tbuckley/cabot-search huggingface dataset:
The oral CYP17-Lyase (L) inhibitor VT-464 in patients with CRPC.
Authors: Johann Sebastian De Bono, Carmel Jo Pezaro, Silke Gillessen, Neal D. Shore, Luke T. Nordquist, Eleni Efstathiou, John C. Araujo, William R. Berry, Glenn Liu, Nicholas J. Vogelzang, Aurelius Gabriel Omlin, Robert J. Schotzinger, Joel Robert Eisner, William R. Moore
Journal: Journal of Clinical Oncology (2015)

187 Background: VT-464 is an oral, non-steroidal inhibitor of CYP17-L and an antagonist of androgen receptor (AR) variants F876L and T877A which are associated with resistance to enzalutamide (ENZ) and abiraterone/prednisone (AA), respectively. INO-VT-464-CL-001 is a Phase (Ph) 1/2 study of VT-464 in treatment-naïve (TN) and treatment-failure (TF) patients with CRPC. Results are reported for Ph 1 (TN patients) and early results from Ph 2 patients. Methods: Phase 1: safety, tolerability, PK and initial efficacy (PSA and steroid concentrations) in M0 and M1 TN patients in escalated dose-cohorts from 50 to 600 mg bid in 28-day continuous dosing cycles. Phase 2: preliminary efficacy in M0 and M1 TN and TF (post-AA, -ENZ, and/or CHEMO) patients at 450 mg bid. Results: In Ph 1, 26 TN patients received VT-464 at 50 mg bid (n=1), 100 mg bid (n=1), 200 mg bid (n=4), 300 mg bid (n=8), 450 mg bid (n=9) and 600 mg bid (n=3) with 2 patients currently on study (15 and 29 months). Another 10 TN patients received VT-464 in Ph 2 at 450 mg bid. Most Ph 1 adverse events (AEs) were grade 1 or 2 and not considered drug related. There were 18 grade 3 AEs and 1 grade 5 AE considered not related to study drug, plus 4 grade 3 AEs (vasovagal/syncope) considered at least possibly related. For a single oral 450 mg dose, t½ was 6.8±0.8h (mean±SEM), Cmax was 8.6±1.2uM and Tmax was 3.4±0.7h. 19 of 26 Ph 1 and Ph 2 TN patients who received from 300 to 600 mg bid had PSA responses (6 PSA30%, 2 PSA50% and 1 PSA90% response). Preliminary PSA responses in Ph 2 TF patients included a PSA90% response in a prior-ENZ pre-chemo patient and a PSA50% response in a prior-ENZ and -chemo patient. No mineralocorticoid excess syndrome (MES) or changes in ACTH response or LFTs were observed. Plasma testosterone concentrations were reduced to near or below the limit of quantification in most patients at ≥ 450 mg bid, with normal progesterone and cortisol concentrations. No supplemental steroids were used. Conclusions: Clinical results at the doses evaluated support VT-464 CYP17 L-selectivity. The PSA50% and PSA90% responses in 2 of 7 prior Xtandi patients, combined with a lack of MES despite no supplemental steroids, warrants further investigation in the ongoing Ph 2 study, particularly in prior ENZ and AA patients. Clinical trial information: NCT02012920.
A novel approach to prevent post-operative ileus after continuous-flow left ventricular assist device implantation: A retrospective cohort study
Authors: Abbasali Badami, Erika A. Fehrenbach Prell, Margaret A. Murray, Maryl R. Johnson, Shahab A. Akhter, Lucian Lozonschi, Satoru Osaki, Entela Lushaj, Takushi Kohmoto
Journal: International Journal of Surgery (2015)
The impact of COPD care bundles on compliance of care in northwest London
Authors: Laura Lennox, Urvashi Sharma, Hannah Musgrave
Journal: European Respiratory Journal (2012)

