tbuckley/cabot-search huggingface dataset:
Rapid and accurate identification of genomic species from the Acinetobacter baumannii (Ab) group by MALDI-TOF MS
Authors: P. Espinal, H. Seifert, L. Dijkshoorn, J. Vila, I. Roca
Journal: Clinical Microbiology and Infection (2011)

The closely related members of the Acinetobacter baumannii (Ab) group (A. baumannii, A. pittii and A. nosocomialis) are difficult to identify with phenotypic tests in diagnostic laboratories. Genotypic identification methods require special skills and most do not provide rapid results. The aim of this study was to investigate the ability of MALDI-TOF MS to identify members of the Ab group. Sixty epidemiologically unrelated Acinetobacter spp. isolates were investigated by MALDI-TOF MS: 18 A. baumannii, 17 A. pittii, 18 A. nosocomialis and seven additional isolates representing other Acinetobacter spp. All strains were verified by ARDRA, rRNA intergenic spacer (ITS), recA sequencing and bla(OXA-51) . MALDI-TOF MS correctly identified all the genomic strains but erroneously identified A. nosocomialis as A. baumannii because there was no reference strain within the Bruker database. Peak analysis of individual spectra from representative strains of each member of A. baumannii, A. pittii and A. nosocomialis suggested enough differences between their protein signatures to allow accurate identification using MALDI-TOF MS. Inclusion of specific signature profiles for A. nosocomialis within the Bruker database allowed the correct identification of this genomic species. MALDI-TOF MS spectra can be used as a fast, simple and reliable method to identify members of the Ab group. The rapid and accurate identification of clinically significant Acinetobacter strains will improve insight into their epidemiology and allow for targeted therapeutic and infection control measures against clinically important strains.
Studies on a Transplantable Mastocytoma in Mice. II. Electron Microscopic Observations&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: H. E. Christensen, O. H. Iversen, R. Rask-Nielsen
Journal: JNCI Journal of the National Cancer Institute (1963)

The ultrastructure of a highly differentiated, transplantable, mouse mast cell neoplasm, examined with the electron microscope after Vestopal-W embedding of three tumors from the first transfer generation, had the following characteristics: a well-developed Golgi region; numerous ribosomes, free or attached to membranes; a highly organized endoplasmic reticulum; a smooth membrane-like inner surface in the lacunae, which lodged the mast cell granules; mast cell granules located in the outer zone of the cytoplasm in most cells, but occasionally occupying the entire cell body and appearing as loose curls with all transitional stages to condensed, homogeneous material; long, slender protusions projecting from the cell surface. From previous and present investigations, it is suggested that there may be a direct connection from the interior of the mast cell through the channels of the endoplasmic reticulum to the lacunae, and from the lacunae during the release of the mast cell granules to the extracellular space. This system may reflect the synthesis of the tumor mast cell granules.—J Nat Cancer Inst 30: 763–781, 1963.
Fluoroquinolone-resistant E. coli in intestinal flora of patients undergoing transrectal ultrasound-guided prostate biopsy-should we reassess our practices for antibiotic prophylaxis?
Authors: D. Steensels, K. Slabbaert, L. De Wever, P. Vermeersch, H. Van Poppel, J. Verhaegen
Journal: Clinical Microbiology and Infection (2011)
Sodium thiophene carboxylate does not facilitate expectoration
Authors: E Streit, TC Medici
Journal: European Respiratory Journal (1991)

A randomised double-blind crossover study compared the clinical effectiveness of a 21-day treatment with 600 mg per day of sodium thiophene carboxylate and placebo in 33 patients with stable chronic bronchial disease. During the seven week trial, subjective symptoms and findings were recorded, pulmonary function tests performed and sputum physical characteristics determined. Side-effects were closely monitored. Both subjective assessment of overall clinical efficacy and statistical analysis of the above mentioned factors failed to show any significant advantage of sodium thiophene carboxylate to placebo. Sodium thiophene carboxylate appears to be an expectorant and mucoregulatory drug, lacking evidence of clinical effectiveness in the treatment of patients with stable chronic bronchitis.
A paper that changed my practice: A more helpful technique
Authors: A. Williams
Journal: BMJ (2000)

Urinary tract infection in young children is an easy diagnosis to miss not only because of its unusual mode of presentation but also because of the difficulty in the collection of a urine sample. It is reported that around 3-5% of girls and 1-2% of boys will have a symptomatic urinary tract infection in childhood. In children under 2 this may be due to a structural abnormality that may lead to permanent scarring and eventually to hypertension or renal failure.

