tbuckley/cabot-search huggingface dataset:
Outcome After Pathologic Complete Eradication of Cytologically Proven Breast Cancer Axillary Node Metastases Following Primary Chemotherapy
Authors: Bryan T. Hennessy, Gabriel N. Hortobagyi, Roman Rouzier, Henry Kuerer, Nour Sneige, Aman U. Buzdar, Shu Wan Kau, Bruno Fornage, Aysegul Sahin, Kristine Broglio, S. Eva Singletary, Vicente Valero
Journal: Journal of Clinical Oncology (2005)

Pathologic complete remission (pCR) of primary breast tumors after primary chemotherapy (PCT) is associated with higher relapse-free survival (RFS) and overall survival (OS) rates. The purpose of this study was to determine long-term outcome in patients achieving pCR of cytologically proven axillary lymph node (ALN) metastases.Patients with cytologically documented ALN metastases were treated in five prospective PCT trials. After surgery, patients were subdivided into those with and without residual ALN carcinoma. Survival was calculated by the Kaplan-Meier method.Of 925 patients treated, 403 patients had cytologically confirmed ALN metastases. Eighty-nine patients (22%) achieved ALN pCR after PCT. Compared with the group without ALN pCR, 5-year OS and RFS were improved in patients achieving ALN pCR (93% [95% CI, 87.5 to 98.5] and 87% [95% CI, 79.7 to 94.3] v 72% [95% CI, 66.5 to 77.5] and 60% [95% CI, 54.1 to 65.9], respectively; P < .0001). Residual primary tumor did not affect outcome of those with ALN pCR. Combination anthracycline/taxane-based PCT resulted in significantly more ALN pCRs, although outcome after ALN pCR was not improved by taxanes. We constructed a nomogram demonstrating that patients who do not benefit from neoadjuvant anthracyclines are unlikely to benefit from subsequent taxanes.ALN pCR is associated with an excellent prognosis, even with a residual primary tumor, pointing to biologic differences between primary and metastatic cells. ALN pCR represents an early surrogate marker of long-term outcome. Response to initial PCT has important potential as a guide to subsequent therapy.
Association Between Hyperglycemia at Admission During Hospitalization for Acute Myocardial Infarction and Subsequent Diabetes: Insights From the Veterans Administration Cardiac Care Follow-up Clinical Study
Authors: Supriya Shore, Joleen A. Borgerding, Ina Gylys-Colwell, Kelly McDermott, P. Michael Ho, Maggie N. Tillquist, Elliott Lowy, Darren K. McGuire, Joshua M. Stolker, Suzanne V. Arnold, Mikhail Kosiborod, Thomas M. Maddox
Journal: Diabetes Care (2013)

Among patients with acute myocardial infarction (AMI) without known diabetes, hyperglycemia at admission is common and associated with worse outcomes. It may represent developing diabetes, but this association is unclear. Therefore, we examined the association between hyperglycemia (≥140 mg/dL) at admission and evidence of diabetes among patients with AMI without known diabetes within 6 months of their hospitalization.We studied a national cohort of consecutive patients with AMI without known diabetes presenting at 127 Veterans Affairs hospitals between October 2005 and March 2011. Evidence of diabetes either at discharge or in the following 6 months was ascertained using diagnostic codes, medication prescriptions, and/or elevated hemoglobin A1c. Association between hyperglycemia at admission and evidence of diabetes was evaluated using regression modeling.Among 10,499 patients with AMI without known diabetes, 98% were men and 1,761 (16.8%) had hyperglycemia at admission. Within 6 months following their index hospitalization, 208 patients (11.8%) with hyperglycemia at admission had evidence of diabetes compared with 443 patients (5.1%) without hyperglycemia at admission (P < 0.001). After multivariable adjustment, hyperglycemia at admission was significantly associated with subsequent diabetes odds ratio 2.56 (95% CI 2.15-3.06). Among those with new evidence of diabetes, 41% patients (267 of 651) had a hemoglobin A1c ≥6.5% without accompanying diagnostic codes or medication prescriptions, suggesting they had unrecognized diabetes.Hyperglycemia at admission occurred in one of six patients with AMI without known diabetes and was significantly associated with new evidence of diabetes in the 6 months following hospitalization. In addition, two of five patients with evidence of diabetes were potentially unrecognized. Accordingly, diabetes-screening programs for hyperglycemic patients with AMI may be an important component of optimal care.
Apoptosis in different cutaneous manifestations of lupus erythematosus
Authors: B. Baima, M. Sticherling
Journal: British Journal of Dermatology (2001)

