tbuckley/cabot-search huggingface dataset:
Left ventricular diastolic dysfunction in idiopathic pulmonary fibrosis: a tissue Doppler echocardiographic study
Authors: C. E. Papadopoulos, G. Pitsiou, T. D. Karamitsos, H. I. Karvounis, T. Kontakiotis, G. Giannakoulas, G. K. Efthimiadis, P. Argyropoulou, G. E. Parharidis, D. Bouros
Journal: European Respiratory Journal (2007)

It was hypothesised that, apart from right ventricular (RV) dysfunction, patients with idiopathic pulmonary fibrosis (IPF) also exhibit left ventricular (LV) impairment, which may affect disease progression and prognosis. The aim of the present study was to evaluate LV performance in a cohort of IPF patients using conventional and tissue Doppler ECG. IPF patients exhibiting mild-to-moderate pulmonary arterial hypertension (mean age 65+/-9 yrs; n = 22) and healthy individuals (mean age 61+/-6 yrs; n = 22) were studied. Conventional and tissue Doppler ECG were used for the evaluation of RV and LV systolic and diastolic function. In addition to the expected impairment in RV function, all patients showed a characteristic reversal of LV diastolic filling to late diastole compared with controls (early diastolic peak filling velocity (E)/late diastolic peak filling velocity 0.7+/-0.2 versus 1.5+/-0.1, respectively). Patients with IPF also exhibited lower peak myocardial velocities in early diastole (E(m); 5.7+/-1.1 versus 10.3+/-1.6 cm x s(-1), respectively), higher in late diastole (A(m); 8.9+/-1.3 versus 5.5+/-0.8 cm x s(-1), respectively), lower E(m)/A(m) ratio (0.6+/-0.1 versus 1.9+/-0.5, respectively) and higher E/E(m) ratio (10.8+/-3 versus 6+/-0.6, respectively), all indicative of LV diastolic dysfunction. Moreover, LV propagation velocity was significantly lower in IPF patients (46+/-13 versus 83+/-21 cm x s(-1), respectively). Physicians should be aware that patients with idiopathic pulmonary fibrosis exhibit early impairment of left ventricular diastolic function.
Chromosomal Aneusomy in Bronchial High-Grade Lesions Is Associated with Invasive Lung Cancer
Authors: Steinn Jonsson, Marileila Varella-Garcia, York E. Miller, Holly J. Wolf, Tim Byers, Sarah Braudrick, Porntip Kiatsimkul, Marina Lewis, Timothy C. Kennedy, Robert L. Keith, Johannes Bjornsson, Annette McWilliams, Stephen Lam, Fred R. Hirsch, Wilbur A. Franklin
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

The development of lung cancer (LC) is accompanied by field changes in the airway mucosa that may have prognostic importance.To compare patients with prevalent LC to control subjects regarding their histologic dysplasia scores and chromosomal aneusomy as measured by fluorescence in situ hybridization (FISH).The most advanced bronchial histology lesion was assessed from each of 44 LC cases and 90 cancer-free control subjects using a four-color FISH probe set encompassing the chromosome 6 centromere, 5p15.2, 7p12 (epidermal growth factor receptor), and 8q24 v-myc myelocytomatosis viral oncogene homolog (MYC) sequences. Histology grades were coded as dysplasia (moderate or severe) or carcinoma in situ (CIS).CIS was the highest histologic grade for 32 subjects, and dysplasia was the highest grade for 102 subjects (54 moderate, 48 severe). Chromosomal aneusomy was seen in 64% of the LC cases, but in only 31% of the control subjects (odds ratio [OR], 4.68; 95% confidence interval [CI]. 1.97-11.04). Among those with any level of dysplasia, the OR for positive FISH and LC was 2.28 (95% CI, 0.75-6.86). Among those with CIS, the OR for positive FISH and LC was 5.84 (95% CI, 1.31-26.01).Chromosomal aneusomy is associated with LC. Prospective examination of aneusomy as a precursor lesion that predicts LC is needed.
Ancient DNA Identification of Early 20th Century Simian T-Cell Leukemia Virus Type 1
Authors: Sébastien Calvignac, Jean-Michel Terme, Shannon M. Hensley, Pierre Jalinot, Alex D. Greenwood, Catherine Hänni
Journal: Molecular Biology and Evolution (2008)

