tbuckley/cabot-search huggingface dataset:
Na+ ions as spatial intracellular messengers for co-ordinating Ca2+ signals during pH heterogeneity in cardiomyocytes
Authors: Pawel Swietach, Kenneth W. Spitzer, Richard D. Vaughan-Jones
Journal: Cardiovascular Research (2014)

Contraction of the heart is regulated by electrically evoked Ca(2+) transients (CaTs). H(+) ions, the end products of metabolism, modulate CaTs through direct interactions with Ca(2+)-handling proteins and via Na(+)-mediated coupling between acid-extruding proteins (e.g. Na(+)/H(+) exchange, NHE1) and Na(+)/Ca(2+) exchange. Restricted H(+) diffusivity in cytoplasm predisposes pH-sensitive Ca(2+) signalling to becoming non-uniform, but the involvement of readily diffusible intracellular Na(+) ions may provide a means for combatting this.CaTs were imaged in fluo3-loaded rat ventricular myocytes paced at 2 Hz. Cytoplasmic [Na(+)] ([Na(+)]i) was imaged using SBFI. Intracellular acidification by acetate exposure raised diastolic and systolic [Ca(2+)] (also observed with acid-loading by ammonium prepulse or CO₂ exposure). The systolic [Ca(2+)] response correlated with a rise in [Na(+)]i and sarcoplasmic reticulum Ca(2+) load, and was blocked by the NHE1 inhibitor cariporide (CO₂/HCO₃(-)-free media). Exposure of one half of a myocyte to acetate using dual microperfusion (CO₂/HCO₃(-)-free media) raised diastolic [Ca(2+)] locally in the acidified region. Systolic [Ca(2+)] and CaT amplitude increased more uniformly along the length of the cell, but only when NHE1 was functional. Cytoplasmic Na(+) diffusivity (DNa) was measured in quiescent cells, with strophanthidin present to inhibit the Na(+)/K(+) pump. With regional acetate exposure to activate a local NHE-driven Na(+)-influx, DNa was found to be sufficiently fast (680 µm(2)/s) for transmitting the pH-systolic Ca(2+) interaction over long distances.Na(+) ions are rapidly diffusible messengers that expand the spatial scale of cytoplasmic pH-CaT interactions, helping to co-ordinate global Ca(2+) signalling during conditions of intracellular pH non-uniformity.
A simple ultrasound approach for detection of recurrent proximal-vein thrombosis.
Authors: P Prandoni, A Cogo, E Bernardi, S Villalta, P Polistena, P Simioni, F Noventa, L Benedetti, A Girolami
Journal: Circulation (1993)

BACKGROUND The objective of this study was to develop a simple ultrasound method for measuring thrombus regression in patients with proximal deep-vein thrombosis (DVT) and to test its utility for the detection of DVT recurrence. METHODS AND RESULTS The study comprised a cross-sectional survey and a prospective investigation (149 and 145 patients, respectively). In both phases, the normalization rate of a previously abnormal ultrasound test, applying the criterion of full compressibility of the common femoral and popliteal veins (C-US method), was assessed. In the prospective study, the vein diameter under maximum compression (thrombus thickness) was measured in the abnormal venous segments at scheduled times (1, 3, 6, and 12 months). In patients presenting with suspected DVT recurrence, the procedure was repeated and results were compared with those available from the previous examination. Noncompressibility of a previously normal(ized) venous segment and enlargement of thrombus thickness (&gt; or = 2 mm) were considered diagnostic of proximal DVT recurrence. The diagnostic accuracy of the C-US method alone, as well as of the combined ultrasound methods (C-US + thrombus thickness), was assessed against contrast phlebography. C-US test normalization occurred in only 30% of patients within 1 year. A significant reduction of the thrombus mass (P &lt; .0001) was recorded throughout the entire study period. However, a major decrease in thrombus mass (&gt; 50%) was recorded within the first 3 months. Of 29 patients who developed a suspected recurrent DVT, phlebography confirmed diagnosis in 11. The C-US method alone showed an excellent accuracy (100%) but was applicable in only 6 patients (21%). Both the sensitivity and the specificity for proximal DVT recurrence of the combined ultrasound methods were 100% (95% confidence interval, 69% to 100% and 81% to 100%, respectively) and were applicable in all patients. CONCLUSIONS The serial ultrasound measurement of thrombus mass after an acute episode of DVT may allow the correct identification of patients who develop a recurrent proximal-vein thrombosis.
Extracolonic findings at computed tomography colonography are a challenge
Authors: B Ginnerup Pedersen
Journal: Gut (2003)