It has been shown that dysregulation of apoptosis may play an important part in the development of autoimmune diseases such as lupus erythematosus (LE).The aim of the study was to investigate whether apoptosis may contribute to the pathogenesis of cutaneous changes in LE and whether certain apoptosis-related markers such as Fas antigen, Fas ligand (FasL), Bcl-2 and Bax proteins take part in this process.Cryostat sections of lesional skin from 31 patients with LE-specific skin lesions [discoid (DLE) n = 17, subacute cutaneous (SCLE) n = 10 and acute cutaneous (ACLE) n = 4] and normal skin samples (n = 10) were stained with monoclonal antibodies against Fas antigen, FasL, Bcl-2 and Bax proteins. For the detection of apoptotic nuclei, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling technique (TUNEL) was employed.The keratinocytes of the epidermis and mononuclear cells of the dermal infiltrate in LE showed a significant increase in Fas antigen expression as compared with normal skin. The anti-Bcl-2 staining intensity within the epidermis was markedly decreased, while the mononuclear infiltrate stained for this protein just like single lymphocytes scattered in normal skin. There was an increase of FasL and/or Bax-positive cells within the dermal infiltrate, but not in the epidermis or in the hair follicles. Accumulation of FasL-bearing cells around hair follicles was a hallmark of DLE. Numerous cells with pyknotic, TUNEL-positive nuclei were demonstrated in the epidermis, in hair follicles and among the cells of the dermal infiltrate. The extent of apoptosis in lesional skin was greater in acute and subacute cutaneous than in discoid forms of LE.The exact stimulus triggering apoptosis in cutaneous LE still remains unknown but the present study provides strong evidence that the reduction of Bcl-2 expression in the basal cells is associated with the overexpression of Fas antigen and correlates directly with the extent of apoptosis in the epidermis. Furthermore, the current study indicates that the extent of apoptosis in both the epidermis and dermal infiltrate may correlate with the chronological development of LE skin lesions.
PTU-137 Pneumococcal Vaccination In Patients With Liver Cirrhosis – Is The Message Being Heard?
Authors: V Sehgal, H Alexander, K Besherdas
Journal: Gut (2014)

<h3>Introduction</h3> Patients with liver cirrhosis are immunocompromised and prone to invasive infection where outcomes are usually poor. In particular, cirrhosis is a major risk factor for severe pneumococcal infection which has a mortality rate of up to 20%. Whilst patients awaiting liver transplantation routinely receive the pneumococcal vaccine, it is less clear whether the remainder of patients with cirrhosis do so or not. The present literature suggests that pneumococcal vaccination prophylaxis should be administered in cirrhotic patients and revaccination desirable at 5-yearly intervals. The aims of this study were to assess whether patients with liver cirrhosis received pneumococcal vaccination in line with current recommendations at a single centre in the UK. <h3>Methods</h3> A retrospective analysis of all patients with biopsy-proven liver cirrhosis, irrespective of aetiology, over a 7-year period (2005–2012) at Barnet and Chase Farm Hospitals was performed. We used a database of patients with biopsy-proven cirrhosis created by our histopathology department. Patient’s primary care physicians were contacted in writing to assess whether they had received the pneumococcal vaccine. <h3>Results</h3> 37 patients had biopsy-proven liver cirrhosis over the audit period. There was no response from the primary care physicians of 6 patients. Data for 31 patients (17 male, 14 female), median age 50 years were analysed. 14 (45%) patients had received the pneumococcal vaccine. 4 (28.5%) of these patients were vaccinated after their histopathological diagnosis of cirrhosis was proven. The median time interval from diagnosis to vaccination was 24 months in this group of patients. Of the 7 patients vaccinated before 2007, none had received a repeat vaccine after 5 years. <h3>Conclusion</h3> More than half of patients with biopsy-proven liver cirrhosis in our study did not receive the pneumococcal vaccine placing these patients at risk of life threatening preventable disease. None of the patients who received the vaccine initially were revaccinated at five yearly intervals as present literature would recommend. We would recommend an increased awareness of the importance of regular pneumococcal vaccination to all healthcare professionals, primary care physicians and those in secondary care, who come into contact with this important and growing cohort of patients. <h3>Disclosure of Interest</h3> None Declared.
Pharmacology of Laxatives
Authors: H J Binder
Journal: The Annual Review of Pharmacology and Toxicology (1977)