The molecular identification of proviruses from ancient tissues (and particularly from bones) remains a contentious issue. It can be expected that the copy number of proviruses will be low, which magnifies the risk of contamination with retroviruses from exogenous sources. To assess the feasibility of paleoretrovirological studies, we attempted to identify proviruses from early 20th century bones of museum specimens while following a strict ancient DNA methodology. Simian T-cell leukemia virus type 1 sequences were successfully obtained and authenticated from a Chlorocebus pygerythrus specimen. This represents the first clear evidence that it will be possible to use museum specimens to better characterize simian and human T-tropic retrovirus genetic diversity and analyze their origin and evolution, in greater detail.
Nail involvement in pemphigus vulgaris
Authors: N. Schlesinger, M. Katz, A. Ingber
Journal: British Journal of Dermatology (2002)

Involvement of the nail unit in pemphigus vulgaris (PV) is thought to be rare.To determine the frequency of nail changes among patients with PV.Nail changes were recorded in patients with PV and were analysed retrospectively. Biopsies were taken from the nail bed and nail matrix for histological and immunofluorescence observations. Microscopic (potassium hydroxide) examination and fungal culture were performed.Nail changes were present in 30 of 64 (47%) patients with PV. Sixteen patients had onychomycosis and 14 had nail changes due to PV. These included onychomadesis, discoloration, deformity, onychorrhexis, onycholysis, subungual haemorrhage, subungual hyperkeratosis and paronychia. Onychomycosis affected fingernails and toenails, but changes due to PV occurred only in fingernails, most commonly on the thumb and index finger. No connection was found between the patient's occupation and nail involvement, and there was no correlation with the severity or duration of PV. In a control group of 64 patients of similar sex and age, only two had non-specific fingernail changes.Nail changes in PV may be more frequent than previously thought.
Pharmacogenetics in severity of bronchial hyperresponsiveness in asthma
Authors: Maartje Nieuwenhuis, Gerard Koppelman, Judith Vonk, Dirkje Postma
Journal: European Respiratory Journal (2013)

Introduction

Treatment with inhaled corticosteroids (ICS) reduces bronchial hyperresponsiveness (BHR), a core feature of asthma. Not all asthmatics show the desired treatment response. Genetic variability is an important determinant of therapeutic efficacy of ICS.

Aim

To identify genes that alter the response of BHR to ICS in asthma.

Methods

Out of the 920 asthmatics in the Dutch Asthma GWAS, 650 with complete data were included. A genome wide interaction study (GWIS) using linear regression was performed on BHR severity (ln(slope dose-response curve)) with interactions between SNPs and ICS, adjusted for smoking. Significance was reached when: 1. p<10-4 for interaction, or 2. p<10-3 for the interaction combined with p<10-4 on the main effect of the SNP in either the ICS treated or untreated group.

Results

ICS treated asthmatics (n=426) had significantly better BHR than non ICS treated asthmatics (n=224). 26 SNPs had a significant ICS interaction and 28 had a combination of significant interaction and main effect. Three top-hits were located near ADAMTS12 (fig. 1). These SNPs were associated with more severe BHR in subjects with ICS.

Conclusion

In total, 54 SNPs altered the response to ICS with regard to the severity of BHR in asthmatics. Replication in two independent cohorts will be performed to confirm these results.

Figure 1: Top-hit rs4867517, individuals with ICS use and ADAMTS12 variant have more sever BHR then those without ICS (mean±sem).

![Figure][1]  [1]: pending:yes
Learning from low income countries: what are the lessons?: Health information technology need not cost the earth
Authors: Luis Carlos Silva, Pedro Urra
Journal: BMJ (2004)

EDITOR—In the early 1990s the Soviet Union's disintegration produced a sudden shrinkage of Cuba's economy. US sanctions were tightened, and Cuba was in economic crisis. Long hours of blackout daily became common.

These adverse circumstances affected a country with limited material resources and few computers and telephone lines, as …
Commentaries on this month's Cardiovascular Controversy: the merits and demerits of animal experimentation From M J Janse
Authors: M J Janse
Journal: Cardiovascular Research (1994)

Journal Article Commentaries on this month's Cardiovascular Controversy: the merits and demerits of animal experimentation From M J Janse Get access M J Janse M J Janse Laboratory of Experimental Cardiology, Academic Medical Centre. Meibergdreef 9. Amsterdam. The Netherlands. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 7, July 1994, Pages 1111–1112, https://doi.org/10.1093/cvr/28.7.1111 Published: 01 July 1994
US doctors reaffirm opposition to euthanasia
Authors: C.-G. Mcdaniel
Journal: BMJ (1996)

In the face of growing public and legal support for doctor assisted suicide, the American Medical Association has reaffirmed its adamant opposition to the practice.

