tbuckley/cabot-search huggingface dataset:
Phase II Trial of CHOP Plus Rituximab in Patients With HIV-Associated Non-Hodgkin’s Lymphoma
Authors: Michele Spina, Cecilia Simonelli, Umberto Tirelli
Journal: Journal of Clinical Oncology (2007)

TO THE EDITOR: Recently Boue et al 1 published the results of a French phase II trial with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in 61 patients with HIVassociated non-Hodgkin’s lymphoma (HIV-NHL). They reported a complete remission rate of 77% and a 2-year survival of 75% without any increase of both toxic deaths and life-threatening infections. These results are similar to that of our pooled analysis of three international phase two studies using rituximab plus infusional cyclophosphamide, doxorucin and etoposide (R-CDE) 2 in 74 patients with HIV-NHL with a complete remission rate of 70% and a 2-year survival of 64%. However, a significant increase in hematologic toxicity and infections were found in the R-CDE study, in particular, grade 3 to 4 neutropenia in 78% of patients and infection in 31% of patients. These differences could be related to several factors. First, in the R-CDE study all patients were treated, while in the R-CHOP study only patients with good or intermediate prognosis (ie, no more than one of the following prognostic factors: CD4 cell count 100/dL, prior history of opportunistic infections, and Eastern Cooperative Oncology Group performance status 2) were enrolled. Second, due to the continuous infusion of R-CDE all patients used a central venous catheter, which is a risk factor for bacterial infections. Third, in the R-CDE study all antiretroviral drugs were allowed while in the R-CHOP study, the use of mielotoxic antiretroviral drugs, such as zidovudine or ritonavir, was avoided, leading to a low rate of grade 3 or 4 neutropenia (33% in R-CHOP v 78% in R-CDE). Last, the use of etoposide could have contributed to the increase of bone marrow toxicity. Overall, the results of the French study confirm the results of R-CDE with a high efficacy of the addition of rituximab to chemotherapy in the treatment of patients with HIV-NHL without any overall increase in severe toxicity. These results are in contrast with the previous US data published by Kaplan et al 3 where rituximab was associated to an unacceptable rate of treatment-related infectious deaths; although, the patient selection could be the reason for this toxicity. In conclusion, rituximab plus chemotherapy should be considered the standard treatment of patients with HIV-NHL. Randomized studies comparing rituximab plus CHOP versus rituximab plus infusional chemotherapy (CDE or etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin [EPOCH]) could be warranted in order to improve both response rate and overall survival.
High liver glycogen in hereditary fructose intolerance
Authors: A. R. R. Cain, B. E. Ryman
Journal: Gut (1971)

A case of hereditary fructose intolerance is reported in a girl aged 2 years at the time of her death. She had apparently progressed normally until the age of 14 months. At 19 months she was admitted to hospital with failure to thrive, hepatomegaly, and superficial infections. Investigations revealed hypoglycaemia, persistent acidosis, aminoaciduria, and a high liver glycogen level which suggested that she had glycogen storage disease. There was also some evidence of malabsorption. At necropsy the liver enzyme estimations showed that fructose 1-phosphate aldolase activity was absent and that fructose 1,6-diphosphate aldolase activity was reduced. Hereditary fructose intolerance and glycogen storage disease have been confused in the past on clinical grounds, but a high liver glycogen level has not previously been reported in hereditary fructose intolerance.
Antiperinuclear factor, a marker autoantibody for rheumatoid arthritis: colocalisation of the perinuclear factor and profilaggrin.
Authors: R M Hoet, A M Boerbooms, M Arends, D J Ruiter, W J van Venrooij
Journal: Annals of the Rheumatic Diseases (1991)

