tbuckley/cabot-search huggingface dataset:
Primary Prevention of Sudden Death as a Novel Treatment Strategy in Hypertrophic Cardiomyopathy
Authors: Barry J. Maron, N. A. Mark Estes, Martin S. Maron, Adrian K. Almquist, Mark S. Link, James E. Udelson
Journal: Circulation (2003)

A 20-year-old asymptomatic man was diagnosed with hypertrophic cardiomyopathy (HCM) after routine physical examination during which a systolic heart murmur was detected.Echocardiography showed massive left ventricular (LV) hypertrophy with ventricular septal thickness of 36 mm extending into the anterolateral wall (30 mm); outflow obstruction was absent.Ambulatory (Holter) ECG showed 3 isolated premature ventricular contractions, and blood pressure response to exercise was normal.Echocardiographic examinations in parents and siblings were negative for HCM.Although 2 centers advised against an implantable cardioverter-defibrillator (ICD) based on the presence of only 1 risk factor for sudden death (ie, extreme hypertrophy), a prophylactic device was recommended by a third cardiac consultant.After an uneventful 16-month period during which the ICD neither detected nor treated arrhythmias, an unprovoked episode of ventricular fibrillation triggered a defibrillation shock that immediately restored sinus rhythm (Figure 1).
S33 Sputum Colour In The Light Of The Health Related Quality Of Life, Airways And Systemic Biomarkers In Exacerbations Of Copd
Authors: V. Kim, N. Williams, K. Ostridge, A. Barton, M. Wojtas, E. Aris, M. Peeters, J. Devaster, S. Bourne, T. Wilkinson
Journal: Thorax (2014)

<h3>Introduction</h3> Acute exacerbations of COPD have a major impact on patients’ health related quality of life (HRQoL), and the utilisation of health care resources. Current guidelines recommend oral corticosteroids and/or antibiotics for the treatment of acute exacerbations of COPD based on patients’ symptoms. With increasing bacterial resistance to antibiotics and the rising costs of COPD treatment, further research into diagnostic tools to aid the management of COPD in its stable and exacerbating states is required. Sputum colour (SC) is an accessible marker of underlying bronchial inflammation. We investigated the contribution of objective measures of SC as a component of the clinical assessment of exacerbations and relationships with symptom severity. <h3>Methods</h3> Data from 36 patients with moderate to very severe COPD was assessed in this prospective observational cohort study (AERIS). There were 122 exacerbations in total over a year. Sputum and blood sampling were performed at enrolment, routine follow up and exacerbation visits. A five-point sputum colour chart was developed to objectively report the SC. Sputum samples from all visits were graded against this chart by the trained laboratory staff. Data from mild, moderate and severe exacerbations were included in the analysis. <h3>Results</h3> We found a correlation between SC at exacerbations and disease severity (FEV1%) at exacerbations. SC was also related to sputum neutrophilia at exacerbations. SC was significantly associated with systemic markers such as blood neutrophilia, CRP and fibrinogen. Interestingly, we observed no statistically significant correlation between SC and Procalcitonin levels. We also found no statistically significant relationship between SC and symptom scores (CAT and EXACT-PRO) at exacerbations. However, we found a significant association between CAT and EXACT-PRO scores (rho 0.46; p &lt; 0.01). <h3>Conclusion</h3> We observed that visual colour score of sputum at exacerbations is related to underlying airway and systemic inflammation but not to symptom scores. The use of a SC combined with other clinical and laboratory biomarkers, as part of a multicomponent diagnostic tool, may further improve its clinical utility to better guide effective exacerbation treatment. Further analysis of the full AERIS cohort will explore this.
Abstract 4874: CXCR2 signaling axis- a helping hand to KRAS(G12D) mutation in pancreatic cancer initiation
Authors: Abhilasha Purohit, Michelle Varney, Satya Rachagani, Michel Ouellette, Surinder K. Batra, Rakesh K. Singh
Journal: Cancer Research (2014)

