tbuckley/cabot-search huggingface dataset:
Clinical evaluation of the histochemical diagnosis of Hirschsprung's disease.
Authors: L C Barr, J Booth, M I Filipe, J O Lawson
Journal: Gut (1985)

The histochemical staining of suction rectal biopsies for acetylcholinesterase (AChE) activity is a safe and accurate diagnostic tool in the management of patients with symptoms and signs of Hirschsprung's disease. In this study 101 patients who have undergone AChE analysis of suction rectal biopsies are presented in order to correlate histochemical findings with subsequent clinical course after a minimum of 18 months follow up. There were no false positive results, but the limitations and problems associated with the technique which we have encountered are discussed. Equivocal, atypical, or negative results when contradicting clinical features are indications for repeat biopsy or full thickness biopsy, and awareness of the situations in which false negative results may occur is essential.
Bone turnover in postmenopausal osteoporosis. Effect of calcitonin treatment.
Authors: R Civitelli, S Gonnelli, F Zacchei, S Bigazzi, A Vattimo, L V Avioli, C Gennari
Journal: Journal of Clinical Investigation (1988)

To investigate the effectiveness of calcitonin treatment of postmenopausal osteoporosis in relation to bone turnover, we examined 53 postmenopausal osteoporotic women before and after one year of therapy with salmon calcitonin (sCT), at the dose of 50 IU every other day. Baseline evaluation revealed that 17 (32%) patients had high turnover (HTOP), and 36 (68%) normal turnover osteoporosis (NTOP) as assessed by measurement of whole body retention (WBR) of 99mTc-methylene diphosphonate. The two groups did not differ in terms of bone mineral content (BMC) measured by dual photon absorptiometry at both lumbar spine and femoral diaphysis. However, HTOP patients had higher levels of serum osteocalcin (OC) and urinary hydroxyproline excretion (HOP/Cr). Multivariate regression analysis showed no correlation between parameters of bone turnover (WBR, OC, HOP/Cr) and both femoral and vertebral bone density; the latter being negatively correlated only with the years elapsed since menopause (R2 = 0.406). Treatment with sCT resulted in a significant increase of vertebral BMC in the 53 patients taken as a whole group (+/- 7%, P less than 0.001). When the results obtained in HTOP and NTOP were analyzed separately, only those with HTOP showed a marked increment of spinal BMC (+22%, P less than 0.001), NTOP subjects neither gained nor lost bone mineral during the study. Femoral BMC decreased in the whole group after sCT therapy (-3%, P less than 0.003). However, HTOP patients maintained initial BMC values, whereas those with NTOP lost a significant amount of bone during the study period (-5%, P less than 0.001). The increase of vertebral bone mass was associated with a marked depression of bone turnover detectable in both subsets of patients and in the whole group.(a) assessment of bone turnover cannot help predict the severity of bone loss in postmenopausal osteoporosis; (b) calcitonin therapy appears to be particularly indicated for patients with high-turnover osteoporosis, resulting in a net gain of bone mineral in the axial skeleton and a slowing of bone loss in the appendicular bones.
Epidemiological and Mechanistic Studies of Atrial Fibrillation as a Basis for Treatment Strategies
Authors: J. Thomas Bigger
Journal: Circulation (1998)

