tbuckley/cabot-search huggingface dataset:
Low Levels of Transthyretin in the CSF of Depressed Patients
Authors: Gregory M. Sullivan, Julie A. Hatterer, Joseph Herbert, Xi Chen, Steven P. Roose, Evelyn Attia, J. John Mann, Lauren B. Marangell, Raymond R. Goetz, Jack M. Gorman
Journal: American Journal of Psychiatry (1999)

Transthyretin plays an important role in the transport and distribution of thyroid hormone in the central nervous system (CNS). This study replicated and extended to patients with nonrefractory depressive illness a pilot study indicating that patients with refractory major depression have significantly lower levels of CSF transthyretin than do healthy comparison subjects.Lumbar punctures were performed in drug-free subjects with DSM-III-R major depression (N = 18), DSM-III-R bipolar disorder, depressed phase (N = 1), and healthy comparison subjects (N = 24). CSF concentrations of transthyretin, determined by a quantitative dot-immunobinding assay, of the depressed patients and comparison subjects were compared by analysis of covariance (ANCOVA). The relationship between CSF transthyretin levels and Hamilton Depression Rating Scale scores was determined in a subset of the depressed patients.CSF concentrations of transthyretin were significantly lower in the depressed patients than in the comparison subjects by ANCOVA. Within the depressed group there was no significant overall correlation between CSF transthyretin levels and Hamilton depression scale scores, but there was a significant inverse correlation in male depressed patients (N = 8) between CSF transthyretin concentrations and Hamilton depression scores.Lower CSF transthyretin concentrations in depressed patients may reflect either a stable trait in this population or a state change secondary to depression or other factors. Lower CSF transthyretin concentrations may result in altered CNS thyroid hormone homeostasis. Such alteration could account for certain mood and neurovegetative symptoms of depression and might contribute to failure of standard antidepressant treatment.
BDNF Val66Met Polymorphism and GAD<sub>67</sub> mRNA Expression in the Prefrontal Cortex of Subjects With Schizophrenia
Authors: Takanori Hashimoto, David A. Lewis
Journal: American Journal of Psychiatry (2006)

OBJECTIVE: In the prefrontal cortex of subjects with schizophrenia, decreased signaling mediated by brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase (TrkB) appears to contribute to the reduced expression of mRNA encoding the 67-kilodalton isoform of glutamate decarboxylase (GAD67), an enzyme for GABA synthesis. The authors examined in subjects with schizophrenia the effect in the human BDNF gene of a single nucleotide polymorphism (Val66Met), which reduces the trafficking and secretion of BDNF protein, on the expression of GAD67 mRNA. METHOD: BDNF Val66Met genotyping was performed in 27 matched pairs of schizophrenia and comparison subjects. The impact of this polymorphism on prefrontal cortex GAD67 mRNA expression in schizophrenia subjects was assessed by comparing within-pair differences in GAD67 mRNA expression between schizophrenia subjects with versus without the Met66 allele after the level of BDNF mRNA expression was controlled. RESULTS: In contrast to expectations, the within-pair reduction in GAD67 mRNA expression was not greater in schizophrenia subjects who were hetero- or homozygous for the Met66 allele. These subjects did tend to exhibit less marked within-pair reductions in both GAD67 and BDNF mRNA expression compared with schizophrenia subjects homozygous for the Val allele. CONCLUSIONS: The presence of the BDNF Met66 allele does not contribute to the decreased level of GAD67 mRNA expression in the prefrontal cortex of subjects with schizophrenia.
Cystic fibrosis presenting with hypokalemia and metabolic alkalosis in a previously healthy adolescent.
Authors: C M Bates, M Baum, R Quigley
Journal: Journal of the American Society of Nephrology (1997)

Cystic fibrosis (CF) is an exocrine disease affecting multiple organ systems. Patients with CF usually present with respiratory or gastrointestinal abnormalities. This study presents a case of a previously healthy 17-yr-old man who was diagnosed with CF after presenting with metabolic alkalosis and hypokalemia. The defect associated with CF is in the cystic fibrosis transmembrane regulator (CFTR), which acts primarily as a chloride channel. Partially functional CFTR may be associated with less severe pulmonary and gastrointestinal manifestations, as in the case presented. Dysfunctional CFTR in the sweat ducts of CF patients are responsible for excessive chloride and sodium losses, especially in warm weather. Hypokalemia seen with heat stress is secondary to sweat as well as renal potassium wasting. Metabolic alkalosis is maintained by the excessive sweat sodium chloride losses which leads to extracellular fluid (ECF) volume contraction and chloride depletion. Generation of alkalosis may be related to dysfunctional CFTR in the kidney, but is most likely secondary to hypokalemia with ECF volume contraction. Finally, one must consider CF when confronted with hypokalemia and alkalosis in a previously healthy patient.
A phase I study of pazopanib in patients with advanced hepatocellular carcinoma
Authors: C. C. Yau, P. J. Chen, C. M. Curtis, P. S. Murphy, A. B. Suttle, T. Arumugham, J. P. Hodge, M. M. Dar, R. Poon
Journal: Journal of Clinical Oncology (2009)

