tbuckley/cabot-search huggingface dataset:
The role of liver biopsy in hepatitis C
Authors: R P Perrillo
Journal: Hepatology (1997)

This article reviews the ways in which liver biopsy provides a resource to the clinician when making management decisions for patients with chronic hepatitis C. Liver biopsy provides information about the extent and distribution of inflammation and allows grading and staging of the disease (the amount of fibrosis). Furthermore, the liver biopsy allows some assessment of the rate of disease progression whenever the date of onset of infection is known. The presence of diffuse fibrosis or cirrhosis correlates with a lower likelihood of response to antiviral therapy, and the finding of severe necroinflammatory and fibrotic changes is helpful in determining the relative importance of beginning treatment early rather than deferring therapy. The importance of liver biopsy in the selection of patients for treatment is underscored by the fact that hepatitis C is a condition in which therapy is currently unable to successfully treat the majority of patients. There are no strong correlations between serum viral RNA, alanine aminotransferase (ALT) levels, and liver histopathology; therefore, the utility of aminotransferases and hepatitis C virus (HCV) RNA as surrogate tests for measuring disease activity in individual cases is limited. It is concluded that liver biopsy should be performed before initiating interferon therapy. At the present time, it is not known if and when repeat histological assessment is necessary. Preferably, it should only be performed in instances when the findings from the biopsy are likely to lead to a change in management of the patient.
Further observations upon HLA-B27, Yersinia enterocolitica, and ankylosing spondylitis.
Authors: P.E Pease, S.E Balmer, J.E Tallack, H Chahal, J Ibbotson, L.R Bartlett, M Lane, R.N Allan
Journal: Annals of the Rheumatic Diseases (1986)

Rheumatic manifestations of brucellosis SIR, We read with interest the article by Norton on the rheumatic manifestations of brucellosis.'We reported our experience with 304 patients infected with Brucella melitensis in 1982.2Recently we have completed a prospec- tive evaluation of 194 additional patients.Of these 498 patients, 180 (36%) presented with arthritis.In contrast to Norton's findings, sacoiliitis and peripheral arthritis were the most common forms of joint involvement, accounting for 90% of all the arthritis cases.Spondylitis was seen in only 18 patients (10%).As reported by others3 4 these patients were predominantly middle aged and older males with chronic brucellosis.The discrepancy can be explained by the different age distribution of the populations studied.Only one of the 55 patients reported by Norton was younger than 15, while in our group 354 patients (71%) were younger than 35 and 125 (25%) younger than 15.We agree with Norton in that immune abnormalities occur in human brucellosis, particularly during periods of active disease.Low titres of antinuclear antibodies were present in 25% and rheumatoid factor in 37-5% of a group of patients evaluated by US.5 Circulating immune complexes were detected by the Raji cell assay in 91.5%.As in other infectious diseases6 7 infectious and reactive arthritis occur in human brucellosis.In our series, using a selective culture medium for brucella,8 one third of the patients had sterile synovial fluids fulfilling the definition of reactive arthritis.9Furthermore, the arthritis was non-destructive and resolved spontaneously in most of these patients, an event not commonly seen in infectious arthritis.'0Interestingly, in one of the patients described by Norton the arthritis resolved after an intra-articular injection of corticosteroids.'The immune abnormalities described above strongly suggest that an immune mechanism plays a part in the arthritis of these patients.
Role of acetaldehyde in the ethanol-induced impairment of hepatic glycoprotein secretion in the ratIn vivo
Authors: Gary D. Volentine, Kathleen A. Ogden, David K. Kortje, Dean J. Tuma, Michael F. Sorrell
Journal: Hepatology (1987)

