tbuckley/cabot-search huggingface dataset:
Mechanisms Underlying Mammalian Hybrid Sterility in Two Feline Interspecies Models
Authors: Brian W Davis, Christopher M Seabury, Wesley A Brashear, Gang Li, Melody Roelke-Parker, William J Murphy
Journal: Molecular Biology and Evolution (2015)

The phenomenon of male sterility in interspecies hybrids has been observed for over a century, however, few genes influencing this recurrent phenotype have been identified. Genetic investigations have been primarily limited to a small number of model organisms, thus limiting our understanding of the underlying molecular basis of this well-documented "rule of speciation." We utilized two interspecies hybrid cat breeds in a genome-wide association study employing the Illumina 63 K single-nucleotide polymorphism array. Collectively, we identified eight autosomal genes/gene regions underlying associations with hybrid male sterility (HMS) involved in the function of the blood-testis barrier, gamete structural development, and transcriptional regulation. We also identified several candidate hybrid sterility regions on the X chromosome, with most residing in close proximity to complex duplicated regions. Differential gene expression analyses revealed significant chromosome-wide upregulation of X chromosome transcripts in testes of sterile hybrids, which were enriched for genes involved in chromatin regulation of gene expression. Our expression results parallel those reported in Mus hybrids, supporting the "Large X-Effect" in mammalian HMS and the potential epigenetic basis for this phenomenon. These results support the value of the interspecies feline model as a powerful tool for comparison to rodent models of HMS, demonstrating unique aspects and potential commonalities that underpin mammalian reproductive isolation.
Clinical Pharmacology and General Patient Care in Two Teaching Hospitals<sup>1</sup>
Authors: Susan M Wood, Paul Turner, Duncan Vere
Journal: Journal of the Royal Society of Medicine (1980)

The clinical responsibilities and activities over 12-month periods of the Departments of Clinical Pharmacology of two London teaching hospitals have been analysed. The results suggest that clinical pharmacology should not be regarded only as an academic specialty but that it has an important role in patient care.
Phase I Dose-Finding Study of a New Taxane, RPR 109881A, Administered as a One-Hour Intravenous Infusion Days 1 and 8 to Patients With Advanced Solid Tumors
Authors: Karen A. Gelmon, Jean Latreille, Anthony Tolcher, Luc Génier, Bryn Fisher, Dominique Forand, Susan D’Aloisio, Laurent Vernillet, Luc Daigneault, Ann Lebecq, Michele Besenval, Elizabeth Eisenhauer
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To define the maximum-tolerated dose, recommended phase II dose (RD), dose-limiting toxicity (DLT), and pharmacokinetics of a novel taxane, RPR 109881A, administered on days 1 and 8 of a 21-day cycle. PATIENTS AND METHODS: Twenty-nine patients were enrolled and treated according to a modified continual reassessment method from a starting dose of 7.5 mg/m 2 to 52.5 mg/m 2 . Detailed pharmacokinetic analyses of blood and urine were performed on days 1 and 8 of the first cycle. Toxicity was monitored weekly. RESULTS: DLT consisting of grade 3 or 4 diarrhea was seen in three of six patients at 52.5 mg/m 2 . Grade 3 or 4 granulocytopenia was also seen in five of six patients treated at this dose (four of six in the first cycle). At the next lower dose level, 45 mg/m 2 toxicity was moderate, with only one of 12 patients experiencing severe diarrhea and grade 4 granulocytopenia with associated infection. Drug concentrations were consistent with a three-compartment open model. The total-body clearance suggests a linear dose-concentration relationship. RPR 109881A has a high clearance (mean, 42.6 L/h/m 2 ), a large volume of distribution (mean, 952 L/m 2 ), and a long terminal half-life (mean, 24 hours). There was no drug accumulation between days 1 and 8. One partial response was seen in a patient with renal cell carcinoma. CONCLUSION: The RD of RPR 109881A given as a 1-hour infusion on days 1 and 8 of a 21-day cycle is 45 mg/m 2 . At this dose the drug is well tolerated and should be further studied.
Incidence and risk factors of MRSA pneumonia
Authors: Katia Verhamme, Francis Maton, Kristien Van Vaerenbergh, Paul Jordens
Journal: European Respiratory Journal (2011)

