tbuckley/cabot-search huggingface dataset:
Therapy of Hepatitis C: From Empiricism to Eradication
Authors: Jean-Michel Pawlotsky
Journal: Hepatology (2006)

The complications of chronic hepatitis C virus infection can be prevented by antiviral therapy. The initial choice of interferon alfa and, subsequently, ribavirin as potential treatments for chronic hepatitis C was empirical. Nevertheless, the combination of pegylated interferon alfa and ribavirin has become the standard treatment of chronic hepatitis C. Since the advent of interferon-based therapy, enormous progress has been made in understanding the mechanisms of treatment efficacy and failure, and in everyday patient management. The principal advances are: a better understanding of hepatitis C virus steady-state kinetics and the antiviral mechanisms of interferon and ribavirin; easier treatment decisions thanks to novel assays to assess liver disease severity and the virological characteristics of infection; a better use of virological tests to tailor therapy; a better management of adverse effects; a better understanding of virological treatment failure; and a better management of “special” populations, including patients with decompensated cirrhosis and end-stage liver disease, liver transplant recipients, hemodialysis patients and renal transplant recipients, human immunodeficiency virus-coinfected patients, intravenous drug users and patients on opiate replacement therapy, or virological non responders to previous therapies. Steady-state HCV kinetics offers several potential targets for new drugs. These targets should ideally be hit simultaneously in order to achieve viral eradication within a reasonable time frame. Future drugs for HCV infection will belong to four main categories, including new interferons, alternatives to ribavirin, specific HCV inhibitors, and immune modulators. New treatments and vaccines might make it possible to eradicate HCV in the future.
Plasma Cholesterol Regulates Soluble Cell Adhesion Molecule Expression in Familial Hypercholesterolemia
Authors: T. Sampietro, M. Tuoni, M. Ferdeghini, A. Ciardi, P. Marraccini, C. Prontera, G. Sassi, M. Taddei, A. Bionda
Journal: Circulation (1997)

Background Hypercholesterolemia is associated with endothelial dysfunction. On the basis of the hypothesis that high plasma cholesterol per se may be a sufficient stimulus to upregulate endothelial adhesiveness and that this phenomenon might be reversible, soluble endothelial leukocyte adhesion molecules (sELAMs) were studied in patients with familial hypercholesterolemia undergoing LDL apheresis. Methods and Results Selective LDL absorption by dextran sulfate columns was used to treat plasma volumes of 6.5 to 9.2 L; after LDL apheresis, total cholesterol, LDL cholesterol, apolipoprotein B, triglycerides, and lipoprotein(a) levels were reduced by 74%, 82%, 79%, 56%, and 86%, respectively. Soluble intercellular adhesion molecule-1 (sICAM-1) and sELAM-1 were measured before, immediately after, and 2 and 6 days after LDL apheresis. Basal sICAM-1 and sELAM-1 values were higher than in healthy control subjects. After LDL apheresis, they decreased ( P &lt;.0001 and P &lt;.0004, respectively); their removal by extracorporeal circulation components was excluded. Individual pretreatment and posttreatment values of sICAM-1 and sELAM-1 were positively correlated ( P &lt;.0001 and P &lt;.001, respectively) with total cholesterol; their rebound curves showed patterns similar to the total cholesterol rebound curve but not to the triglyceride and lipoprotein(a) curves. Conclusions In the absence of changes in clinical chemical parameters, tumor necrosis factor-α, interleukin-6, and acute-phase reactant proteins, these results confirm in a clinical setting the upregulation of endothelial adhesiveness observed in experimental hypercholesterolemia and suggest a direct role for cholesterol in regulating this phenomenon, at least in familial hypercholesterolemia.
Reinduction With Certolizumab Pegol in Patients With Relapsed Crohn's Disease: Results From the PRECiSE 4 Study
Authors: William J. Sandborn, Stefan Schreiber, Stephen B. Hanauer, Jean–Frédéric Colombel, Ralph Bloomfield, Gary R. Lichtenstein
Journal: Clinical Gastroenterology and Hepatology (2010)
Association of infection with a specific hepatitis G virus strain with fulminant hepatitis
Authors: L. Sheng, A. Soumillion, N. Beckers, C.-G. Wu, C. Verslype, F. Nevens, J. Pirenne, R. Aerts, H. Kosala, J. Fevery, S. H. Yap
Journal: Journal of Hepatology (1998)
PWE-141 Hepatocellular carcinoma and microvascular invasion in cirrhotic and non-cirrhotic livers: are they different diseases?
Authors: R Young, A Hakeem, A Nair, A Young, J Wyatt, G Toogood, P Lodge, R Prasad
Journal: Gut (2012)

