tbuckley/cabot-search huggingface dataset:
Shortening of fast pathway refractoriness after slow pathway ablation. Effects of autonomic blockade.
Authors: A Natale, G Klein, R Yee, R Thakur
Journal: Circulation (1994)

BACKGROUND Shortening of the anterograde effective refractory period (ERP) of the fast pathway has been reported after radiofrequency ablation of the slow pathway. We hypothesized that ERP shortening may be related to autonomic changes, possibly catecholamine release, as a result of ablation. METHODS AND RESULTS To test this, 10 consecutive patients with atrioventricular node reentry undergoing slow pathway ablation were given autonomic blockade before the ablation procedure. This was achieved by atropine 0.03 mg/kg and propranolol 0.15 mg/kg IV supplemented by half the initial dose after ablation and before the final study. A control group of 10 patients underwent the protocol without autonomic blockade. Before ablation, autonomic blockade did not alter the ERP of either the fast pathway (295 +/- 22 versus 298 +/- 26 milliseconds) or the slow pathway (264 +/- 36 versus 269 +/- 38 milliseconds). Autonomic blockade obscured dual pathway physiology in 2 patients and brought it out in another 2 without dual pathway physiology initially. Slow pathway ablation shortened the ERP of the fast pathway for the group as a whole (331.5 +/- 54 versus 305.5 +/- 60 milliseconds, mean +/- SD, n = 20, P &lt; .04). There was no difference in degree of ERP shortening in control patients (23.5 +/- 58 milliseconds) or autonomic blockade patients (25.5 +/- 52 milliseconds). CONCLUSIONS These data suggest that shortening of the ERP of the fast pathway after slow pathway ablation is not mediated by autonomic changes.
The Question Is Answered: Now what?
Authors: Ruth Farkas-Hirsch, Irl B Hirsch
Journal: Diabetes Care (1994)

The 1993 20th annual meeting of the American Association of Diabetes Educators (AADE) had a joyous overtone because it was the beginning of the celebration of 20 years of work and dedication. The record attendance of over 1,900 individuals listened to excellent presentations on a variety of exciting topics. Much of the meeting emphasized the recently publicized findings of the Diabetes Control and Complications Trial (DCCT). The results of the trial generated a tremendous amount of enthusiasm and optimism. It now appears that the question is finally answered.
Tuberculosis: When Not to Order Roentgenograms
Authors: George M. Lordi
Journal: JAMA (1985)

IN 1979, the National Center for Devices and Radiological Health of the Food and Drug Administration sponsored the formation of a Chest X-ray Panel to review the selection of patients for chest x-ray screening examinations. The panel's recommendations have recently been published.<sup>1</sup>The panel's statements regarding pulmonary tuberculosis are of particular interest and should be emphasized. Essentially, the panel concluded that (1) the yield of tuberculosis cases found by screening or repeated chest x-ray examinations was not sufficient to justify the monetary cost or added radiation exposure, (2) mandated chest x-ray examinations as a condition of initial or continued employment were not productive for tuberculosis detection, (3) repeated chest x-ray examinations of persons with significant tuberculin reactions (without current disease), including those not treated with isoniazid, were not of value, (4) repeated chest x-ray examinations of asymptomatic patients with tuberculosis who had completed treatment were of insufficient clinical value,
Epidemiological studies with anti-hepatitis C virus
Authors: Joseph R. Bove
Journal: Hepatology (1991)

In a survey carried out from 1985 through 1986, volunteer blood donors to The Greater New York Blood Program were tested for two surrogate markers for non-A, non-B hepatitis-elevation of alanine aminotransferase level and presence of antibody to hepatitis B core antigen. Stored serum samples from selected donors were also recently tested for antibody to hepatitis C virus (anti-HCV). Anti-HCV was detected in 0.9% to 1.4% of donors and was higher in black and Hispanic donors than in white donors. Anti-HCV prevalence increased with increasing age through the fourth decade of life, but decreased thereafter, possibly reflecting the disappearance of detectable antibody with time. Anti-HCV correlated with both alanine aminotransferase level and the presence or absence of antibody to hepatitis B core antigen. These associations suggest that donor screening for elevation of alanine aminotransferase level and presence of antibody to hepatitis B core antigen was, as expected, at least partially effective in preventing transfusionassociated non-A, non-B hepatitis. The detection of anti-HCV in donors who have neither an elevation of alanine aminotransferase level nor presence of antibody to hepatitis B core antigen suggests that donor screening for anti-HCV will further reduce the risk of transfusion-associated hepatitis.
Abstract A7: Targeting mutant p53 and cell-cell adhesion in ovarian cancer
Authors: Marcin P. Iwanicki, Marian Novak, Ioannis K. Zervantonakis, Tan A. Ince, Ronny Drapkin, Joan S. Brugge
Journal: Clinical Cancer Research (2013)

