tbuckley/cabot-search huggingface dataset:
Predictors of spontaneous viral clearance and outcomes of acute hepatitis C infection
Authors: Yoo-Kyung Cho, Young Nam Kim, Byung-Cheol Song
Journal: Clinical and Molecular Hepatology (2014)

Background/Aims This study evaluated the predictors of spontaneous viral clearance (SVC), as defined by two consecutive undetectable hepatitis C virus (HCV) RNA tests performed â¥12 weeks apart, and the outcomes of acute hepatitis C (AHC) demonstrating SVC or treatment-induced viral clearance. Methods Thirty-two patients with AHC were followed for 12-16 weeks without administering antiviral therapy. Results HCV RNA was undetectable at least once in 14 of the 32 patients. SVC occurred in 12 patients (37.5%), among whom relapse occurred in 4. SVC was exhibited in 8 of the 11 patients exhibiting undetectable HCV RNA within 12 weeks. HCV RNA reappeared in three patients (including two patients with SVC) exhibiting undetectable HCV RNA after 12 weeks. SVC was more frequent in patients with low viremia than in those with high viremia (55.6% vs. 14.3%; P=0.02), and in patients with HCV genotype non-1b than in those with HCV genotype 1b (57.1% vs. 22.2%; P=0.04). SVC was more common in patients with a â¥2 log reduction of HCV RNA at 4 weeks than in those with a smaller reduction (90% vs. 9.1%, P<0.001). A sustained viral response was achieved in all patients (n=18) receiving antiviral therapy. Conclusions Baseline levels of HCV RNA and genotype non-1b were independent predictors for SVC. A â¥2 log reduction of HCV RNA at 4 weeks was a follow-up predictor for SVC. Undetectable HCV RNA occurring after 12 weeks was not sustained. All patients receiving antiviral therapy achieved a sustained viral response. Antiviral therapy should be initiated in patients with detectable HCV RNA at 12 weeks after the diagnosis. Keywords: Acute hepatitis C; Spontaneous viral clearance; Interferon; HCV RNA
Nasal nitric oxide and nasal allergy
Authors: V. M. D. Struben, M. H. Wieringa, L. Feenstra, J. C. De Jongste
Journal: Allergy (2006)

Measurements of nasal nitric oxide (nNO) are attractive because they are completely noninvasive and can easily be performed. The measurements may be useful in the early diagnosis of patients with chronic airway disorders such as Kartager's syndrome and cystic fibrosis. The possible use of nNO measurements in the diagnosis and treatment of allergic rhinitis still needs to be further evaluated because of the variable and also contradicting findings of nNO concentrations in this disease. In this review we will discuss the origin, production and measurement of nNO as well as the effect of allergic rhinitis, nasal allergen challenge and medication on nNO. Subsequently, we examine published data on allergic rhinitis and nNO, and summarize the effect of treatment of rhinitis on nNO. Finally, we discuss the potential future role for nNO in the diagnosis and management of allergic rhinitis.
A case of tumour necrosis factor-α inhibitor- and rituximab-induced plantar pustular psoriasis that completely resolved with tocilizumab
Authors: P. Jayasekera, R. Parslew, A. Al-Sharqi
Journal: British Journal of Dermatology (2014)

Rituximab, a chimeric B-cell-depleting monoclonal antibody, is a well-established therapy for rheumatoid arthritis. It is emerging that classical psoriatic lesions and plantar pustular psoriasis (PPP) are cutaneous side-effects of this drug. Antitumour necrosis factor (anti-TNF) therapies have multiple documented side-effects including PPP and psoriasis. We report a patient who has rheumatoid arthritis, who failed on anti-TNF therapies and then was commenced on rituximab. Subsequently she developed localized PPP. Due to deterioration of her joint disease she was switched to the interleukin-6 blocker tocilizumab, and the PPP resolved.
Emergency in emergency departments.
Authors: J K Gosnold
Journal: BMJ (1977)

susceptible to obstruction as a result of lymnphoid hyperplasia until involution of this lymphoid tissue occurs.This relationship would account for the characteristic age distribution of acute appendicitis.On this basis lymphoid hyperplasia occurring during viral exanthemata and bacterial infections could lead to appendicitis.However, one study has shown that there is no greater incidence of acute appendicitis in children with these infections than there is in children who are otherwise well."An alternative explanation is that obstruction is due to muscular spasm in the appendix associated with a low-fibre diet, as is thought to occur in the colon, and this would account for the geographical distribution of the disease.
Understanding and Targeting Alkylator Resistance in Glioblastoma
Authors: Wolfgang Wick, Michael Platten
Journal: Cancer Discovery (2014)

