tbuckley/cabot-search huggingface dataset:
Pancreatic secretory trypsin inhibitor as a diagnostic marker for adult-onset type II citrullinemia
Authors: K Kobayashi, M Horiuchi, T Saheki
Journal: Hepatology (1997)

Adult-onset type II citrullinemia is characterized by which deficiency of argininosuccinate synthetase (ASS) protein is found specifically in the liver of patients. Our recent study using differential messenger RNA (mRNA) display showed that the expression of human pancreatic secretory trypsin inhibitor (hPSTI) mRNA increases significantly in the liver of all type II patients tested. In the present work, we found that the concentration of hPSTI protein was higher in the liver of type II patients than controls. Because it is well known that PSTI is a secretory protein and because serum PSTI has been proposed as a marker of pancreatic and nonpancreatic diseases, we measured the hPSTI level in the blood of type II patients and compared it with other serum markers such as elastase 1, trypsin, phospholipase A2, alpha-fetoprotein, CA19-9, and C-reactive protein (CRP). We found a significant increase in serum hPSTI level with no change in the other serum markers. These results suggest that serum hPSTI is useful as a diagnostic marker for adult-onset type II citrullinemia.
Prognostic Factors and Life Expectancy in Myelodysplastic Syndromes Classified According to WHO Criteria: A Basis for Clinical Decision Making
Authors: Luca Malcovati, Matteo Giovanni Della Porta, Cristiana Pascutto, Rosangela Invernizzi, Marina Boni, Erica Travaglino, Francesco Passamonti, Luca Arcaini, Margherita Maffioli, Paolo Bernasconi, Mario Lazzarino, Mario Cazzola
Journal: Journal of Clinical Oncology (2005)

The aim of this study was to evaluate the prognostic value of the WHO proposal, to assess the role of the main prognostic factors in myelodysplastic syndromes (MDSs) classified into WHO subgroups, and to estimate mortality (standardized mortality ratio [SMR]) and life expectancy in these groups as a basis for clinical decision making.Four hundred sixty-seven patients who were diagnosed as having de novo MDS at the Division of Hematology, University of Pavia (Pavia, Italy), between 1992 and 2002, were evaluated retrospectively for clinical and hematologic features at diagnosis, overall survival (OS), and progression to leukemia (leukemia-free survival).Significant differences in survival were noted between patients with refractory anemia (RA), refractory cytopenia with multilineage dysplasia, RA with excess blasts, type 1 (RAEB-1), and RAEB-2. The effect of demographic factors on OS was observed in MDS patients without excess blasts (age, P = .001; sex, P = .006), as in the general population. The mortality of RA patients 70 years or older did not differ significantly from that of the general population (SMR, 1.62; P = .06). Cytogenetics was the only International Prognostic Scoring System variable showing a prognostic value in MDS classified into WHO subgroups. Transfusion-dependent patients had a significantly shorter survival than patients who did not require transfusions (P < .001). Developing a secondary iron overload significantly affected the survival of transfusion-dependent patients (P = .003).These data show that the WHO classification of MDSs has a relevant prognostic value. This classification, along with cytogenetics, might be useful in decisions regarding transplantation. MDS with isolated erythroid lineage dysplasia identifies a subset of truly low-risk patients, for whom a conservative approach is advisable.
Diagnosis and significance of liver metastases in small cell carcinoma of the lung.
Authors: J L Mulshine, R W Makuch, A Johnston-Early, M J Matthews, D N Carney, D C Ihde, M H Cohen, H R Bates, N R Dunnick, J D Minna
Journal: Journal of Clinical Oncology (1984)

One hundred fifty-seven consecutive patients with small cell lung cancer seen at the National Cancer Institute over a four-year period underwent a series of pretherapy liver staging procedures to determine optimal means of detection and prognostic implications of hepatic metastases. Liver evaluation included physical examination, liver function tests, and liver scan (radionuclide or computerized tomography [CT]), as well as percutaneous and/or peritoneoscopy-directed liver biopsy when possible (74%). Liver metastases were detected in 26% of patients. Peritoneoscopy was the most sensitive method of liver evaluation and increased the detection of liver metastases when done in a sequential fashion after percutaneous liver biopsy from 18 to a total of 27 patients. Of the noninvasive procedures, radionuclide and CT liver scan were the most accurate concurring with liver biopsy in 87% of patients but permitting correct discrimination of stage in excess of 96% of patients. The accuracy of this noninvasive procedure was enhanced by an algorithm combining the results of radionuclide liver scan with liver function tests to detect patients with high or low likelihood of liver involvement. The survival and response of patients with liver metastases was significantly worse than those without such metastases with no three-year disease-free survivors among patients with liver metastases.
Lymphoma models for B cell activation and tolerance. X. Anti-mu-mediated growth arrest and apoptosis of murine B cell lymphomas is prevented by the stabilization of myc.
Authors: G Fischer, S C Kent, L Joseph, D R Green, D W Scott
Journal: The Journal of Experimental Medicine (1994)