Background:  Chronic Obstructive Pulmonary Disease (COPD) is one of the most common respiratory diseases in the UK, causing around 25,000 deaths a year and with a large portion of patients not receiving ideal care for COPD exacerbations. Care bundles, a sequence of evidence based interventions, have been identified as a way of delivering consistent patient care.   Aims : National Institute for Health Research (NIHR) Collaboration for Applied Health Research and Care (CLAHRC) for Northwest London implemented COPD discharge care bundles across 7 sites over 18 months (beginning in April 2009) to improve compliance to existing evidence based interventions.   Methods:  The COPD discharge care bundles initially included smoking cessation, pulmonary rehabilitation, patient information on self-management, inhaler technique training, and follow-up appointment. Each of the sites adapted the bundle according to available resources and local settings. Weekly data on compliance was entered into a web reporting tool.   Results:  The results from the data showed that 1052 patients were discharged with the care bundle; 668 of these patients were discharged having received all the elements of the care bundle (63.5% were fully-compliant). The bundle element with the highest overall compliance was smoking cessation with 95.2%, and lowest was recorded with the follow-up appointment at 77.8%. Overtime improvement to overall compliance was seen across all sites.   Conclusions:  This study reveals aspects that impact compliance of care with COPD care bundle elements. The findings offer valuable lessons to future sites interested in implementing COPD care bundles and should be considered in order to improve COPD care.
STUDIES OF SERUM ELECTROLYTES
Authors: F. William Sunderman, J. Harold Austin, Priscilla Williams
Journal: Journal of Clinical Investigation (1932)

Many studies have appeared in the literature on the effect of insulin on various constituents of the blood or blood serum of normal and diabetic individua,s.These have been reviewed by Peters and Van Slyke (1).The evidence in the literature indicates that coincident with the fall of glucose, insulin produces a simultaneous fall in the concentration of
Gemcitabine as a Single Agent in the Treatment of Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma
Authors: A. Fosså, A. Santoro, W. Hiddemann, L. Truemper, N. Niederle, S. Buksmaui, G. Bonadonna, S. Seeber, M. R. Nowrousian
Journal: Journal of Clinical Oncology (1999)

PURPOSE: A multicenter phase II trial was conducted to evaluate the efficacy and toxicity of gemcitabine in patients with relapsed or refractory aggressive non-Hodgkin's lymphomas (NHL). PATIENTS AND METHODS: Thirty-one patients with B-cell intermediate or high-grade NHL (Working Formulation) were enrolled onto the study. The median age was 61 years, with a Karnofsky performance status of ≤ 80% in 65% of patients. Forty-eight percent had stage III or IV (Ann Arbor Classification) at study entry. Pretreatment consisted of one, two, or three chemotherapeutic regimens in nine, 11, and 11 patients, respectively. Gemcitabine 1,250 mg/m 2 was administered intravenously over 30 minutes on days 1, 8, and 15 of a 28-day schedule. RESULTS: Thirty patients were assessable for efficacy, and 31 were assessable for toxicity. No complete responses were observed, but six patients showed a partial response, 11 stable disease, and 13 progressive disease. The overall response rate was 20% (95% confidence interval, 8% to 39%) for assessable patients and 19% (95% confidence interval, 8% to 34%) for the intent-to-treat analysis. The median duration of partial response was 6 months (range, 3.7 to 15+ months). Nonhematologic World Health Organization grade 3 toxicity included hepatic toxicity in four patients and infection in two. Hematologic toxicity was observed as grade 3 anemia in three patients, grade 3 leukopenia in two patients, grade 3/4 neutropenia in two patients, and grade 3/4 thrombocytopenia in six patients. CONCLUSION: The present schedule of gemcitabine displays modest efficacy and mild toxicity in pretreated aggressive NHL.
Prognostic value of clinical and immunological markers in acute phase of SFTS virus infection
Authors: Y.-P. Ding, M.-F. Liang, J.-b. Ye, Q.-h. Liu, C.-h. Xiong, B. Long, W.-b. Lin, N. Cui, Z.-q. Zou, Y.-l. Song, Q.-f. Zhang, S. Zhang, Y.-z. Liu, G. Song, Y.-y. Ren, S.-h. Li, Y. Wang, F.-q. Hou, H. Yu, P. Ding, F. Ye, D.-X. Li, G.-Q. Wang
Journal: Clinical Microbiology and Infection (2014)
Parachlamydia acanthamoebae as a respiratory pathogen: Challenge dose titration in a bovine model
Authors: Markus Lohr, Annette Prohl, Carola Ostermann, Wieland Schroedl, Elisabeth Liebler-Tenorio, Gilbert Greub, Petra Reinhold
Journal: European Respiratory Journal (2014)