<h3>Introduction</h3> Hepatocellular carcinoma (HCC) behaves differently in cirrhotic and non-cirrhotic livers. Microvascular invasion (MVI) is a key determinant of outcome following curative treatment for HCC. Despite attempts to reach a consensus, reliably identifying microvascular invasion remains difficult. Interrogating factors influencing MVI in patients with or without cirrhosis may determine more reliably identifiable factors or surrogates for MVI and provide valuable insight into the underlying biology of HCC. <h3>Methods</h3> Review of a prospective database of 229 consecutive patients undergoing hepatectomy (n=164) or transplantation (n=65) for HCC at St James9s University Hospital, UK between 1998 and 2011. Diagnosis was based on published guidelines and incidental explant tumours excluded. 115, 50.2% occurred in cirrhotic compared to 114, 49.8% in non-cirrhotic livers. Clinico-pathological characteristics were correlated with survival and MVI. Survival was calculated using the Kaplan–Meier method with Log-rank and Cox stepwise regression for survival comparisons. Univariate χ<sup>2</sup> and multivariate logistic regression were used to analyse relationships between clinico-pathological variables and MVI (p&lt;0.05 was indicative of statistical significance). <h3>Results</h3> In non-cirrhotic patients recurrence independently predicted overall survival (OS) (p=0.001) while multifocal tumours (p=0.042) and viral aetiology (p=0.029) independently predicted disease free survival (DFS). In cirrhotic patients recurrence (p&lt;0.001), MVI (p&lt;0.001) and tumour size &gt;5 cm (p&lt;0.005) predicted overall survival (OS) and disease free survival (DFS) in univariate analysis. Only recurrence (p=0.001) for OS and MVI (p=0.002) and tumour size &gt;5 cm (p=0.027) for DFS retained independence on multivariate analysis. Univariate analysis of pre-operative variables revealed MVI was significantly associated with multifocal HCC and poor differentiation in non-cirrhotic patients (p=0.04 and p=0.019), and with viral aetiology in cirrhotic patients (p=0.047). <h3>Conclusion</h3> In cirrhotic patients MVI was an independent predictor of DFS while recurrence strongly determined OS. Viral aetiology was the only significant pre-operative factor associated with MVI in the explant. In non-cirrhotic patients multifocality strongly predicted DFS and was associated with MVI. We hypothesise that multifocality in non-cirrhotic HCC may actually be representative of MVI rather than multifocal de novo tumour formation. Given the challenges of robustly identifying MVI in these patients, multifocality could be an extremely useful prognosticator and histopathological indicator of MVI, which we know carries series implications for our patients. <h3>Competing interests</h3> None declared.
Tumor Endothelial Cells Join the Resistance
Authors: Andrew C. Dudley, Michael Klagsbrun
Journal: Clinical Cancer Research (2009)

Abstract The field of antiangiogenesis research has been met with some surprises, including the realization that tumor blood vessels are more complex and labile than expected. In this issue of Clinical Cancer Research, Xiong and colleagues show that tumor-specific endothelial cells are less sensitive to cytotoxic and antiangiogenic drugs compared to their normal counterparts.
IgE reactivity to latex allergens among sensitized healthcare workers before and after immunotherapy with latex
Authors: J. Sastre, M. Raulf‐Heimsoth, H.‐P. Rihs, M. Fernández‐Nieto, D. Barber, M. Lombardero, S. Martín, S. Quirce
Journal: Allergy (2006)