Treatment of the WEHI-2131 or CH31 B cell lymphomas with anti-mu or transforming growth factor (TGF)-beta leads to growth inhibition and subsequent cell death via apoptosis. Since anti-mu stimulates a transient increase in c-myc and c-fos transcription in these lymphomas, we examined the role of these proteins in growth regulation using antisense oligonucleotides. Herein, we demonstrate that antisense oligonucleotides for c-myc prevent both anti-mu- and TGF-beta-mediated growth inhibition in the CH31 and WEHI-231 B cell lymphomas, whereas antisense c-fos has no effect. Furthermore, antisense c-myc promotes the appearance of phosphorylated retinoblastoma protein in the presence of anti-mu and prevents the progression to apoptosis as measured by propidium iodide staining. Northern and Western analyses show that c-myc message and the levels of multiple myc proteins were maintained in the presence of antisense c-myc, results indicating that myc species are critical for the continuation of proliferation and the prevention of apoptosis. These data implicate c-myc in the negative signaling pathway of both TGF-beta and anti-mu.
Effect of Schizophrenia on Frontotemporal Activity During Word Encoding and Recognition: A PET Cerebral Blood Flow Study
Authors: J D Ragland, R C Gur, J Raz, L Schroeder, C G Kohler, R J Smith, A Alavi, R E Gur
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Neuropsychological studies have shown that deficits in verbal episodic memory in schizophrenia occur primarily during encoding and retrieval stages of information processing. The current study used positron emission tomography to examine the effect of schizophrenia on change in cerebral blood flow (CBF) during these memory stages. METHOD: CBF was measured in 23 healthy comparison subjects and 23 patients with schizophrenia during four conditions: resting baseline, motor baseline, word encoding, and word recognition. The motor baseline was used as a reference that was subtracted from encoding and recognition conditions by using statistical parametric mapping. RESULTS: Patients' performance was similar to that of healthy comparison subjects. During word encoding, patients showed reduced activation of left prefrontal and superior temporal regions. Reduced left prefrontal activation in patients was also seen during word recognition, and additional differences were found in the left anterior cingulate, left mesial temporal lobe, and right thalamus. Although patients' performance was similar to that of healthy comparison subjects, left inferior prefrontal activation was associated with better performance only in the comparison subjects. CONCLUSIONS: Left frontotemporal activation during episodic encoding and retrieval, which is associated with better recognition in healthy people, is disrupted in schizophrenia despite relatively intact recognition performance and right prefrontal function. This may reflect impaired strategic use of semantic information to organize encoding and facilitate retrieval.
Axis I Comorbidity in Patients With Borderline Personality Disorder: 6-Year Follow-Up and Prediction of Time to Remission
Authors: Mary C Zanarini, Frances R Frankenburg, John Hennen, D Bradford Reich, Kenneth R Silk
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The purpose of this study was to assess the prevalence of axis I disorders among patients with borderline personality disorder over 6 years of prospective follow-up. METHOD: A semistructured interview of demonstrated reliability was used to assess presence or absence of comorbid axis I disorders in 290 patients who met Revised Diagnostic Interview for Borderlines criteria and DSM-III-R criteria for borderline personality disorder and 72 patients who did not meet these criteria but did meet DSM-III-R criteria for another axis II disorder. Over 94% of surviving patients were reinterviewed about their axis I disorders at 2-year, 4-year, and 6-year follow-up periods. RESULTS: Although the patients with borderline personality disorder experienced declining rates of many axis I disorders over time, the rates of these disorders remained high, particularly the rates of mood and anxiety disorders. Patients whose borderline personality disorder remitted over time experienced substantial decline in all comorbid disorders assessed, but those whose borderline personality disorder did not remit over time reported stable rates of comorbid disorders. When the absence of comorbid axis I disorders was used to predict time to remission, the absence of substance use disorders was a far stronger predictor of remission from borderline personality disorder than was the absence of posttraumatic stress disorder, mood disorders, other anxiety disorders, or eating disorders, respectively. CONCLUSIONS: The results of this study suggest that axis I disorders are less common over time in patients with initially severe borderline personality disorder, particularly for patients whose borderline personality disorder remits over time. The findings also suggest that substance use disorders are most closely associated with the failure to achieve remission from borderline personality disorder.
Nanoparticle Delivery of Cancer Drugs
Authors: Andrew Z. Wang, Robert Langer, Omid C. Farokhzad
Journal: Annual Review of Medicine (2011)