The association's 430 member house of delegates gave a near unanimous vote against euthanasia during its annual meeting in Chicago last week. Members representing the various state and specialty medical societiesstated that doctors should be healers and not killers.

The association also said it would work to develop programmes to “facilitate referrals to physicians qualified to provide necessary palliative and other care for patients …
Evidence That Humans Metabolize Benzene via Two Pathways
Authors: Stephen M. Rappaport, Sungkyoon Kim, Qing Lan, Roel Vermeulen, Suramya Waidyanatha, Luoping Zhang, Guilan Li, Songnian Yin, Richard B. Hayes, Nathaniel Rothman, Martyn T. Smith
Journal: Environmental Health Perspectives (2009)

BackgroundRecent evidence has shown that humans metabolize benzene more efficiently at environmental air concentrations than at concentrations > 1 ppm. This led us to speculate that an unidentified metabolic pathway was mainly responsible for benzene metabolism at ambient levels.ObjectiveWe statistically tested whether human metabolism of benzene is better fitted by a kinetic model having two pathways rather than one.MethodsWe fit Michaelis-Menten-like models to levels of urinary benzene metabolites and the corresponding air concentrations for 263 nonsmoking Chinese females. Estimated benzene concentrations ranged from less than 0.001 ppm to 299 ppm, with 10th and 90th percentile values of 0.002 ppm and 8.97 ppm, respectively.ResultsUsing values of Akaike's information criterion obtained under the two models, we found strong statistical evidence favoring two metabolic pathways, with respective affinities (benzene air concentrations analogous to Km values) of 301 ppm for the low-affinity pathway (probably dominated by cytochrome P450 enzyme 2E1) and 0.594 ppm for the high-affinity pathway (unknown). The exposure-specific metabolite level predicted by our two-pathway model at nonsaturating concentrations was 184 μM/ppm of benzene, a value close to an independent estimate of 194 μM/ppm for a typical nonsmoking Chinese female. Our results indicate that a nonsmoking woman would metabolize about three times more benzene from the ambient environment under the two-pathway model (184 μM/ppm) than under the one-pathway model (68.6 μM/ppm). In fact, 73% of the ambient benzene dose would be metabolized via the unidentified high-affinity pathway.ConclusionBecause regulatory risk assessments have assumed nonsaturating metabolism of benzene in persons exposed to air concentrations well above 10 ppm, our findings suggest that the true leukemia risks could be substantially greater than currently thought at ambient levels of exposure—about 3-fold higher among nonsmoking females in the general population.
Does a hypertonic saline load predict fluid retention in pacing induced heart failure?
Authors: Y Fu
Journal: Cardiovascular Research (1997)