Since Ahmad and colleagues …
Long-term results in a cohort of medullary thyroid cancer (MTC) patients (pts) in a phase I study of XL184 (BMS 907351), an oral inhibitor of MET, VEGFR2, and RET.
Authors: R. Kurzrock, E. E. Cohen, S. I. Sherman, D. G. Pfister, R. B. Cohen, D. Ball, D. S. Hong, C. S. Ng, R. Salgia, M. J. Ratain
Journal: Journal of Clinical Oncology (2010)

5502 Background: XL184 is an oral inhibitor of MET, VEGFR2, and RET that exhibits anti-angiogenic, antiproliferative, and anti-invasive effects in preclinical models and promising clinical activity in various tumor types in phase I and II trials. MET and RET have been implicated as key factors in the pathobiology of MTC. Methods: Pts with advanced malignancies were enrolled in a phase I dose escalation study of XL184. Primary objectives include safety and pharmacokinetics (PK) and maximum tolerated dose (MTD) determination. RECIST response was assessed on day 28 and every 8 weeks thereafter. Pharmacodynamics, tumor markers, and RET mutational status were analyzed. Adverse events (AEs) and PK results as of 12/2009 are reported. Genotyping and efficacy data are reported for the MTC subgroup (34 of whom are response- assessable). Results: 85 pts were enrolled in this phase I study; the MTD was 175 mg qd. The most frequently occurring possibly related grade 3/4 AEs were fatigue and palmar-plantar erythrodysesthesia (PPE; 10% each); increased lipase (9%); diarrhea (7%); increased amylase (5%); decreased weight and increased AST and ALT (3% each); hypertension and hypocalcemia (2% each). 37 of the 85 pts had a diagnosis of advanced MTC with a minimum follow up period of 17+ months (m). Twenty MTC pts received prior systemic therapy, 16 of whom had prior TKIs (including RET inhibitors). The median duration of response for pts with a cPR has not been reached. Onset of response in 5 pts was rapid with PR reported at the first radiographic evaluation. Ten pts had a confirmed PR (29%, 10/34) and 4 additional pts had at least 30% regression on one scan (total= 41%, 14/34). Fifteen pts (41%, 15/37) had a best response of SD ≥ 6 months. Responses have occurred or been maintained at doses from 75-175 mg. Most MTC pts had reductions in plasma calcitonin and CEA, although these did not correlate with response. Responses have been observed in MTC pts with and without RET mutations. Conclusions: XL184 has demonstrated antitumor activity at and below the MTD. In MTC pts with measurable disease, 29% had a cPR and 68% (25/37) had either cPR or prolonged SD ≥ 6 months. A randomized phase III study in MTC is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Exelixis Exelixis Bristol-Myers Squibb, Exelixis
The association among inflammation-related genes, fractional exhaled nitric oxide (FeNO), and symptom severity in adult asthma: A structural equation model (SEM)
Authors: Simone Accordini, Lucia Calciano, Cristina Bombieri, Giovanni Malerba, Francesca Belpinati, Marcello Ferrari, Anna Rita Lo Presti, Mario Olivieri, Pier Franco Pignatti, Roberto de Marco
Journal: European Respiratory Journal (2014)