Background: New IgE sensitizations to proteins in allergen extracts have been shown to occur during allergen‐specific immunotherapy (IT). Methods: Twenty‐four healthcare workers (HCWs) – patients included in a latex IT study – were analysed, 16 in active treatment and eight in placebo. Sera were obtained at baseline and after 6 months of IT and analysed with immunoblotting and CAP System with eight single recombinant latex allergens (rHev b 1, 3, 5, 6.01, 8, 9, 10, 11, and a mix of rHev b1, 5, 6.01 and 8). Results: After IT with latex, three patients in the active treatment group had new IgE sensitizations, one to Hev b 5, one to Hev b 11 and another to Hev b 6.01. No other significant variation in mean of specific IgE to latex or recombinant allergens were observed in patients who received placebo or active treatment. A significant ( P = 0.012) negative correlation (−0.72) was observed between maximal tolerated dose and specific IgE to Hev b 6.01 at baseline. After IT, immunoblot analysis demonstrated a significant increase in IgE binding in a band of approximately 22 kDa ( P = 0.032) that may correspond to Hev b 6.01. New or more intense bands appeared in seven patients of the active group, while in three subjects a reduction was observed. Conclusions: Hev b 6.01 seems to be the most relevant latex allergen in HCWs. New or more intense IgE binding to latex allergenic components occurs during latex immunotherapy. However, the levels of specific IgE against these new components are low and do not seem to have clinical relevance.
Age-sex registers as a screening tool for general practice: size of the wrong address problem
Authors: A. J Silman
Journal: BMJ (1984)

Age-sex registers were compiled and updated for the east London general practices participating in a screening study for hypertension. Of 1435 addresses in the registers of two practices that were checked, 228 (16%) were incorrect, according to the return by the post office of the screening invitations and checking the addresses of the non-responders using telephone directories and the medical records. The non-responders to the screening invitation for whom a new address was not found, were visited at the address as recorded on the age-sex register. This showed that the true address error rate from the original age-sex registers was 26% and thus substantially greater than that calculated from returned letters. It is concluded that the non-acceptance rate of screening in general practice might be exaggerated as a result of the lack of a correct address for a substantial proportion of the patients on a general practice list.
Implementation of a Voluntary Hospitalist Service at a Community Teaching Hospital: Improved Clinical Efficiency and Patient Outcomes
Authors: Andrew D. Auerbach
Journal: Annals of Internal Medicine (2002)

Background: Previous investigations of the effect of the hospitalist model on resource use and patient outcomes have focused on academic medical centers or have used short follow-up periods. Objective: To determine the effects of hospitalist care on resource use and patient outcomes and whether these effects change over time. Design: Retrospective cohort study. Setting: Community-based, urban teaching hospital. Patients: 5308 patients cared for by community or hospitalist physicians in the 2 years after implementation of a voluntary hospitalist service. Measurements: Length of stay, costs, 10-day readmission rates, use of consultative services, in-hospital mortality rate, and mortality rate at 30 and 60 days. Results: Patients of hospitalists were younger than those of community physicians (65 years vs. 74 years; P < 0.001) and were more likely to be of black than of white ethnicity (33.3% vs. 17.9%; P < 0.001), have Medicaid insurance (25.1% vs. 10.2%; P < 0.001), and receive intensive care (19.9% vs. 15.8%; P < 0.001). After adjustment in multivariable models, length of stay and costs were not different in the first year of the study. In year 2, patients of hospitalists had shorter stays (0.61 day shorter; P = 0.002) and lower costs ($822 lower; P = 0.002). Over the 2 years of this study, patients of hospitalists had lower risk for death in the hospital (adjusted relative hazard, 0.71 [95% CI, 0.54 to 0.93]) and at 30 and 60 days of follow-up. Conclusions: A voluntary hospitalist service at a community-based teaching hospital produced reductions in length of stay and costs that became statistically significant in the second year of use. A mortality benefit extending beyond hospitalization was noted in both years. Future investigations are needed to understand the ways in which hospitalists increase clinical efficiency and appear to improve the quality of care.
A novel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function
Authors: Nicole Soranzo, Augusto Rendon, Christian Gieger, Chris I. Jones, Nicholas A. Watkins, Stephan Menzel, Angela Döring, Jonathan Stephens, Holger Prokisch, Wendy Erber, Simon C. Potter, Sarah L. Bray, Philippa Burns, Jennifer Jolley, Mario Falchi, Brigitte Kühnel, Jeanette Erdmann, Heribert Schunkert, Nilesh J. Samani, Thomas Illig, Stephen F. Garner, Angela Rankin, Christa Meisinger, John R. Bradley, Swee Lay Thein, Alison H. Goodall, Tim D. Spector, Panos Deloukas, Willem H. Ouwehand
Journal: Blood (2009)