Abstract Summary: Alkylating chemotherapy is the mainstay in the treatment of pediatric and adult glioblastoma despite primary and acquired resistance and scientific efforts to precisely define therapies for individual patients. A focus on non–MGMT-mediated temozolomide resistance for pediatric glioblastoma suggests options for new drug combinations. Cancer Discov; 4(10); 1120–2. ©2014 AACR. See related article by Agnihotri et al., p. 1198
A Prospective Study of the Value of Monitoring Heparin Treatment with the Activated Partial Thromboplastin Time
Authors: Dilip Basu, Alexander Gallus, Jack Hirsh, John Cade
Journal: New England Journal of Medicine (1972)

Two hundred and thirty-four patients treated with continuous intravenous infusions of heparin were studied prospectively to seek a relation between the activated partial thromboplastin time (APTT) and recurrent venous thromboembolism or bleeding during treatment. One hundred and sixty-two patients were treated for venous thromboembolism and the remaining 72 for other diseases. The heparin dose was adjusted to keep the APTT between 1 1/2 and 2 1/2 times control levels. The five patients with venous thromboembolism in whom recurrence developed had a significantly lower APTT than patients without recurrence even though they received similar amounts of heparin. No recurrence developed in any patient with a mean APTT within the therapeutic range. Bleeding occurred in 19 patients whose mean heparin dose and APTT were similar to those of patients without bleeding. Thus, recurrence of venous thromboembolism during heparin treatment appears to be rare if the APTT is prolonged to 1 1/2 times or more control values at all times.
Body-Mass Index and Mortality in Korean Men and Women
Authors: Sun Ha Jee, Jae Woong Sull, Jungyong Park, Sang-Yi Lee, Heechoul Ohrr, Eliseo Guallar, Jonathan M. Samet
Journal: New England Journal of Medicine (2006)

Obesity is associated with diverse health risks, but the role of body weight as a risk factor for death remains controversial.We examined the association between body weight and the risk of death in a 12-year prospective cohort study of 1,213,829 Koreans between the ages of 30 and 95 years. We examined 82,372 deaths from any cause and 48,731 deaths from specific diseases (including 29,123 from cancer, 16,426 from atherosclerotic cardiovascular disease, and 3362 from respiratory disease) in relation to the body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters).In both sexes, the average baseline BMI was 23.2, and the rate of death from any cause had a J-shaped association with the BMI, regardless of cigarette-smoking history. The risk of death from any cause was lowest among patients with a BMI of 23.0 to 24.9. In all groups, the risk of death from respiratory causes was higher among subjects with a lower BMI, and the risk of death from atherosclerotic cardiovascular disease or cancer was higher among subjects with a higher BMI. The relative risk of death associated with BMI declined with increasing age.Underweight, overweight, and obese men and women had higher rates of death than men and women of normal weight. The association of BMI with death varied according to the cause of death and was modified by age, sex, and smoking history.
Down-regulation of Hepatoma-Derived Growth Factor Inhibits Anchorage-Independent Growth and Invasion of Non–Small Cell Lung Cancer Cells
Authors: Jun Zhang, Hening Ren, Ping Yuan, Wenhua Lang, Li Zhang, Li Mao
Journal: Cancer Research (2006)

Abstract We recently reported that a high level of hepatoma-derived growth factor (HDGF) expression in tumors correlates with a high incidence of tumor relapse or distant metastasis and shortened survival time in patients with non–small cell lung cancer (NSCLC). However, the mechanisms of the HDGF-associated aggressive biological behavior are unknown. In this study, we knocked down HDGF expression in NSCLC cells to determine the biological consequences. Transfection with HDGF-specific small interfering RNA (siRNA) resulted in down-regulation of HDGF expression in four NSCLC cell lines. Down-regulation of HDGF resulted in no detectable effect on anchorage-dependent cell growth as determined with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, a microelectronic cell sensor system, and flow cytometry. In contrast, cells transfected with HDGF-siRNA grew more slowly and formed significantly fewer colonies in soft agar than did cells treated with LipofectAMINE alone or transfected with negative control siRNA. In an in vitro invasion assay, significantly fewer cells transfected with HDGF-siRNA than cells treated with LipofectAMINE alone were able to invade across a Matrigel membrane barrier. In an in vivo mouse model, A549 cells treated with HDGF-siRNA grown significantly slower than the cells treated with LipofectAMINE alone or negative control siRNA. Morphologically, HDGF-siRNA–treated tumors exhibited markedly reduced blood vessel formation and increased necrosis, whereas the Ki67 labeling indices were similar in tumors treated with controls. Our results suggest that HDGF is involved in anchorage-independent growth, cell invasion, and formation of neovasculature of NSCLC. These qualities may contribute to the HDGF-associated aggressive biological behavior of NSCLC. (Cancer Res 2006; 66(1): 18–23)
Roll-out of 111 telephone hotline causes hospitals severe problems
Authors: G. Iacobucci
Journal: BMJ (2013)