Background. Airway inflammation is a key component of asthma that depends on the interplay of multiple genes. However, the association between health outcomes and genetic factors is usually evaluated by testing each candidate gene variant individually.  Aim. To simultaneously assess the association of symptom severity with tag-SNPs located in inflammation-related genes and the FeNO level.  Methods. In Verona (Italy), 327 asthmatics (aged 20-64) were identified from the general population in the GEIRD study (2008/2010). Individuals underwent a clinical interview, blood sampling for genotyping, and the measurement of FeNO (200 ml/s). SNPs in the CHI3L1, RAD50/IL4/IL5/IL13, IL33, and MS4A2 gene regions were genotyped by a custom GoldenGate Genotyping Assay. A symptom severity score (SSS) was computed by a multiple correspondence analysis on the basis of asthma-like symptoms, asthma attacks and hospitalization in the past year. The association of the SSS with SNPs and FeNO was assessed by a SEM. SNPs were summarised by a latent variable; atopy, gender, smoking habits and ICS use in the past year were considered as potential confounders.  Results. The SEM is described in figure 1:  Conclusions. This preliminary analysis suggests that inflammation-related genes could have a direct effect (not mediated by FeNO and atopy) on symptom severity in adult asthmatics.
The lung in a dish - A new tool to study interactions of inhaled (nano)materials with lung cells
Authors: Corinne Jud, Silvia Angeloni, Loretta Müller, Martha Liley, Alke Petri-Fink, Barbara Rothen-Rutishauser
Journal: European Respiratory Journal (2012)

The human lung is exposed to a huge number of nanosized materials with each breath. To study the interaction of those materials with the lung, biomimetic cell culture models are needed.  The human air-blood tissue barrier consisting of epithelial cells, the basal lamina and endothelial cells is less than 1μm thick. Conventional cell culture inserts have a thickness of ∼10μm which has been a major drawback to establish realistic models. Therefore, a novel ultrathin porous membrane with a thinness of 500nm was developed to refine an established human air-blood tissue barrier model consisting of epithelial cells (A549), monocyte-derived macrophages and dendritic cells by replacing the conventional inserts with the novel membranes but also complement it with endothelial cells (EA.hy926).  Epithelial cells seeded on the upper side of the membrane and endothelial cells on the lower side grow to confluence and form a tight bilayer. Immune fluorescence stainings revealed the typical characteristics of epithelial/endothelial cells and specific markers (von Willebrand factor and PECAM) were exclusively detected in the endothelial cell layer. Experiments with all four cell types have been performed and showed that all cell types can be cultured together as a quadruple model on the new ultrathin membrane.  Once fully established and characterized, this new system will offer an advanced 3D cell culture model of the human airway barrier and an excellent tool to study the effects of inhalable substances (e.g. nanomaterials) with a realistic lung model. This will significantly reduce the number of animals used to perform inhalation risk assessments and will offer a controlled system for different studies.
Suppression of erythro-megakaryocytopoiesis and the induction of reversible thrombocytopenia in mice transgenic for the thymidine kinase gene targeted by the platelet glycoprotein alpha IIb promoter.
Authors: D Tronik-Le Roux, V Roullot, A Schweitzer, R Berthier, G Marguerie
Journal: The Journal of Experimental Medicine (1995)

The mechanisms that regulate the commitment of a totipotent stem cell to the megakaryocytic lineage are largely unknown. Using a molecular approach to the study of megakaryocytopoiesis and platelet production, mice in which thrombocytopoiesis could be controlled were produced by targeting the expression of the herpes simplex virus thymidine kinase toxigene to megakaryocytes using the regulatory region of the gene encoding the alpha subunit of the platelet integrin alpha IIb beta 3. The programmed eradication of the megakaryocytic lineage was induced by treating transgenic mice bearing the hybrid construct (alpha IIbtk) with the antiherpetic drug ganciclovir (GCV). After 10 d of treatment, the platelet number was reduced by &amp;gt; 94.6%. After discontinuing GCV, the bone marrow was repopulated with megakaryocytes and the platelet count was restored within 7 d. Prolonged GCV treatment induced erythropenia in the transgenic mice. Assays of myeloid progenitor cells in vitro demonstrated that the transgene was expressed in early erythro-megakaryocytic progenitor cells. The reversibility and facility of this system provides a powerful model to determine both the critical events in megakaryocytic and erythroid lineage development and for evaluating the precise role that platelets play in the pathogenesis of a number of vascular occlusive disorders.
Bacterial translocation and cardiovascular complications of cirrhosis.
Authors: U Thalheimer, A K Burroughs
Journal: Gut (2008)

We read with interest the recent review on cardiovascular complications of cirrhosis by Moller and Henriksen ( Gut 2008; 57 :268).

