tbuckley/cabot-search huggingface dataset:
Amoxicillin for Acute Rhinosinusitis
Authors: Jane M. Garbutt, Christina Banister, Edward Spitznagel, Jay F. Piccirillo
Journal: JAMA (2012)

<h3>Context</h3>Evidence to support antibiotic treatment for acute rhinosinusitis is limited, yet antibiotics are commonly used.<h3>Objective</h3>To determine the incremental effect of amoxicillin treatment over symptomatic treatments for adults with clinically diagnosed acute rhinosinusitis.<h3>Design, Setting, and Participants</h3>A randomized, placebo-controlled trial of adults with uncomplicated, acute rhinosinusitis were recruited from 10 community practices in Missouri between November 1, 2006, and May 1, 2009.<h3>Interventions</h3>Ten-day course of either amoxicillin (1500 mg/d) or placebo administered in 3 doses per day. All patients received a 5- to 7-day supply of symptomatic treatments for pain, fever, cough, and nasal congestion to use as needed.<h3>Main Outcome Measures</h3>The primary outcome was improvement in disease-specific quality of life after 3 to 4 days of treatment assessed with the Sinonasal Outcome Test-16 (minimally important difference of 0.5 units on a 0-3 scale). Secondary outcomes included the patient's retrospective assessment of change in sinus symptoms and functional status, recurrence or relapse, and satisfaction with and adverse effects of treatment. Outcomes were assessed by telephone interview at days 3, 7, 10, and 28.<h3>Results</h3>A total of 166 adults (36% male; 78% with white race) were randomized to amoxicillin (n = 85) or placebo (n = 81); 92% concurrently used 1 or more symptomatic treatments (94% for amoxicillin group vs 90% for control group; P = .34). The mean change in Sinonasal Outcome Test-16 scores was not significantly different between groups on day 3 (decrease of 0.59 in the amoxicillin group and 0.54 in the control group; mean difference between groups of 0.03 [95% CI, −0.12 to 0.19]) and on day 10 (mean difference between groups of 0.01 [95% CI, −0.13 to 0.15]), but differed at day 7 favoring amoxicillin (mean difference between groups of 0.19 [95% CI, 0.024 to 0.35]). There was no statistically significant difference in reported symptom improvement at day 3 (37% for amoxicillin group vs 34% for control group; P = .67) or at day 10 (78% vs 80%, respectively; P = .71), whereas at day 7 more participants treated with amoxicillin reported symptom improvement (74% vs 56%, respectively; P = .02). No between-group differences were found for any other secondary outcomes. No serious adverse events occurred.<h3>Conclusion</h3>Among patients with acute rhinosinusitis, a 10-day course of amoxicillin compared with placebo did not reduce symptoms at day 3 of treatment.<h3>Trial Registration</h3>clinicaltrials.gov Identifier: NCT00377403
Combination of budesonide/formoterol on demand improves asthma control by reducing exercise-induced bronchoconstriction
Authors: Nikolaos Lazarinis, Leif Jørgensen, Tommy Ekström, Leif Bjermer, Barbro Dahlén, Teet Pullerits, Gunilla Hedlin, Kai-Håkon Carlsen, Kjell Larsson
Journal: Thorax (2013)

<h3>Background</h3> In mild asthma exercise-induced bronchoconstriction (EIB) is usually treated with inhaled short-acting β<sub>2</sub> agonists (SABAs) on demand. <h3>Objective</h3> The hypothesis was that a combination of budesonide and formoterol on demand diminishes EIB equally to regular inhalation of budesonide and is more effective than terbutaline inhaled on demand. <h3>Methods</h3> Sixty-six patients with asthma (&gt;12 years of age) with verified EIB were randomised to terbutaline (0.5 mg) on demand, regular budesonide (400 μg) and terbutaline (0.5 mg) on demand, or a combination of budesonide (200 μg) + formoterol (6 μg) on demand in a 6-week, double-blind, parallel-group study (ClinicalTrials.gov identifier: NCT00989833). The patients were instructed to perform three to four working sessions per week. The main outcome was EIB 24 h after the last dosing of study medication. <h3>Results</h3> After 6 weeks of treatment with regular budesonide or budesonide+formoterol on demand the maximum post-exercise forced expiratory volume in 1 s fall, 24 h after the last medication, was 6.6% (mean; 95% CI −10.3 to −3.0) and 5.4% (−8.9 to −1.8) smaller, respectively. This effect was superior to inhalation of terbutaline on demand (+1.5%; −2.1 to +5.1). The total budesonide dose was approximately 2.5 times lower in the budesonide+formoterol group than in the regular budesonide group. The need for extra medication was similar in the three groups. <h3>Conclusions</h3> The combination of budesonide and formoterol on demand improves asthma control by reducing EIB in the same order of magnitude as regular budesonide treatment despite a substantially lower total steroid dose. Both these treatments were superior to terbutaline on demand, which did not alter the bronchial response to exercise. The results question the recommendation of prescribing SABAs as the only treatment for EIB in mild asthma.
Prognosis of asymptomatic patients with hypertrophic cardiomyopathy and nonsustained ventricular tachycardia.
Authors: P Spirito, C Rapezzi, C Autore, P Bruzzi, P Bellone, P Ortolani, P V Fragola, F Chiarella, M Zoni-Berisso, A Branzi
Journal: Circulation (1994)