Abstract Pancreatic cancer (PC) is the fourth leading cause of cancer-related deaths in the United States. The high mortality can be accredited to late clinical presentation and early metastasis. Somatic mutations in oncogene KRAS(G12D) are the most common and earliest events during development of PC, suggesting their crucial role in tumor initiation; however, the precise functional molecular mechanism(s) of action remains unclear. CXCR2, a CXC chemokine receptor, and its ligands have also been found to be important in regulating inflammation, angiogenesis, and metastasis in various cancers. The purpose of the current study was to test the functional role of CXCR2 signaling in KRAS(G12D)-induced PC development. Immunohistochemical analysis of tumors derived from PDX-cre-LSL-kras(G12D) mice demonstrated significantly higher expression of Cxcr2 and its ligands Cxcl1 and -3. Expression of Cxcr2 and its ligands Cxcl1 and -3 was observed as early as 10 weeks and increased consistently as the lesions advanced. We demonstrated the direct link between KRAS(G12D) mutation and CXCR2 signaling using cell line models hTERT-HPNE and hTERT-HPNE -E6-E7-st with or without exogenously expressed KRAS(G12D). Real time PCR, ELISA and western blot analysis of these cells revealed that KRAS (G12D) up-regulates the expression of CXCR2 and its ligands at both the transcriptional and protein levels. In order to delineate the significance of CXCR2 in KRAS(G12D) induced autocrine growth, we treated the cell line models with various concentrations of SCH-527123 (CXCR2 antagonist) or CXCR2 neutralizing antibody. Our data shows that KRAS(G12D) bearing cells show significantly (P ≤ 0.05) greater percent inhibition in cell growth in comparison to their control counterparts. Next to evaluate the role of CXCR2 autocrine signaling in KRAS(G12D) induced cell migration, we performed a scratch assay by treating the hTERT-HPNE -E6/E7-st- KRAS(G12D) cells with SCH-527123 for 24 hours. Our data demonstrated a significant inhibition of cell migration in CXCR2 antagonist treated cultures. Together, our data demonstrate that KRAS(G12D) mutation up regulates CXCR2 and its ligands, which, in turn, play key roles in the autocrine regulation of cellular growth and migration in PC. Note: This abstract was not presented at the meeting. Citation Format: Abhilasha Purohit, Michelle Varney, Satya Rachagani, Michel Ouellette, Surinder K. Batra, Rakesh K. Singh. CXCR2 signaling axis- a helping hand to KRAS(G12D) mutation in pancreatic cancer initiation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4874. doi:10.1158/1538-7445.AM2014-4874
RADICALISM AND CONSERVATISM IN GYNECOLOGIC SOCIETIES.
Authors: F. H. HENROTIN
Journal: JAMA (1895)

An address by the retiring President seems to be one of the leading features of the annual meeting of this Society, and I see by the program that I am not to be spared this year. Gynecologic societies are generally organizations of comparatively recent nativity, and are the result of the recognition of gynecology as a distinct and all-important branch of medical science. I am not in possession of facts by which I could outline to you the history of these societies generally, but the work they accomplish is so important that I thought I might entertain you upon their peculiarities and their field of usefulness. Previous to the last two or three decades, the work now accomplished by these associations was made a part of the transactions of the general medical societies, and later on, of the obstetrical societies. As gynecology developed, however, and the womb of alma mater
Popular herbal remedy for hot flushes is no better than placebo
Authors: Roger Dobson
Journal: BMJ (2005)

The widely used herbal remedy black cohosh offers little relief from menopausal hot flushes, a new US study shows.

The researchers found no significant differences between women using herbal products and those using placebo in the frequency or intensity of hot flushes ( Maturitas 2005;16:134–46).

“Given the serious health risks associated with hormone therapy, we were disappointed to discover that a popular herbal alternative appears to be no more effective than the placebo,” said Katherine Newton, lead researcher on the herbal alternatives for menopause study. “Regrettably, we found that black cohosh has little potential to …
PTU-159 Characterisation of Oesophageal Muc1 Expression in the Progression to Oesophageal Adenocarcinoma
Authors: M A Butt, D Oukrif, R J Haidry, M Rashid, S-U-R Khan, H Pye, E S Bloom, M Deonarain, D Swallow, M R Banks, M Rodriguez-Justo, M Novelli, L B Lovat
Journal: Gut (2013)