Our aim was to perform a prospective evaluation of the frequency and diagnostic consequences of extracolonic findings at multidetector array computed tomography colonography (MDCTC) in asymptomatic patients undergoing surveillance for former colorectal polyps or cancer.Seventy five consecutive patients undergoing surveillance for former colorectal cancer (CRC) or large bowel adenoma were examined with MDCTC. Two independent observers evaluated the images with regard to extracolonic findings. Patient records and radiological information systems were reviewed to determine the results and consequences of the workup derived from MDCTC.Sixty five per cent (95% confidence interval (CI) 55-73%) of patients had extracolonic abnormalities and in 12% (CI 7-18%) of patients additional workup was indicated. Two patients (3% (CI 1-6%)) underwent surgery because of the findings (one) or because of complications of the workup (one).MDCTC identifies a large number of extracolonic findings. Approximately 12% of asymptomatic patients undergo additional workup, of benefit to only a few. The high prevalence of extracolonic findings may make MDCTC a problematic colorectal screening tool for both ethical and economic reasons.
Screening for familial dysautonomia will begin soon
Authors: Judy Siegel-Itzkovic
Journal: BMJ (2001)

Mass screening tests for familial dysautonomia, a degenerative, fatal, and incurable neurological disorder that affects only people of Ashkenazi Jewish origin, will begin soon in Israel and the United States.

This development follows the Israeli and US discovery of the mutant recessive gene responsible for familial dysautonomia, which is as common as the better known Tay-Sachs disease, which also particularly affects Ashkenazi Jews. Two single base pair mutations in this gene account for nearly all cases of familial dysautonomia, and the finding is expected to revolutionise genetic testing for the condition.

The responsible gene, IKBKAP (inhibitor of kapelite polypeptide gene enhancer in β cell complex associated kinase protein), encodes for the IKAP protein (inhibitor of …
Psychiatric Emergencies: Dispositional Determinants and the Validity of the Decision to Admit
Authors: SEYMOUR BAXTER, ROBERT UNDERHILL, BERNARD CHODORKOFF
Journal: American Journal of Psychiatry (1968)

Determinants of the evaluation and disposition of psychiatric emergencies were studied at Detroit General Hospital. Although the decision to hospitalize an individual was based at least in part upon subjective factors influencing the emergency room resident, this initial decision to admit was generally well supported by later observations made about the patient on the ward. Other judgments made in the emergency room, such as diagnosis and prognosis, were not later validated. The authors conclude that the brief psychiatric interview in an emergency setting is most useful if goals are modest and all that is required is a decision about whether to hospitalize the individual.
Prognostic Factors in Primary Cutaneous B-Cell Lymphoma: The Italian Study Group for Cutaneous Lymphomas
Authors: Pier Luigi Zinzani, Pietro Quaglino, Nicola Pimpinelli, Emilio Berti, Gianandrea Baliva, Serena Rupoli, Maurizio Martelli, Mauro Alaibac, Giovanni Borroni, Sergio Chimenti, Renato Alterini, Lapo Alinari, Maria Teresa Fierro, Nazario Cappello, Alessandro Pileri, Davide Soligo, Marco Paulli, Stefano Pileri, Marco Santucci, Maria Grazia Bernengo
Journal: Journal of Clinical Oncology (2006)

Primary cutaneous B-cell lymphomas (PCBCLs) are a distinct group of primary cutaneous lymphomas with few and conflicting data on their prognostic factors.The study group included 467 patients with PCBCL who were referred, treated, and observed in 11 Italian centers (the Italian Study Group for Cutaneous Lymphomas) during a 24-year period (1980 to 2003). All of the patients were reclassified according to the WHO-European Organisation for Research and Treatment of Cancer (EORTC) classification.Follicle center lymphoma (FCL) accounted for 56.7% of occurrences, followed by marginal-zone B-cell lymphoma (MZL; 31.4%); diffuse large B-cell lymphoma (DLBCL), leg type, was reported in 10.9% of patients. Radiotherapy was the first-line treatment in 52.5% of patients and chemotherapy was the first-line treatment in 24.8% of patients. The complete response rate was 91.9% and the relapse rate was 46.7%. The 5- and 10-year overall survival (OS) rates were 94% and 85%, respectively. Compared with FCL/MZL, DLBCL, leg type, was characterized by statistically significant lower complete response rates, higher incidence of multiple cutaneous relapses and extracutaneous spreading, shorter time to progression, and shorter OS rates. The only variable with independent prognostic significance on the OS was the clinicopathologic diagnosis according to the WHO-EORTC classification (DLBCL, leg-type, showed a significantly worse prognosis v FCL and MZL; P < .001), whereas the only variable with independent prognostic significance on disease-free survival was the presence of a single cutaneous lesion (P = .001).Our study identifies a possible PCBCL subclassification and the extent of cutaneous involvement as the two most relevant prognostic factors in PCBCL. These data can be considered reasonably as the clinical background for an appropriate management strategy.
Alcohol-induced depression of albumin synthesis: reversal by tryptophan
Authors: Marcus A. Rothschild, Murray Oratz, Joseph Mongelli, Sidney S. Schreiber
Journal: Journal of Clinical Investigation (1971)

