matrigel plugs, which was accompanied by increased VEGF-VEGFR2 signaling in matrigel. We further found that these phenotypes were dependent on transcriptional activation of HIF-1 as a pharmacological or genetic inhibition of HIF-1α completely suppressed the phenotypes in mice deficient for pVHL in myeloid cells. Importantly, we found that HIF-1 activation in myeloid cells regulate not only VEGF but also S100A8 production and identified that monocytes were the major effector driving angiogenesis. Together these results suggest that transcriptional activation of HIF-1 in myeloid cells plays a critical role in promoting angiogenesis. We are currently investigating how HIF-1 in myeloid cells regulates tumor microenvironment thereby affecting tumor progression. Citation Format: G-One Ahn, Young-Eun Kim, Beom-Ju Hong, Seoyeon Bok, Chan-Ju Lee, Hak Jae Kim, Il Han Kim, Jun Seita, Irving Weissman, J Martin Brown. Hypoxia-inducible factor-1 (HIF-1) in myeloid cells promotes angiogenesis by regulating VEGF and S100A8 production. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A13. doi:10.1158/1538-7445.CHTME14-A13
Editorial: Shake well before using
Authors: S. Vaisrub
Journal: JAMA (1973)

A unique episodic hypothermia, though apparently extremely rare, is currently attracting considerable attention because of its distinctive clinical and pathological features. Also known as recurrent, relapsing, spontaneous, and periodic, this hypothermia usually begins in childhood or adolescence. Characteristically, a sudden bout of profuse sweating and vasodilatation ushers in a precipitous drop of temperature that may reach a nadir of 30 C or less. The episode, which can last anywhere between one half to two hours, may recur many times in a day, with or without prolonged remissions of weeks', months', or years' duration. A curious absence of the corpus callosum was demonstrated roentgenologically in three patients<sup>1,2</sup>and confirmed at autopsy in a fourth<sup>3</sup>—the latter also manifesting heavy fibrillary gliosis with neuronal loss in the premammillary region and in the arcuate nuclei of the hypothalamus. The exact mechanism of this curious hypothermia is poorly understood. It is tempting
Another Facet of Brittle Diabetes
Authors: Julio V. Santiago
Journal: JAMA (1986)

"Brittle diabetes" has been defined by Tattersall<sup>1</sup>as a condition in which the life of a person with diabetes is constantly disrupted by repeated episodes of hypoglycemia or hyperglycemia. Less than 5% of insulin-treated diabetic patients have this condition.<sup>2,3</sup>Although brittle diabetes can have many causes, the most common form involves an adolescent or young adult, most often female, who repeatedly does well under conventional treatment in the hospital but develops ketoacidosis at home. The majority of these patients have a serious behavioral, psychiatric, or social problem that interferes with appropriate treatment.<sup>2,3</sup>Although there are many causes for recurrent hospitalization for ketoacidosis, severe insulin resistance, and hypoglycemia,<sup>4,5</sup>the fact remains that few patients with insulindependent diabetes who adhere to a reasonable treatment plan that consists of two daily insulin injections and diet and blood glucose monitoring ever need in-hospital care for recurrent hyperglycemia or hypoglycemia. Indeed,
Effective Treatment of Insulin-Induced Edema Using Ephedrine
Authors: David F C Hopkins, Stephen J Cotton, Gareth Williams
Journal: Diabetes Care (1993)

Objective— To control insulin-induced edema in a patient with poorly controlled IDDM. Research Design and Methods— A 31-yr-old woman with a 14-yr history of poorly controlled IDDM first developed peripheral edema 3 yr after diagnosis of IDDM; the edema worsened whenever insulin dosage was increased. In August 1991, severe edema developed after treatment of ketoacidosis, with body weight increasing from 46 to 61 kg. No evidence of cardiac dysfunction or autonomic neuropathy existed, and serum albumin was consistently normal. Results— Treatment with 15 mg of ephedrine every 8 h produced a prompt diuresis, with body weight falling by 4 kg in 48 h and by 12 kg within 1 wk. Conclusions— Ephedrine may be an effective treatment for insulin-induced edema and may be preferable to the use of diuretics in such patients.
The N. S. Davis Memorial.
Authors: Henry O. Marcy
Journal: JAMA (1906)