The antiperinuclear factor, an autoantibody specific for rheumatoid arthritis, was found in 51/63 (81%) patients with rheumatoid arthritis by indirect immunofluorescence on human buccal mucosa cells. The sensitivity of the antiperinuclear factor test was increased by pretreating the buccal mucosa cells with 0.5% Triton-X100. The specificity of the test for rheumatoid arthritis as compared with control serum samples was maintained. The localisation of the perinuclear factor in the keratohyalin granules of the buccal mucosa cells was verified by immunoelectron microscopy. The perinuclear factor was found to be an insoluble protein whose antigenicity was sensitive to various fixation procedures. In serum samples from patients with rheumatoid arthritis there was a positive correlation between the presence of antiperinuclear factor and the presence of the so called antikeratin antibodies as detected by immunofluorescence on unfixed rat oesophagus cryostat sections. No relation was found between the presence of the perinuclear factor and either the rheumatoid factor, Epstein-Barr virus components, or any cytokeratin. By double immunofluorescence an exact colocalisation of the perinuclear factor and profilaggrin was found. Although the precise biochemical identity of the perinuclear factor remains unclear, our results suggest that it is a protein only present in the fully differentiated squamous epithelial cell layer.
Clear Cell Sarcoma of the Kidney: Up-regulation of Neural Markers with Activation of the Sonic Hedgehog and Akt Pathways
Authors: Colleen Cutcliffe, Donna Kersey, Chiang-Ching Huang, Yong Zeng, David Walterhouse, Elizabeth J. Perlman
Journal: Clinical Cancer Research (2005)

Clear cell sarcoma of the kidney (CCSK), the second most common renal tumor in children, poses significant diagnostic challenges. No positive diagnostic markers are available, and the pathogenesis of CCSK remains an enigma. To address these challenges, the gene expression patterns of 14 CCSKs were compared with 15 Wilms tumors and 3 fetal kidney samples using oligonucleotide arrays.Using unsupervised methods, the gene expression profile of CCSK was distinctive: differentially expressed genes could largely be grouped into four categories: (a) a wide variety of neural markers, (b) members of the Sonic hedgehog pathway, (c) members of the phosphoinositide-3-kinase/Akt cell proliferation pathway, and (d) known therapeutic targets. Corresponding changes in critical proteins using Western blot and/or immunohistochemistry confirmed the up-regulation of these pathways and proteins. In particular, CD117 and epidermal growth factor receptor are up-regulated at the protein level in many CCSKs, providing potential therapeutic targets. One of the neural markers, nerve growth factor receptor, represents a promising diagnostic tool for CCSK.This study suggests that CCSKs arise within a renal mesenchymal cell that shows a wide variety of neural markers. As such, it seems to be susceptible to genetic changes also seen in a variety of other neuroectodermal and neuronal tumors, including activation of Sonic hedgehog and phosphoinositide-3-kinase/Akt pathways. Involvement of these pathways in CCSKs implicates their widening role in tumorigenesis.
Effect of lidocaine on the early inward transient current in sheep cardiac Purkinje fibers.
Authors: F M Weld, J T Bigger
Journal: Circulation Research (1975)

We used two experimental techniques to study the effect of lidocaine hydrochloride on the early inward transient (sodium) current as it is reflected by the maximum rate of change of action potential phase 0 (Vmax). We assessed the effect of lidocaine on Vmax as Purkinje fibers were slowly depolarized by increasing the extracellular potassium concentration from 4.0 to 16.0 mM; these voltage-dependent effects were compared with lidocaine's effect on membrane responsiveness (which measures both the time and the voltage dependence of Vmax). We also used a voltage clamp technique to establish the effect of lidocaine on the voltage dependence of Vmax by measuring Vmax 800-1000 msec after transmembrane voltage (Vm) had been changed in small steps. We studied the effect of lidocaine on the time course of early inward transient current reactivation by depolarizing the membrane to -25 +/- 5 mv for 100 msec to inactivate this current, clamping Vm to a repolarized test voltage for various periods, and then measuring phase 0 Vmax of action potentials elicited immediately after termination of the voltage clamp. We showed that lidocaine at 5 mg/liter, but not a 1 mg/liter, shifted the steady-state Vmax- Vm relationship to a more negative position on its voltage axis by about 5 mv and markedly slowed the reactivation of the measure early inward transient current.
Glutathione peroxidase-2 protects from allergen-induced airway inflammation in mice
Authors: A. M. Dittrich, H-A. Meyer, M. Krokowski, D. Quarcoo, B. Ahrens, S. M. Kube, M. Witzenrath, R. S. Esworthy, F-F. Chu, E. Hamelmann
Journal: European Respiratory Journal (2009)