Objective: We examined the response to hypertonic saline challenge (SC) as a potential predictor of fluid retention during heart failure induced by rapid ventricular pacing. Methods: Twelve dogs (22 ± 4 kg) were given an intra-arterial bolus of 30 ml of 20% saline after establishing baseline fluid intake and urine output (24 h). Dogs were classified according to whether they drank more (Group A) or less (Group B) than the amount required to dilute the SC to isotonicity. Fluid retention was then assessed during heart failure after rapid ventricular pacing according to a graded ordinal scale and correlated with the responses to SC. Results: No difference was noted in baseline fluid intake (1112 ± 236 ml in Group A vs. 809 ± 129 ml in Group B). Five hours after SC cumulative water intake was significantly greater in Group A than in Group B (1018 ± 136 vs. 591 ± 17 ml) (P < 0.01). Urine sodium concentration was 113 ± 11 and 124 ± 28 mmol/l at baseline in Group A and B, respectively; increased to 190 ± 21 and 295 ± 59 mmol/l at 5 h and remained elevated 24 h after SC, 177 ± 60 and 274 ± 55 mmol/l (both P < 0.01 for within-group comparisons vs. baseline). Urine sodium concentration was less in Group A than in Group B at 5 and 24 h (P < 0.05). The fluid retention score was greater in Group A (3.6 ± 0.5) than in Group B (0.8 ± 0.4) (P < 0.01). Fluid retention in heart failure correlated with water intake after the pre-pacing SC (r = 0.68, P < 0.025) and inversely with urine concentrating ability (r = −0.58, P < 0.02). Furthermore, water intake and urine concentrating ability following the SC were inversely related (r = −0.67, P < 0.02). Conclusions: We conclude that normal dogs may be classified according to their fluid intake after SC. Those dogs that drank excessively and produced a dilute urine were more likely to retain fluid during pacing-induced heart failure. Hence, fluid intake and the ability to excrete a concentrated urine after a saline challenge may be useful variables to predict fluid retention in pacing-induced heart failure.
Clozapine Augmented With Risperidone in the Treatment of Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Richard C. Josiassen, Ashok Joseph, Eva Kohegyi, Sudhir Stokes, Mahmood Dadvand, Wynn Wynn Paing, Rita A. Shaughnessy
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The authors evaluated the efficacy and safety of augmenting clozapine with risperidone in patients with treatment-resistant schizophrenia. METHOD: In a randomized, double-blind, placebo-controlled 12-week trial, 40 patients unresponsive or partially responsive to clozapine monotherapy received a steady dose of clozapine combined with either placebo (N=20) or up to 6 mg/day of risperidone (N=20). Patient psychopathology was assessed at 2-week intervals with the Brief Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative Symptoms (SANS), among other measures. Movement disorders were assessed with the Simpson-Angus Rating Scale. RESULTS: From baseline to week 6 and week 12, mean BPRS total and positive symptom subscale scores were reduced significantly in both groups, but the reductions were significantly greater with clozapine/risperidone treatment. Reductions in SANS scores were also significantly greater with clozapine/risperidone treatment than with clozapine/placebo. The adverse event profile for clozapine/risperidone treatment was similar to that for clozapine/placebo. Simpson-Angus Rating Scale scores were lower with clozapine/risperidone treatment throughout the trial but increased to approach those of clozapine/placebo treatment at week 12. Clozapine/risperidone treatment did not induce additional weight gain, agranulocytosis, or seizures compared with clozapine/placebo treatment. CONCLUSIONS: In patients with a suboptimal response to clozapine, the addition of risperidone improved overall symptoms and positive and negative symptoms of schizophrenia. The combination appears to be safe and well tolerated. Augmentation of clozapine with risperidone may provide additional clinical benefit for patients who are nonresponsive or only partially responsive to clozapine alone.
Inhibition of Intracellular Clusterin Attenuates Cell Death in Nephropathic Cystinosis
Authors: Poonam Sansanwal, Li Li, Minnie M. Sarwal
Journal: Journal of the American Society of Nephrology (2014)