Background : The majority of community acquired pneumonia (CAP) in humans fails to be diagnosed aetiologically. Besides  Chlamydia  spp.,  Chlamydia -like organisms are thought to be causative in CAP. Pneumopathogenic potential has been described for  Parachlamydia  ( P. )  acanthamoebae , a well studied agent among the  Chlamydia -like organisms.   Objective : This study aimed to evaluate the pathogenicity of  Parachlamydia  ( P. )  acanthamoebae  as a potential agent of lower respiratory tract disease. A bovine model of induced lung infection was introduced for translational reasons.   Method : Intrabronchial inoculation with  P. acanthamoebae  was performed in healthy calves aged 2-3 months (n=30) using two different challenge doses: 10 8  and 10 10  inclusion-forming units (ifu) per animal. Controls received heat inactivated pathogen.   Results : While the challenge with 10 8  ifu of viable  Parachlamydia  resulted in a mild degree of clinical illness, the dose of 10 10  ifu induced a respiratory desease that became clinically apparent 1-2 days after challenge.  Parachlamydiae  were detected in neutrophils and alveolar macrophages within pulmonary lesions by immunohistochemistry. This was in accordance with molecularbiological findings as well as with re-isolation of  Parachlamydia . Clinical outcome, acute phase reactants, pathological findings and antigen load exhibited an initial dose-dependent effect of severity.   Conclusion : The bovine lung was shown to be susceptible for  P. acanthamoebae.  Recommending the challenge dose of 10 10  ifu, this large animal model is suitable to elucidate host-pathogen interactions.
Abstract 654: Targeting K-ras mutant cancer cells with a lupus anti-guanosine antibody
Authors: Melissa R. Young, Philip W. Noble, Richard H. Weisbart, James E. Hansen
Journal: Cancer Research (2014)

Abstract Aberrant G-protein signaling due to mutations in genes encoding the Ras family of small GTPases is associated with approximately 30% of human cancers, and K-ras is one of the most commonly mutated Ras proteins. Development of targeted therapies that are preferentially toxic to cancer cells harboring K-ras mutations is therefore an important goal in cancer research. We have identified an unusual cell-penetrating lupus autoantibody, 4H2, as a potential candidate for development as a targeted therapy for tumors with activating K-ras mutations. 4H2 is an anti-guanosine antibody that has previously been shown to penetrate living cells and inhibit cAMP formation. Taken together, the ability of 4H2 to bind guanosine (a component of GDP/GTP) and to inhibit cAMP formation suggests that 4H2 perturbs G-protein signaling. We therefore hypothesized that 4H2 would be selectively toxic to cancer cells with aberrant G-protein signaling due to activating K-ras mutations compared to cells without mutations in K-ras. To test this hypothesis, we evaluated the effects of 4H2 on a panel of isogenic pairs of cells with and without activating K-ras mutations, including Cal12T lung cancer cells (with and without a G12C activating K-ras mutation), NCI-H1975 lung cancer cells (with and without a G12D activating K-ras mutation), and SW48 colon cancer cells (with and without a G12A activating K-ras mutation). Immunofluorescence experiments confirmed that 4H2 penetrates into and localizes to the cytoplasm of cells with and without an activating K-ras mutation. In cell proliferation assays the matched pairs of cells were treated with 4H2 while growing as subconfluent monolayers, and 4H2 was observed to significantly inhibit the proliferation of the cells with activating K-ras mutations but not the cells without K-ras mutations. Next, colony formation assays confirmed that treatment with 4H2 was significantly more toxic to cells with activating K-ras mutations compared to cells without K-ras mutations. Mechanistically, Western blot analyses suggest a differential effect of 4H2 on the MAP kinase and Akt signaling pathways in K-ras mutant and wild type cells, consistent with the hypothesis that 4H2 interferes with G-protein associated intracellular signaling pathways. In summary, this work has demonstrated that 4H2 is an intriguing candidate for further study and development as a potential targeted therapy for tumors with activating mutations in K-ras. Citation Format: Melissa R. Young, Philip W. Noble, Richard H. Weisbart, James E. Hansen. Targeting K-ras mutant cancer cells with a lupus anti-guanosine antibody. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 654. doi:10.1158/1538-7445.AM2014-654
Peripheral muscle strength and exercise capacity in children with cystic fibrosis and non-cystic fibrosis
Authors: Baki Umut Tugay, Hulya Arikan, Ugur Özçelik, Nazan Tugay
Journal: European Respiratory Journal (2012)