The aim of the present study was to identify and validate the biological significance of new genes/proteins involved in the development of allergic airway disease in a murine asthma model. Gene microarrays were used to identify genes with at least a two-fold increase in gene expression in lungs of two separate mouse strains with high and low allergic susceptibility. Validation of mRNA data was obtained by western blotting and immunohistochemistry, followed by functional analysis of one of the identified genes in mice with targeted disruption of specific gene expression. Expression of two antioxidant enzymes, glutathione peroxidase-2 (GPX2) and glutathione S-transferase omega (GSTO) 1-1 was increased in both mouse strains after induction of allergic airway disease and localised in lung epithelial cells. Mice with targeted disruption of the Gpx-2 gene showed significantly enhanced airway inflammation compared to sensitised and challenged wild-type mice. Our data indicate that genes encoding the antioxidants GPX2 and GSTO 1-1 are common inflammatory genes expressed upon induction of allergic airway inflammation, and independently of allergic susceptibility. Furthermore, we provide evidence to illustrate the importance of a single antioxidant enzyme, GPX2, in protection from allergen-induced disease.
Skinned fibers of human atrium and ventricle: myosin isoenzymes and contractility.
Authors: I Morano, H Arndt, C Gärtner, J C Rüegg
Journal: Circulation Research (1988)

Different myosin isoenzymes of pig and human atrium and ventricle and rat ventricle were characterized by two approaches: pyrophosphate polyacrylamide gel electrophoresis (PP-PAGE) and analysis of the myosin P light chains by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). We further investigated the relation between atrial and ventricular myosin isoenzymes of human, pig, and rat, and the maximum (unloaded) shortening velocity (Vmax) and the Ca2+ sensitivity of chemically skinned fibers of the same species. The myosin isoenzymes of both human and pig atrium comigrated in the PP-PAGE with rat V2 isomyosin, whereas the ventricle of human and pig comigrated with rat V3. In both human and pig ventricle, a myosin P light chain polymorphism exists (two phosphorylatable P light chains with the same molecular weight but different isoelectric points). In contrast, we found no P light chain polymorphism in the atrium of human and pig and in the ventricle of rat (one phosphorylatable P light chain only). A correlation exists between Vmax, Ca2+ sensitivity, and atrium- and ventricle-specific myosin isoenzymes of human and pig. Vmax was determined by the slack-test method. Plots of delta l versus delta t of atrial and ventricular skinned fibers were well fitted by a single straight line up to delta l = 15% and delta l = 13%, respectively. Vmax of skinned ventricular fibers was lower than Vmax of skinned atrial fibers in both human and pig. Ca2+ sensitivity of skinned fibers of ventricle, however, was higher than Ca2+ sensitivity of atrial skinned fibers in both human and pig.
Two Cases of Diabetic Ketoacidosis in HNF1A-MODY Linked to Severe Dehydration
Authors: Stepanka Pruhova, Petra Dusatkova, David Neumann, Erik Hollay, Ondrej Cinek, Jan Lebl, Zdenek Sumnik
Journal: Diabetes Care (2013)

OBJECTIVE Hepatocyte nuclear factor-1A maturity-onset diabetes of the young (HNF1A-MODY) is a monogenic form of diabetes caused by heterozygous mutations in HNF1A. Currently, a history of diabetic ketoacidosis (DKA) is an exclusion criterion for genetic testing for MODY. HISTORY AND EXAMINATION In this article, we describe two unrelated patients aged 17 and 24 years with severe DKA developed several years after the diagnosis of HNF1A-MODY. INVESTIGATION Both patients were treated with insulin, but their metabolic control was poor (HbA1c 15%, 140 mmol/mol and 13%, 119 mmol/mol, respectively) due to noncompliance and missed insulin injections. In both patients, DKA followed a course of recurrent vomiting with dehydration and prerenal acute kidney injury. Their glycemia, blood pH, and base excess at admission were 97 mmol/L [1,748 mg/dL], 6.80, and −33 mmol/L (patient 1) and 34 mmol/L [613 mg/dL], 7.03, and −14 mmol/L (patient 2). CONCLUSIONS This anecdotal observation supports the notion that a history of DKA does not exclude MODY.
<i>CEBPA</i> Mutations in Younger Adults With Acute Myeloid Leukemia and Normal Cytogenetics: Prognostic Relevance and Analysis of Cooperating Mutations
Authors: Stefan Fröhling, Richard F. Schlenk, Ina Stolze, Jörg Bihlmayr, Axel Benner, Sylvia Kreitmeier, Karen Tobis, Hartmut Döhner, Konstanze Döhner
Journal: Journal of Clinical Oncology (2004)