Effective laxative action results in an increase in fecal water excretion, and increased fecal water excretion is usually secondary to altered intestinal fluid and electrolyte movement. Both an understanding of the process(es) by which laxatives work and a classification of laxatives therefore should be based on the mechanism(s) by which cathartics either increase fecal water excretion or alter intestinal fluid and elec­ trolyte movement. Since most laxatives were initially introduced into clinical prac­ tice on an empirical basis, the traditional classification of laxatives found in textbooks of pharmacology and therapeutics employ arbitrary categories that do not reflect the pathophysiological principles of altered intestinal fluid and electrolyte transport (1-3). Diarrhea, as well as laxative action, is characterized by increased fecal water excretion. Recent studies of intestinal fluid and electrolyte movement in patients with various diarrheal illnesses have revealed alteration of water and sodium move­ ment (4-6). Dihydroxy bile acids and ricinoleic acid are classical laxatives and have also been implicated in the pathophysiology of diarrhea of ileal resection and the diarrhea of steatorrhea respectively (7,8). Further, laxative abuse has been identified as responsible for an occasional case of previously undiagnosed watery diarrhea (9, 10). Although clinicians are now beginning to consider diarrhea in terms of in­ creased fecal water excretion, altered intestinal electrolyte movement, and intestinal electrolyte secretion, much less attention has been given to similar considerations in regard to the pharmacology of laxatives (11). This review summarizes recent observations of the effect of laxatives on intestinal function, which indicate that most laxatives alter intestinal electrolyte transport, and provides a basis for the develop­ ment of a classification of laxatives based on the effect of these drugs on intestinal electrolyte transport.
Glycosaminoglycans Enhance the Trifluoroethanol-Induced Extension of β2-Microglobulin–Related Amyloid Fibrils at a Neutral pH
Authors: Suguru Yamamoto, Itaru Yamaguchi, Kazuhiro Hasegawa, Shinobu Tsutsumi, Yuji Goto, Fumitake Gejyo, Hironobu Naiki
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. β<sub>2</sub>-Microglobulin–related (Aβ2M) amyloidosis is a frequent and serious complication in patients on long-term dialysis, and β<sub>2</sub>-microglobulin is a major structural component of Aβ2M amyloid fibrils. Several biologic molecules inhibiting the depolymerization of Aβ2M amyloid fibrils at a neutral pH were found recently. The effect of trifluoroethanol and glycosaminoglycans (GAG) on the extension of the fibrils at a neutral pH was investigated with the use of fluorescence spectroscopy with thioflavin T, circular dichroism spectroscopy, and electron microscopy. Trifluoroethanol at concentrations of up to 20% (vol/vol) caused fibril extension of heparin-stabilized seeds, inducing a subtle change in the tertiary structure of β<sub>2</sub>-microglobulin and stabilizing the fibrils at a neutral pH. This extension reaction followed a first-order kinetic model. In addition, some GAG, especially heparin, dose-dependently enhanced the fibril extension. These results suggest that some GAG, especially heparin, may bind to the fibrils and enhance their deposition <i>in vivo</i>. Thus, the experimental system described here should be useful to search for the factors that accelerate Aβ2M amyloid deposition <i>in vivo</i>. In addition, the interference of the binding of GAG to Aβ2M amyloid fibrils may be an attractive therapeutic modality. E-mail: naiki@fmsrsa.fukui-med.ac.jp
Reply to Catania
Authors: B. F. Skinner
Journal: Behavioral and Brain Sciences (1984)

What is selected? Around the turn of the century, Samuel Butler made the point that a hen is only an egg's way of making another egg. He was anticipating the view that the organism is the servant of the gene. But the organism is needed by the gene. Variations occur in genes but must be selected in organisms. If we regard a culture as a social environment that shapes the behavior of new members of a group, then we can say that a culture is simply an individual's way of producing other enculturated individuals. Variations occur in the individual, but it is the culture with its practices that survives. Many practices evolve and survive independently of particular cultures, just as eyes, ears, wings, and legs – the “practices” of species – evolve and survive independently of particular species.
Mass Treatment with Single-Dose Azithromycin for Trachoma
Authors: Anthony W. Solomon, Martin J. Holland, Neal D.E. Alexander, Patrick A. Massae, Aura Aguirre, Angels Natividad-Sancho, Sandra Molina, Salesia Safari, John F. Shao, Paul Courtright, Rosanna W. Peeling, Sheila K. West, Robin L. Bailey, Allen Foster, David C.W. Mabey
Journal: New England Journal of Medicine (2004)