n this issue of Circulation, Benjamin et al 1 provide evidence from the Framingham cohort that atrial fibrillation (AF) increases the mortality rate and that this association persists when adjusted for age, hypertension, smoking, diabetes, electrocardiographic left ventricular hypertrophy, myocardial infarction, congestive heart failure, valvular heart disease, and stroke or transient ischemic attack.The current analysis showed that of the 5209 residents of Framingham who originally enrolled in this population study, 621 developed AF during follow-up.Participants who developed AF were more likely to have hypertension, a smoking habit, electrocardiographic left ventricular hypertrophy, myocardial infarction, congestive heart failure, valvular heart disease, and stroke or transient ischemic attack at baseline.Echocardiographic left atrial dimension was not available for analysis.The age-adjusted odds ratios for death with AF were 2.4 for men and 3.5 for women.After adjusting for risk factor status at each biennial examination, the odds ratios for death were 1.5 for men and 1.9 for women.Much of the excess death attributable to AF occurred soon after diagnosis of AF, but after the first 30-day mortality experience was excluded, there was still a significant association of AF with death during follow-up.There was no interaction between age and AF for death during follow-up; ie, AF increased the likelihood of dying at all ages.
Histopathology of the Effects of Tuneable Dye Laser on Monkey Retina
Authors: William E. Smiddy, Arnall Patz, Harry A. Quigley, Gregory R. Dunkelberger
Journal: Ophthalmology (1988)

The tuneable dye laser was used to simulate treatment of choroidal neovascularization and panretinal photocoagulation (PRP) in monkey retina. The histopathologic effects of wavelengths from 560 to 630 nm in juxtafoveal, papillomacular bundle, and nonfoveal areas were investigated. An unexpected observation using high-intensity burns in juxtafoveal and, to a lesser extent, in papillomacular bundle areas was inner retinal damage with 600-nm light. At moderate energy levels, the effects of 600 nm were more comparable with those with other wavelengths and included much less damage to the inner retinal layers. At mild energy levels, the effects were comparable with other wavelengths. During and after the application of the burns, the energy levels and ophthalmoscopic appearances were comparable for each wavelength for the high-, moderate-, and mild-intensity burns. The histopathologic effects of 630-nm light (tuneable dye red) were comparable with those of the standard krypton red (647 nm) laser. Nonmacular and PRP effects were similar with all wavelengths. These results indicate that power levels may need to be reduced when placing 600-nm (orange) laser burns in the macula.
CCR5 Δ32 homozygous cord blood allogeneic transplantation in a patient with HIV: a case report
Authors: Rafael F Duarte, María Salgado, Isabel Sánchez-Ortega, Montserrat Arnan, Carmen Canals, Eva Domingo-Domenech, Alberto Fernández-de-Sevilla, Eva González-Barca, Sara Morón-López, Nuria Nogues, Beatriz Patiño, Maria Carmen Puertas, Bonaventura Clotet, Lawrence D Petz, Sergio Querol, Javier Martinez-Picado
Journal: The Lancet HIV (2015)
Ulcerative colitis as a sole mucosal disease: another misunderstanding?: Figure 1
Authors: Joana Torres, Vincent Billioud, Laurent Peyrin-Biroulet, Jean-Frédéric Colombel
Journal: Gut (2011)

We read with great interest the paper by D'Haens and Ochsenkuhn about the importance of mucosal healing (MH) in ulcerative colitis (UC).1 MH is considered to be a reliable indicator of treatment efficacy and a prognostic marker in UC. Since UC is classically described as a mucosal disease, as opposed to Crohn's disease (CD), MH seems the perfect therapeutic goal. In CD, it is accepted that treatment should go beyond symptomatic control and target the progressive course of the disease with reduction in bowel damage, prevention of complications and maintenance of gastrointestinal (GI) physiology. For UC, these goals have translated, for most investigators, in …
Age at onset and persistence of eczema and the subsequent risk of asthma and allergic rhinitis
Authors: Bianca Angelica, John Su, Caroline Lodge, David Hill, Cliff Hosking, Erbas Bircan, Catherine Bennett, Lyle Gurrin, Christine Axelrad, Michael Abramson, Katie Allen, Shyamali Dharmage, Adrian Lowe
Journal: European Respiratory Journal (2012)