To assess the prognostic relevance of mutations in the CEBPA gene encoding CCAAT/enhancer binding protein alpha (C/EBP alpha) in a large prospective series of younger adults with acute myeloid leukemia (AML) and normal cytogenetics.The entire CEBPA coding region was sequenced in diagnostic samples from 236 AML patients 16 to 60 years of age with normal cytogenetics who were uniformly treated on two consecutive protocols of the AML Study Group Ulm, and CEBPA mutation status was correlated with clinical outcome.CEBPA mutations were detected in 36 (15%) of 236 patients. Twenty-one (9%) of 236 patients had mutations predicted to result in loss of C/EBP alpha function. Remission duration and overall survival (OS) were significantly longer for the 36 patients with CEBPA mutations (P =.01 and P =.05, respectively). On multivariate analysis, wild-type CEBPA was an independent prognostic marker affecting remission duration (hazard ratio, 2.85; P =.01) and OS (hazard ratio, 1.87; P =.04). Analysis of cooperating mutations (both types of activating FLT3 mutations and MLL partial tandem duplications) showed that FLT3 mutations had no significant prognostic influence in patients with CEBPA mutations. Furthermore, there was no significant overlap between the subgroup of patients with CEBPA mutation with predicted loss of C/EBP alpha function and patients with FLT3 or MLL mutations, suggesting that CEBPA loss-of-function mutations define a distinct biologic subclass of AML with normal cytogenetics.Mutant CEBPA predicts favorable prognosis and may improve risk stratification in AML patients with normal cytogenetics.
ABC of AIDS: Treatment of infections
Authors: I. V D Weller
Journal: BMJ (2001)

In those who are severely immunosuppressed the treatment and prophylaxis of opportunistic infections remains important.

This article has been adapted from the forthcoming 5th edition of ABC of AIDS. The book will be available from the BMJ bookshop and at http://www.bmjbooks.com/ 

Nowadays Pneumocystis carinii pneumonia most commonly occurs in those at risk of HIV infection who fail to take adequate prophylaxis or in those who are newly diagnosed with advanced disease, where it is frequently the presenting illness.

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Chest x ray appearance of Pneumocystis carinii pneumonia showing interstitial infiltrates

Clinical suspicion is aroused early in patients who are under regular medical supervision, leading to earlier diagnosis. Later diagnosis is asssociated with more severe disease and poorer treatment outcome. Techniques of diagnosis include sputum induction with nebulised saline; this obviates the need for bronchoscopy but the diagnostic sensitivity is lower. The use of lavage alone at bronchoscopy avoids transbronchial biopsy with its complications of haemorrhage and pneumothorax. Exercise oximetry and alternative imaging techniques with radiolabelled compounds are also being used in diagnosis. Monoclonal antibodies to pneumocystis proteins and sensitive DNA probes have been developed but have yet to reach the bedside. In the absence of a confirmatory test, a presumptive diagnosis may be made based on the clinical presentation and chest x ray appearances in a patient severely immunosuppressed and at risk.

Prophylaxis for Pneumocystis carinii pneumonia is essential after a first attack (secondary prophylaxis) but is also recommended for all patients once their CD4 cell counts falls below 200×106/l (primary prophylaxis). The risk of a first episode of infection below this CD4 count level in patients not on antiretroviral therapy is estimated to be 18% at 12 months for those who are asymptomatic, rising to 44% for those who have early symptomatic disease (eg oral candida, fever). Co-trimoxazole …

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Sulfation-dependent recognition of high endothelial venules (HEV)-ligands by L-selectin and MECA 79, and adhesion-blocking monoclonal antibody.
Authors: S Hemmerich, E C Butcher, S D Rosen
Journal: The Journal of Experimental Medicine (1994)