3561 Background: Patients (pts) with advanced hepatocellular carcinoma (HCC) have a poor prognosis. HCC is a highly vascular tumor with increased levels of angiogenic factors including VEGF and VEGFR. Pazopanib (GW786034) is an oral angiogenesis inhibitor targeting VEGFR, PDGFR, and c-Kit. A Phase I study was conducted to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics and efficacy of pazopanib in patients with locally unresectable and/or advanced HCC. Methods: Eligibility criteria included unresectable and/or metastatic HCC with at least 1 target lesion, recovery from prior systemic regimens, ECOG PS 0 or 1, Child-Pugh A, and adequate organ function. Doses of pazopanib were escalated from 200 mg once daily (QD) to 800 mg QD in a 3 + 3 design. DCE- MRI was performed to assess changes in tumor permeability. Results: 27 Asian pts have been enrolled at QD doses of 200 (4 pts), 400 (10), 600 (8), 800 (5): median (range) age = 61 (38–76); M/F = 85%/15%; ECOG 0/1 = 59%/41%; 81% with metastatic disease; 67% with Stage IV; 22% with prior systemic therapy, 26% with prior TACE. Most common AEs were: diarrhea (59%; 4% Gr 3); hypertension (44%; 26% Gr 3), cough (19%); fatigue (19%; 4% Gr 3); and hair depigmentation (15%). Hepatobiliary lab abnormalities were: AST elevation (63%; 15% Gr 3), hyperbilirubinemia (63%; 4% Gr 3), ALT elevation (41%; 7% Gr 3), and Alk phos (37%; 4% Gr 3). DLTs were Gr 3 malaise (1 pt) and Gr 3 AST/ALT elevation (1 pt) at 800 mg. MTD was determined to be 600 mg QD. Median (range) days on study was 85 (4–663) overall; 106 days (4–274) at the MTD. Best response was PR in 2 pts (7%; 1 at 800mg, 1 at 600 mg) and SD &gt; 4 mos in 11 pts (41%). Median TTP at the MTD was 137.5 days (4–280 days). Median % change in tumor permeability (K trans ) following 3 weeks of pazopanib administration at the MTD (5 pts) was 45%. Predose and maximum plasma pazopanib concentrations at 800 mg QD were similar to values observed previously at the same dose. Conclusions: Pazopanib has a manageable safety profile in HCC at the MTD of 600mg QD. Preliminary evidence of antitumor activity was observed. Changes in tumor DCE-MRI parameters were seen following repeated dose pazopanib administration. [Table: see text]
Maximal lipidic power in high competitive level triathletes and cyclists
Authors: C González-Haro, P A Galilea, J M González-de-Suso, F Drobnic, J F Escanero
Journal: British Journal of Sports Medicine (2006)

To describe the fat-oxidation rate in triathlon and different modalities of endurance cycling.34 endurance athletes (15 male triathletes, 4 female triathletes, 11 road cyclists and 4 male mountain bikers) underwent a progressive cycloergometer test until exhaustion. Relative work intensity (VO(2max)), minimal lactate concentration (La(-)(min)), lactic threshold, individual lactic threshold (ILT), maximal fat-oxidation rate (Fat(max), Fat(max) zone) and minimal fat-oxidation rate (Fat(min)) were determined in each of the groups and were compared by means of one-way analysis of variance.No significant differences were found for Fat(max), Fat(min) or for the Fat(max) zone expressed as fat oxidation rate (g/min). Intensities -20%, -10% and -5% Fat(max) were significantly lower for mountain bikers with respect to road cyclists and female triathletes, expressed as % VO(2max). Intensities 20%, 10% and 5% Fat(max) were significantly lower for mountain bikers with respect to male triathletes and female triathletes, and for male triathletes in comparison with female triathletes, expressed as % VO(2max). Lactic threshold and La(-)(min) did not show significant differences with respect to Fat(max). Lactic threshold was found at the same VO(2max) with respect to the higher part of the Fat(max) zone, and La(-)(min) at the same VO(2max) with respect to the lower part of the Fat(max) zone.The VO(2max) of Fat(max) and the Fat(max) zone may explain the different endurance adaptations of the athletes according to their sporting discipline. Lactic threshold and La(-)(min) were found at different relative work intensities with respect to those of Fat(max) even though they belonged to the Fat(max) zone.
Sentinel Lymph Node Biopsy for Breast Cancer Treatment During Pregnancy - on Behalf of the International Network of Cancer, Infertility and Pregnancy (Incip) and the German Breast Group (Gbg)
Authors: S.N. Han, F. Amant, C. Sangalli, S. Loibl, O. Gheysens, C.A.R. Lok, K. Dahl Steffensen, M.J. Halaska, F.A. Peccatori, O. Gentilini
Journal: Annals of Oncology (2014)
Dissemination of multidrug-resistant, class 1 integron-carrying Acinetobacter baumannii isolates in Taiwan
Authors: L.-Y. Huang, T.-L. Chen, P.-L. Lu, C.-A. Tsai, W.-L. Cho, F.-Y. Chang, C.-P. Fung, L.K. Siu
Journal: Clinical Microbiology and Infection (2008)
A new method for detection of flow limitation in COPD using dynamic chest X-ray examination
Authors: Norihisa Motohashi, Takehiko Abe, Misako Aoki, Kozo Morimoto, Yuji Shiraishi, Hideo Ogata, Shoji Kudoh
Journal: European Respiratory Journal (2011)