In the early 1980s, studies performed in highly selected referral patients with hypertrophic cardiomyopathy reported a strong association between the presence of brief episodes of ventricular tachycardia (VT) on ambulatory ECG monitoring and sudden death. These observations led to antiarrhythmic treatment in many patients with hypertrophic cardiomyopathy and brief episodes of VT. In recent years, however, a growing awareness of the potential arrhythmogenic effects of antiarrhythmic medications has raised doubts regarding such a therapeutic approach, particularly in less selected and lower-risk patient populations.In the present study, we examined the prognostic significance of nonsustained VT in a population of 151 patients with hypertrophic cardiomyopathy who were asymptomatic or had only mild symptoms at the time of their initial ambulatory ECG recording. Of the 151 study patients, 42 had episodes of VT and 109 did not. The runs of VT ranged from 3 to 19 beats, with 35 patients (83%) having < 10 beats. The number of runs of VT ranged from 1 to 12 in 24 hours, with 36 patients (86%) having < or = 5 episodes of VT. Thus, in most patients, the episodes of VT were brief and infrequent. Follow-up averaged 4.8 years. Of the 151 study patients, 6 died suddenly, 3 in the group with VT and 3 in the group without VT. Two other patients, both in the group without VT, died of congestive heart failure. The total cardiac mortality rate was 1.4% per year in the patients with VT (95% CI, 0.4% to 3.5%) and 0.9% in those without VT (95% CI, 0.4% to 2.0%; P = .43). The relative risk of cardiac death for patients with VT was 1.4 compared with patients without VT (95% CI, 0.6 to 6.1). The sudden death rate was 1.4% per year in the patients with VT (95% CI, 0.4% to 3.5%) and 0.6% in those without VT (95% CI, 0.2% to 1.5%; P = .24). The relative risk of sudden death for patients with VT compared with those without VT was 2.4 (95% CI, 0.5 to 11.9). Of the 151 patients included in the study, 88 (58%) remained asymptomatic and were not treated with cardioactive medications during follow-up. Of these 88 patients, 20 were in the group with VT and 68 in the group without VT. None of these patients died.Our results show that cardiac mortality is low in patients with hypertrophic cardiomyopathy who are asymptomatic or only mildly symptomatic and have brief and infrequent episodes of VT on ambulatory ECG monitoring. Our findings also suggest that brief and infrequent episodes of VT should not be considered, per se, an indication for antiarrhythmic treatment in such patients.
Circulating Fibrocytes as Biomarker of Prognosis in Hermansky-Pudlak Syndrome
Authors: Aaron Trimble, Bernadette R. Gochuico, Thomas C. Markello, Roxanne Fischer, William A. Gahl, Jae K. Lee, Youngchul Kim, Marie D. Burdick, Robert M. Strieter, Borna Mehrad
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