Cystic fibrosis (CF) is a chronic disease associated with pulmonary involvement, malnutrition, increased respiratory muscle work and musculoskeletal manifestations. Bronchiectasis not caused by CF is often perceived to be rare in western societies, but remains an important cause of chronic suppurative lung disease in the developing world among children. Therefore the aim of this study is to document the differences in exercise response and the possible underlying mechanisms between CF and non-CF patient groups. 24 patients with non-CF bronchiectasis (mean age 13.2(3.4) years) and 24 patients with CF (mean age 11.6(3.3) years) participated in the study. Pulmonary function testing and 6 minute walk test (MWT) were performed and peripheral muscle strength was measured by a hand held digital manual muscle tester to selected muscles. There was no significant difference between the physical characteristics, pulmonary functions, peripheral muscle strength and the distance walked in the 6 MWT (p>0.05). Non-CF patient group reached higher heart rate and maximum heart rate percentage in the 6 MWT (p 0.05). Our data suggests that the major limitation to exercise seems to be related to nutritional factors in CF patients.
Usefulness of chest ultrasound to detect and monitor pneumonia in pregnancy
Authors: Riccardo Inchingolo, Andrea Smargiassi, Giuseppe Corbo, Salvatore Valente
Journal: European Respiratory Journal (2013)

Backgroud : Usefulness of ultrasound (US) in pregnancy is approved as low-risk diagnostic technique if compared to ionizing radiations. Chest US evaluation can be performed at patient bed-side and can help physicians to get the correct diagnoses. We tried to apply chest US evaluation in order to detect, diagnose and monitor pathologic processes of both peripheral lung parenchyma and pleural space in pregnant women.

Materials and methods : Pregnant women admitted to Obstetric Pathology Hospital Department for respiratory diseases were enrolled. Patients underwent chest US examination when there was a respiratory disease highly suggestive of pneumonia and/or pleural effusion (i.e. fever, dispnoea, leukocytosis, cough, chest pain) and chest X-ray (CXR) should have been obtained.

Both convex and linear probes were used. We identified 3 kinds of chest US patterns: lung consolidation (LC), pleural effusion (PE) and echographic interstitial syndrome (IS). When chest US pathologic signs were reported, one or more subsequent chest US examinations were performed in order to follow-up the patient until their complete resolution.

Results : 13 inpatients underwent 28 chest US evaluations. We identified: 6 LCs, 5 PEs and 3 ISs. 7 patients showed leukocytosis and 1 leukopenia. Total number of CXRs was 6 (8 females avoided X-rays exposure and 1 underwent 2 CXR evaluations on the advice of Gynecologist).

Chest US follow-up, during and after therapy, showed complete resolution of echographic patterns previously described.

Conclusions : chest US evaluation during pregnancy can be a usefull diagnostic tool to detect respiratory diseases and monitor them during therapy, avoiding eccessive X-rays exposure.
Horace Townshend Fleming Betty Hargreaves Cyril ("Cecil") Jeffrey Levy Diana Jennie Margaret Lister Kate Wilkins
Authors: R. Fleming, M. Hargreaves, C. Hargreaves, A. Thornton, D. Taylor, C. L. Green, P. L. Green, C. Carver
Journal: BMJ (1999)

He first came to Enniskillen as county surgeon and later director of the Erne Hospital.At one time he was in sole charge of medicine, surgery, obstetrics and gynaecology, and ear, nose and throat surgery, as well as x rays and dispensing.He converted rooms in the basement to form an outpatient department.He had many outside interests and was a member of the yacht club, golf club, and amateur dramatic society and was a keen fisherman and bridge player.
Unusual cause of pulmonary haemorrhage in adolescent
Authors: Natasa Savic, Predrag Minic, Milan Rodic
Journal: European Respiratory Journal (2013)

We present a case of 14-year old, previously healthy girl with recurrent cough and hemoptysis. Chest X-ray showed round right lower lobe infiltration, she received antibiotics, but this finding persisted.

![Figure][1] 



Laboratory markers of inflammation, tests for tuberculosis and sarcoidosis were negative. Initial flexible bronchoscopy did not detect anatomic abnormalities nor site of active pulmonary hemorrhage. Chest MRI ruled out arteriovenous malformation or pulmonary sequestration. Various antibodies: pANCA, cANCA, anti-MPO, anti-PR3, anti-dsDNA, ANA were negative. The last episode of pulmonary hemorrhage was profuse and repeated flexible bronchoscopy revealed the presence of foreign body very laterally in right lower lobe. It was successfully removed by wire basket and corresponded to wall barley grass (Hordeum murinum).

![Figure][1] 



She received antibiotics and corticosteroid treatment and is symptom free, with normal chest X-ray and finding on physical examination. Conclusion: Occult foreign body in respiratory tract should be suspected in all patients with repeated respiratory symptoms, no matter of age. Bronchoscopic examination should be performed sometimes several times before diagnosis is established.