Ongoing problems with the new 111 urgent care hotline are contributing to the “severe pressure” on emergency departments, the president of the College of Emergency Medicine, Mike Clancy, has warned.

He told the BMJ that reported failings in the new system must be dealt with to ensure that patients are seen safely in the right setting. He said that this would help relieve the pressure on emergency departments, and enable them to concentrate on patients who really need emergency care.

Chair of the House of Commons health select committee Stephen Dorrell pledged to investigate the issue,1 after further reports of seriously ill patients facing lengthy waits when dialling 111, and patients being inappropriately transferred …
Mesenteric Vascular Occlusion in Children
Authors: William E. DeMuth
Journal: JAMA (1962)

Mesenteric vascular occlusion in children has seldom been diagnosed before operation or postmortem examination. Delay in diagnosing this urgent surgical condition is striking. Diagnosis is usually that of some more usual surgical disease. Delay in diagnosis is due to a low index of suspicion, unreliability of scout films in infancy, and lack of a consistent pattern of signs and symptoms. Except for embolic occlusion, etiology usually is obscure. Surgery and manipulations (cardiac catheterization, and the like) of the heart and great vessels probably will re. sult in an increasing incidence. These conclusions are based on 13 cases selected from published reports and on 2 additional cases from the experience of the author.
Postoperative Radiotherapy in the Treatment of Single Metastases to the Brain
Authors: Roy A. Patchell, Phillip A. Tibbs, William F. Regine, Robert J. Dempsey, Mohammed Mohiuddin, Richard J. Kryscio, William R. Markesbery, Kenneth A. Foon, Byron Young
Journal: JAMA (1998)

Context.-For the treatment of a single metastasis to the brain, surgical resection combined with postoperative radiotherapy is more effective than treatment with radiotherapy alone.However, the efficacy of postoperative radiotherapy after complete surgical resection has not been established.Objective.-Todetermine if postoperative radiotherapy resulted in improved neurologic control of disease and increased survival.Design.-Multicenter, randomized, parallel group trial.Setting.-University-affiliated cancer treatment facilities.Patients.-Ninety-fivepatients who had single metastases to the brain that were treated with complete surgical resections (as verified by postoperative magnetic resonance imaging) between September 1989 and November 1997 were entered into the study.Interventions.-Patients were randomly assigned to treatment with postoperative whole-brain radiotherapy (radiotherapy group, 49 patients) or no further treatment (observation group, 46 patients) for the brain metastasis, with median followup of 48 weeks and 43 weeks, respectively.Main Outcome Measures.-Theprimary end point was recurrence of tumor in the brain; secondary end points were length of survival, cause of death, and preservation of ability to function independently.Results.-Recurrence of tumor anywhere in the brain was less frequent in the radiotherapy group than in the observation group (9 [18%] of 49 vs 32 [70%] of 46; PϽ.001).Postoperative radiotherapy prevented brain recurrence at the site of the original metastasis (5 [10%] of 49 vs 21 [46%] of 46; PϽ.001) and at other sites in the brain (7 [14%] of 49 vs 17 [37%] of 46; PϽ.01).Patients in the radiotherapy group were less likely to die of neurologic causes than patients in the observation group (6 [14%] of 43 who died vs 17 [44%] of 39; P = .003).There was no significant difference between the 2 groups in overall length of survival or the length of time that patients remained functionally independent.Conclusions.-Patients with cancer and single metastases to the brain who receive treatment with surgical resection and postoperative radiotherapy have fewer recurrences of cancer in the brain and are less likely to die of neurologic causes than similar patients treated with surgical resection alone.
Generating oculomotor and neuronal behavior in a neural field model of the superior colliculus
Authors: Thomas P. Trappenberg, Raymond M. Klein
Journal: Behavioral and Brain Sciences (1999)