The rate of progression of most interstitial lung diseases (ILD) is unpredictable. Fibrocytes are circulating bone marrow-derived cells that have been implicated in the pathogenesis of lung fibrosis. Hermansky-Pudlak syndrome (HPS), a genetic cause of ILD in early adulthood, allows for study of biomarkers of ILD in a homogeneous population at near-certain risk of developing fibrotic lung disease.To test the hypothesis that, in subjects with HPS, the number or phenotype of circulating fibrocytes predicts progression and outcome of ILD.We measured circulating fibrocyte counts and chemokine levels in a cohort of subjects with HPS and healthy control subjects and correlated the results to disease outcome.In a cross-sectional analysis, peripheral blood fibrocyte concentrations were markedly elevated in a subset of subjects with HPS who had ILD but not subjects without lung disease or normal control subjects. The blood concentration of fibrocytes expressing the chemokine receptor CXCR4 correlated significantly with the plasma concentration of the CXCR4 ligand, CXCL12. In a longitudinal study, we found marked episodic elevations in circulating fibrocyte counts over a median follow-up period of 614 days. Elevations in both maximal values and final values of peripheral blood CXCR4(+) fibrocyte concentration were strongly associated with death from ILD.CXCR4(+) fibrocyte concentration may be useful as a biomarker for outcome of ILD in subjects with HPS.
cAMP-Dependent Regulation of Cardiac L-Type Ca2+ Channels Requires Membrane Targeting of PKA and Phosphorylation of Channel Subunits
Authors: Tianyan Gao, Atsuko Yatani, Mark L Dell'Acqua, Hidenori Sako, Stuart A Green, Nathan Dascal, John D Scott, M.Marlene Hosey
Journal: Neuron (1997)
Early Histopathologic Events to Evolution of Colon Cancer in C57BL/6 and CF1 Mice Treated With 1,2-Dimethylhydrazine&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M J Wargovich, A Medline, W R Bruce
Journal: JNCI Journal of the National Cancer Institute (1983)

After administration of the intestinal carcinogen 1,2-dimethylhydrazine (DMH), C57BL/6J and CF1 mice were observed for early precursor lesions to large bowel cancer. Among the initial events seen following DMH treatment, an abrupt reduction in colonic DNA synthesis was the earliest lesion detectable. The frequency of aberrant colonic nuclei rose shortly after DMH treatment, reaching a maximum value 24 hours later and remaining elevated for 3 days following the exposure. Mucin changes, detected histochemically, and cell kinetic alterations in crypt proliferation rates were observed much later and were a constant feature for both strains following 4 weekly treatments with DMH, while carcinomas appeared in all animals 32 weeks after the start of DMH treatment. The quantitative comparison of these histopathologic observations for the early detection of colon cancer suggests that the induction of colonic nuclear aberrations in the mucosa of the large bowel might provide a sensitive and rapid indication of genotoxicity to this organ and thus might provide the basis for a screening methodology for colon carcinogens.
Experimental autoimmune thyroiditis. In vitro cytotoxic effects of T lymphocytes on thyroid monolayers.
Authors: P Creemers, N R Rose, Y M Kong
Journal: The Journal of Experimental Medicine (1983)

Effector mechanisms in experimental autoimmune thyroiditis (EAT) were studied in vitro by establishing a cytotoxicity system with thyroid target cells. Lymph node cells (LNC) from popliteal and inguinal lymph nodes were obtained from CBA/J mice (8-10 wk old) 12-18 d after immunization with 120 micrograms mouse thyroglobulin (MTg) in complete Freund's adjuvant (0.2 ml to both hind footpads and thighs) and were cultured with MTg (10-50 micrograms/ml). On day 5 of culture, viable LNC were added to labeled thyroid monolayers and their cytoxicity was assayed after 16 h. Functional thyroid target cells, as reflected by MTg production for up to 9 d, were prepared by adding 1 mM dibutyryl adenosine 3',5'-cyclic monophosphate and 60 microU thyroid-stimulating hormone/ml to the culture medium. On days 5-7, confluent monolayers were labeled with 111In and used as targets. Specific 111In-release ranged from 56 to 85%. The cytotoxic response is MTg specific and H-2 restricted. Pretreatment of thyroid target cells with rabbit antiserum to MTg completely inhibited cytotoxicity. Pretreatment with mouse antiserum to either Kk or Dk products resulted in approximately 50% inhibition, whereas the combined use of both antisera led to total inhibition. No cytotoxicity was observed when control BALB/c thyroid cultures were the target cells. The kinetics of the expansion of Thy-1+ cytotoxic cells by in vitro exposure to MTg were then studied. The cytotoxic response required 5 d to develop and was abolished by treating LNC on day 4 with monoclonal antibody to Lyt-1.1, but not to Lyt-2.1, plus complement. In contrast, by day 5, cytotoxicity was abrogated by similar treatment with antiserum to Lyt-2.1, but not to Lyt-1.1. We conclude that cytotoxic cells derived from MTg-immunized mice are Lyt-2-bearing cells but require the presence of Lyt-1-bearing cells for their generation and/or differentiation.
The present and future state of hormonal treatment for male infertility
Authors: P. Y. Liu
Journal: Human Reproduction Update (2003)