<h3>Introduction</h3> Studies on oesophageal MUC1 expression have shown conflicting results. One found MUC1 in 100% of 52 oesophageal adenocarcinoma (OA) patient’s using an anti-MUC1 antibody(1), whilst another found no expression in 23 OA cases at the RNA level(2). It is probable that detection of MUC1 repeat domains varies in the progression to cancer due to changes in glycosylation. This study aims to characterise oesophageal MUC1 expression using antibodies binding extracellular peptide repeats and an intracellular epitope unaffected by surface glycosylation. <h3>Methods</h3> 138 paraffin embedded specimens were selected from 106 patients containing normal squamous (Sq; n = 34), normal gastric (G; n = 15), non-dysplastic Barrett’s (NDBE; n = 27), low grade dysplasia (LGD; n = 22), carcinoma in-situ (HGD/IMC; n = 35) and invasive OA (IOA; n = 21). 11 IOA cases had matched specimens containing infiltrated lymph nodes (LN). Immunohistochemistry was performed using the antibodies CT2 (binding the MUC1 cytoplasmic tail)(3), NCL-MUC-1(binding the epitope PDTRPAP of the extracellular peptide) and HuHMFG1 (binding PDTR of the extracellular peptide). Intensity (0 to 3+) and extent (0; &lt; 1% = 1; 1–10% = 2; 10–33% = 3; 33–66% = 4; &gt; 66% = 5) of tissue staining was scored. Positive cases were defined as those staining 2+/3+ in &gt; 10% of the pathology examined. <h3>Results</h3> MUC1 was shown to be significantly expressed using our antibody panel (HuHMFG1; CT2; NCL-MUC-1) in Sq (61%; 38%; 40%), G (100%; 100%; 86%), NDBE (96%; 100%; 6%), LGD (91%; 86%; 12%), HGD/IMC (91%; 97%; 19%) and IOA (95%; 91%; 82%). 100% of the metastatic OA group with infiltrated LNs stained positively with HuHMFG1. Using internal MUC1 detection with CT2 for comparison, the sensitivity &amp; positive predictive value for external MUC1 detection were 95%; 95% for HuHMFG1 and 40%; 93% for NCL-MUC-1. <h3>Conclusion</h3> This study suggests MUC1 expression inferred by detection with HuHMFG1 and CT2, binding extra and intracellularly, increases early in progression to OA. The MUC1 epitope bound by NCL-MUC-1 appears later. This may be due to changes in glycosylation during progression. Therapeutic modalities targeting MUC1 may be applicable to the majority of patients with preneoplastic BE and OA. <h3>Disclosure of Interest</h3> None Declared <h3>References</h3> Piessen <i>et al.</i> J. Clin. Pathol.62, 1144–1146. Guillem <i>et al.</i> Int. J. Cancer88, 856–861. Courtosy of Prof. Sandra Gendler. Mayo clinic. USA.
Haiti reconstruction is failing to reduce maternal mortality, report warns
Authors: P. Moszynski
Journal: BMJ (2011)

Lack of access to reproductive and maternal healthcare in Haiti is causing additional suffering for vulnerable women and girls still displaced after the earthquake in January 2010, warns a report from Human Rights Watch.

The charity finds that recovery efforts have failed to adequately meet the needs of women and girls, particularly their rights to health and security, despite developments in other health services. 

“More than a year and a half after the earthquake, some women and girls give birth unattended on the muddy floors of tents or trade sex for food without any protection from unwanted pregnancy,” said Kenneth Roth, executive director …
Clinical Alert Gives Breast Cancer Data, Revises Recommendations
Authors: Beverly Merz
Journal: JAMA (1988)

THE NATIONAL CANCER Institute (NCI) is still getting responses to a clinical alert it mailed out six weeks ago. In the now-familiar missive, dispatched to 13 000 physicians who treat patients with breast cancer, NCI Director Vincent T. DeVita, Jr, MD, urged consideration of adjuvant chemotherapy, hormonal therapy, or both after primary treatment for invasive earlystage breast cancer that has not spread to the lymph nodes. He did so on the basis of early results from three multicenter trials, which indicated that these adjuvant therapies improved diseasefree survival rates in women with this type of breast cancer. Because the data presented in the alert are still somewhat sketchy, physician response has been mixed, according to NCI officials. Some, who want to start patients on chemotherapy immediately, have received further information on treatment programs from the institute's Physician Data Query computer database. Others say they prefer to wait until they have
Liver-specific β-catenin knockout mice have bile canalicular abnormalities, bile secretory defect, and intrahepatic cholestasis
Authors: Tzu-Hsuan Yeh, Lindsay Krauland, Vijay Singh, Baobo Zou, Prathab Devaraj, Donna B. Stolz, Jonathan Franks, Satdarshan P. S. Monga, Eizaburo Sasatomi, Jaideep Behari
Journal: Hepatology (2010)