Boston, April 23, 1906. <h3>To the Editor:</h3> —I am sure your readers will be glad to know, through the columns ofThe Journal, something of the progress which is being made by their committee in the raising of funds for some suitable memorial to the late Dr. N. S. Davis of Chicago. I am delighted to report that the committees from each of the several states have already taken up the work with enthusiasm. It is the purpose of your committee to make this movement in honor of the founder of our great Association an especial honor and privilege to every member. The sum of 25 cents each would aggregate a total ample for this purpose, and your committee feels that such universal remembrance would be an honor and a privilege to every one of the great army of over 100,000 physicians to be sharers. It is the desire of
P151 Laryngopharyngeal Pepsin Reflux in Patients with Upper Airway Symptoms
Authors: A Spyridoulias, S Lillie, A Vyas, SJ Fowler
Journal: Thorax (2012)

<h3>Background</h3> Laryngopharyngeal reflux (LPR) is implicated in inducing laryngeal hyper-responsiveness which is a unifying feature underlying chronic cough and vocal cord dysfunction. A lack of response to standard anti-reflux therapy in patients with LPR may be due to persistence of non-acid-reflux and pepsin causing ongoing laryngeal epithelial inflammation. We investigated: (a) the prevalence of pepsin reflux in respiratory patients requiring nasendoscopy for the investigation of upper airway symptoms; (b) the performance of commonly used clinical LPR-diagnostic tools in predicting the presence of salivary pepsin. <h3>Methods</h3> Subjects had symptoms and signs of laryngeal inflammation quantified using, the Reflux Symptom Index (RSI) and Reflux Finding Score (RFS). Salivary pepsin was measured with a lateral flow device using monoclonal antibody labelling (Peptest, RDBiomed). Patients with severe signs of laryngeal inflammation were referred for impedance-pH oesophageal studies to assess for objective evidence of reflux. <h3>Results</h3> Of the 78 subjects recruited, 76% were female, mean age 55 (range 17–82). Ten were undergoing investigation for chronic cough, and 68 for possible vocal cord dysfunction (confirmed in 45). 30 had concomitant asthma, and 42 were prescribed anti-reflux treatment. 87% had a high RSI, and 51% a high RFS. Pepsin was detected in the saliva of 49/78 subjects (63%), and prevalence did not vary significantly between treatment group. There was a weak correlation between the RFS and pepsin concentration (r=0.28, p=0.01) and the positive and negative predictive values for pepsin detection for those with a high RFS were 63% and 69% respectively. To date all 8 patients tested have had significant proximal reflux on impedance study, of which 6 had a positive pepsin assay. <h3>Conclusion</h3> Salivary pepsin was frequently present in patients with upper airway symptoms, but only weakly related to clinical findings of reflux, suggesting a high prevalence of LPR that is not associated with typical laryngeal findings. The significance of such sub-clinical reflux remains to be seen however the use of pepsin assay in patients with upper airway symptoms may be most valuable in directing diagnosis in milder cases where symptoms and signs lack specificity and the condition may otherwise be missed.
Balance Between Right and Left Ventricular Output
Authors: Dean L. Franklin, Robert L. Van Citters, Robert F. Rushmer
Journal: Circulation Research (1962)

The right ventricular ejection pattern is characterized by early onset, gradual rise to peak flow velocities in midsystole and gradual return to baseline. Left ventricular ejection begins very shortly after right ventricular systole, abruptly reaches peak flow, and diminishes during the remainder of the systolic interval, terminating with a brief, sharp, retrograde surge as the aortic valves close. The duration of ejection is shorter in the left ventricle than in the right. In healthy dogs, respiratory activity produces very slight fluctuations in right and left ventricular output that are almost in phase. In dogs with hydrothorax and pulmonary atelectasis, the right and left ventricular outputs fluctuate in greatly exaggerated fashion with each forced respiratory effort. Under such conditions, the changes in right and left ventricular stroke volume are nearly 180 Degrees out of phase. Pulmonary outflow resistance is increased and the right ventricular ejection pattern closely resembles those generally characteristic of the left ventricle. Assume that the erect posture causes cardio-acceleration and large changes in right and left ventricular stroke volume. which are essentially synchronous. Treadmill exercise with sudden and unexpected onset produces changes in the outputs of the right and left ventricles without obvious lead or lag of one ventricle over the other. These experiments do not support the concept that changes in "venous return" are dominant mechanisms inducing alterations in cardiac output.
Protein carbamylation is associated with heart failure and mortality in diabetic patients with end-stage renal disease
Authors: Christiane Drechsler, Sahir Kalim, Julia B. Wenger, Pirianthini Suntharalingam, Tammy Hod, Ravi I. Thadhani, S. Ananth Karumanchi, Christoph Wanner, Anders H. Berg
Journal: Kidney International (2015)
94 FUNCTIONAL ANALYSIS OF HEPATIC GENE EXPRESSION PROFILING FROM PATIENTS WITH ALCOHOLIC HEPATITIS REVEALS NEW TARGETS FOR THERAPY
Authors: M. Domínguez, J.J. Lozano, A. Loaeza, R. Miquel, J. Colmenero, M. Moreno, J.-C. García-Pagán, J. Bosch, V. Arroyo, P. Ginès, R. Bataller
Journal: Journal of Hepatology (2009)
Hydroxyurea (HU) for prevention of recurrent stroke in sickle cell anemia (SCA)
Authors: Abraham Sumoza, Renate de Bisotti, David Sumoza, Virgil Fairbanks
Journal: American Journal of Hematology (2002)