Ethanol administration inhibits hepatic protein and glycoprotein secretion. Previous studies have shown that the metabolism of ethanol is required for this effect. Experiments were designed to determine whether acetaldehyde, the first metabolite of ethanol oxidation, mediated the ethanol-induced secretory defect in rats with normal and stimulated (inflammation-induced) rates of hepatic protein secretion. This study used cyanamide, an aldehyde dehydrogenase inhibitor, to correlate enhanced acetaldehyde levels with an increased ethanol-induced inhibition of hepatic protein secretion. Inflammation was induced by turpentine 24 hr prior to cyanamide (5 mg per kg body weight) or saline pretreatment. Nonfasted rats were intragastrically gavaged with ethanol (4 to 6 gm per kg body weight) or isocaloric glucose 1 hr following pretreatment. [ 3 H]Fucose and/or [ 14 C]leucine were injected intravenously 2 hr following intubation. With elevated levels of acetaldehyde, the ethanol-induced impairment of secretion of labeled proteins and their parallel retention in the liver were markedly potentiated.During inflammation, this inhibition of secretion by ethanol was maintained and further increased with cyanamide pretreatment. These results indicate that the ethanol-induced impairment of hepatic glycoprotein secretion is mediated by acetaldehyde in both normal and inflammation-stimulated animals.
Effect of uncoupling endothelial nitric oxide synthase on calcium homeostasis in aged porcine endothelial cells
Authors: E. Perrier, M.-P. Fournet-Bourguignon, E. Royere, S. Molez, H. Reure, L. Lesage, W. Gosgnach, Y. Frapart, J.-L. Boucher, N. Villeneuve, J.-P. Vilaine
Journal: Cardiovascular Research (2009)

The requirement of endothelial NO synthase (NOS3) calcium to produce NO is well described, although the effect of NO on intracellular calcium levels [Ca(2+)](i) is still confusing. Therefore, NO and [Ca(2+)](i) cross-talk were studied in parallel in endothelial cells possessing a functional or a dysfunctional NO pathway.Dysfunctional porcine endothelial cells were obtained either in vitro by successive passages or in vivo from regenerated endothelium 1 month after coronary angioplasty. Activity of NOS3 was characterized by conversion of arginine to citrulline, BH(4) intracellular availability, cGMP, and superoxide anion production. Imaging of the Ca(2+) indicator FURA 2-AM was recorded and sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) pump activity was analysed by (45)Ca(2+) uptake into cells. In endothelial cells with a functional NO pathway, NOS3 inhibition increased [Ca(2+)](i) and, conversely, an NO donor decreased it. In aged cells with an uncoupled NOS3 as shown by the reduced BH(4) level, the increase in superoxide anion and the lower production of cGMP and the decrease in NO bioavailability were linearly correlated with the increase in basal [Ca(2+)](i). Moreover, when stimulated by bradykinin, the calcium response was reduced while its decay was slowed down. These effects on the calcium signalling were abolished in calcium-free buffer and were similarly induced by SERCA inhibitors. In aged cells, NO improved the reduced SERCA activity and tended to normalize the agonist calcium response.In control endothelial cells, NO exerts a negative feedback on cytosolic Ca(2+) homeostasis. In aged cells, uncoupled NOS3 produced NO that was insufficient to control the [Ca(2+)](i). Consequently, under resting conditions, SERCA activity decreased and [Ca(2+)](i) increased. These alterations were reversible as exogenous NO, in a cGMP-independent way, refilled intracellular calcium stores, reduced calcium influx, and improved the agonist-evoked calcium response. Therefore, prevention of the decrease in NO in dysfunctional endothelium would normalize the calcium-dependent functions.
Subarachnoid haemorrhage above the age of 59: are intracranial investigations justified?
Authors: B V Martindale, J Garfield
Journal: BMJ (1978)

Out of 186 patients aged over 59 referred to a neurosurgical department after spontaneous subarachnoid haemorrhage, 143 underwent cerebral angiography; only 28 (15%) of the patients had surgery, of whom 16 were independent one year later. The doubtful benefit of surgery and the small proportion of patients who underwent surgery have economic and ethical implications; in particular, neurosurgical beds and neuroradiological facilities should not be occupied by such patients if this delays the admission of younger patients and those requiring investigation of intracranial space-occupying and spinal lesions.
18F-FDG PET/CT Metabolic Variability in Functioning Oncocytic Parathyroid Adenoma With Brown Tumors
Authors: Matthew S. Guy, Celine Jacob, Stephen D. McDonald, Yvonne G. Dowdy, Arash Kardan
Journal: Clinical Nuclear Medicine (2014)