Abstract One of the most important challenges in the ovarian cancer research is to identify new molecular pathways that can be targeted to kill ovarian cancer cells. High-grade serous ovarian cancer (HGS-OvCa) cells survive, proliferate, and assemble into multicellular clusters that have a capacity to disseminate within the peritoneum. Therefore, it is important to identify specific molecular mechanisms that can be targeted to block survival, growth, and assembly of ovarian cancer multicellular clusters that metastasize within peritoneum. High-grade ovarian tumors originate from the fallopian tube epithelium (FTE) and almost all have mutations in theTP53 gene. The contribution of various mutant p53 proteins (m-p53) to ovarian cancer and whether targeting mutant p53 –dependent molecular mechanisms in ovarian cancer is poorly understood and of clinical significance. We have developed new methodologies and used them to identify m-p53-dependent pathways that support HGS-OvCa survival, proliferation and assembly of multicellular aggregates under condition mimicking peritoneal suspension. To determine whether mutations in TP53 contribute to the ability of HGS-OvCa cells to survive, proliferate, and assemble into multicellular clusters we introduced different variants of mutant p53 (m-p53) into normal human non-transformed FTE cells. We found that expression of m-p53 variants (R175H; R249S; R273H) in FTE cells promoted survival, growth, and assembly of multicellular clusters under conditions mimicking peritoneal suspension. Interestingly m-p53-driven phenotypes were not induced by the loss of p53 expression; and more importantly, these phenotypes were blocked by the reactivation of p53 pathway with small molecule inhibitor NSC319726. We further found that m-p53 induced phenotypes were dependent on the expression of integrin β 1 (ITGB1). The evidence that activated ITGB1 is enriched at cell's surface of precursors of HGS-OvCa within the fallopian tube and HGS-OvCa isolated from ovarian cancer patients highlighted the relevance of these findings to ovarian cancer. We hypothesize that mutant p53 supports survival, growth, and assembly of multicellular HGS-OvCa clusters through mechanisms in which ITGB1 plays a critical role. Our data indicate that observed phenotypes are the consequence of the m-p53 gain of function mechanisms that are amenable to therapeutic inhibitions and targeting m-p53 in HGS-OvCa might be of clinical significance. Citation Format: Marcin P. Iwanicki, Marian Novak, Ioannis K. Zervantonakis, Tan A. Ince, Ronny Drapkin, Joan S. Brugge. Targeting mutant p53 and cell-cell adhesion in ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A7.
LB-006 Quality Of Methods Reporting In Colitis Experiments And The Subsequent Impact On The Development Of A Gut Knowledge Base
Authors: ML Bramhall, O Flórez-Vargas, R Stevens, J Wilson, S Cruickshank, A Brass
Journal: Gut (2014)

<h3>Introduction</h3> Current gastroenterological research generates vast quantities of clinical or animal model-derived data that is necessary to the study of IBD, yet much of it lies unused in repositories after publication. There is a growing need to develop more appropriate, structured storage systems that can be used by researchers to query this wealth of information with emerging questions. A domain-specific knowledge base combining clinical and laboratory datasets, annotated and connected via ontological terms, would be a valuable tool for gastroenterologists. However, development of a gut domain knowledge base may be severely impeded by incomplete methods reporting in the literature. This is further compounded by two factors. Firstly, non-domain experts, who may not be well suited to identifying missing methods, usually undertake construction of a knowledge base. Secondly, variations in experimental protocols may make it difficult for investigators to compare results from similar, but not identical, experiments. <h3>Methods</h3> In order to address these issues we have systematically collated published papers that employed the widely used DSS colitis model. The papers were assessed against a checklist of essential parameters that should be reported for the experiment to be accurately described to allow for correct annotation and entry into a knowledge base. <h3>Results</h3> We provide a comprehensive review of the quality of methods reporting in experiments using the DSS colitis model. We also report on the heterogeneity of the DSS colitis model currently in use. <h3>Conclusion</h3> We provide a number of recommendations in order for researchers to standardise their methods and ensure that all relevant factors are reported during the publication of their research. Building from this, we will use what we have learnt to better inform the construction of a gut domain knowledge base. <h3>Disclosure of Interest</h3> M. Bramhall Grant/research support from: Epistem Ltd., O. Flórez-Vargas: None Declared, R. Stevens: None Declared, J. Wilson: None Declared, S. Cruickshank: None Declared, A. Brass: None Declared.
Staphylococcal enterotoxin B-derived haptens promote sensitization
Authors: Shao-Bo Yang, Tong-Li Li, Xiao Chen, Yun-Fang An, Chang-Qing Zhao, Jun-Bao Wen, Dao-Fa Tian, Zhong Wen, Min-Qiang Xie, Ping-Chang Yang
Journal: Cellular and Molecular Immunology (2012)
Pharmacovigilance: towards a better understanding of the benefit to risk ratio
Authors: L S Simon
Journal: Annals of the Rheumatic Diseases (2002)