We would like to add to their overview what we believe to be one of the major contributors to cardiovascular derangement in cirrhosis—that is, bacterial translocation,1 as this was not mentioned by them.

Bacterial translocation leads to the presence of bacteria, endotoxins and cytokines in the systemic circulation, thus enhancing nitric oxide production.2 …
The Eczema Priority Setting Partnership: a collaboration between patients, carers, clinicians and researchers to identify and prioritize important research questions for the treatment of eczema
Authors: J.M. Batchelor, M.J. Ridd, T. Clarke, A. Ahmed, M. Cox, S. Crowe, M. Howard, S. Lawton, M. McPhee, A. Rani, J.C. Ravenscroft, A. Roberts, K.S. Thomas
Journal: British Journal of Dermatology (2012)

Background Eczema is a common condition, yet there are uncertainties regarding many frequently used treatments. Knowing which of these uncertainties matter to patients and clinicians is important, because they are likely to have different priorities from those of researchers and funders. Objectives To identify the uncertainties in eczema treatment that are important to patients who have eczema, their carers and the healthcare professionals (HCPs) who treat them. Methods An eczema Priority Setting Partnership was established, including patients, HCPs and researchers. Eczema treatment uncertainties were gathered from patients and clinicians, and then prioritized in a transparent process, using a methodology advocated by the James Lind Alliance. Results In the consultation stage 493 participants (including 341 patients/carers) made 1070 submissions, of which 718 were uncertainties relating to the treatment of eczema. Treatment uncertainties with more than one submission were grouped into 52 'indicative uncertainties', which were then ranked by 514 participants (including 399 patients/carers). The top 14 treatment uncertainties were prioritized for research. The first four were common to patients/carers and HCPs (shared uncertainties): (i) the best and safest way of using topical steroids (including frequency of application, potency, length of time, alternation with other topical treatments and age limits); (ii) the long‐term safety of topical steroids; (iii) the role of food allergy tests; and (iv) the most effective and safe emollients in treating eczema. The remaining 10 of the top 14 uncertainties comprised the next five highest ranked uncertainties for patients and the next five highest ranked uncertainties for HCPs. At a workshop involving 40 participants (patients, HCPs and researchers), shared uncertainties were formulated into possible research questions. Conclusions The top 14 treatment uncertainties around the treatment of eczema provide guidance for researchers and funding bodies to ensure that future research answers questions that are important to both clinicians and patients.
Ambulatory antibiotic prescribing for acute bronchitis and cough and hospital admissions for respiratory infections: time trends analysis
Authors: Arch G Mainous, Sonia Saxena, William J Hueston, Charles J Everett, Azeem Majeed
Journal: Journal of the Royal Society of Medicine (2006)

ObjectivesTo examine the relationship between ambulatory antibiotic prescribing for acute bronchitis and cough with hospital admissions for respiratory infections in the USA between 1996 and 2003. DesignAnalysis of data on antibiotic prescribing for episodes of acute bronchitis/cough illness in ambulatory care and hospitalization for respiratory infections for adults between 1996 and 2003 in the USA. SettingUSA: ambulatory prescribing behaviour was derived from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey while hospitalizations in acute care hospitals were assessed in the National Hospital Discharge Survey. Main outcome measuresProportion of visits for acute bronchitis/cough receiving a prescription for antibiotics and hospitalization for respiratory infections. ResultsAmbulatory antibiotic prescribing practices for acute bronchitis/cough and hospitalizations for respiratory infections exhibited non-linear patterns over the 8 year period. However, antibiotic prescribing practices for acute bronchitis/cough and hospitalizations for respiratory infections had a weak/moderate negative association. For three of the seven yearly changes in prescribing and hospitalizations as one increased the other decreased (P <0.01). ConclusionsAmbulatory antibiotic prescribing for respiratory tract infections was inversely associated with hospital admissions for respiratory tract infections.
Accretion of Biopsy Specimens of Vaginal Adenosis From Patients Exposed in Utero to Diethylstilbestrol, When Transplanted to Athymic Nude Mice2
Authors: Marek M. Pienkowski, Laurene C. Mann, Edward F. Rosloniec, Clifford W. Welsch
Journal: JNCI Journal of the National Cancer Institute (1979)