A 29-year-old female patient exhibited a solitary neck mass, severe hypercalcemia, and multiple skeletal lytic lesions consistent with metastatic neoplastic disease. Fine-needle aspiration (FNA) cytology of the neck lesion indicated a follicular thyroid neoplasm. CT-guided bone biopsy was non-diagnostic. Subsequent 18F-FDG PET/CT examination demonstrated avid glucose uptake within the neck mass and diffuse bony lesions of variable metabolic activity. Repeat biopsy utilizing PET/CT guidance produced core tissue with classic histologic features of a brown tumor. Postoperative histology revealed an exclusively oncocytic parathyroid adenoma. Atypical radiotracer uptake of this rare functioning adenoma subtype is illustrated with discussion of improved procedural diagnostic yield utilizing PET/CT.
In Vitro Tumor Necrotic Factor Alpha Responses To Persistent Chlamydia Pneumoniae Infection From PBMC Of Asthmatic Children
Authors: Kobkul Chotikanatis, Diana Weaver, Danielle Lent, Eva Estrella, Margaret R. Hammerschlag, Rauno O. Joks, Stephan Kohlhoff
Journal: Journal of Allergy and Clinical Immunology (2014)
Multiple Histology Phase II Trials
Authors: Michael LeBlanc, Cathryn Rankin, John Crowley
Journal: Clinical Cancer Research (2009)

Testing agents in cancers with multiple disease subtypes, in which the activity of a new treatment may vary between subtypes, presents statistical and logistical challenges. We propose a flexible phase II strategy which includes both analyses for each histology or stratum and a combined analysis which borrows information from all the patients in the study. Sequential futility analyses are conducted once each subgroup or the overall group reaches a specified minimum accrual.Examples based on a soft tissue sarcoma phase II trial, which includes multiple histologies and simulation studies, are used to assess the statistical properties of the proposed strategy.The combined analyses in one phase II trial lead to smaller expected sample sizes when the drug is broadly inactive, and to greater statistical power if there is modest activity across multiple strata as compared with conducting several smaller phase II studies. In addition, by retaining the stratum-specific tests, the design allows the identification of subgroups for which the agents are most active.To consider phase II testing with multiple biological subtypes, a strategy which combines both the individual subgroup tests and overall combined tests has promising statistical properties. Our results support the appropriate use of statistical borrowing of information in phase II studies in this setting. More broadly, this work fits the paradigm that phase II studies should include as broad a group of patients as scientifically reasonable, but incorporate design considerations for subsets of patients with potentially differing responses to therapy.
Local Presynaptic Activity Gates Homeostatic Changes in Presynaptic Function Driven by Dendritic BDNF Synthesis
Authors: Sonya K. Jakawich, Hassan B. Nasser, Michael J. Strong, Amber J. McCartney, Amanda S. Perez, Neal Rakesh, Cynthia J.L. Carruthers, Michael A. Sutton
Journal: Neuron (2010)
Oestrogen Replacement Therapy for Prevention of Osteoporosis after Oophorectomy
Authors: J. M. Aitken, D. M. Hart, R. Lindsay
Journal: BMJ (1973)

The value of oestrogen therapy in the prevention of osteoporosis after oophorectomy was assessed in 114 middle-aged women who participated in a double-blind controlled trial of mestranol in an average daily dose of 23 mug. The skeletal response to treatment was measured by a photon absorption technique. Where treatment was started within two months of operation subsequent bone mineral loss was prevented. Treatment started three years after oophorectomy caused a highly significant increase in bone mineral content. When treatment was delayed for six years mestranol failed to prevent subsequent bone mineral loss with age. These effects occurred independently of the associated humoral changes in calcium and phosphorus homoeostasis. Mestranol in this dosage appeared to be relatively safe, but it is too early to evaluate the long-term hazards of such therapy.
Characterization of Binding Sites of Eukaryotic Transcription Factors
Authors: Jiang Qian, Jimmy Lin, Donald J. Zack
Journal: Genomics Proteomics & Bioinformatics (2006)

Abstract To explore the nature of eukaryotic transcription factor (TF) binding sites and determine how they differ from surrounding DNA sequences, we examined four features associated with DNA binding sites: G+C content, pattern complexity, palindromic structure, and Markov sequence ordering. Our analysis of the regulatory motifs obtained from the TRANSFAC database, using yeast intergenic sequences as background, revealed that these four features show variable enrichment in motif sequences. For example, motif sequences were more likely to have palindromic structure than were background sequences. In addition, these features were tightly localized to the regulatory motifs, indicating that they are a property of the motif sequences themselves and are not shared by the general promoter “environment” in which the regulatory motifs reside. By breaking down the motif sequences according to the TF classes to which they bind, more specific associations were identified. Finally, we found that some correlations, such as G+C content enrichment, were species-specific, while others, such as complexity enrichment, were universal across the species examined. The quantitative analysis provided here should increase our understanding of protein-DNA interactions and also help facilitate the discovery of regulatory motifs through bioinformatics.
1060-80 Female sex: A more important prognostic marker than treatment assignment or comorbid conditions among patients with acute myocardial infarction in the GUSTO V trial
Authors: Harmony R Reynolds, Michael E Farkouh, Eva Swahn, Jennifer A White, Zygmunt P Sadowski, A.M Lincoff, Eric J Topol, Judith S Hochman
Journal: Journal of the American College of Cardiology (2004)
Megaloblastic Changes in Cervical Epithelium
Authors: Leopold G. Koss
Journal: JAMA (1974)