Introduction:  Data on the incidence of MRSA pneumonia in Europe are scarce.   Objective:  To study the incidence of MRSA pneumonia and its related mortality.   Methods:  Data from the OLV hospital, a 939-bed, university-affiliated teaching hospital in Belgium, were used. The study period ran from 2006 to 2009. All respiratory tract samples, positive for MRSA, were retrospectively collected from the automated microbiology database. As multiple samples per patient were available during follow-up, only the first MRSA respiratory tract sample was considered. Of all patients with MRSA positive respiratory tract samples, the complete medical records, including chest X-ray or chest CT scans were reviewed by a pulmonologist. Patients were defined to have pneumonia according to the ECDC criteria. Risk factors such as comorbidity and previous use of antibiotics were studied.   Results:  During follow-up, 197 patients with a MRSA positive respiratory tract sample were identified. 46 of these 197 patients developed an MRSA pneumonia of which 30 had a nosocomial pneumonia. The overall incidence of MRSA pneumonia was 0.49/10000 patient days. 25 of the 46 MRSA pneumonia were detected at ICU. In patients with MRSA pneumonia, the mortality was high, 24 of the 46 patients (52%) died during follow-up versus 32% in patients with MRSA colonization of the respiratory tract was 32%. The mean time from admission to MRSA pneumonia was 13.6 days. 50% of patients with MRSA pneumonia were previously (during current hospital admission) treated with an antibiotic vs 32.5% in MRSA colonized patients.   Conclusion:  The incidence of MRSA pneumonia is low but mortality in these patients is high. Previous use of antibiotics is one of the main risk factors of an MRSA pneumonia.
Characteristics and outcomes of GOLD C and D COPD patients
Authors: Hana Müllerová, MeiLan Han, Richard Baxter, Kourtney Davis
Journal: European Respiratory Journal (2014)

Aims: We evaluated characteristics and outcomes of COPD patients classified as GOLD 2013 Grade C or D in a primary care database.

Methods: A cohort of diagnosed COPD patients with MRC dyspnoea score and FEV1 % predicted recorded on the same day, and COPD exacerbation history collected the previous 12 months, was derived from the UK Clinical Practice Research Datalink (1/1/2004-31/12/2012). GOLD 2013 Grades C and D were further stratified based on qualification by airflow limitation only (C1/D1), exacerbation history only (C2/D2), or both (C3/D3). Future events (exacerbations/death/GOLD Grade change) were enumerated and incidence derived using person-time methods till censoring at death/leaving practice event or 31/12/2013.

Results: In a cohort of 52,237 COPD patients, 21% qualified as C and 28% as D. Of these, the majority were further classified as C1 and D1 (Table1). During follow-up, patients in C2/D2 most frequently changed to lower risk GOLD grades (A/B). Future exacerbations were most frequent in the C3 and D3 subgroups; mortality was highest for the D3 group (Table 2).

Conclusions: We identified important differences in COPD outcomes among pre-defined GOLD C/D subgroups among COPD patients managed in primary care.

Sponsored by GSK RD.[table1

View this table:

Table 2: Outcomes in GOLD 2013 Grades C/D





View this table:

Table 1: Baseline GOLD 2013 classification, N (%)
TIETZE'S SYNDROME
Authors: M BERNREITER
Journal: Annals of Internal Medicine (1956)