The influence of alcohol on albumin synthesis was studied in the isolated perfused rabbit liver. Carbonate-(14)C was used to label the intracellular arginine pool which serves as the precursor of both the carbon of urea and the guanido carbon of arginine in albumin. The control group synthesized albumin at a rate of 33 mg/100 g of wet liver weight during 2.5 hr of perfusion. When alcohol, 220 mg/100 ml, was added to the perfusate, albumin synthesis decreased to between 7 and 11 mg, less than one-third the control rate. The addition of 10 mM tryptophan to perfusates containing alcohol prevented most of the inhibitory effects and albumin synthesis increased to average 24 mg. Further, the addition of alcohol to the perfusate decreased the hepatic protein/DNA ratio from 70 to 54 and the RNA/DNA ratio from 2.3 to 1.8, changes equivalent to those seen after a 24 hr fast. The addition of tryptophan to the perfusate prevented these findings in both instances. Endoplasmic membrane-bound polysomes were examined for aggregation. Alcohol decreased the quantity of heavier aggregates. Reaggregation occurred when tryptophan was added but quantitative changes in albumin synthesis could not be related to the degree of reaggregation.
Relapse patterns in IgG4-related disease: Table 1
Authors: Motohisa Yamamoto, Hiroki Takahashi, Keisuke Ishigami, Hidetaka Yajima, Yui Shimizu, Tetsuya Tabeya, Mikiko Matsui, Chisako Suzuki, Yasuyoshi Naishiro, Kohzoh Imai, Yasuhisa Shinomura
Journal: Annals of the Rheumatic Diseases (2012)

Immunoglobulin (Ig)G4-related disease (IgG4-RD) is a chronic inflammatory disorder characterised by elevated levels of serum IgG4 and swollen organs with fibrosis and infiltration by abundant IgG4-positive plasmacytes.1 ,2 Glucocorticoid treatment is effective for achieving clinical remission in the short term,3 but about 20%–30% of cases present with relapse after steroid doses are reduced.4 Serial changes of serum IgG4 levels are often considered to reflect the disease activity in routine clinical practice,5 but how disease relapse occurs is not well understood. We therefore analysed relapse patterns in IgG4-RD on the basis of data from the Sapporo Medical university And …
Acidosis-Induced Coronary Arteriolar Dilation Is Mediated by ATP-Sensitive Potassium Channels in Vascular Smooth Muscle
Authors: Hiroshi Ishizaka, Lih Kuo
Journal: Circulation Research (1996)

Although a decrease in extravascular pH has been suggested to be involved in coronary flow regulations during hypoxia, ischemia, and increased metabolic demand of the heart, its vasomotor control mechanism has not been elucidated. To examine the effect of acidosis of vasomotor tone, porcine coronary arterioles (40 to 110 microns) were isolated, cannulated, and pressurized to 60 cm H2O intraluminal pressure without flow for in vitro study. Acidosis (pH 7.4 to 7.0) was produced by adding HCl to the extravascular solution. The involvement of potassium channels in the vasomotor response to acidosis was evaluated by using BaCl2 (100 mumol/L, nonspecific potassium channel inhibitor), glibenclamide (5 mumol/L, ATP-sensitive potassium channel inhibitor), and iberiotoxin (100 nmol/L, calcium-activated potassium channel inhibitor). To determine whether endothelial hyperpolarization contributes to the acidosis-induced dilation, the pH-diameter relation of the vessel was examined under a high intraluminal concentration of KCl (40 mmol/L). The involvement of nitric oxide and prostaglandins was assessed by using NG-monomethyl-L-arginine (L-NMMA, 10 mumol/L) and indomethacin (10 mumol/L), respectively. To evaluate the role of endothelium in the acidosis-induced dilation, the pH-diameter relation was studied after endothelial removal. All vessels developed a similar level of spontaneous tone (internal diameter, 75 +/- 4 microns [approximately 69 +/- 1% of maximum diameter) and dilated to HCl in dose-dependent manner. Glibenclamide completely abolished vasodilation to a mild level of acidosis (pH 7.2 to 7.3) and attenuated the vasodilation by 70% at pH 7.0. Acidosis-induced dilation was also inhibited by BaCl2 but not by iberiotoxin. L-NMMA, indomethacin, and intraluminal KCl did not alter the pH-diameter relation. Vasodilation to acidosis of the endothelium-denuded vessels was identical to that of the endothelium-intact vessels. In addition, glibenclamide attenuated the acidosis-induced arteriolar dilation of endothelium-denuded vessels. These results suggest that the opening of ATP-sensitive potassium channels in vascular smooth muscle mediates the coronary arteriolar dilation during acidosis.
CN-05 * DO PEDIATRIC BRAIN TUMOR SURVIVORS SUFFER AN INCREASED RISK OF OVARIAN/ENDOCRINE DYSFUNCTION AS COMPARED TO NON-BRAIN TUMOR SURVIVORS?
Authors: S. Z. Elsarrag, J. C. Eickhoff, D. M. Puccetti, S. M. Salih
Journal: Neuro-Oncology (2014)