Mean platelet volume (MPV) and platelet count (PLT) are highly heritable and tightly regulated traits. We performed a genome-wide association study for MPV and identified one SNP, rs342293, as having highly significant and reproducible association with MPV (per-G allele effect 0.016 +/- 0.001 log fL; P < 1.08 x 10(-24)) and PLT (per-G effect -4.55 +/- 0.80 10(9)/L; P < 7.19 x 10(-8)) in 8586 healthy subjects. Whole-genome expression analysis in the 1-MB region showed a significant association with platelet transcript levels for PIK3CG (n = 35; P = .047). The G allele at rs342293 was also associated with decreased binding of annexin V to platelets activated with collagen-related peptide (n = 84; P = .003). The region 7q22.3 identifies the first QTL influencing platelet volume, counts, and function in healthy subjects. Notably, the association signal maps to a chromosome region implicated in myeloid malignancies, indicating this site as an important regulatory site for hematopoiesis. The identification of loci regulating MPV by this and other studies will increase our insight in the processes of megakaryopoiesis and proplatelet formation, and it may aid the identification of genes that are somatically mutated in essential thrombocytosis.
British doctor appears in recruitment video for Taliban
Authors: C. Dyer
Journal: BMJ (2014)

A British doctor who fled the country while awaiting trial on charges of violent assault in the United Kingdom has reappeared in a recruitment video for the Taliban.

Mirza Tariq Ali, 39, who qualified in Pakistan and came to the UK in 2004, was convicted in his absence and sentenced to 15 months in jail in June this year. His case …
DIAGNOSTIC CLINIC FOR REHABILITATION
Authors: R. SHANDS
Journal: JAMA (1949)

With insufficient information and an inaccurate diagnosis a patient may start a program of rehabilitation totally unsuited to his handicap; hence the first major division in the organization of services for the rehabilitation of the handicapped is the diagnostic clinic. The physical qualities, mental characteristics and vocational abilities of the patient must be determined, recorded and evaluated before treatment is started. Then and then only can a rational plan leading to the restoration of this handicapped person to the best possible physical, economic and social status be formulated. The purpose of this paper is to present a few ideas on the organization and value of the diagnostic clinic for rehabilitation with several related thoughts on other problems of rehabilitation. In the practice of curative medicine, if the physician is not certain of a diagnosis, the patient is sent to a clinic in which there are medical specialists with x-ray and
Thalassemia: Recent insights into molecular mechanisms
Authors: Martin H. Steinberg, Junius G. Adams
Journal: American Journal of Hematology (1982)

Abstract Recent advances in defining the molecular basis for the thalassemia syndromes are discussed. We now realize that the causes of the thalassemia phenotype are diverse and include gene deletions, nuclear RNA processing defects, nonsense mutations, fusion genes, termination codon mutants, and unstable globin chains.
Morphological and histological features of resected hepatocellular carcinoma in cirrhotic patients in the west
Authors: François Kemeny, Jacqueline Vadrot, Andrew Wu, Claude Smadja, Jonathan L. Meakins, Dominique Franco
Journal: Hepatology (1989)

The pathological findings of 26 consecutive resections for hepatocellular carcinomas developing in cirrhotic patients were analyzed morphologically with a special interest in the presence of a capsule, vascular extension and satellite nodules. Tumor sizes varied from 2 to 11 cm. There were 20 expanding (76.9%) and six infiltrating tumors. Infiltrating tumors were significantly larger than expanding tumors (p&lt;0.01). Histologically, the most common subgroups were the trabeculated pattern (65.4%) and the Edmonson-Steiner Type II (53.9%). Of the 20 expanding tumors, only six had direct spread in the liver parenchyma adjacent to the tumor (p&lt;0.02). There was a significant relationship between the presence of a tumor extension in the distal portal branches and the presence of satellite nodules around the tumor (p&lt;0.01). Survival at 6 months was significantly lower in patients with infiltrating (16.7%) than in those with expanding tumors (75%), (p&lt;0.05). The present results indicate that pathological features of hepatocellular carcinomas in cirrhotic patients in Western countries are similar to those encountered in the East: (a) tumors are frequently encapsulated; (b) the propensity for the tumor to spread is closely related to the presence of a tumor capsule. This study suggests that a thorough preoperative search for the capsule should be made whenever resection of a hepatocellular carcinoma in a cirrhotic patient is contemplated.
Ultrasonic Diagnosis of Cruveilhier-Baumgarten Syndrome
Authors: H. B. Eisenstadt
Journal: JAMA (1982)