Case Reports1 July 1956TIETZE'S SYNDROMEMICHAEL BERNREITER, M.D., F.A.C.P.MICHAEL BERNREITER, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-45-1-132 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTietze's syndrome is a painful, nonsuppurative swelling of the costochondral or sternoclavicular junction. Since Tietze's original description in 1921,1 over 100 patients with chest pain caused by this syndrome have been described by foreign authors. A search for reports concerning this entity in the American literature reveals that Tietze's syndrome has been discussed only twice: the first paper by Motulsky and Rohn in 1953,2 and the second by Wehrmacher in 1955.3In the differential diagnosis of chest pain, Tietze's syndrome should always be considered. Tenderness over the involved cartilage at times is extreme and may be exaggerated by effort as...Bibliography1. Tietze A: Ueber eine eigenartige Häufung von Fällen mit Dystrophy der Rippenknorpel, Berl. klin. Wchnschr. 58: 829-831, 1921. Google Scholar2. MotulskyRohn ARJ: Tietze's syndrome: cause of chest pain and chest wall swelling, J. A. M. A. 152: 504-506, 1953. CrossrefMedlineGoogle Scholar3. Wehrmacher WH: Significance of Tietze's syndrome in differential diagnosis of chest pain, J. A. M. A. 157: 505-507, 1955. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Kansas City, Missouri*Received for publication April 8, 1955.Requests for reprints should be addressed to Michael Bernreiter, M.D., 432-36 Professional Bldg., Kansas City, Mo. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySonography of the costal cartilage: Normal anatomy and preliminary clinical applicationSternocostal Joint Swelling–Clinical Tietze's SyndromeTietze's syndrome: Report of two cases and review of the literatureTietze's SyndromePARASTERNAL CHONDRODYNIA (TIETZE'S SYNDROME)*NEALE BARNES, M.D., JAMES GRAHAM, M.D.Tietze's syndrome (painful nonsuppurative swelling of costochondral cartilages)Tietze's Syndrome: An Unusual Cause of Chest Wall Swelling 1 July 1956Volume 45, Issue 1Page: 132-134KeywordsCartilageInflammationIschemiaMalnutritionThorax ePublished: 1 December 2008 Issue Published: 1 July 1956 PDF downloadLoading ...
R3327 Adenocarcinoma of the Copenhagen Rat as a Model for the Study of the Immunologic Aspects of Prostate Cancer 2
Authors: David M. Lubaroff, Larry Canfield, Thomas L. Feldbush, William W. Bonney
Journal: JNCI Journal of the National Cancer Institute (1977)

The Dunning R3327 prostate adenocarcinoma of the Copenhagen rat was developed as a suitable model of human prostate cancer. Inoculation of tumor tissue mince or cells sc in the flanks of recipient rats produced tumors that had the macroscopic and microscopic characteristics of the human disease. The histologic picture of these tumors was that of a well-differentiated adenocarcinoma with the formation of glands and acid secretions within the acini. Tumors were also produced in the dorsolateral lobe of the prostate by the injection of cells. The intraprostate tumor, although initially confined to the injected lobe, grew to involve the surrounding tissues and eventually metastasized to the lymph nodes and lungs. Occasional metastatic lesions were found in other organs also. Acid phosphatase could be domonstrated by histochemical staining of frozen tumor sections, and elevated levels of the enzyme were seen in the sera of rats bearing long-term subcutaneous tumors. During investigation of the tumor, a fast-growing tumor line arose that grew equally as well in females as in males. The histology of this tumor was that of an undifferentiated anaplastic tumor.
Effects of ghrelin on the dyspnea pattern in cachectic COPD: Exploratory analysis of a substudy of a multicenter, randomized, double-blind, placebo-controlled trial of ghrelin treatment
Authors: Keisuke Miki, Ryoji Maekura, Noritoshi Nagaya, Seigo Kitada, Mari Miki, Kenji Yoshimura, Hideki Matsui, Akitoshi Satomi, HIsako Hashimoto, Masahide Mori, Kenji Kangawa
Journal: European Respiratory Journal (2013)