Nanomedicine, the application of nanotechnology to medicine, enabled the development of nanoparticle therapeutic carriers. These drug carriers are passively targeted to tumors through the enhanced permeability and retention effect, so they are ideally suited for the delivery of chemotherapeutics in cancer treatment. Indeed, advances in nanomedicine have rapidly translated into clinical practice. To date, there are five clinically approved nanoparticle chemotherapeutics for cancer and many more under clinical investigation. In this review, we discuss the various nanoparticle drug delivery platforms and the important concepts involved in nanoparticle drug delivery. We also review the clinical data on the approved nanoparticle therapeutics as well as the nanotherapeutics under clinical investigation.
Cost of outpatient chemotherapy.
Authors: D O Thomson
Journal: BMJ (1978)

cortical thinning being the only radiological sign of osteomalacia.Thus true osteoporosis was responsible for the cortical thinning in only the cases of steroid therapy and Cushing's syndrome-three out of 18 cases.The other 15 were due to hyperparathyroidism and osteomalacia.Cortical thinning cannot therefore be regarded as synonymous with osteoporosis.
Comprehensive Meta-Analysis of Excess Mortality in Depression in the General Community Versus Patients With Specific Illnesses
Authors: Pim Cuijpers, Nicole Vogelzangs, Jos Twisk, Annet Kleiboer, Juan Li, Brenda W. Penninx
Journal: American Journal of Psychiatry (2014)

The mechanisms linking depression to mortality were found to be related to biological dysregulations or lifestyle factors rather than disease specific in this unprecedented meta-analysis of 247 studies—which included 105,986 depressed and 578,503 nondepressed participants from 31 countries.
1429 BASELINE APOLIPOPROTEIN H (ApoH) IS A PREDICTOR OF EARLY VIROLOGIC RESPONSE TO TRIPLE THERAPY (ANRS CO20-CUPIC)
Authors: P. Sultanik, V. Mallet, C. Dorival-Mouly, Y. Barthe, H. Fonaine, C. Hézode, E. Mottez, J.-P. Bronowicki, F. Carrat, E. Gayat, A. Casrouge, A. Fontanet, I. Theodorou, L. Abel, S. Pol, M. Albert
Journal: Journal of Hepatology (2013)
Chronic growth hormone (GH) hypersecretion induces reciprocal and reversible changes in mRNA levels from hypothalamic GH-releasing hormone and somatostatin neurons in the rat.
Authors: J Bertherat, J Timsit, M T Bluet-Pajot, J J Mercadier, D Gourdji, C Kordon, J Epelbaum
Journal: Journal of Clinical Investigation (1993)

Effects of growth hormone (GH) hypersecretion on somatostatin-(SRIH) and GH-releasing hormone (GHRH) were studied by in situ hybridization and receptor autoradiography in rats bearing a GH-secreting tumor. 6 and 18 wk after tumor induction, animals displayed a sharp increase in body weight and GH plasma levels; pituitary GH content was reduced by 47 and 55%, while that of prolactin and thyrotropin was unchanged. At 18 wk, hypothalamic GHRH and SRIH levels had fallen by 84 and 52%, respectively. In parallel, the density of GHRH mRNA per arcuate neuron was reduced by 52 and 50% at 6 and 18 wk, while SRIH mRNA levels increased by 71 and 83% in the periventricular nucleus (with no alteration in the hilus of the dentate gyrus). The numbers of GHRH- and SRIH-synthetizing neurons in the hypothalamus were not altered in GH-hypersecreting rats. Resection of the tumor restored hypothalamic GHRH and SRIH mRNAs to control levels. GH hypersecretion did not modify 125I-SRIH binding sites on GHRH neurons. Thus, chronic GH hypersecretion affects the expression of the genes encoding for GHRH and SRIH. The effect is long lasting, not desensitizable and reversible.
An activin receptor IIA ligand trap corrects ineffective erythropoiesis in β-thalassemia
Authors: Michael Dussiot, Thiago T Maciel, Aurélie Fricot, Céline Chartier, Olivier Negre, Joel Veiga, Damien Grapton, Etienne Paubelle, Emmanuel Payen, Yves Beuzard, Philippe Leboulch, Jean-Antoine Ribeil, Jean-Benoit Arlet, Francine Coté, Geneviève Courtois, Yelena Z Ginzburg, Thomas O Daniel, Rajesh Chopra, Victoria Sung, Olivier Hermine, Ivan C Moura
Journal: Nature Medicine (2014)
Psychological and sex features of delayed gut transit in functional gastrointestinal disorders
Authors: E J Bennett
Journal: Gut (2000)