To the Editor.—  Jean-Pierre Capron and associates describe the Ultrasonic Diagnosis of Cruveilhier-Baumgarten Syndrome (1982;247:681). This syndrome does not refer to the periumbilical venous dilation of portal hypertension—the caput medusae—but only to the hum, murmur, and thrill that can be heard or felt in some of these cases and that may be confused with cardiac murmurs when transmitted to the chest and may be audible or palpable in the absence of gross, visible, periumbilical venous dilation. Therefore, it cannot be demonstrated by an ultrasonogram.
Cryodynamic hand angiography in the diagnosis and management of Raynaud's syndrome.
Authors: J Rösch, J M Porter, B J Gralino
Journal: Circulation (1977)

Cryodynamic hand angiography (CHA) with angiograms done before, just after, and during rewarming following hand immersion in ice water was performed in 39 patients with Raynaud's syndrome and eight volunteers without it. The normal response to cold stimulus was angiographically evident as mild, transient digital arterial constriction. Most of the patients with Raynaud's syndrome, in addition to organic obstructive disease, exhibited basal vasoconstriction and exaggerated persisting cryogenic vasospasm of the hand arteries. Similar angiographic studies done in 32 cases two days after the selective intra-arterial administration of reserpine revealed no differences in normal subjects but substantially decreased vasospasm in patients with Raynaud's syndrome. CHA with postreserpine studies was found to be diagnostically useful in Raynaud's syndrome, revealing the degree of organic arterial disease and functional vasospasm. In addition, correlation of postreserpine studies with observed clinical responses to long-term vasodilator drug therapy indicated that CHA has a good chance to predict the probable outcome of such therapy in Raynaud's syndrome.
Relative Increase of T Cells Expressing the Gamma/Delta Rather Than the Alpha/Beta Receptor in Ataxia-Telangiectasia
Authors: Maurizio Carbonari, Michela Cherchi, Roberto Paganelli, Giuseppe Giannini, Elena Galli, Carlo Gaetano, Claudia Papetti, Massimo Fiorilli
Journal: New England Journal of Medicine (1990)

In ataxia—telangiectasia, B-cell and T-cell deficiencies are thought to be due to a defect of rearrangements of immunoglobulin and T-cell receptor genes. T cells recognize antigens through two types of CD3-associated receptors: α/β chains on mature cells and γ/δ chains mostly on immature cells.
Specialty Hospitalists
Authors: John R Nelson, Laurence Wellikson, Robert M Wachter
Journal: JAMA (2012)

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Scientific and Clinical Problems in Indexes of Functional Disability
Authors: ALVAN R. FEINSTEIN
Journal: Annals of Internal Medicine (1986)

Indexes of functional disability are being used increasingly to rate the status of patients studied in clinical research or treated in clinical practice. To determine why so many indexes have been developed and to evaluate their scientific quality, we reviewed the construction and other attributes of 43 indexes that offer ratings for activities of daily living. The six most prominent problems, and some proposed solutions, are as follows: Ratings for the magnitude of performed tasks will be misleading unless the patient's effort or collaboration is suitably considered. Each patient's preferences should be sought to determine which types of disability are the most important goals of therapy. Special transition indexes should be developed if subtle or overt changes are not discerned from the repeated use of single-state indexes. Hierarchical scale arrangements can avoid the loss of descriptive power that occurs when multiple variables are aggregated merely as summations. Documentary evidence can be required to demonstrate the anticipated achievements of an index. New indexes can be constructed if the high statistical "reliability" and "validity" of established indexes are not accompanied by satisfactory clinical "sensibility."