Purpose:  Spirometry which requires maximum effort tasks COPD patients. In this study, we proposed a new method for detection of flow limitation without effort breathing.   Subjects:  Dynamic chest X-ray from 10 normal volunteers, 16 mild COPD patients (GOLD Stage I or II) and 12 severe COPD patients (GOLD Stage III or IV) were obtained in the upright position in about 10 seconds of tidal breathing at rest. The dynamic image data captured at 7.5 frames per second was synchronized with the pulsed X-ray. The institutional review board approval and written informed consent were obtained in all persons.   Methods:  We calculated the maximal differential values in each ventilation phase at the corresponding small local area of lung in the series of dynamic chest X-ray. The regional relative flow rate ratio was obtained from the peak values of inspiratory phase divided by the peak values of expiratory phase. All groups were compared about the average of flow rate ratio.   Results:  The regional changes in inspiratory/expiratory flow rate ratio had larger values and broader distribution in COPD patients than those of normal volunteers. The average of the ratio in normal volunteers, in mild COPD patients and in severe COPD patients were 1.08±0.09, 1.17±0.08 and 1.19±0.13 (mean±SD), respectively. A significant difference was confirmed between the normal volunteers and the COPD patients (p = 0.031).   Conclusion:  The inspiratory/expiratory flow rate ratios in COPD patients were larger than those of healthy volunteers. The new method for ventilation function has possibility to evaluate flow limitation without effort breathing.
A potential method for development of a bird flu vaccine
Authors: Sanjoy Basu
Journal: Thorax (2008)

The mechanisms by which animal strains of the influenza virus adapt themselves to invade human hosts are not fully understood, leading to difficulty in effective immunisation and treatment. Attempts are now being made to use structurally modified mutants to develop vaccines and therapeutic antibodies to pre-empt the emergence of human-adapted H5N1 strains of the …
Using induced sputum cell counts to guide management of difficult-to-treat asthmatics
Authors: Mithun Murthy, Julie Scanlan, Robert Niven, Stephen Scott
Journal: European Respiratory Journal (2013)

Background  An ERS task force has recommended phenotype-based management in asthma. Knowledge of airway inflammation helps guide physicians9 decisions in difficult to treat cases where guideline-based treatments no longer apply.  Aim  We assessed how induced sputum cell count results influenced the management strategy of members of the North West Severe Asthma Network (NWSAN)  Method  15 case summaries of physician diagnosed asthma (BTS step 3-5) were sent to members of NWSAN and their responses to a list of management options (figure) was noted. This was then repeated after differential cell count results.  Results  Cases were phenotyped as eosinophilic (E;n=9), neutrophilic (N;n=3), mixed granulocytic (MG;n=1) and pauci-granulocytic (PG;n=2).  In 63%, responses changed after sputum counts were revealed with greater agreement between physicians. More physicians changed their response when eosinophilia was present than without (67% V 55%). Table shows change in responses (post sputum result) with respect to steroid load.  Conclusion  Knowledge of sputum cell counts is a useful adjunct in the management of asthmatics, especially those with uncontrolled eosinophilia, in whom there was a trend towards increasing steroid load.
Hürthle Cell Carcinoma: A Critical Histopathologic Appraisal
Authors: Alexander Stojadinovic, Ronald A. Ghossein, Axel Hoos, Marshall J. Urist, Ronald H. Spiro, Jatin P. Shah, Murray F. Brennan, Ashok R. Shaha, Bhuvanesh Singh
Journal: Journal of Clinical Oncology (2001)