The functional schema in the Findlay &amp; Walker target article presents an understanding of oculomotor behavior primarily at an algorithmic level of analysis. Although such an analysis is an important first step, present knowledge of the neuroscientific substrate for oculomotor behavior is sufficiently advanced to support, if not warrant, computationally explicit models explaining how oculomotor behavior is implemented by this substrate. The literature contains a growing number of examples of this strategy, which we illustrate using our work.
The Triterpenoid CDDO-Imidazolide Confers Potent Protection against Hyperoxic Acute Lung Injury in Mice
Authors: Narsa M. Reddy, Vegiraju Suryanaraya, Melinda S. Yates, Steven R. Kleeberger, Paul M. Hassoun, Masayuki Yamamoto, Karen T. Liby, Michael B. Sporn, Thomas W. Kensler, Sekhar P. Reddy
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Oxygen supplementation (e.g., hyperoxia) is used to support critically ill patients with noninfectious and infectious acute lung injury (ALI); however, hyperoxia exposure can potentially further contribute to and/or perpetuate preexisting ALI. Thus, developing novel therapeutic agents to minimize the side effects of hyperoxia is essential to improve the health of patients with severe ALI and respiratory dysfunction. We have previously shown that mice with a genetic disruption of the Nrf2 transcription factor, which squelches cellular stress by up-regulating the induction of several antioxidant enzymes and proteins, have greater susceptibility to hyperoxic lung injury. Moreover, we have recently demonstrated that Nrf2-deficiency impairs the resolution of lung injury and inflammation after nonlethal hyperoxia exposure.Objectives: To test the hypothesis that amplification of endogenous Nrf2 activity would prevent or dampen ALI induced by hyperoxia.Methods: Here, we tested our hypothesis using a synthetic triterpenoid compound CDDO-imidazole (CDDO-Im) (1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole) in Nrf2-sufficient and Nrf2-deficient mice subjected to hyperoxia-induced ALI.Measurements and Main Results: We demonstrate that oral administration of CDDO-Im at a dose of 30 μmol/kg body weight during the hyperoxic exposure is sufficient to markedly attenuate hyperoxia-induced ALI in Nrf2-sufficient but not Nrf2-deficient mice. This protection by the CDDO-Im against hyperoxic insult was accompanied by increased levels of Nrf2-regulated cytoprotective gene expression and reduced levels of DNA damage in the lung.Conclusions: These results suggest that up-regulation of Nrf2 signaling by CDDO-Im or its analogs may provide a novel therapeutic strategy to minimize the adverse effects of hyperoxia.
Perspectives and Limitations of Microarray-Based Gene Expression Profiling of Thyroid Tumors
Authors: Markus Eszlinger, Knut Krohn, Aleksandra Kukulska, Barbara Jarząb, Ralf Paschke
Journal: Endocrine Reviews (2007)

Microarray technology has become a powerful tool to analyze the gene expression of tens of thousands of genes simultaneously. Microarray-based gene expression profiles are available for malignant thyroid tumors (i.e., follicular thyroid carcinoma, and papillary thyroid carcinoma), and for benign thyroid tumors (such as autonomously functioning thyroid nodules and cold thyroid nodules). In general, the two main foci of microarray investigations are improved understanding of the pathophysiology/molecular etiology of thyroid neoplasia and the detection of genetic markers that could improve the differential diagnosis of thyroid tumors. Their results revealed new features, not known from one-gene studies. Simultaneously, the increasing number of microarray analyses of different thyroid pathologies raises the demand to efficiently compare the data. However, the use of different microarray platforms complicates cross-analysis. In addition, there are other important differences between these studies: 1) some studies use intraindividual comparisons, whereas other studies perform interindividual comparisons; 2) the reference tissue is defined as strictly nonnodular healthy tissue or also contains benign lesions such as goiter, follicular adenoma, and hyperplastic nodules in some studies; and 3) the widely used Affymetrix GeneChip platform comprises several GeneChip generations that are only partially compatible. Moreover, the different studies are characterized by strong differences in data analysis methods, which vary from simple empiric filters to sophisticated statistic algorithms. Therefore, this review summarizes and compares the different published reports in the context of their study design. It also illustrates perspectives and solutions for data set integration and meta-analysis, as well as the possibilities to combine array analysis with other genetic approaches.
Gut hormones in adaptation.
Authors: S R Bloom
Journal: Gut (1987)