Beta-catenin plays important roles in liver physiology and hepatocarcinogenesis. While studying the role of β-catenin in diet-induced steatohepatitis, we recently found that liver-specific β-catenin knockout (KO) mice exhibit intrahepatic cholestasis. This study was undertaken to further characterize the role of β-catenin in biliary physiology. KO mice and wild-type (WT) littermates were fed standard chow or a diet supplemented with 0.5% cholic acid for 2 weeks. Chow-fed KO mice had higher serum and hepatic total bile acid levels and lower bile flow rate than WT mice. Expression levels of bile acid biosynthetic genes were lower and levels of major bile acid exporters were similar, which therefore could not explain the KO phenotype. Despite loss of the tight junction protein claudin-2, KO mice had preserved functional integrity of tight junctions. KO mice had bile canalicular morphologic abnormalities as evidenced by staining for F-actin and zona occludens 1. Electron microscopy revealed dilated and tortuous bile canaliculi in KO livers along with decreased canalicular and sinusoidal microvilli. KO mice on a cholic acid diet had higher hepatic and serum bile acid levels, bile ductular reaction, increased pericellular fibrosis, and dilated, misshapen bile canaliculi. Compensatory changes in expression levels of several bile acid transporters and regulatory genes were found in KO livers. Conclusion: Liver-specific loss of β-catenin leads to defective bile canalicular morphology, bile secretory defect, and intrahepatic cholestasis. Thus, our results establish a critical role for β-catenin in biliary physiology. (Hepatology 2010)
Characterization of von willebrand factor in factor VIII concentrates
Authors: William A. Fricke, Mei‐Ying Wong Yu
Journal: American Journal of Hematology (1989)

Commercial concentrates of factor VIII (FVIII) were analyzed in order to 1) determine the effects of viral inactivation on von Willebrand factor (vWF); 2) evaluate the vWF content of the new, immunopurified concentrates; and 3) assess their potential for correcting the long bleeding time of von Willebrand disease (vWD). Included in our study were products that had been treated to inactivate viruses; older, untreated products; and the new, immunopurified concentrates. We measured von Willebrand factor antigen (vWF:Ag), ristocetin cofactor activity (RCoF), and vWF multimeric and subunit composition. A newly developed radioimmunoassay (RIA) was used to quantitate vWF:Ag. The vWF:Ag content varied from 0.083 micrograms/IU FVIII:C for Hemofil M to 32.2 micrograms/IU FVIII:C for Humate-P, whereas pooled normal human plasma (NHP) contained 6.3 micrograms/IU FVIII:C. The RCoF varied from 0.0007 to 2.09 U/IU FVIII:C, with the immunopurified concentrates having the lowest values and Humate-P the highest. The ratio of RCoF to vWF:Ag ranged from 11 to 96 U/mg, as compared to a ratio of 160 for NHP. All of the concentrates lacked the largest vWF multimers, and all had abnormal triplet patterns. Modest differences between some untreated concentrates and their treated counterparts were noted. As expected, the immunopurified concentrates had much lower levels of all vWF activities than the conventionally prepared products. Our data suggest that none of the concentrates have as great a capacity as NHP to correct the prolonged bleeding time of von Willebrand disease.
Clinical significance of worsening portal hypertension during long-term medical treatment in patients with cirrhosis who had been classified as early good-responders on haemodynamic criteria
Authors: Carlo Merkel, Massimo Bolognesi, Annalisa Berzigotti, Piero Amodio, Lucia Cavasin, Ilaria Maria Casarotto, Marco Zoli, Angelo Gatta
Journal: Journal of Hepatology (2009)
Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis
Authors: S. Trelle, S. Reichenbach, S. Wandel, P. Hildebrand, B. Tschannen, P. M. Villiger, M. Egger, P. Juni
Journal: BMJ (2011)