<h3>BACKGROUND</h3> The relation of demographic and psychological factors to the presence and extent of gut transit impairment in the functional gastrointestinal disorders has received little attention. <h3>AIMS</h3> To compare the psychosocial and demographic features of patients with functional gastrointestinal disorders and delayed transit in one region of the gastrointestinal tract with those displaying more widespread delayed transit (that is, delay in two or three regions), and those with normal transit in all three regions. <h3>PATIENTS</h3> Of 110 outpatient participants who satisfied standardised criteria for functional gastrointestinal disorders, 46 had delayed transit in one region, 32 had delay in two or three regions, and 17 exhibited normal transit in all regions. <h3>METHODS</h3> Transit in the stomach, the small intestine, and the large intestine was assessed concurrently using a wholly scintigraphic technique; psychological status was assessed using established psychometric measures. <h3>RESULTS</h3> Patients with delayed transit displayed demographic and psychological features that contrasted with patients with normal transit in all regions. In particular, widespread delayed transit featured female sex, a highly depressed mood state, increased age, frequent control of anger, and more severe gastric stasis, while the features distinguishing normal transit were male sex and high levels of hypochondriasis. <h3>CONCLUSION</h3> These data suggest the existence of a distinct psychophysiological subgroup, defined by the presence of delayed transit, in patients with functional gastrointestinal disorders.
Bad press for doctors: 21 year survey of three national newspapers
Authors: N. Y Ali, T. Y S Lo, V. L Auvache, P. D White
Journal: BMJ (2001)

and communication problem were similar in Derbyshire and the West Midlands.Communication problems were less likely if the call was made by a health professional (for example, general practitioner, carer, nurse) rather than by someone else (21/220, 9.5% v 461/1610, 28.6%; 2 = 26.4;P < 0.001).
Pirfenidone for IPF: pro/con debate; the ‘con’ viewpoint
Authors: Ganesh Raghu, David R Thickett
Journal: Thorax (2013)

Improving outcomes for patients with idiopathic pulmonary fibrosis (IPF) remains a major unmet healthcare need—in this, we entirely agree with the ‘pro’ debate article by Gisli Jenkins.1 In this regard, the efforts of drug companies in developing novel drugs and collaboration with expert clinical investigators in the field of IPF in wanting to demonstrate the therapeutic efficacy for patients with IPF are commendable.

Unfortunately, several clinical trials of novel therapy for IPF have yielded negative results. In 1999, the therapeutic potential of pirfenidone as the first antifibrotic pharmacologic agent with promises/hopes that it would improve outcomes for IPF patients was demonstrated in a phase II study.2 Some 13 years later, initial enthusiasm is being questioned—hence, the rationale for this pro/con debate. In this article, it is our aim to provide a balance to Dr Gisli Jenkins's pro article,1 and we hope to provide the readers of this debate a balanced view of the topic. Undoubtedly, the reader will realise that the truth probably exists between the two ends of this polarised academic debate. We believe that the clinician must assess the benefits and risks of pirfenidone treatment by addressing the following specific issues.