Trachoma, caused by repeated ocular infection with Chlamydia trachomatis, is an important cause of blindness. Current recommended dosing intervals for mass azithromycin treatment for trachoma are based on a mathematical model.We collected conjunctival swabs for quantitative polymerase-chain-reaction assay of C. trachomatis before and 2, 6, 12, 18, and 24 months after mass treatment with azithromycin in a Tanzanian community in which trachoma was endemic. For ethical reasons, at 6, 12, and 18 months, we gave tetracycline eye ointment to residents who had clinically active trachoma.At baseline, 956 of 978 residents (97.8 percent) received either one oral dose of azithromycin or (if azithromycin was contraindicated) a course of tetracycline eye ointment. The prevalence of infection fell from 9.5 percent before mass treatment to 2.1 percent at 2 months and 0.1 percent at 24 months. The quantitative burden of ocular C. trachomatis infection in the community was 13.9 percent of the pretreatment level at 2 months and 0.8 percent at 24 months. At each time point after baseline, over 90 percent of the total community burden of C. trachomatis infection was found among subjects who had been positive the previous time they were tested.The prevalence and intensity of infection fell dramatically and remained low for two years after treatment. One round of very-high-coverage mass treatment with azithromycin, perhaps aided by subsequent periodic use of tetracycline eye ointment for persons with active disease, can interrupt the transmission of ocular C. trachomatis infection.
POLYUNSATURATED FATTY ACID REGULATION OF GENES OF LIPID METABOLISM
Authors: Harini Sampath, James M. Ntambi
Journal: Annual Review of Nutrition (2005)

▪ Abstract Apart from being an important macronutrient, dietary fat has recently gained much prominence for its role in regulating gene expression. Polyunsaturated fatty acids (PUFAs) affect gene expression through various mechanisms including, but not limited to, changes in membrane composition, intracellular calcium levels, and eicosanoid production. Furthermore, PUFAs and their various metabolites can act at the level of the nucleus, in conjunction with nuclear receptors and transcription factors, to affect the transcription of a variety of genes. Several of these transcription mediators have been identified and include the nuclear receptors peroxisome proliferator-activated receptor (PPAR), hepatocyte nuclear factor (HNF)-4α, and liver X receptor (LXR) and the transcription factors sterol-regulatory element binding protein (SREBP) and nuclear factor-κB (NFκB). Their interaction with PUFAs has been shown to be critical to the regulation of several key genes of lipid metabolism. Working out the mechanisms by which these interactions and consequent effects occur is proving to be complicated but is invaluable to our understanding of the role that dietary fat can play in disease management and prevention.
Chronic bronchitis before age 50 years predicts incident airflow limitation and mortality risk
Authors: S Guerra, D L Sherrill, C Venker, C M Ceccato, M Halonen, F D Martinez
Journal: Thorax (2009)

Previous studies on the relationship of chronic bronchitis to incident airflow limitation and all-cause mortality have provided conflicting results, with positive findings reported mainly by studies that included populations of young adults. This study sought to determine whether having chronic cough and sputum production in the absence of airflow limitation is associated with onset of airflow limitation, all-cause mortality and serum levels of C-reactive protein (CRP) and interleukin-8 (IL-8), and whether subjects' age influences these relationships.1412 participants in the long-term Tucson Epidemiological Study of Airway Obstructive Disease who at enrolment (1972-1973) were 21-80 years old and had FEV(1)/FVC (forced expiratory volume in 1 s/forced vital capacity) > or = 70% and no asthma were identified. Chronic bronchitis was defined as cough and phlegm production on most days for > or = 3 months in two or more consecutive years. Incidence of airflow limitation was defined as the first follow-up survey with FEV(1)/FVC <70%. Serum IL-8 and CRP levels were measured in cryopreserved samples from the enrolment survey.After adjusting for covariates, chronic bronchitis at enrolment significantly increased the risk for incident airflow limitation and all-cause mortality among subjects <50 years old (HR 2.2, 95% CI 1.3 to 3.8; and HR 2.2, 95% CI 1.3 to 3.8; respectively), but not among subjects > or = 50 years old (HR 0.9, 95% CI 0.6 to 1.4; and HR 1.0, 95% CI 0.7 to 1.3). Chronic bronchitis was associated with increased IL-8 and CRP serum levels only among subjects <50 years old.Among adults <50 years old, chronic bronchitis unaccompanied by airflow limitation may represent an early marker of susceptibility to the effects of cigarette smoking on systemic inflammation and long-term risk for chronic obstructive pulmonary disease and all-cause mortality.
Siderophore Biosynthesis But Not Reductive Iron Assimilation Is Essential for<i>Aspergillus fumigatus</i>Virulence
Authors: Markus Schrettl, Elaine Bignell, Claudia Kragl, Chistoph Joechl, Tom Rogers, Herbert N. Arst, Ken Haynes, Hubertus Haas
Journal: The Journal of Experimental Medicine (2004)