OBJECTIVE: Various treatments of brain tumors may affect ovarian and endocrine function, resulting in a plethora of disorders. The purpose of this study was to analyze the impact of brain tumors on ovarian health and endocrine function in female childhood survivors. STUDY DESIGN: Ovarian and endocrine function in 222 childhood cancer survivors diagnosed with brain tumors at a tertiary comprehensive cancer center between 1997-2008 was retrospectively analyzed and compared. RESULTS: An equal proportion of childhood survivors of brain tumors (N = 39) and survivors of non-brain tumors (N = 183) developed ovarian dysfunction. Of those children older than 13 years, menstrual cycle irregularity (36% of brain tumor survivors vs. 21% of non-brain survivors, p = 0.3), amenorrhea (22% vs. 22% respectively, p = 0.9), and elevated FSH levels (40% vs. 50%, p = 0.9) were not statistically significant between the two groups. Brain tumor survivors experienced increased risk of endocrine disorders, such as precocious puberty (13% vs. 2%, P = 0.005), delayed puberty (8% vs. 1%, P = 0.0178), and hypopituitarism (10% vs. 1%, P = 0.01). Furthermore, children with brain tumors were significantly more likely to develop multiple endocrine disorders at the same time (31% vs. 7%, P = 0.001 for two endocrine disorders and 23% vs. 2%, P= 0.0001 for three or more endocrine disorders) and were more likely to visit with an endocrinologist (46% vs. 14%, p = 0.0001), when compared to non-brain tumor cancer survivors. While all brain tumor patients were seen at the multi-specialty neuroncology clinic, they were less likely to attend survivor clinic (4% vs. 28%, p = <0.003), and more likely to receive assistance from survivor clinic staff (97% vs. 57%, p = 0.001), when compared to non-brain tumor cancer survivors. CONCLUSIONS: Female pediatric brain tumor survivors are equally likely to experience ovarian insufficiency when compared to non-brain tumor survivors, but were significantly more likely to suffer coexistence of multiple endocrine problems.
Association of breastfeeding and respiratory infections in infants
Authors: Jingying Wang, Cristian Dogaru, Aniña Pescatore, Maja Jurca, Caroline Beardsmore, Claudia Kuehni
Journal: European Respiratory Journal (2014)

Introduction  Published studies on breastfeeding (BF) and infant respiratory infections are inconclusive, suggesting either protective effects of BF or no protection. Many studies assessed general upper or lower respiratory tract infections, only one infection at a time or did not control for confounding. This study estimates the association of BF and various respiratory infections in infants controlling for relevant confounders.  Methods  We analysed parent-reported questionnaire data of 1-year-olds from a population-based cohort in Leicestershire, UK. BF duration(0, 6mo), ear infections, frequent colds(>4 times during last 12 months), pneumonia, whooping cough, bronchiolitis, croup, other chest and throat infections were assessed in 1998. We used multivariable logistic regression to estimate the association of BF and infections controlling for socio-demographic, prenatal, perinatal and environmental confounders.  Results  Among 4246 infants whose parents replied in 1998(response rate 79%), 58% were breastfed. The most prevalent infections were frequent colds(54%) and ear infections(42%), followed by throat infections, croup, chest infections and bronchiolitis(reported by 6-11%); whooping cough and pneumonia were rare(2% and 1% respectively). We found negative associations between BF and whooping cough(OR 0.5, 95%CI 0.2-1.0) or bronchiolitis(0.7, 0.5-0.9), but positive association between BF and frequent colds(1.3, 1.1-1.7).  Conclusion  The association between BF and respiratory infections seems to differ by type of disease. Future studies should have a prospective design with continuous assessment of BF and respiratory infections.  Funding:  SNF PDFMP3 137033; SNF32003B-144068; Asthma UK 07/048; CSC201308340039.
Abstract 5102: Analysis of CTCs enriched from whole blood samples of Breast, Lung and Colorectal cancer patients with a flexible microspring array device.
Authors: Ramdane Harouaka, Ming-Da Zhou, Yin-Ting Yeh, Cristina Truica, Avisnata Das, Jussuf Kaifi, Wafik El-Deiry, Xin Liu, Chandra Belani, Tara Baney, Jeffrey Allerton, Si-Yang Zheng
Journal: Cancer Research (2013)