Vaginal adenosis biopsy specimens from 10 patients exposed in utero to diethylstilbestrol were transplanted for 30 days into athymic (nude) mice. Almost all grafts were recovered, and they had morphologic features closely resembling those of the original biopsy specimens, i.e., cystic, complex, and simple occult glands covered mainly with an endocervical type of epithelium showing extensive squamous metaplasia. Autoradiographic analysis of these grafts after pulse administration of [3H]thymidine into the mice revealed extensive labeling of epithelial cells. These results imply that female athymic (nude) mice are compatible hosts for accretion of the human adenosis.
Cardiovascular medications and mortality in patients hospitalised with acute exacerbations of COPD
Authors: John Steer, Carlos Echeverria, John Gibson, Stephen Bourke
Journal: European Respiratory Journal (2013)

Background 

It has been suggested that patients with COPD treated with statins, beta-blockers or ACE-inhibitors have a reduced mortality risk. We studied the relationship between cardiovascular drugs and in-hospital mortality in patients hospitalised with acute exacerbations of COPD (AECOPD).

Methods 

Clinical data, comorbidities, maintenance medication and survival data were collected on consecutive patients hospitalised with AECOPD. The cohort was split based on the presence of vascular disease (ischaemic heart disease, cerebrovascular disease or peripheral vascular disease).

Results 

920 patients were recruited, most: were elderly (mean (SD) age 73.1 (10.0) years); were female (53.9%) and had severe airflow obstruction (mean FEV1 43.6 (17.2) % pred). 383 (41.6%) had prior vascular disease. 96 (10.4%) died in-hospital: mortality was slightly higher in those with vascular disease (11.7% v. 9.5%, p=0.28).

In the total population, mortality was not related to cardiovascular medications. In those with vascular disease, statin therapy was associated with a lower mortality risk (p=0.011).

View this table:

In-hospital mortality and cardiovascular medications





Conclusions 

In patients with vascular disease, statin therapy was associated with a lower in-hospital mortality rate. In unselected patients hospitalised with AECOPD, cardiovascular medications were not related to outcome.
Is parenteral adrenaline used unnecessarily in the treatment of asthma patients in the pre-hospital setting?
Authors: Craig Mortimer
Journal: European Respiratory Journal (2014)

Introduction:  Adrenaline has been removed from the asthma guidelines for both the National Institute for Health and Clinical Excellence and Scottish Intercollegiate Guidelines Network. However the Joint Royal Colleges Ambulance Liaison Committee has retained it within their UK pre-hospital guidelines. Has their reluctance to remove adrenaline resulted in it being used excessively by ambulance crews?   Aims:  To assess whether adrenaline is overused in the treatment of asthma within the pre-hospital setting compared to other drug options.   Method:  All asthma related Patient Clinical Records (PCR) over a 12 month period were collated from within one UK ambulance service. Those PCRs where patients received adrenaline as part of their treatment regime were isolated and the data provided was then reviewed with a specific focus upon the presenting condition and the corresponding drug therapy provided.   Results:  Over this time frame 3,217 asthma related calls were attended and only 36 (1.1%) resulted in the patient receiving adrenaline as part of their treatment regime. Of these 36 patients; 1 (2.8%) received adrenaline as the first line drug; 20 (55.5%) received it as the second line drug; 12 (33.3%) received it as the third line drug and 3 (8.3%) received it as the fourth line drug. This group consisted of 17 (47.2%) patients with signs and symptoms (S&S) of an Acute Severe attack and 19 (52.8%) with S&S of a Life Threatening attack.   Conclusion:  The results show that despite being freely available, parenteral adrenaline has been solely administered by ambulance clinicians to asthma patients that are severely compromised and then only as part of a stepwise approach.