L-selectin is a lectin-like receptor that mediates the attachment of lymphocytes to high endothelial venules (HEV) of lymph nodes during the process of lymphocyte recirculation. Two sulfated, mucin-like glycoproteins known as Sgp50/GlyCAM-1 and Sgp90/CD34 have previously been identified as HEV-associated ligands for L-selectin. These proteins were originally detected with an L-selectin/Ig chimera called LEC-IgG. GlyCAM-1 and CD34 are also recognized by an antiperipheral node addressin (PNAd) mAb called MECA 79, which blocks L-selectin-dependent adhesion and selectively stains lymph node HEV. The present study compares the requirements for the binding of MECA 79 and LEC-IgG to HEV-ligands. Whereas desialylation of GlyCAM-1 and CD34 drastically reduced binding to LEC-IgG, this treatment enhanced the binding of GlyCAM-1 to MECA 79. In contrast, the binding of both MECA 79 and LEC-IgG to GlyCAM-1 and CD34 was greatly decreased when the sulfation of these ligands was reduced with chlorate, a metabolic inhibitor of sulfation. Because MECA 79 stains HEV-like vessels at various sites of inflammation, recognition by L-selectin of ligands outside of secondary lymphoid organs may depend on sulfation. In addition to their reactivity with GlyCAM-1 and CD34, both MECA 79 and LEC-IgG recognize an independent molecule of approximately 200 kD in a sulfate-dependent manner. Thus, this molecule, which we designate Sgp200, is an additional ligand for L-selectin.
The Rebirth of Bioethics: Extending the Original Formulations of Van Rensselaer Potter
Authors: Peter J. Whitehouse
Journal: The American Journal of Bioethics (2003)

Van Rensselaer Potter's original concept of bioethics as a global integration of biology and values was designed to guide human survival. His attention to the creation of human knowledge and the incorporation of ecological concepts and values into medicine and health remain important, yet largely neglected, contributions deserving of further elaboration. Bioethicists should heed his warning about unsustainable progress, particularly in health care systems, and work toward changing their behaviors. Incorporating life-affirming spiritual values and extending Potter's global bioethics to a deeper bioethics seem essential.
Spondylitis following Weil's Disease
Authors: J. H. Jacobs
Journal: Annals of the Rheumatic Diseases (1951)

Cases of infective spondylitis following typhoid, paratyphoid, undulant fever, and gonococcal and staphylococcal infections are well recorded, and Brailsford (1948) reports arthritis of the spine as a complication of most of the infectious diseases.Ashe and others (1941), in their review of the world's literature on Weil's disease, record meningitis, leptospiral endocarditis, peripheral neuritis, optic atrophy, and iridocyclitis as complications, but no case of spondylitis following this infection appears to have been reported.The early radiological changes occurring in infective spondylitis may be confined to narrowing of the intervertebral disk spaces and osteoporosis of the neighbouring bone.This is later followed by loss of bony detail, small marginal erosions, and sclerosis of the opposing surfaces of the bodies, with bridging between them and possibly ultimate fusion of the vertebrae.Paravertebral abscesses may also be present. Case HistoryA man, aged 59, a plumber by trade, was admitted to hospital on 13 April, 1949, with a history of lassitude and shivering attacks for a week, and jaundice for the last two days.He stated that he had been working in a rat-infested factory until a week before admission.Examination revealed a febrile, drowsy, dehydrated, jaundiced man with purpuric spots on his trunk.A clinical diagnosis of sub-acute hepatic necrosis was made.Blood Examination.-White-cellcount 13,300; agglutinations positive to Leptospira icterohaemorrhagica to 1: 1,000, but negative to L. canicola.Three weeks later, white-cell count 25,000; agglutinations positive to L. icterohaemorrhagica to 1: 3,000, and positive to L. canicola up to a titre of 1: 300.Agglutinations positive to B. typhosus H. to 1: 50, but negative to B. typhosus 0, B. para- typhosus A and B, and Brucella abortus.Treatment.-He was treated with penicillin and improved after a slow and stormy course, but discharged himself from hospital on May 30, although still unable to walk.He does not remember suffering from pain in his back while in hospital, although an x ray of his spine taken on May 12, 1949, showed some osteo-arthritic changes in the mid- dorsal region and no other abnormality.Later Developments.-Afterreturning home he complained of pain across his back on attempting to get up, and he remained bed-ridden until November 16, 1949, when he was seen in the Rheumatic Unit and admitted to the wards.61
Adjuvant chemotherapy in gastric cancer: 5-year results of a randomised study by the Italian Trials in Medical Oncology (ITMO) Group
Authors: E. Bajetta, R. Buzzoni, L. Mariani, E. Beretta, F. Bozzetti, G. Bordogna, E. Aitini, S. Fava, G. Schieppati, G. Pinotti, M. Visini, G. Ianniello, M. Di Bartolomeo
Journal: Annals of Oncology (2002)