Background : Few studies have simultaneously addressed the importance of age of onset and persistence of eczema for the subsequent development of asthma and allergic rhinitis in children.   Objective : To examine age of eczema onset and eczema persistence as predictors for childhood asthma and allergic rhinitis at ages 6, 7 and 12 years.   Methods : A prospective birth cohort was recruited comprising 620 infants with a family history of allergic diseases. Telephone interviews were conducted 18 times in the first two years of life, annually from age 3 to 7, and at 12 years to document any episodes of eczema. Current asthma and allergic rhinitis were assessed at ages 6, 7 and 12.   Results : Very early-onset (  2 years) were associated with current asthma and allergic rhinitis. These results were consistent with the 6-7 year findings.   Conclusion : Eczema which commences very early in life and persists into toddler years is strongly associated with childhood asthma and allergic rhinitis, and is possibly mediated by aero-allergen sensitization. However remitting and late-onset eczema do not appear to be related to these outcomes. With effective early intervention, the risk of diseases associated with early-onset eczema might be reduced.
NADPH-Oxidase 4 Protects against Kidney Fibrosis during Chronic Renal Injury
Authors: Stellor Nlandu Khodo, Eva Dizin, Gaetan Sossauer, Ildiko Szanto, Pierre-Yves Martin, Eric Feraille, Karl Heinz Krause, Sophie de Seigneux
Journal: Journal of the American Society of Nephrology (2012)

NADPH oxidases synthesize reactive oxygen species that may participate in fibrosis progression. NOX4 and NOX2 are NADPH oxidases expressed in the kidneys, with the former being the major renal isoform, but their contribution to renal disease is not well understood. Here, we used the unilateral urinary obstruction model of chronic renal injury to decipher the role of these enzymes using wild-type, NOX4-, NOX2-, and NOX4/NOX2-deficient mice. Compared with wild-type mice, NOX4-deficient mice exhibited more interstitial fibrosis and tubular apoptosis after obstruction, with lower interstitial capillary density and reduced expression of hypoxia-inducible factor-1α and vascular endothelial growth factor in obstructed kidneys. Furthermore, NOX4-deficient kidneys exhibited increased oxidative stress. With NOX4 deficiency, renal expression of other NOX isoforms was not altered but NRF2 protein expression was reduced under both basal and obstructed conditions. Concomitant deficiency of NOX2 did not modify the phenotype exhibited by NOX4-deficient mice after obstruction. NOX4 silencing in a mouse collecting duct (mCCD(cl1)) cell line increased TGF-β1-induced apoptosis and decreased NRF2 protein along with expression of its target genes. In addition, NOX4 silencing decreased hypoxia-inducible factor-1α and expression of its target genes in response to hypoxia. In summary, these results demonstrate that the absence of NOX4 promotes kidney fibrosis, independent of NOX2, through enhanced tubular cell apoptosis, decreased microvascularization, and enhanced oxidative stress. Thus, NOX4 is crucial for the survival of kidney tubular cells under injurious conditions.
In vivo estimation of myocardial infarct size and left ventricular function by prospectively gated computerized transmission tomography.
Authors: R A Slutsky, R F Mattrey, S A Long, C B Higgins
Journal: Circulation (1983)