Pharmacovigilance is a critical component for determining the benefit to risk ratio of treatment. The potential for drug toxicity is determined throughout the lifetime of use of a drug or biological agent, including the development cycle. This includes both the preclinical as well as clinical data. Preclinical data are rarely extensive for biological therapies because it is difficult to study these drugs in animal models, whereas pharmacotoxicology can be very informative in the development of new drugs.

Toxic events caused by drugs or biological therapies may be identified at any time during treatment, as there is no absolutely safe treatment. There are certain patterns to the onset of these potential events. One pattern of onset for some treatments is early onset. In this situation, if patients continue to take the drug, the incidence of the toxic event may decrease over time. Other toxic events might be delayed and only noted with continued use of a drug. There is a third possible pattern—namely, treatment that induces a chronic but constant event, such as the use of non-selective non-steroidal anti-inflammatory drugs, which are believed to cause one or two gastric ulcers a month …
Beauty spot or blemish.
Authors: I McGregor
Journal: BMJ (1977)

<h3>Background</h3> Long-term complications after COVID-19 are common, but the potential cause for persistent symptoms after viral clearance remains unclear. <h3>Objective</h3> To investigate whether gut microbiome composition is linked to post-acute COVID-19 syndrome (PACS), defined as at least one persistent symptom 4 weeks after clearance of the SARS-CoV-2 virus. <h3>Methods</h3> We conducted a prospective study of 106 patients with a spectrum of COVID-19 severity followed up from admission to 6 months and 68 non-COVID-19 controls. We analysed serial faecal microbiome of 258 samples using shotgun metagenomic sequencing, and correlated the results with persistent symptoms at 6 months. <h3>Results</h3> At 6 months, 76% of patients had PACS and the most common symptoms were fatigue, poor memory and hair loss. Gut microbiota composition at admission was associated with occurrence of PACS. Patients without PACS showed recovered gut microbiome profile at 6 months comparable to that of non-COVID-19 controls. Gut microbiome of patients with PACS were characterised by higher levels of <i>Ruminococcus gnavus</i>, <i>Bacteroides vulgatus</i> and lower levels of <i>Faecalibacterium prausnitzii</i>. Persistent respiratory symptoms were correlated with opportunistic gut pathogens, and neuropsychiatric symptoms and fatigue were correlated with nosocomial gut pathogens, including <i>Clostridium innocuum</i> and <i>Actinomyces naeslundii</i> (all p&lt;0.05). Butyrate-producing bacteria, including <i>Bifidobacterium pseudocatenulatum</i> and <i>Faecalibacterium prausnitzii</i> showed the largest inverse correlations with PACS at 6 months. <h3>Conclusion</h3> These findings provided observational evidence of compositional alterations of gut microbiome in patients with long-term complications of COVID-19. Further studies should investigate whether microbiota modulation can facilitate timely recovery from post-acute COVID-19 syndrome.
Induction/Maintenance Treatment Regimens for HIV
Authors: Julio S. G. Montaner
Journal: JAMA (1999)