Abstract Cerebrovascular accident (CVA) is a major cause of morbidity and death in sickle cell anemia (SCA). Transfusion of packed erythrocytes is widely used to prevent this complication. However, chronic transfusion may lead to iron overload, alloimmunization, or infections. Cost and compliance may compromise transfusion therapy. A possible alternative, the prophylactic use of hydroxyurea (HU), has not been tried to determine whether it may prevent recurrent stroke. We used HU in five children with SCA who had suffered stroke, in three of them after a first episode and in the other two after a second CVA. Four had infarctive stroke and one a transient ischemic attack (TIA). Four patients took HU at a dose of 40 mg/kg/d, one patient at 30 mg/kg/d. None of the patients had recurrent stroke during 42–112 months of observation. None experienced pain crises. In all, HbF increased significantly and was maintained above 14.7% during treatment. The total Hb concentration increased 19.5 g/L (median) above the value before treatment. HU was well tolerated. None of the five children had leukopenia or thrombocytopenia during therapy. HU appears to prevent recurrence of stroke in SCA without risk of major toxicity. Am. J. Hematol. 71:161–165, 2002. © 2002 Wiley‐Liss, Inc.
Evidence for a reversible oxygen radical-mediated component of reperfusion injury: reduction by recombinant human superoxide dismutase administered at the time of reflow.
Authors: G Ambrosio, M L Weisfeldt, W E Jacobus, J T Flaherty
Journal: Circulation (1987)

It has been suggested that the beneficial effects of reperfusing ischemic myocardium might be in part reversed by the occurrence of "reperfusion injury." One possible mechanism could be the generation of oxygen free radicals. Superoxide dismutase enzymatically scavenges superoxide radicals by dismutation to hydrogen peroxide. This study tested the hypothesis that administration of recombinant human superoxide dismutase (h-SOD) at the time of reflow after a period of prolonged global ischemia would result in improved recovery of myocardial metabolism and function by preventing or reducing a potentially harmful component of reperfusion. We also sought to determine whether catalase, an enzymatic scavenger of hydrogen peroxide, was a necessary addition for optimal benefit. Langendorff perfused rabbit hearts were subjected to 30 min of normothermic (37 degrees C) total global ischemia. At the moment of reperfusion, 12 control hearts received a 10 ml bolus of normal perfusate followed by 15 min of reperfusion with normal perfusate (group I), 12 hearts received 60,000 IU of h-SOD as a bolus followed by a continuous infusion of 100 IU/ml for 15 min (group II), and 12 hearts received 60,000 IU of h-SOD and 60,000 IU of catalase as a bolus followed by 100 IU/ml of both enzymes for 15 min (group III). Myocardial ATP and phosphocreatine (PCr) content and intracellular pH during ischemia and reperfusion were continuously monitored with 31P nuclear magnetic resonance (NMR) spectroscopy. During 30 min of normothermic global ischemia intracellular pH dropped from 7.11-7.18 to 5.58-5.80 in all three groups of hearts. Likewise myocardial PCr content fell rapidly to 7% to 8% and ATP fell more slowly to 29% to 36% of preischemic control content. After 45 min of reperfusion PCr recovered to 65 +/- 5% of control in untreated (group I) hearts compared with 89 +/- 8% in h-SOD-treated (group II) hearts (p less than .01 vs group I) and with 83 +/- 6% of control in h-SOD/catalase-treated (group III) hearts (p less than .05 vs group I). Recovery of isovolumic left ventricular developed pressure was 68 +/- 5% of control in h-SOD-treated (group II) hearts and 66 +/- 6% of control in h-SOD/catalase-treated (group III) hearts after 45 min of reflow, compared with 48 +/- 6% of control in untreated (group I) hearts (p less than .005 for groups II and III vs group I). The NMR data confirmed equal depletion of ATP and PCr content in all three groups of hearts.(ABSTRACT TRUNCATED AT 400 WORDS)