Current evidence suggests that in a genetically predisposed person, IPF is manifested as a result of an aberrant response to an unidentified alveolar epithelial injury. Theories speculate that IPF results from abnormal wound-healing response which results in a persistently abnormal epithelial repair that promotes fibroblast proliferation generating a reticulum of activated fibroblasts and collagen which progressively restructures the lung architecture.3 ,4 In addition to myofibroblast foci formation and epithelial cell injury, there is variable evidence of inflammation as evidenced by increased macrophage and neutrophil counts,5 ,6 intra-alveolar coagulapathy,7 and the formation of new blood vessels in the IPF lung.8 …
Comparison of effects of two interval-training programmes on lactate and ventilatory thresholds.
Authors: J Burke, R Thayer, M Belcamino
Journal: British Journal of Sports Medicine (1994)

Twenty-one women subjects were matched in terms of their Vo2max and assigned to one of two groups: (1) training at 30 s; or (2) 2 min with a 1:1 work: relief ratio (1:1 WR) before participating in a 7-week training programme which began at an intensity of 85% Vo2max and increased 5% every two weeks (90% and 95% Vo2max). The subjects trained to exhaustion four times per week. Maximal oxygen consumption (Vo2max), lactate threshold (Tlac) and ventilatory threshold (Tvent) were determined before and after the training programme. After training, there were significant increases (P < 0.05) in Vo2max (5% and 6%), Tlac (19.4% and 22.4%), and Tvent (19.5% and 18.5%). There were no significant group differences on any dependent measure but this research adds support to previous training studies in that a strong correlation (P < 0.05) between Tlac and Tvent is maintained from before to after the test. It was concluded that both formats of high intensity aerobic interval-training produce similar changes in Vo2max, Tlac and Tvent and that these changes appear to be independent of the length of the work interval.
Novel Synthetic Antagonists of Canonical Wnt Signaling Inhibit Colorectal Cancer Cell Growth
Authors: Jo Waaler, Ondrej Machon, Jens Peter von Kries, Steven Ray Wilson, Elsa Lundenes, Doris Wedlich, Dietmar Gradl, Jan Erik Paulsen, Olga Machonova, Jennifer L. Dembinski, Huyen Dinh, Stefan Krauss
Journal: Cancer Research (2011)

Abstract Canonical Wnt signaling is deregulated in several types of human cancer where it plays a central role in tumor cell growth and progression. Here we report the identification of 2 new small molecules that specifically inhibit canonical Wnt pathway at the level of the destruction complex. Specificity was verified in various cellular reporter systems, a Xenopus double-axis formation assay and a gene expression profile analysis. In human colorectal cancer (CRC) cells, the new compounds JW67 and JW74 rapidly reduced active β-catenin with a subsequent downregulation of Wnt target genes, including AXIN2, SP5, and NKD1. Notably, AXIN2 protein levels were strongly increased after compound exposure. Long-term treatment with JW74 inhibited the growth of tumor cells in both a mouse xenograft model of CRC and in ApcMin mice (multiple intestinal neoplasia, Min). Our findings rationalize further preclinical and clinical evaluation of these new compounds as novel modalities for cancer treatment. Cancer Res; 71(1); 197–205. ©2010 AACR.
Inhaled corticosteroid dosage in asthma
Authors: H K Reddel
Journal: Thorax (2002)

GM-CSF therapy in pulmonary alveolar proteinosisTreatment with granulocyte-macrophage colony stimulating factor (GM-CSF) has been shown to benefit a subset of patients with adult pulmonary alveolar proteinosis (PAP).A 47 year old woman with PAP, confirmed by lung biopsy, and severe physiological and symptomatic disturbances was not improved by repeated unilateral whole lung lavages.Six months after the last lavage we started treatment with daily subcutaneous GM-CSF in increasing doses beginning at 3 µg/kg.When a daily dose of 6 µg/kg was reached a haematological response was detected and dose escalation ceased.After 4 weeks at this dose the patient began to improve.By week 11 at a dose of 6 µg/kg/day the treatment was stopped and after a further 3 weeks without treatment she attained maximal clinical, radiological, and physiological improvement (from arterial oxygen tension (PaO 2 ) 6.1 kPa, alveolar-arterial oxygen gradient ((A-a)O 2 ) 8.2 kPa, total lung capacity (TLC) 63.3%, and carbon monoxide transfer factor (TLCO) 58.7% at diagnosis to 10.9 kPa, 2.6 kPa, 99%, and 101.1%, respectively).At that point, as the haematological parameters were normal, we decided empirically to restart treatment at a maintenance dose of 3 µg/kg/day twice a week to avoid relapse.Five months later, with no evidence of clinical deterioration or haematological response, treatment was stopped and after a further 18 months the patient remains symptom free.The successful remission of our patient, the seven published cases of GM-CSF in the treatment of PAP, 1-3 and the low incidence of side effects compared with the whole lung lavage technique prompt us to recommend GM-CSF as a first line treatment option in these patients.