<b>Objective</b> To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs. <b>Design</b> Network meta-analysis. <b>Data sources</b> Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data. <b>Study selection</b> All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility. <b>Data extraction</b> The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data. <b>Data synthesis</b> 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death. <b>Conclusions</b> Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.
Migration of cytotoxic lymphocytes in cell cycle permits local MHC I–dependent control of division at sites of viral infection
Authors: Silvia S. Kang, Jasmin Herz, Jiyun V. Kim, Debasis Nayak, Phillip Stewart-Hutchinson, Michael L. Dustin, Dorian B. McGavern
Journal: The Journal of Experimental Medicine (2011)

After virus infection, cytotoxic T lymphocytes (CTLs) divide rapidly to eradicate the pathogen and prevent the establishment of persistence. The magnitude of an antiviral CTL response is thought to be controlled by the initiation of a cell cycle program within lymphoid tissues. However, it is presently not known whether this division program proceeds during migration or is influenced locally at sites of viral infection. We demonstrate that antiviral CTLs remain in cell cycle while transiting to infected tissues. Up to one third of virus-specific CTLs within blood were found to be in cell cycle after infection with lymphocytic choriomeningitis virus or vesicular stomatitis virus. Using two-photon microscopy, we found that effector CTL divided rapidly upon arrest in the virus-infected central nervous system as well as in meningeal blood vessels. We also observed that MHC I–dependent interactions, but not costimulation, influenced the division program by advancing effector CTL through stages of the cell cycle. These results demonstrate that CTLs are poised to divide in transit and that their numbers can be influenced locally at the site of infection through interactions with cells displaying cognate antigen.
Perez on Medicine
Authors: T. Treasure
Journal: BMJ (1994)

Jose Perez, Wayman R Spence WRS Publishing, $29.95, pp 64 ISBN 1-56796-005-7

In a series of 29 oil paintings, reproduced as full page colour plates, the American artist Jose Perez shows us how he sees the medical profession. If it makes you any more comfortable, it is how he sees the American medical profession, but we are not that far away and are getting closer, and it does no harm to have a mirror held up to us sometimes.

Perez's pictures are wonderfully complicated, crowded with detail. As the gaze runs over the page one thing after another catches the eye. Sometimes just two …
Dietary sodium intake and the risk of airway hyperreactivity in a random adult population.
Authors: J Britton, I Pavord, K Richards, A Knox, A Wisniewski, S Weiss, A Tattersfield
Journal: Thorax (1994)

BACKGROUND--High dietary sodium intake has been identified as a potential cause of asthma and airway hyperreactivity. This study was designed to test the hypothesis that dietary sodium intake is an independent determinant of the risk of hyperreactivity in the general population, and to assess the role of atopy in the association between these factors. METHODS--Airway reactivity to methacholine, atopy, 24 hour urinary sodium excretion, and self-reported smoking and symptom history were measured in a random sample of 1702 adults aged 18-70 from an administrative district of Nottingham. Hyperreactivity was defined as a PD20FEV1 of 12.25 mumol or less, and atopy was defined quantitatively as the mean allergen skin weal response to Dermatophagoides pteronyssinus, cat fur, and grass pollen, and categorically as the occurrence of any allergen response 1 mm or greater than the saline control. Multiple logistic regression analysis was used to estimate the independent relative odds of hyperreactivity, atopy, or symptoms in relation to sodium excretion in all 1702 subjects, and multiple linear regression to assess the independent relation between sodium excretion and mean allergen skin weal diameter, and the PD20 value amongst hyperreactive subjects. RESULTS--There was no relation between the relative odds of hyperreactivity to methacholine and 24 hour urinary sodium excretion, either before or after adjustment for age, smoking, allergen skin weal diameter, and sex, and similarly no relation if the analysis was restricted to men or women only. The relative odds of having at least one allergen skin test response 1 mm greater than the saline control were increased in relation to sodium excretion after adjustment for age, sex, and smoking by a ratio of 2.08 (95% CI 1.04 to 4.15) per log10 unit increase in sodium excretion, but there was no evidence of an association between sodium excretion and the occurrence of self-reported wheeze, hay fever, eczema, or asthma. There was no relation between 24 hour sodium excretion and the magnitude of the mean allergen skin weal response or the PD20 value. CONCLUSIONS--These findings do not support the hypothesis that a high dietary sodium intake is a risk factor for airway hyperreactivity or atopic disease in the general adult population.