We evaluated 11 dogs using computerized transmission tomography (CTT); eight were studied after coronary occlusion and three served as sham controls.Ungated scans (1 cm deep) of the left ventricle (LV) were obtained from LV apex to base to determine infarct size (IS).At the middle LV level, prospectively gated scans were obtained to determine LV function.In all infarct dogs, contrast medium enhancement of the entire infarct or the periphery of the infarct occurred.Autopsy IS was compared with the IS by CTT using either the inner (IM) or outer margin (OM) of the contrast-enhanced periphery of the infarcts as the border of the infarct.IS by both CTT techniques correlated well with autopsy IS (r = 0.89 for IM; r = 0.93 for OM).The estimate using OM (26.5 + 12 g) gave IS sizes similar to autopsy values (25.5 + 11.7 g), but IS derived using IM (14.1 8.0 g) underestimated autopsy values by approximately 45% (p < 0.01).From the prospectively gated CTT images, we calculated mid-LV end-diastolic (EDA) and end- systolic areas (ESA) as well as percent area change before and after coronary occlusion.EDA increased from 17.0 + 5.3 cm2 to 23.7 + 7.6 cm2 (p < 0.05).ESA increased from 12.1 + 4.1 cm2 to 18.6 7.2 cm2 (p < 0.05), and percent area change decreased from 29.3 5.0% to 21.7 9.9% (p < 0.05).We conclude that CTT imaging can reliably estimate IS, particularly when the area of rim enhancement of the infarct is included within the presumed infarct region.Estimates of chamber function can be made from gated CTT scans.Anterior myocardial infarctions produce left ventricular dilatation with reduced chamber function, which can be detected by gated CTT scans.QUANTITATION of myocardial infarct size is impor- tant in assessing clinical prognosis after infarction and in evaluating the effects of interventions designed to reduce the myocardial damage during ischemia.'-5Ex vivo studies have shown that computerized transmis- sion tomography (CTT) can be used to accurately quantitate irreversibly damaged myocardial tissue.6-9Recent reports have also shown the ability of CTT to quantitate infarct size in vivo, though the method var- ied in each study.'0 1 The present study was designed to define the accuracy of CTT scans for quantitating
Differentiating Prion Strains Using Dendrimers
Authors: James M. McCarthy, Beatriz Rasines, Dietmar Appelhans, Mark Rogers
Journal: Advanced Healthcare Materials (2012)

A panel of repetitively branched synthetic molecules known as dendrimers is used to identify and differentiate between different strains of the prion infectious agent, the protein-based pathogen responsible for prion disorders—a group of invariably fatal neurodegenerative diseases.
Transgenic overexpression of the secreted, extracellular EGF-CUB domain-containing protein SCUBE3 induces cardiac hypertrophy in mice
Authors: H YANG, C CHENG, B DJOKO, W LIAN, C TU, M TSAI, Y CHEN, C CHEN, C CHENG, R YANG
Journal: Cardiovascular Research (2007)

Objective The aim of this study was to investigate in a transgenic animal model the cardiac expression and function of a novel extracellular protein SCUBE3 [signal peptide-CUB (complement proteins C1r/C1s, Uegf, and Bmp1)-EGF (epidermal growth factor)-like domain-containing protein 3]. Methods and results Real-time quantitative reverse transcriptase (RT)-PCR analysis showed that SCUBE3 is expressed in the ventricular myocardium. Male transgenic (TG) mice overexpressing SCUBE3 appeared normal during development, from birth to adulthood. However, echocardiography and histopathological examination revealed significant cardiac hypertrophy in TG animals as they aged, at 8 months. Interestingly, left-ventricle hypertrophy occurred more rapidly and more severely under pressure overload in TG mice, as compared to age-matched wild-type littermates. Induced SCUBE3 expression, together with elevated transforming growth factor (TGF)-β1 level under pressure overload, may account for the accelerated onset and progression of cardiac hypertrophy in TG mice. Furthermore, biochemical and molecular studies revealed that the carboxyl-terminal portion of SCUBE3 could physically interact with TGF-β1 and promote the TGF-β1-mediated transcriptional activation. Conclusion This report is the first demonstration that SCUBE3 may play a role in the regulation of cardiac growth and remodeling responses, possibly through the stabilization of the TGF-β1 signaling pathway.
Thromboxane A <sub>2</sub> Regulates Vascular Tone via Its Inhibitory Effect on the Expression of Inducible Nitric Oxide Synthase
Authors: Takehiro Yamada, Takayuki Fujino, Koh-ichi Yuhki, Akiyoshi Hara, Hideji Karibe, Osamu Takahata, Yuji Okada, Chun-Yang Xiao, Koji Takayama, Shuhko Kuriyama, Takanobu Taniguchi, Takahiro Shiokoshi, Yoshinobu Ohsaki, Kenjiro Kikuchi, Shuh Narumiya, Fumitaka Ushikubi
Journal: Circulation (2003)