Background: The substudy of the ghrelin treatment, multicenter, randomized, double-blind, placebo-controlled trial demonstrated that ghrelin administration was associated with improved exertional capacity and improvements in ventilatory-cardiac parameters in cachectic COPD patients. To clarify more precisely the dyspnea pattern during exercise, the data from the substudy were analyzed in an exploratory manner.  Method: Of 20 cachectic COPD patients who were randomized to pulmonary rehabilitation with intravenous ghrelin (2 mg/kg, n = 10) or placebo (n = 10) twice daily for 3 weeks in the substudy, 17 patients (ghrelin = 9, placebo = 7) could be investigated for the dyspnea break-point on the dyspnea-ratio (%) of delta oxygen uptake (Vo2) (= peak minus resting Vo2) curve.  Results: No treatment effect compared with placebo was found in the Borg scale at the dyspnea break-point, or in the plasma lactate level at the lactate break-point. However, a significant treatment effect by ghrelin administration in the percentage of delta Vo2 at the dyspnea break-point (treatment effect -18%, 95% CI -35.9 to -0.0; p = 0.049) was obtained. Similarly, the percentage of delta Vo2 at the lactate break-point was significantly shifted to the early exercise phase compared with placebo (treatment effect -19%, 95% CI -34.1 to -4.2; p = 0.017).  Conclusions: Cachectic patients with COPD benefited from ghrelin treatment in terms of shifts to the early exercise phase in the dyspnea break-point and in the lactate threshold during a standardized exercise program.  Trial Registration: UMIN, number 00061.
Comparison of Nebulized Budesonide and Oral Prednisolone with Placebo in the Treatment of Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: FRANÇOIS MALTAIS, JULIETTE OSTINELLI, JEAN BOURBEAU, ANDRÉ BERNARD TONNEL, NADINE JACQUEMET, JENNIFER HADDON, MICHEL ROULEAU, MOHAMED BOUKHANA, JEAN BENOÎT MARTINOT, PIERRE DUROUX
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Nebulized budesonide has been used successfully to treat acute asthma exacerbation, and we hypothesized that it could also be effective for exacerbations of chronic obstructive pulmonary disease (COPD). In this multicenter, double-blind, randomized, placebo-controlled trial, the efficacy of nebulized budesonide (Pulmicort Respules/Nebuamp), oral prednisolone, and placebo was compared in 199 patients with acute exacerbations of COPD requiring hospitalization. Patients received from randomization (H0) to 72 h (H72), 2 mg of budesonide every 6 h (n = 71), 30 mg of oral prednisolone every 12 h (n = 62), or placebo (n = 66). All received standard treatment, including nebulized β2-agonists, ipratropium bromide, oral antibiotics, and supplemental oxygen. The mean change (95% confidence interval) in postbronchodilator FEV1 from H0 to H72 was greater with active treatments than with placebo: budesonide versus placebo, 0.10 L (0.02 to 0.18 L); prednisolone versus placebo, 0.16 L (0.08 to 0.24 L). The difference in FEV1 between budesonide and prednisolone was not significant, − 0.06 L ( − 0.14 to 0.02 L). The occurrence of serious adverse events was similar for all groups. Budesonide had less systemic activity than prednisolone as indicated by a higher incidence of hyperglycemia observed with prednisolone. Both budesonide and prednisolone improved airflow in COPD patients with acute exacerbations when compared with placebo. Nebulized budesonide may be an alternative to oral prednisolone in the treatment of nonacidotic exacerbations of COPD but further studies should be done to evaluate its long-term impact on clinical outcomes after an initial episode of COPD exacerbation.
Dedicated severe asthma services improve healthcare utilisation and quality of life
Authors: David Gibeon, Suzanne Regan, Christopher Brightling, Rob Niven, Adel Mansur, Rekha Chaudhuri, Christine Bucknall, Neil Thomson, Kian Fan Chung, Liam Heaney, Andrew Menzies-Gow
Journal: European Respiratory Journal (2013)

Introduction:   5% of asthmatics have severe disease. This group have a high morbidity and represent a significant unmet clinical need. Patients referred with difficult asthma to centres within the BTS severe asthma registry undergo a Systematic Assessment of Severe Asthma (SAA), comprising a set of coordinated investigations accompanying a detailed history and examination.   Methods:   493 patients, collected as part of the National Registry for dedicated UK Difficult Asthma Services, underwent a SAA. Lung function, healthcare utilisation, medication burden and QoL at baseline were compared with outcomes after one year.   Results:   397 (81%) patients were diagnosed with severe asthma. 56% of patients had a significant comorbidity. At follow-up (median 286-days [248–376]) more patients were receiving anti-IgE-therapy or steroid-sparing agents. There were significant reductions in healthcare utilisation and improved QoL.   Conclusion:   Entry into dedicated severe asthma services provides a structured and thorough assessment, which identifies alternative/additional diagnoses, leading to targeted interventions, improved care and reduced healthcare utilisation and improved QoL.
The FEV1/TLC ratio: Can it differentiate between normal subjects and patients with airflow obstruction and restrictive ventilatory defects - a preliminary analysis?
Authors: Adrian Kendrick
Journal: European Respiratory Journal (2013)