Controversy exists over the ability of morphology to predict the biologic behavior of Hürthle cell carcinoma. The aim of this study was to conduct a critical histopathologic review of Hürthle cell carcinoma and to correlate morphologic parameters with clinical outcome.Patients with histologically confirmed Hürthle cell carcinoma treated between 1940 and 2000 form the basis of this study. Adenomas were excluded. Tumors of unknown malignant behavior ([UMB] n = 17) had solid growth pattern, incomplete capsular invasion (Ci), or both but no vascular invasion (Vi). Minimally invasive carcinomas ([MIC] n = 23) had one focus of intra- or extracapsular Vi, one focus of complete Ci, or both. Widely invasive carcinomas ([WIC] n = 33) demonstrated more than one focus of Vi, more than one focus of Ci, or both. The primary end points were relapse-free survival (RFS) and disease-specific survival (DSS). Rates of recurrence/death were estimated by Kaplan-Meier method. The univariate influence of prognostic factors on end points was analyzed by log-rank test, and multivariate analysis was performed by Cox regression.Median follow-up was 8 years. No patients with UMB or MIC relapsed or died of disease. Of WIC, 73% relapsed and 55% died of disease. Age, size, and extent of resection did not influence outcome. Adverse predictors of RFS and DSS among WIC were extrathyroidal extension, nodal metastasis, positive margin, and solid growth pattern (P <.05). Both Ci and Vi were associated with worse DSS (P <.05). On multivariate analysis, extrathyroidal extension and nodal metastases were independent predictors of outcome (P <.05).Patients with Hürthle cell carcinoma have a prognosis that is predicted by well-defined histomorphologic characteristics. Unlike differentiated thyroid cancer, nodal metastases predict a worse outcome in widely invasive Hürthle cell carcinoma, as does extrathyroidal extension.
In vitro susceptibility of TB- and MDR-TB-strains against linezolid at a local center in Berlin/Germany
Authors: Timo Weiss, Nicolas Schönfeld, Ralf Otto-Knapp, Lena Bös, Gudrun Bettermann, Mauch Harald, Rüssmann Holger, Bauer Torsten
Journal: European Respiratory Journal (2013)

Background   Due to migration the spectrum of  Mycobacterium tuberculosis  (Mtb) in patients with active tuberculosis treated at the largest TB center in Berlin, Germany, changed in the last decades, with an increasing prevalence of multidrug resistance tuberculosis (MDR-Tb). In this context, drug susceptibility testing has a high impact for treatment decisions.   Aims   The aim of our study was to evaluate the  in vitro   susceptibility of linezolid assessed by minimal inhibitory concentrations (MICs) against Tb- and MDR-Tb-strains isolated from patients treated in our center.   Methods   From 148 Mtb-cultures (18 MDR-Tb) from 2002 to 2012 we retrospectively evaluated the sensitivity and MIC of linezolid. Testing for MIC was performed on solid Middlebrook-7H10 and -7H11 agar plates.   Results   The MICs for 18 MDR-Tb-strains were in the range of 0,25 – 0,5 µg/ml and for 130 Non-MDR-Tb between 0,12 and 0,5 µg/ml (4 strains with MIC= 0,12 µg/ml, 83 with 0,25 µg/ml and 5 with 0,5 µg/ml, respectively). During the time period no change in susceptibility could be observed neither for the tested MDR- nor the Non-MDR-Tb-strains.   Conclusions   Our study shows a high sensitivity rate of linezolid against the tested local Mtb-strains, and with low MICs. No major difference for MICs could be shown between the strains of MDR and Non-MDR-Tb.
Transmission of MDR-TB by a Haarlem genotype mycobacterium tuberculosis strain among native Greeks
Authors: Stamatoula Tsikrika, Panagiotis Ioannidis, Dimitris Papaventsis, Apostolos Papavasileiou, Simona Karabela, Ioanna Marinou, Eythymia Konstantinidou, Anastasios Skouroglou, Jessica De Beer, Madeline Stone, Dick van Soolingen, Francis Drobniewski, Kostantinos Kostantinou, Evangelos Vogiatzakis
Journal: European Respiratory Journal (2013)