 [1]: pending:yes
Confetti-like depigmentation: A potential sign of rapidly progressing vitiligo
Authors: Juan Jesús Sosa, Sharif D. Currimbhoy, Uzoamaka Ukoha, Samantha Sirignano, Ryan O'Leary, Travis Vandergriff, Linda S. Hynan, Amit G. Pandya
Journal: Journal of the American Academy of Dermatology (2015)
Pancreastatin receptor is coupled to a guanosine triphosphate-binding protein of the G<sub>g/11</sub>α family in rat liver membranes
Authors: José Santos-Álvarez, Carmen González-Yanes, Víctor Sánchez-Margalet
Journal: Hepatology (1998)

Pancreastatin (PST), a recently discovered regulatory peptide derived from chromogranin A, has been shown to have a glycogenolytic effect in the hepatocyte that is mediated by increasing intracellular calcium. Our previous studies on pancreastatin signaling suggested that PST receptor is coupled to some G proteins in the plasma membrane of the hepatocyte. The nature of this interaction was investigated using antisera against G(q/11)alpha by different approaches. Indirect evidence of a pertussis toxin (PT)-insensitive G protein of the family of G(q/11)alpha was obtained by measuring high-affinity guanosine triphosphatase (GTPase) activity in soluble rat liver membranes. PST increased GTPase activity in a dose-dependent manner. This effect was only slightly inhibited by PT pretreatment of the membranes, whereas anti-G(q/11)alpha antisera blocked most of the PST-stimulated GTPase activity. The selective association of the PST receptor with this G protein was further studied by the coelution in wheat germ agglutinin semipurification of the receptor and by immunoprecipitation of the G protein-PST receptor complexes using G-protein-specific antisera. A G protein of the family of G(q/11)alpha was found to be associated with the semipurified PST receptor. Moreover, anti-G(q/11)alpha antisera immunoprecipitated most PST-binding activity (95%), bringing down most of the specific G protein, whereas anti-G(il,2)alpha and -G(o,i3)alpha failed to immunoprecipitate the PST-binding activity. Finally, the coupling of the PST receptor with the effector phospholipase C was disrupted by blocking with G(q/11)alpha antisera, suggesting that a G protein of the family of G(q/11)alpha is a signal mediator from PST receptors to phospholipase C activation in rat liver membranes.
CT for occult cancer is unnecessary in people with unexpected venous thromboembolism, study finds
Authors: S. Mayor
Journal: BMJ (2015)

Computed tomography (CT) of the abdomen and pelvis to look for undiagnosed cancer in people with unprovoked venous thromboembolism is unnecessary, a Canadian study has found, after this screening approach detected a very low rate of occult cancers.1

Unprovoked venous thromboembolism can be an early sign of cancer, and previous studies have shown that as many as 10% of patients who have a blood clot with no apparent cause get a cancer diagnosis in the subsequent year. One …
Relevance of respiratory infections in preschool wheeze - A hospital based study
Authors: Katarina Stenberg Hammar, Gunilla Hedlin, Jon R. Konradsen, Björn Nordlund, Inger Kull, Christian G. Giske, Christophe Pedroletti, Cilla Söderhäll, Erik Melén
Journal: European Respiratory Journal (2013)

Objective : To clinically characterize preschool children with acute wheeze and examine the underlying microbial findings that might cause symptoms of bronchial obstruction.   Background:  Viral wheeze is very common in preschool children, 30-40% will still have wheeze at school age.   Methods:  100 preschool children, 6 months to 4 years old with on-going acute wheeze and 92 age-matched healthy controls without history of wheeze or known sensitization to airborne allergens were recruited. Parents answered questionnaires regarding background factors and triggers for childhood wheeze. Specific IgE to airborne and food allergens were analysed. The children with acute wheeze were tested for presence of virus and bacteria.   Results:  Significant differences between cases and controls (p  Moraxella catarrhalis  dominated (52%).   Conclusion:  Children with acute wheeze have had significantly more respiratory infections, including pneumonias, and attend daycare centers in significantly higher proportion than a healthy control group. Parental asthma and pollen allergy were confirmed as significant risk factors for wheeze. Both virus and bacteria were found together or alone, suggesting that they act as triggers of acute wheeze in preschool children independently.
How to investigate complaints
Authors: David M B Hall
Journal: BMJ (2008)

In his open letter to the president of the General Medical Council (GMC) about the case of David Southall, Wheatley refers to a previous inquiry conducted by “a panel far better qualified and more competent than your own on child protection issues.”1

I was responsible for setting up that panel. As president of the Royal College of Paediatrics and Child Health I was asked in 2000 to assist Southall’s employing trust in its investigation of complaints about his child protection work, by putting forward names of paediatricians who would …