A reduced FEV 1  is as a marker of airflow obstruction where TLC is normal or increased, whilst both TLC and FEV 1  are reduced in a restrictive ventilatory defect.  Aim : To determine the usefulness of the FEV 1 /TLC ratio in determining the presence of an obstructive or restrictive ventilatory defect.  Methods : Lung function measurements of FEV 1 , VC and TLC were reviewed and divided into four principle groups - 1) normal (both FEV 1  and TLC > -1.64 SR), 2) airways obstruction (FEV 1 %VC   +1.65SR), 3) restrictive defect (TLC  Results : The group (n = 806; age 20 - 97 yrs) and sub-group analysis is shown in the table.  The FEV 1 /TLC ratio was significantly lower (p  co  and K co ), no significant differences were observed.  Conclusion:  In this preliminary analysis, the FEV 1 /TLC can differentiate between normal subjects and those with a restrictive and an obstructive ventilatory defect.
Treatment of Atrial Fibrillation and Paroxysmal Supraventricular Tachycardia With Bidisomide
Authors: Investigators
Journal: Circulation (1997)

Background Atrial fibrillation and paroxysmal supraventricular tachycardia are common disorders of the heart rhythm for which antiarrhythmic drug therapy is commonly prescribed. The Atrial Fibrillation Investigation with Bidisomide (AFIB) study was a randomized, placebo-controlled clinical trial designed to accomplish three goals in a single protocol: (1) to determine the efficacy of the antiarrhythmic drug bidisomide in the treatment of these two arrhythmias; (2) to establish the appropriate dose range for bidisomide; and (3) to detect an adverse mortality effect of bidisomide if one were present in patients with atrial fibrillation. Methods and Results In this clinical trial, 1227 patients with atrial fibrillation and 187 with paroxysmal supraventricular tachycardia were randomly assigned to bidisomide (200, 400, or 600 mg BID) or placebo; patient groups with each arrhythmia were analyzed separately. Symptomatic recurrences of atrial fibrillation and paroxysmal supraventricular tachycardia were documented with the use of transtelephonic ECG monitoring. The time to the first symptomatic arrhythmia recurrence was measured in each patient and compared among treatment groups. Among the atrial fibrillation patients, there was no significant difference in the time to first symptomatic recurrence between the placebo group and any of the three bidisomide treatment groups; the hazard ratios (placebo:treatment) were 1.19, 1.03, and 1.14 for bidisomide 200, 400, and 600 mg BID, respectively. Among paroxysmal supraventricular tachycardia patients, there was a similar lack of a significant treatment effect; the hazard ratios were 1.30, 1.93, and 1.59 for bidisomide 200, 400, and 600 mg BID, respectively. In the primary safety analysis of mortality, 3 of 493 patients taking placebo died, compared with 9 of 488 patients taking one of the two higher doses of bidisomide ( P &gt;.10). Conclusions Bidisomide in the doses tested did not have a clinically important antiarrhythmic effect. The AFIB study provided a novel clinical trial design to test antiarrhythmic drugs for both safety and efficacy.
Hidradenitis suppurativa and immune dysregulation
Authors: G.B.E. Jemec
Journal: British Journal of Dermatology (2012)

Conflicts of interest None declared. Hidradenitis suppurativa (HS) is a disease in dire need of more efficient treatment options. The development of new treatments has hitherto been empirical as the aetiology of HS remains a topic for speculation.1 Nevertheless, significant progress has recently been achieved leading not only to more therapeutic options for patients, but also increasing our understanding of the pathogenesis of this disease. In contrast to the common view of HS as primarily an infectious disease, the concept of HS as an immunological disease has gradually been accepted. The use of immunosuppressive agents in the treatment of HS has been recognized for a long time, but has been poorly evidenced.2 In 2001, a serendipitous observation of the therapeutic success of infliximab in a patient with concomitant Crohn disease suggested that tumour necrosis factor (TNF)‐α blockers could have an effect on HS.3 In consequence, several further cases were reported, and the initial enthusiasm was supported by small randomized controlled trials of infliximab and adalimumab.4–6 More recently, a larger controlled trial has indicated that adalimumab, at a dosage commonly used for Crohn disease, has a significant effect.7 In a back‐handed way, the rising level of evidence in favour of treating HS with anti‐TNF‐α antibodies is now providing a stronger footing for studies concerning the aetiology of the disease.