BackgroundCombination antiretroviral therapy with
indinavir, zidovudine, and lamivudine can suppress the level of human
immunodeficiency virus (HIV) RNA in plasma below the threshold of
detection for two years or more. We investigated whether a less
intensive maintenance regimen could sustain viral suppression after an
initial response to combination therapy.MethodsHIV-infected subjects who had CD4 cell counts greater
than 200 per cubic millimeter, who had been treated with indinavir,
lamivudine, and zidovudine, and who had less than 200 copies of HIV RNA
per milliliter of plasma after 16, 20, and 24 weeks of induction
therapy were randomly assigned to receive either continued triple-drug
therapy (106 subjects), indinavir alone (103 subjects), or a
combination of zidovudine and lamivudine (107 subjects). The primary
end point was loss of viral suppression, which was defined as a plasma
level of at least 200 copies of HIV RNA per milliliter on two
consecutive measurements during maintenance therapy.ResultsDuring maintenance treatment, 23 percent of the
subjects receiving indinavir and 23 percent of those receiving
zidovudine and lamivudine, but only 4 percent of those receiving all
three drugs, had loss of viral suppression (P<0.001 for the
comparison between triple-drug therapy and the other two maintenance
regimens). Subjects with greater increases in CD4 cell counts during
induction therapy, higher viral loads at base line (i.e., at the
beginning of induction therapy), and slower rates of viral clearance
were at greater risk for loss of viral suppression. The presence of
zidovudine-resistance mutations in HIV RNA at base line was strongly
predictive of the loss of viral suppression in subjects treated with
zidovudine and lamivudine.ConclusionsThe suppression of plasma HIV RNA after six months of
treatment with indinavir, zidovudine, and lamivudine is better
sustained by the continuation of these three drugs than by maintenance
therapy with either indinavir alone or zidovudine and
lamivudine.
RED-CELL-VOLUME DISTRIBUTION CURVES IN DIAGNOSIS OF GLOMERULAR AND NON-GLOMERULAR HAEMATURIA
Authors: Masayoshi Shichiri, Yasuhide Nishio, Matsuhiko Suenaga, Shigeo Tomura, Kazushige Hosoda, Mitsuo Ogura, Hiroshi Saito, Tatsuo Shiigai
Journal: The Lancet (1988)
Prevalence, classification and perception of allergic and nonallergic rhinitis in Belgium
Authors: C. Bachert, P. Van Cauwenberge, J. Olbrecht, J. Van Schoor
Journal: Allergy (2006)

Background: Allergic rhinitis (AR) and noninfectious, nonallergic rhinitis (NINA) are common disorders, which may prompt patients to seek medical help. Methods: We performed a survey in a representative sample of the Belgian population ( n = 4959) with an overall prevalence of self‐declared recent rhinitis symptoms of 39.3%. Detailed information on patients having experienced nasal symptoms over the past year was then obtained from a random sample of respondents ( n = 743). Results: The adjusted prevalence was 29.8% for AR and 9.6% for NINA, respectively. According to the ARIA classification, there was significantly more ‘persistent’ symptomatology in the AR group (40.8%) than in NINA (23.5%) ( P &lt; 0.001), and more ‘moderate/severe’ symptom intensity in AR (75.4%) than in NINA (53.1%) ( P &lt; 0.001). Allergic rhinitis patients suffered from a greater number of symptoms than NINA patients ( P &lt; 0.001). Asthma, skin and food allergy as co‐morbidities were all found to be significantly more prevalent in the AR vs the NINA group ( P &lt; 0.05 for all). The percentage of consulting patients (total: 66.8%), who subjectively perceived their rhinitis as moderate/severe, was 94.0%, whereas 75.6% of these patients were classified accordingly based on ARIA criteria. Conclusions: We found a high prevalence of self‐declared rhinitis symptoms in the Belgian population, AR being about three times more prevalent than NINA. In addition, AR patients suffered from a greater number of symptoms and displayed a more ‘persistent’ and ‘moderate–severe’ ARIA profile than NINA. About 75% of patients seeking medical help suffer from ‘moderate to severe’ forms of rhinitis.
Cholecystokinin (CCK): Negative feedback control for opioid analgesia
Authors: Ji-Sheng Han
Journal: Behavioral and Brain Sciences (1997)

Negative feedback is an important mechanism whereby the organism maintains its balance in a complicated system. It may be regarded as a modern version of the ancient Eastern wisdom of Yin and Yang balance. Control of pain and analgesia, is no exception: CCK seems to serve as a built-in mechanism for the modulation of opioid analgesia system [dickenson] .
Remission of Cerebellar Dysfunction after Pneumonectomy for Bronchogenic Carcinoma
Authors: Joseph F. Paone, K. Jeyasingham
Journal: New England Journal of Medicine (1980)