The presence of a circulating factor affecting gut growth can be surmised from the findings in gut isolated from the main food stream and not under direct nutritional influence. Thus when a Thiry Vella fistula is constructed and the crypt cell production rate counted in the fistula it can be shown to correlate with the degree of resection of the main bowel left in continuity. The only hormones which become raised in a similar pattern are enteroglucagon and peptide tyrosine tyrosine (PYY). Enteroglucagon has been shown to be part of preproglucagon, which contains in addition oxyntomodulin, glucagon like peptide 1 1-37 and 6-36NH2 and glucagon like peptide 2. These form the main candidates for the 'hormone of gut growth'. Peptide tyrosine tyrosine has been tested by direct administration over 12 days, matching the natural rise, but no affect on crypt cell production rate was seen. Glucagon like peptide 1 1-37 was similarly tested and also found to produce no effect. It remains to test the other members of the glucagon family to confirm or refute the hypothesis that one of them is the enigmatic small gut growth factor.
UK researchers switch off genes that trigger cervical cancer
Authors: S. Mayor
Journal: BMJ (2002)

UK researchers have reported that they have been able to switch off a human papillomavirus gene that triggers cervical cancer, using a new highly targeted technique—RNA interference.

A team at the University of York reported last week that RNA interference, which works by selectively “silencing” homologous genes, completely eliminated all human cervical cancer cells in vitro yet left healthy cells unharmed ( Oncogene 2002;21: 6041-8)

This was the first evidence that RNA interference can turn off genes of infectious viruses in tumour cells, rendering them harmless.

The researchers chose human cervical cancer cells that are …
686. Bone Formation Inhibitors in Animal Sera
Authors: Jin Zhong Li, Ann-Shung Lieu, Gerald R. Hankins, Gregory A. Helm
Journal: Molecular Therapy (2005)

Based on previous gene therapy studies in bone formation induced by BMP adenoviral vectors, the osteogenic potentials of different BMP adenoviral vectors (ADhBMP-2, -4, -6, -7, and -9) are very high in immunodeficient animals but vary significantly among immunocompetent animals. We have demonstrated that the amounts of bone formation in immunocompetent animals were not significantly affected by use of different generations of adenoviral vectors and different species of BMPs. The similar protein expression curves between immunodeficient and immunocompetent rats indicated that reduced amount of BMP expression was not the main factor limiting the bone formation. Nevertheless, some components of sera may specifically block the signal transduction pathways of particular BMPs, thus interrupting bone formation. We use the term |[ldquo]|bone formation inhibitors (BFIs)|[rdquo]| to describe these immune factors to distinguish them from |[ldquo]|BMP antagonists|[rdquo]|, which are mainly secreted by bone tissue. A mouse skeletal muscle myoblast cell line (C2C12) was used as a model. Reduction of alkaline phosphatase (AP) expression was used as an index to evaluate the inhibiting activity of serum. The distribution of BFIs among different animal species and strains was investigated. Sera from rabbit, rat, and mice were tested. Sera from two strains of rabbit included 14 normal control sera and five adenovirus-vaccinated sera. Most rabbit sera did not exhibit significant inhibiting activity on cell response to any BMP. Only one serum from adenovirus-vaccinated rabbit displayed inhibiting activity on cell response to BMP6. Two sera from NOD SCID mice did not show any inhibiting activity on cell response to BMP2, -6 and -9. Forty-four sera obtained from athymic nude, SD, and Wistar rats were tested. From athymic nude rats we obtained five normal and seven adenovirus-vaccinated sera. All the rat sera inhibited response of cells to BMP6. Two sera obtained from adenovirus (ADLUC)-vaccinated athymic nude rats 16 months after the vaccination inhibited cell response to BMP2, -6, and -9. Four sera from untreated Wistar rats demonstrated inhibiting activities to all three BMPs. Sera from 13 normal, and 15 adenovirus-vaccinated SD rats, all displayed inhibiting activity to BMP6. Some sera also showed inhibition of cell response to BMP2 and -9. The results indicate that BFIs are widely distributed among different animal species and strains. Adenovirus-vaccinated sera may have higher titers than normal sera. This finding will provide a new point of view to assess the relationship between the immune system and BMPs.