<h3>To the Editor.—</h3> The article by Whitehead, Reyner, and Lindenbaum (226, 1421, 1973) implicating folate deficiency as a causative factor in epithelial cell abnormalities in the uterine cervix should not remain unchallenged. By the authors' own admission, their thesis is not supported by any other evidence of folate deficiency. The contention of this article is based primarily on a very modest clinical trial on eight patients whose abnormalities "improved" three weeks after initiation of folic acid therapy. The fate of the remaining 14 patients who should have served as controls is not given. Nothing is more fallacious in the follow-up of patients than the assessment of the status of cervix epithelium based on a single smear. A smear obtained three weeks after a preceding smear may show no abnormalities of note in the presence of a substantial lesion. The authors did not use colposcopy to ascertain the status of the
Fundamental ethical principles in health care.
Authors: I E Thompson
Journal: BMJ (1987)

In an attempt to clarify which requirements of morality are logically primary to the ethics of health care, two questions are examined: is there sufficient common ground among the medical, nursing, paramedical, chaplaincy, and social work professions to justify looking for ethical principles common to health care? Do sufficient logical grounds or consensus among health workers and the public exist to speak of "fundamental ethical principles in health care"? While respect for persons, justice, and beneficence are fundamental principles in a formal sense, how we view these principles in practice will depend on our particular culture and experience and the kinds of metaethical criteria we use for applying these principles.
Physician specialty and survival following hospitalization for heart failure
Authors: JoAnne M. Foody, Saif S. Rathore, Yongfei Wang, Jeph Herrin, Frederick A. Masoudi, Edward P. Havranek, Martha J. Radford, Diana L. Ordin, Harlan M. Krumholz
Journal: Journal of the American College of Cardiology (2003)
Incidence of Non-central Fixation in Children with Squint
Authors: J. Scully, E. J. Naylor
Journal: BMJ (1961)

Evidence of Undiagnosed Undulant Fever None of the participants showed any evidence of undulant fever at the time of investigation.From our inquiries into their past histories, however, we believe that two of them had undiagnosed attacks in the past.Case 6.-This man at first denied any history of febrile illness.The symptoms produced by his brucellin test (malaise, headache, limb pains, sweating) recalled to his memory an illness with exactly similar symptoms which he had suffered 10 years previously.It lasted three months, but was not serious enough to cause more than a few days' loss of work.His doctor found no abnormality, and sent him to hospital for pathological tests.It seems that these were of little help, because no satisfactory diagnosis was made and the symptoms disappeared spontaneously.It was not possible to obtain further clinical details or the results of the pathological tests.Nevertheless, we believe that the patient's description of his illness is fully consistent with a diagnosis in retrospect of the ambulant form of undulant fever.Case 12.-Between 1936 and 1940 this farmer had experienced several bouts of fever with profuse sweating, each one lasting several days.At the time he was having much trouble with contagious abortion in his milking herd.His doctor was unable to find the cause of the pyrexia, but commented that the clinical picture resembled malaria.The patient had not, however, been abroad.About the year 1950 he had a prolonged pyrexial illness which kept him off work for three months, including convalescence.The pyrexia was swinging and accompanied by profuse sweating, malaise, and limb pains.There was no response to penicillin or sulphonamides, but the fever subsided promptly with chloramphenicol and there was no recurrence.
Development of A Noninvasive Ultrasound Color M-Mode Means of Estimating Pulmonary Vascular Resistance in Pediatric Pulmonary Hypertension
Authors: Robin Shandas, Craig Weinberg, D.Dunbar Ivy, Ewen Nicol, Curt G. DeGroff, Jean Hertzberg, Lilliam Valdes-Cruz
Journal: Circulation (2001)