The ability to acquire iron in vivo is essential for most microbial pathogens. Here we show that Aspergillus fumigatus does not have specific mechanisms for the utilization of host iron sources. However, it does have functional siderophore-assisted iron mobilization and reductive iron assimilation systems, both of which are induced upon iron deprivation. Abrogation of reductive iron assimilation, by inactivation of the high affinity iron permease (FtrA), has no effect on virulence in a murine model of invasive aspergillosis. In striking contrast, A. fumigatus l-ornithine-N 5-monooxygenase (SidA), which catalyses the first committed step of hydroxamate-type siderophore biosynthesis, is absolutely essential for virulence. Thus, A. fumigatus SidA is an essential virulence attribute. Combined with the absence of a sidA ortholog—and the fungal siderophore system in general—in mammals, these data demonstrate that the siderophore biosynthetic pathway represents a promising new target for the development of antifungal therapies.
"Odd-looking" oesophageal varices
Authors: A Wiechowska-Kozlowska, A Bialek, M Wojcicki, P Milkiewicz
Journal: Gut (2009)

A 62-year-old male presented with mild dysphagia and upper abdominal discomfort. He underwent upper gastrointestinal endoscopy, which was described as showing “unusual- looking” oesophageal varices. …
Intrahepatic cholangiocarcinoma can arise from Notch-mediated conversion of hepatocytes
Authors: Sayaka Sekiya, Atsushi Suzuki
Journal: Journal of Clinical Investigation (2012)

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignancy in the liver. ICC has been classified as a malignant tumor arising from cholangiocytes; however, the co-occurrence of ICC and viral hepatitis suggests that ICC originates in hepatocytes. In order to determine the cellular origin of ICC, we used a mouse model of ICC in which hepatocytes and cholangiocytes were labeled with heritable, cell type–specific reporters. Our studies reveal that ICC is generated by biliary lineage cells derived from hepatocytes, rather than cholangiocytes. Additionally, we found that Notch activation is critical for hepatocyte conversion into biliary lineage cells during the onset of ICC and its subsequent malignancy and progression. These findings will help to elucidate the pathogenic mechanism of ICC and to develop therapeutic strategies for this refractory disease.
Differences in the performance of commercially available 10-g monofilaments.
Authors: J Booth, M J Young
Journal: Diabetes Care (2000)

OBJECTIVE: This independent study was designed to determine the accuracy of 10-g monofilaments manufactured and supplied by popular commercial companies. RESEARCH DESIGN AND METHODS: A total of 160 new 10-g monofilaments (30 Semmes-Weinstein monofilaments [North Coast Medical], 30 Timesco/Sensory Testing Systems monofilaments, 50 Owen Mumford Neuropens, and 50 Bailey Instruments monofilaments) were tested using a calibrated load cell. Each monofilament was subjected to 10 mechanical bucklings of 10 mm while the load cell detected the maximum buckling force. Longevity testing was performed on a subset of the monofilaments by subjecting them to continuous compressions until the buckling force was &amp;lt;9 g. RESULTS: The accuracy of monofilaments to produce a buckling force of 10 g varies among manufacturers. Bailey Instruments and Owen Mumford filaments were the most accurate with 100% buckling within +/-1.0 g of 10 g. Only 70% of the Semmes-Weinstein monofilaments from North Coast Medical buckled within +/-1.0 g of 10 g. A total of 80% of Timesco filaments buckled at &amp;lt;8 g. Longevity tests on Bailey Instruments and Owen Mumford monofilaments demonstrated that 80% continued to buckle within 10% of 10 g after 100 compressions, but only 50% were within this range after 200 compressions. The maximum amount of recovery achieved in any monofilament occurred within 24 h. CONCLUSIONS: Monofilaments made by either Bailey Instruments or Owen Mumford are recommended for use in clinical practice. North Coast Medical monofilaments may operate differently in the U.S. because of different environmental conditions such as differences in humidity. Timesco/Sensory Testing Systems monofilaments were neither accurate enough nor Conformity European marked to recommend their use in the U.K. Longevity and recovery testing suggest that each monofilament will survive usage on approximately 10 patients before needing a recovery time of 24 h before further use.