Circulatory failure in sepsis arises from vascular hyporesponsiveness, in which nitric oxide (NO) derived from inducible NO synthase (iNOS) plays a major role. Details of the cross talk between thromboxane (TX) A2 and the iNOS-NO system, however, remain unknown. We intended to clarify the role of TXA2, via the cross talk, in vascular hyporesponsiveness.We examined cytokine-induced iNOS expression and NO production in cultured vascular smooth muscle cells (VSMCs) and cytokine-induced hyporesponsiveness of the aorta from mice lacking the TXA2 receptor (TP-/- mice). The cytokine-induced iNOS expression and NO production observed in wild-type VSMCs were significantly augmented in TP-/- VSMCs, indicating an inhibitory effect of endogenous TXA2 on iNOS expression. Furthermore, in indomethacin-treated wild-type VSMCs, U-46619, a TP agonist, inhibited cytokine-induced iNOS expression and NO production in a concentration-dependent manner, effects absent from TP-/- VSMCs. In an ex vivo system, the cytokine-induced hyporesponsiveness of aortas to phenylephrine was significantly augmented in TP-/- aorta but was almost completely canceled by aminoguanidine, an iNOS inhibitor. Accordingly, cytokine-induced NO production was significantly higher in TP-/- aorta than in wild-type aorta. Moreover, U-46619 significantly suppressed lipopolysaccharide-induced NO production in vivo only in wild-type mice.These results suggest that TXA2 has a protective role against the development of vascular hyporesponsiveness via its inhibitory action on the iNOS-NO system under pathological conditions such as sepsis.
Treatment of Patients With Metastatic Melanoma With Autologous Tumor-Infiltrating Lymphocytes and Interleukin 2
Authors: S. A. Rosenberg, J. R. Yannelli, J. C. Yang, S. L. Topalian, D. J. Schwartzentruber, J. S. Weber, D. R. Parkinson, C. A. Seipp, J. H. Einhorn, D. E. White
Journal: JNCI Journal of the National Cancer Institute (1994)

Background : Studies of human tumor-infiltrating lymphocytes (TILs) derived from patients with a variety of histologic types of cancer have demonstrated that cellular immune reactions against established malignancy exist in humans. Purpose : We report the results of using autologous TILs plus high-dose bolus interleukin 2 (IL-2), with or without the concomitant administration of cyclophosphamide, in the treatment of 86 consecutive patients with metastatic melanoma. Methods : From May 1987 through December 1992, 86 patients (38 female and 48 male) with metastatic melanoma were treated (145 courses) with autologous TILs plus high-dose intravenous bolus IL-2 (720 000 IU/kg every 8 hours). TILs plus IL-2 were administered in two cycles separated by approximately 2 weeks. Two treatment cycles constituted one treatment course. Patients received a maximum of 15 doses of IL-2 per cycle given every 8 hours until grade 3 or 4 toxicity was reached that could not easily be reversed by standard supportive measures. All patients received concomitant medications to abrogate some of the side effects of IL-2 administration: acetaminophen (650 mg every 4 hours), indomethacin (50 mg every 8 hours), and ranitidine (150 mg every 12 hours). Fifty-seven of the 86 patients received a single intravenous dose of 25 mg/kg cyclophosphamide approximately 36 hours before receiving the first intravenous infusion of TILs plus IL-2. Six weeks after treatment, all known sites of disease were evaluated. Results : The overall objective response rate in these patients was 34% and was similar in patients receiving TILs and IL-2 alone (31%) or in conjunction with cyclophosphamide (35%). There was no significant difference in the objective response rate in patients whose therapy with high-dose IL-2 had failed (32%) compared with patients not previously treated with IL-2 (34%). The frequency of response to treatment was greater in those patients who were treated with TILs from younger cultures (P =.0001), TILs with shorter doubling times (P =.03), and TILs that exhibited higher lysis against autologous tumor targets (P =.0008). Patients who received TILs generated from subcutaneous tumor deposits had higher response rates (49%) compared with those receiving TILs from lymph nodes (17%; P =.006). There was one treatment-related death due to respiratory insufficiency. Conclusions: Treatment with TILs and IL-2 with or without cyclophosphamide can result in objective responses in about one third of patients with metastatic melanoma. The side effects of treatment are transient in most patients, and this treatment can be safely administered. These results illustrate the potential value of immune lymphocytes for the treatment of patients with melanoma.
Alterations in contractility and intracellular Ca2+ transients in isolated bundles of skeletal muscle fibers from rats with chronic heart failure.
Authors: C L Perreault, H Gonzalez-Serratos, S E Litwin, X Sun, C Franzini-Armstrong, J P Morgan
Journal: Circulation Research (1993)