Abstract The process by which metastatic cancers release cells that detach from a primary tumor, spread through the circulatory system and invade distant organs accounts for over 90% of cancer related deaths. A fundamental challenge with analysis of these circulating tumor cells (CTCs) in blood samples is the fact that they are so rare, with only a few tumors cells occurring among billions of blood cells. We have developed a flexible micro spring array (FMSA) that employs mechanical separation to effectively enrich CTCs in a nondestructive manner that does not compromise cell viability. The FMSA device geometric design and applied filtration pressures have been optimized to maximize capture efficiency, enrichment against leukocytes, and tumor cell viability. We have successfully enriched and detected varying numbers of CTCs (min=1, max=101) in 7.5mL whole blood samples obtained from Breast, Lung and Colorectal cancer patients. CTCs were analyzed qualitatively and quantitatively based on immunocytochemical determination of phenotype and cell morphological characteristics. Aggregate clusters of cells were observed in all assayed cancer types that comprised of multiple attached CTCs (min=2, max=20) and occasionally leukocytes as well. Citation Format: Ramdane Harouaka, Ming-Da Zhou, Yin-Ting Yeh, Cristina Truica, Avisnata Das, Jussuf Kaifi, Wafik El-Deiry, Xin Liu, Chandra Belani, Tara Baney, Jeffrey Allerton, Si-Yang Zheng. Analysis of CTCs enriched from whole blood samples of Breast, Lung and Colorectal cancer patients with a flexible microspring array device. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5102. doi:10.1158/1538-7445.AM2013-5102
Can financial incentives for improvements in healthcare quality enhance identification of COPD in primary care?
Authors: C. Falzon, S. L. Elkin, J. L. Kelly, F. Lynch, I. D. Blake, N. S. Hopkinson
Journal: Thorax (2010)

Undiagnosed chronic obstructive pulmonary disease (COPD) is a major public health issue, as it leads to patients missing out on appropriate preventive and therapeutic interventions.1–3 The ratio of diagnosed/predicted COPD prevalence differs widely between Primary Care Trusts (PCTs), suggesting that there are unacceptable variations in care.4 A National Clinical Strategy for COPD is to be launched in the UK in 2010 and there is an urgent need for evidence to support strategies to increase the identification of patients, particularly those with early disease.

In 2008 a locally enhanced service (LES) for COPD …
Association of fatigue with an acute phase response in sarcoidosis
Authors: M. Drent, R.M. Wirnsberger, J de Vries, M.p van Dieijen-Visser, E.F.M. Wouters, A.M.W.J. Schols
Journal: European Respiratory Journal (1999)

The pathophysiological explanation for fatigue, one of the most common symptoms in sarcoidosis, still has to be elucidated. It was hypothesized that the presence of fatigue is associated with an acute phase response in sarcoidosis. A cross-sectional study was performed in 38 sarcoidosis patients. Resting energy expenditure (REE) was measured in the fasting state by indirect calorimetry using a ventilated hood and adjusted for fat-free mass (FFM). Patients with fatigue (n=25) also suffered more frequently from other symptoms, such as exercise intolerance (p=0.01), the need for sleep (p=0.02) and weight loss (p=0.01), compared to those without fatigue (n=13). However, no relationship was found between fatigue and serum angiotensin-converting enzyme (sACE) or lung function impairment. Patients with fatigue had higher levels of C-reactive protein (CRP) (11.4+/-6.8 microg x mL(-1), p<0.0001) and REE adjusted for FFM (33.0+/-3.7 kcal x kg FFM(-1), p<0.003) compared to those without fatigue (3.2+/-2.2 mg x mL(-1); 29.2+/-2.8 kcal x kg FF(-1)). Furthermore, REE/FFM was significantly related to CRP (r=0.54, p=0.001). This study confirms the presence of an acute phase response as indicated by metabolic derangements and a moderate increase in C-reactive protein levels in sarcoidosis, particularly in those patients with constitutional symptoms. Future studies should focus on the clinical relevance and therapeutic implications of these findings.