Background — Accurate determination of pulmonary vascular resistance (PVR) is an important component in the evaluation and treatment of pediatric patients with pulmonary hypertension. We developed a novel technique, based on the concept of flow propagation, to estimate PVR noninvasively. The hypothesis is that changes in PVR cause changes in the velocity propagation (Vel prop ) within the main pulmonary artery and that Vel prop can be quantified using color M-mode imaging. Methods and Results — We tested the hypothesis using mathematical modeling, in vitro experiments, and preliminary clinical studies. The mathematical model showed that pressure and velocity tracings are closely correlated in time and that 6 to 18 ms time resolution was needed to resolve propagation times within typical main pulmonary artery lengths (2 to 5 cm). The in vitro experiments demonstrated that it was feasible to use color M-mode to measure Vel prop and that Vel prop correlated well with downstream resistance [y=(−1.01x)+22.77; R =0.96]. The method was then evaluated on patients undergoing acute pulmonary reactivity testing (n=22 measurements). Good correlation between Vel prop and PVR was found [y=(−1.71x)+26.0; R =0.90; SEE=2.41]. Conclusion — This newly developed method promises to be useful in the noninvasive evaluation of adults and children with pulmonary hypertension.
Tumor Cell Dependence on Ran-GTP–Directed Mitosis
Authors: Fang Xia, Connie W. Lee, Dario C. Altieri
Journal: Cancer Research (2008)

Abstract Deregulated cell division is a hallmark of cancer, but whether tumor cells become dependent on specific mitotic mechanisms is not known. Here, we show that the small GTPase Ran, a regulator of mitotic spindle formation, is differentially overexpressed in human cancer as compared with normal tissues, in vivo. Acute silencing of Ran in various tumor cell types causes aberrant mitotic spindle formation, mitochondrial dysfunction, and apoptosis. This pathway does not require p53, Bax, or Smac, but is controlled by survivin as a novel Ran target in cancer. Conversely, loss of Ran in normal cells is well tolerated and does not result in mitotic defects or loss of cell viability. Therefore, tumor cells can become dependent on Ran signaling for cell division, and targeting this pathway may provide a novel and selective anticancer strategy. [Cancer Res 2008;68(6):1826–33]
Fooling the Parathyroid Gland — Will There Be Health Benefits?
Authors: Gary Curhan
Journal: New England Journal of Medicine (2004)

In people with a reduced glomerular filtration rate, the serum parathyroid hormone level is often secondarily elevated as a result of reduced serum levels of calcium and 1,25-dihydroxyvitamin D3 and an increased serum phosphate level (referred to as secondary hyperparathyroidism). The mean parathyroid hormone level is increased by a factor of more than seven in patients who are receiving hemodialysis.1 In addition to the well-described associated metabolic bone disease, secondary hyperparathyroidism and its treatments may play a role in the high rates of death and cardiovascular disease among patients with end-stage renal disease.2,3 The goal of current therapies . . .
Thymic B-cell non-Hodgkin's lymphoma in a child
Authors: Eiichi Azuma, Hidehiro Nishihara, Jiang Qi, Masataka Nagai, Shinya Hiratake, Xiao-Li Zhang, Yoshihiro Komada, Minoru Hamazaki, Minoru Sakurai
Journal: American Journal of Hematology (1998)

A 13-year-old male developed thymic non-Hodgkin's lymphoma. Microscopically, the tumor was composed of large cells, resembling centroblasts. Immunohistochemically, the tumor demonstrated leukocyte common antigen+, L26 (B-cell)+, UCHL1 (T-cell)−, suggesting the B-cell phenotype. In contrast to the terminally differentiated phenotype (CD10−, surface immunoglobulin−) observed in adult cases, flow cytometric analysis showed that they were relatively immature: CD10+, CD19+, HLA-DR−, IgM+/−, kappa+. He was successfully treated with intensive chemotherapy. Since childhood thymic lymphomas are exclusively small non-cleaved cell lymphoma with T-cell phenotype, this case represents a unique entity in children. Am. J. Hematol. 57:48–50, 1998. © 1998 Wiley-Liss, Inc.
Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial
Authors: Peter Dreger, Hartmut Döhner, Matthias Ritgen, Sebastian Böttcher, Raymonde Busch, Sascha Dietrich, Donald Bunjes, Sandra Cohen, Jörg Schubert, Ute Hegenbart, Dietrich Beelen, Matthias Zeis, Michael Stadler, Justin Hasenkamp, Lutz Uharek, Christof Scheid, Andreas Humpe, Thorsten Zenz, Dirk Winkler, Michael Hallek, Michael Kneba, Norbert Schmitz, Stephan Stilgenbauer
Journal: Blood (2010)