Although male factors contribute to over half of all cases of infertility, most infertile men are described as 'idiopathic oligo/asthenozoospermic' rather than diagnosed precisely; hence, specific medical treatment is not possible. One uncommon but treatable cause of male infertility is gonadotrophin deficiency in which gonadotrophin replacement therapy is highly effective at inducing spermatogenesis and fertility. Hormonal therapy is a logical approach for empirical drug therapy given the fundamental role of hormonal regulation in spermatogenesis. However, treatment with GnRH analogues, gonadotrophins, androgens, anti-estrogens, aromatase inhibitors, growth hormone- and prolactin-suppressing drugs is ineffective in unselected infertile men. Prolonged high-dose glucocorticoid therapy for sperm autoimmunity may improve pregnancy rates modestly, but the risks are generally unacceptable compared with IVF or ICSI. For these reasons, modern reproductive technologies, notably ICSI/IVF, have become the de-facto standard empirical treatment of male infertility, despite involving significant though infrequent risks to the fetus and mother. There remains a potential for hormonal methods to improve sperm quality or ultrastructure in subgroups of infertile men more responsive to hormonal manipulation or using novel protein or gene-targeted therapies or biochemical approaches based on post-hormonal receptor mechanisms that stimulate spermatogenesis. How such novel hormonal methods will develop in conjunction with improved ICSI/IVF or cloning technologies, and the potential role of adjunctive hormonal therapy remains to be clarified.
Flow cytometric DNA analysis in longstanding ulcerative colitis: a method of prediction of dysplasia and carcinoma development?
Authors: R Lofberg, B Tribukait, A Ost, O Brostrom, H Reichard
Journal: Gut (1987)

During a prospective study lasting 3.5 years flow cytometric DNA analysis was evaluated as a possible predictor of dysplastic and malignant lesions in longstanding ulcerative colitis. Fifty three patients with total ulcerative colitis (mean disease duration of 22 years) were regularly colonoscoped. Biopsies of colonic mucosa were analysed by flow cytometric technique and were also assessed histologically. Findings of abnormal DNA pattern (aneuploidy) were compared with findings of dysplasia. Five patients (9%) had aneuploidy, four of those at repeated colonoscopies. Four of those patients also had various degrees of dysplasia. In one patient aneuploidy preceded the finding of dysplasia and in another aneuploidy preceded a well differentiated adenocarcinoma, grade Dukes9 A subsequently found at surgery. Four additional patients had dysplasia, all in connection with macroscopic lesions, but were diploid. It is suggested that flow cytometric DNA analysis in long standing ulcerative colitis may be helpful in addition to histopathology in the detection of potential malignancy in ulcerative colitis.
Embryoid-body cells derived from a mouse embryonic stem cell line show differentiation into functional hepatocytes
Authors: Ryoko Chinzei, Yujiro Tanaka, Keiko Shimizu-Saito, Yuzuru Hara, Sei Kakinuma, Mamoru Watanabe, Kenichi Teramoto, Shigeki Arii, Kozo Takase, Chifumi Sato, Naohiro Terada, Hirobumi Teraoka
Journal: Hepatology (2002)

Embryonic stem (ES) cells have a potential to differentiate into various progenitor cells. Here we investigated the differentiation capacity of mouse ES cells into hepatocytes both in vitro and in vivo. During the culture of embryoid bodies (EBs) derived from ES cells, albumin (ALB) messenger RNA (mRNA) was expressed within 12 days after removal of leukemia inhibitory factor, and α-fetoprotein (AFP) mRNA was observed within 9 days without additional exogenous growth factors. In ES cells and early EBs, by contrast, neither ALB mRNA nor AFP mRNA was observed. ALB protein was first detected at day 15 and the level increased with the culture period. The differentiation of EBs facilitated the synthesis of urea with the culture period, whereas early EBs and ES cells produced no urea. These results suggest that cultured EBs contain hepatocytes capable of producing ALB and urea. ES cells and the isolated cells from EBs were transplanted through portal vein to the liver after 30% partial hepatectomy of female mice pretreated with 2-acetylaminofluorene. Four weeks after transplantation with isolated cells from day-9 EBs, ES-derived cells containing Y-chromosome in the liver were positive for ALB (0.2% of total liver cells), whereas teratoma was found in mice transplanted with ES cells or EBs up to day 6. The incidence of teratoma was decreased with the culture duration and no teratoma was observed in the liver transplanted with isolated cells from day-9 EBs. In conclusion, our in vitro and in vivo experiments revealed that cultured EBs contain functional hepatocytes or hepatocyte-like cells. (Hepatology 2002;36:22-29.)
Lack of co‐ordinate expression of the α1(I) and α1(III) procollagen genes in fibroblast clonal cultures
Authors: Y. Yamaguchi, S. Crane, L. Zhou, S.M. Ochoa, V. Falanga
Journal: British Journal of Dermatology (2000)