CORTICAL cerebellar degeneration is a paraneoplastic syndrome in which diffuse atrophy of the cerebellum and of the associated spinocerebellar tracts and systems occurs as a remote effect of a neoplasm. Since the first case report by Brouwer in 1919,1 about 60 cases have appeared in the literature. Progressive, disabling cerebellar dysfunction develops, often before the primary tumor is discovered.2 The neurologic disease usually progresses with tumor growth, although rare remissions have been reported after antineoplastic therapy.3 4 5 We present a patient with acute cortical cerebellar dysfunction secondary to bronchogenic carcinoma, whose symptoms disappeared after radical pneumonectomy.Case ReportIn a 67-year-old . . .
The value of SCORAD and beyond. Towards a standardized evaluation of severity?
Authors: C. Gelmetti, C. Colonna
Journal: Allergy (2004)

The clinical scoring systems of atopic dermatitis were analysed and compared. Some biological parameters that can correlate with the clinical score were also reviewed. After the definition of the disease based on validated clinical criteria, the second necessity was the availability of reliable severity scores to allow clinicians to verify the course of the disease and the efficacy of treatments. After many proposals, the SCORAD (SCORing Atopic Dermatitis), that required more than three years of work, was the first one that was validated. SCORAD is freely available from an internet site and can be easily calculated using dedicated software. EASI (Eczema Area and Severity Index) score has also been validated but it has been modified twice. Simpler systems include SASSAD (Six Area, Six Sign Atopic Dermatitis) and TIS score (Three‐Item Severity score). In parallel, biological parameters were investigated. Eosinophil cationic protein, circulating basophils, major basic protein, soluble E‐selectin, antistaphylococcal enterotoxin B, immunoglobulin E titres and macrophage‐derived chemokine, can correlate significantly with the clinical score. The clinicians will not benefit directly from laboratory techniques and will employ clinical scores.
FRAGMENTS ON INSANITY
Authors: John M. Galt
Journal: American Journal of Psychiatry (1844)

A cure of these with patience and kind care, if music can thus move And those are his sweet strains which charm the weight From madman's chains, and make this hell appear A heav n of sacred silence, hush'd to hear His melody Is interrupted now; we hear the din Of madmen, shriek on shriek, again begin.'"
P165 TB-ST rapid test for tuberculosis diagnosis in a resource poor setting: are cases of tuberculosis going undiagnosed?
Authors: N. Javanshir, D. S. Shah, D. E. Jennings, J. Ivanyi, H. J. Milburn
Journal: Thorax (2010)

<h3>Introduction</h3> Diagnosis of tuberculosis (TB) ideally involves culture and sensitivity of the organism but in low income countries this is not practised routinely. The World Health Organisation estimates that substandard detection occurs in 40% of patients globally, with many diagnosed on clinical suspicion or response to medication. TB produces a strong antibody response suitable for simple, inexpensive and rapid serodiagnostic assays. Ongoing evaluation of a new point of care rapid serological test based on lateral flow immunochromatography (TB-ST Rapid Test, Lionex, Germany) has shown 100% specificity, with no false positive tests in normal controls and latently infected patients, but sensitivity of 36%, with false negatives in culture proven TB. <h3>Aim</h3> Using this test in a resource poor setting to investigate whether cases of active TB may be being missed by current diagnostic methods. <h3>Methods</h3> 498 patients in chest and HIV clinics in two rural Kenyan hospitals were investigated with the TB-ST Rapid Test and a scored questionnaire to determine symptoms and risk of TB. Results were compared with clinical diagnoses made, usually based on symptoms alone. Chest radiographs were performed in only 111 and sputum smears in 75. <h3>Results</h3> 127/498 patients were HIV positive. Of these, only 59(46%) had a clinical diagnosis of TB, whereas 87(68.5%) had significant TB symptoms and/or risk factors, and 82(64.6%) tested TB-ST positive (p&lt;0.001). Therefore clinical diagnosis accounted for significantly fewer diagnoses of active TB than suggested by either symptom and risk score or TB-ST rapid results in the HIV+ population. Of the 375 HIV− patients, 73 (19.7%) had a clinical diagnosis of TB, 46 (12.3%) scored positive for TB on the questionnaire, and 149 (40.2%) were TB-ST+ (p&lt;0.001). Abstract P165 Table 1 shows positive and negative TB-ST results related to positive and negative sputum smears in 34 HIV+ and 41 HIV− patients. <h3>Conclusions</h3> Many more patients had positive TB-ST and risk and symptom scores than were being diagnosed with active TB, suggesting that TB may not always be being diagnosed or treated. Sputum smears were in greater agreement with the TB-ST in HIV− but not HIV+ patients, in whom there were considerably fewer positive smears than TB-ST results.