To determine if chronic heart failure (CHF) leads to functional or structural alterations of skeletal muscle, we compared intracellular Ca2+ signaling, contractility, and the rate of fatigue development, together with electron microscopy (EM), in skeletal muscle preparations from rats with myocardial infarction-induced CHF versus sham-operated control rats. Bundles of 100 to 200 cells were dissected from the extensor digitorum longus (EDL) muscle of control (n = 13) and CHF (n = 19) rats and were either loaded with aequorin or fixed for EM. Muscles from CHF rats exhibited depressed tension development compared with control muscles during twitches (1.4 +/- 0.2 versus 2.8 +/- 0.7 g/mm2, P &lt; .05) and maximal tetani (5.3 +/- 1.4 versus 10.7 +/- 2.4 g/mm2, P &lt; .05). Depressed tension in CHF was accompanied by reduced quantitative [Ca2+]i release during twitches (0.7 +/- 0.1 versus 0.4 +/- 0.1 microM, P &lt; .05) and during maximal tetani (1.8 +/- 0.3 versus 0.9 +/- 0.2 microM, P &lt; .05). Skeletal muscle from CHF rats also demonstrated prolonged intracellular Ca2+ transients during twitches and tetani and accelerated fatigue development. EM revealed a lack of cellular atrophy in the CHF rats. In conclusion, EDL skeletal muscle from rats with CHF had intrinsic abnormalities in excitation-contraction coupling unrelated to cellular atrophy. These findings indicate that CHF is a condition accompanied by EDL skeletal muscle dysfunction.
Comparison between the effects of aerobic and breathing exercises in the clinical and psychosocial factors in asthmatic patients
Authors: Milene Saccomani, Karen Evaristo, Alberto Cukier, Rafael Stelmach, Milton Carvalho, Celso Carvalho
Journal: European Respiratory Journal (2013)

Aerobic and breathing exercises are the most used strategies in the treatment of asthmatic patients; however the comparison between these interventions has never been investigated. Objective: Compare the effect of aerobic and breathing exercises in the clinical control, psychosocial and quality of life in patients with moderate or severe persistent asthma. Methods: Twenty-three adults were randomized in 2 group: Breathing (GB, n =11, 49±8 yrs) and aerobic (GA, n =12, 49±11 yrs). Breathing (GR) or Aerobic exercise programs (GA) was performed during 24 sessions (2xweek, 3 months). Before and after the intervention was assessed: clinical control (ACQ score), health factors related to quality of life (HRQL, AQLQ), depression and anxiety levels (HAD score), hyperventilation syndrome (Nijmegen), pulmonary function and submaximal exercise capacity (Shuttle walking test). Two-way ANOVA was used and significance level was set at 5%. Results: Both groups were similar at baseline. An improvement in clinical control (GR=4.9 and GA=5.2 in the ACQ score) and submaximal exercise capacity (GR=1.5 and GA=1.5 minutes) was observed in both groups; however, only patients from GA reduced the levels of depression (GA=2.6 score, p