Background Several extracellular matrix genes, most notably α1(I) and α1(III) procollagen, are reported to be co-ordinately expressed in cultures of dermal fibroblasts. However, it remains unclear whether the expression of these genes is truly co-ordinate or whether it may be the result of averaging the phenotypic expression of different fibroblast subpopulations present within each culture. Objectives To determine by Northern analysis the correlation between α1(I) and α1(III) procollagen mRNA levels in clonal populations of human dermal fibroblasts. Methods As previously described, clonal cultures were derived from parent strains of human dermal fibroblasts by a microscopically controlled dilution technique and by stimulation of single cells with low oxygen tension in the early phases of clonal growth. Results In agreement with previous reports, we found that baseline steady-state levels of α1(I) procollagen mRNA were co-ordinately regulated with the α1(III) procollagen mRNA in 26 parent strains (r = 0·9003; P < 0·0001). However, this close correlation between the expression of these two procollagen chains was absent in a total of 40 unselected clonal strains derived from four of the parent cultures (r = 0·5745; P < 0·0001). Moreover, this intrachain heterogeneity in α1(I) and α1(III) procollagen mRNA levels in clonal cultures was statistically significant from that measured in parent strains (P = 0·0016). Conclusions α1(I) and α1(III) procollagen mRNA levels in clonal cultures do not show the tight co-ordinate regulation observed in non-clonal cultures, suggesting that these two genes operate under different sets of regulatory controls. This clonal heterogeneity may provide additional flexibility to the process of tissue repair and fibroblast clonal expansion.
Angiotensin-Converting Enzyme Inhibitor Trandolapril Does Not Affect C-Reactive Protein Levels in Myocardial Infarction Patients
Authors: Moniek P.M. de Maat, Cornelis Kluft, Jørgen Gram, Jørgen Jespersen
Journal: Circulation (2003)

reported a direct effect of C-reactive protein (CRP) on the angiotensin system.Their findings add to the accumulating evidence that CRP is not only an indirect risk marker for cardiovascular disease but also causally contributes to the precipitation of the disease.An association between CRP and the angiotensin system also raises the question of what the effect is of angiotensin-converting enzyme (ACE) inhibitors on CRP, given that the ACE inhibitors are often used after coronary events.We studied the effect of the ACE inhibitor, trandolapril, on CRP levels in 80 patients who participated in the TRAndolapril Cardiac Evaluation (TRACE) study, 2 randomized to treatment (0.5 mg daily) or placebo.Citrated blood was collected from these patients during hospitalization after a myocardial infarction but before randomization, and after 1, 3, 6, 9, and 12 months of treatment.CRP was measured in the plasma using a highsensitivity enzyme immunoassay with polyclonal antibodies to human CRP as catching and tagging antibodies (Dako).The effect of treatment on CRP was analyzed using repeatedmeasures ANOVA on logarithmically transformed CRP levels.CRP levels were elevated after the myocardial infarction (geometric mean at randomization, 34.1 mg/L [coefficient of variation {CV}, 1.36]) and had returned to normal levels after 1 month, both in the treated group and in the placebo group (2.50 mg/L [CV 1.20] and 3.20 mg/L [CV 1.53], respectively; NS).The levels were not significantly different at any time point during the treatment period.The results of our study suggest that the association between CRP and the angiotensin system does not include lowering of CRP by ACE inhibitors but may be limited to an effect of CRP on angiotensin I receptor expression as reported by Wang et al. 1 In conclusion, CRP levels after a myocardial infarction and the beneficial effect of ACE-inhibitor treatment of patients after a myocardial infarction do not seem to include a reduction of levels of the inflammatory marker CRP.
Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals
Authors: Ikuroh Ohsawa, Masahiro Ishikawa, Kumiko Takahashi, Megumi Watanabe, Kiyomi Nishimaki, Kumi Yamagata, Ken-ichiro Katsura, Yasuo Katayama, Sadamitsu Asoh, Shigeo Ohta
Journal: Nature Medicine (2007)