Aim: To study possible transmission of MDR-TB among native Greeks by molecular genotyping of the Mycobacterium tuberculosis isolates.  Patients-Methods: Five isolates were retrieved from 4 patients in Athens (3 males and one female; mean age 38y) who were hospitalized between 2009 and 2012. Resistance mutations were traced by using the Genotype MTBDRplus and MTBDRsl assays (Hain Lifescience, Germany). 24-loci VNTR typing was performed to investigate possible transmission in collaboration with the RIVM, The Netherlands, within the framework of an ECDC/RIVM MDR-TB project 2009-2012 and with the NMRL, UK.  Results: All patients were HIV seronegative, without immunosuppression or respiratory diseases other than pulmonary TB. Cavitary lesions on X-ray were described in two cases. The M. tuberculosis isolates harbored the rpoB H526D and katG S315T2 mutations. Two strains also had the gyrA A90V mutation; whereas one had a mixed population of wild-type gyrA and gyrA A90V mutated bacilli. Conventional DST confirmed the molecular data. A gradual clinical, radiological and microbiological improvement was observed in all cases. VNTR profiles of the 4 isolates (one from each patient), were unique in the MIRU-VNTR plus and the UK National Database. However, the VNTR profiles were identical or differed in only one locus and thus revealed active transmission of MDR-TB. Two of the patients were indeed close contacts. The isolates were identified as Haarlem lineage strains.  Conclusion: This study re-emphasizes the transmissibility of MDR-TB and the need of early case finding and infection control. Molecular epidemiology is a very useful tool to reveal this important issue.
Lung function impairment in term infants developing respiratory syncytial virus bronchiolitis is pre-existent in previously healthy infants
Authors: Kim Zomer-Kooijker, Louis Bont, Kors vsn der Ent
Journal: European Respiratory Journal (2013)

Introduction

Respiratory syncytial virus (RSV) is the most frequent cause for hospitalization in infancy and associated with lower lung function at school age. Whether this lung function is pre-existent in previous healthy children that will develop a RSV infection is not known.

Objective

To study whether diminished premorbid lung function in healthy infants predisposed to RSV hospitalization.

Methods

In a prospective birth cohort study, infants were followed from birth through the first year of life with daily questionnaires about respiratory symptoms. Neonatal lung function was performed within the first 2 months of life. Nose and throat swabs were collected in two virus subgroups: one in which infants were sampled during episodes with respiratory symptoms, and one in which infants were sampled irrespectively of symptoms. Polymerase chain reaction was used to detect RSV infections. Patients with a confirmed RSV bronchiolitis were selected based on the general practitioner charts, and compared to non hospitalized RSV positive infant.

Results

Compliance of the respiratory system (Crs) was significantly lower in the hospitalized RSV patients compared to to non hospitalized RSV positive infants (median difference -6.01 (95% CI -11.34 to -0.74)). Resistance of the respiratory system in the hospitalized RSV patients was significantly higher than in the infants that were not hospitalized (median difference 1.146 (95% CI 0.01 to 2.32).

Conclusions

We conclude that premorbid lung function in previously healthy infants that develop a RSV bronchiolitis requiring hospitalization is impaired compared to RSV-positive infants not requiring hospitalization.
Nonclinical Tools to Assess Risk of Drug Hypersensitivity Reactions
Authors: J. Whritenour, S. Casinghino, M. Collinge, X. Zhu
Journal: The Annual Review of Pharmacology and Toxicology (2015)

The term drug hypersensitivity refers to a category of adverse drug reactions mediated by various immunological and nonimmunological mechanisms. Small-molecule drugs and biotherapeutics have been associated with drug hypersensitivity reactions (DHRs), and the mechanisms driving the responses vary. Depending on the mechanism, some DHRs may be detected in nonclinical toxicology studies, and there may be tools and models in place that can be used as part of a risk assessment strategy. In contrast, for other mechanisms, particularly those that are not readily detected during nonclinical development, predictive tools and strategies for risk assessment are not well defined. This chapter provides an overview of the nonclinical tools currently available to assess the risk for developing DHRs.
A New Human Breast Carcinoma Cell Line (PMC42) With Stem Cell Characteristics. I. Morphologic Characterization
Authors: R H Whitehead, I Bertoncello, L M Webber, J S Pedersen
Journal: JNCI Journal of the National Cancer Institute (1983)

A new human breast carcinoma cell line (PMC42) was established from a pleural effusion from a woman with metastatic breast cancer. The cells were significantly pleomorphic even after 3.5 years in continuous culture. Eight different cell types could be characterized morphologically in monolayer culture. Cells cloned in agar and replated in monolayer culture were equally heterogenous. Cells also grew in suspension in papillary clusters that structurally resembled glandular organoids. Electron microscopy confirmed the differentiated structure of these cells in which many of the features of lactating breast tissue were evident. It is proposed that this is a culture derived from a malignant breast stem that has retained its ability to differentiate in vitro.