Nephropathic cystinosis, characterized by accumulation of cystine in the lysosomes, is caused by mutations in CTNS. The molecular and cellular mechanisms underlying proximal tubular dysfunction and progressive renal failure in nephropathic cystinosis are largely unclear, and increasing evidence supports the notion that cystine accumulation alone is not responsible for the end organ injury in cystinosis. We previously identified clusterin as potentially involved in nephropathic cystinosis. Here, we studied the expression of clusterin in renal proximal tubular epithelial cells obtained from patients with nephropathic cystinosis. The cytoprotective secretory form of clusterin, as evaluated by Western blot analysis, was low or absent in cystinosis cells compared with normal primary cells. Confocal microscopy revealed elevated levels of intracellular clusterin in cystinosis cells. Clusterin in cystinosis cells localized to the nucleus and cytoplasm and showed a filamentous and punctate aggresome-like pattern compared with diffuse cytoplasmic staining in normal cells. In kidney biopsy samples from patients with nephropathic cystinosis, clusterin protein expression was mainly limited to the proximal tubular cells. Furthermore, expression of clusterin overlapped with the expression of apoptotic proteins (apoptosis-inducing factor and cleaved caspase-3) and autophagy proteins (LC3 II and p62). Silencing of the clusterin gene resulted in a significant increase in cell viability and attenuation of apoptosis in cystinosis cells. Results of this study identify clusterin as a pivotal factor in the cell injury mechanism of nephropathic cystinosis and provide evidence linking cellular stress and injury to Fanconi syndrome and progressive renal injury in nephropathic cystinosis.
Hematogenous Metastasis in Gastric Cancer Requires Isolated Tumor Cells and Expression of Vascular Endothelial Growth Factor Receptor-1
Authors: Koshi Mimori, Takeo Fukagawa, Yoshimasa Kosaka, Yoshiaki Kita, Kenji Ishikawa, Tsuyoshi Etoh, Hisae Iinuma, Mitsuru Sasako, Masaki Mori
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Recent studies of cancer metastasis have focused on the role of premetastatic gene expression and circulating tumor cells. We did a blind prospective study in gastric cancer to assess the significance of isolated tumor cells (ITC) and to test the hypothesis that vascular endothelial growth factor receptor-1 (VEGFR-1) is expressed within the bone marrow at tumor-specific, premetastatic sites. Experimental Design: Both bone marrow and peripheral blood samples from 810 gastric cancer patients were collected at the Central Hospital, National Cancer Center (Tokyo, Japan). The samples were transferred to Kyushu University Hospital (Beppu, Japan) where they were analyzed by quantitative real-time reverse transcription-PCR for three epithelial cell markers, carcinoembryonic antigen, cytokeratin-19, and cytokeratin-7, as well as VEGFR-1. Results: ITCs were observed in peripheral blood and bone marrow even in early stages of gastric cancer. The frequency of ITC in bone marrow was significantly associated with the stage of disease by ANOVA (P &amp;lt; 0.01). Gastric cancer metastasized when ITCs were observed in the presence of VEGFR-1. In the 380 patients who were ITC negative and showed low VEGFR-1 expression, synchronous (at the time of surgery) and heterochronous (recurrent) metastases were not observed. Conclusions: ITCs circulate even in early stages of disease. Furthermore, elevated expression of VEGFR-1 facilitates the establishment of hematogenous metastases in gastric cancer. This study indicates that the simultaneous presence of ITC and VEGFR-1 expression at premetastatic sites is clinically significant for disease progression.
Comparison of two referral strategies for diagnosis of axial spondyloarthritis: the Recognising and Diagnosing Ankylosing Spondylitis Reliably (RADAR) study
Authors: Joachim Sieper, Shankar Srinivasan, Omid Zamani, Herman Mielants, Denis Choquette, Karel Pavelka, Anne Gitte Loft, Pál Géher, Debashish Danda, Tatiana Reitblat, Fabrizio Cantini, Codrina Ancuta, Shandor Erdes, Helena Raffayová, Andrew Keat, J S H Gaston, Sonja Praprotnik, Nathan Vastesaeger
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To determine which of two referral strategies, when used by referring physicians for patients with chronic back pain (CBP), is superior for diagnosing axial spondyloarthritis (SpA) by rheumatologists across several countries. <h3>Methods</h3> Primary care referral sites in 16 countries were randomised (1 : 1) to refer patients with CBP lasting &gt;3 months and onset before age 45 years to a rheumatologist using either strategy 1 (any of inflammatory back pain (IBP), HLA-B27 or sacroiliitis on imaging) or strategy 2 (two of the following: IBP, HLA-B27, sacroiliitis, family history of axial SpA, good response to non-steroidal anti-inflammatory drugs, extra-articular manifestations). The rheumatologist established the diagnosis. The primary analysis compared the proportion of patients diagnosed with definite axial SpA by referral strategy. <h3>Results</h3> Patients (N=1072) were referred by 278 sites to 64 rheumatologists: 504 patients by strategy 1 and 568 patients by strategy 2. Axial SpA was diagnosed in 35.6% and 39.8% of patients referred by these respective strategies (between-group difference 4.40%; 95% CI −7.09% to 15.89%; p=0.447). IBP was the most frequently used referral criterion (94.7% of cases), showing high concordance (85.4%) with rheumatologists9 assessments, and having sensitivity and a negative predictive value of &gt;85% but a positive predictive value and specificity of &lt;50%. Combining IBP with other criteria (eg, sacroiliitis, HLA-B27) increased the likelihood for diagnosing axial SpA. <h3>Conclusions</h3> A referral strategy based on three criteria leads to a diagnosis of axial SpA in approximately 35% of patients with CBP and is applicable across countries and geographical locales with presumably different levels of expertise in axial SpA.