tbuckley/cabot-search huggingface dataset:
Empirical therapy for nonhospitalized patients with community-acquired pneumonia. Study Group of General Practitioners
Authors: H Laurichesse, F Robin, L Gerbaud, P Pochet, F Gourdon, J Beytout, M Rey
Journal: European Respiratory Journal (1998)

A prospective survey involving a group of 95 general practitioners (GPs) in France was conducted to describe antibiotic therapy prescribed for out-patients with community-acquired pneumonia (CAP). A total of 173 cases of CAP, defined by the association of fever and pulmonary focal crackles and/or radiological changes consistent with a pulmonary infection, were reported between February 1993 and March 1994: 84 males and 89 females (mean age: 48 yrs) of whom 45% had no underlying disease. Nineteen (11%) were immediately hospitalized and the remaining 154 out-patients were treated without microbiological investigation. First-line antibiotic therapy was amoxicillin or amoxicillin-clavulanic acid combination (57%), a first or second generation cephalosporin (12%), ceftriaxone (8%), oral broad-spectrum cephalosporin (3%), a macrolide (16%), a tetracycline (1%) and a fluoroquinolone (2%). A total of 120 (78%) patients recovered with no change in treatment and 34 (22%) patients failed to improve: 18 were hospitalized and 16 had a second-line therapy, mainly a macrolide or a quinolone. Five patients died at hospital. The overall mortality was 3%, and 14% in hospitalized patients. Empirical therapy using a betalactam to target a presumed pneumococcal infection, in agreement with European guidelines, is appropriate for out-patients with mild lobar community-acquired pneumonia.
Maximized Reduction of Primary Breast Tumor Size Using Preoperative Chemotherapy With Doxorubicin and Docetaxel
Authors: Gunter von Minckwitz, Serban Dan Costa, Wolfgang Eiermann, Jens-Uwe Blohmer, Augustinos Harjanto Tulusan, Christian Jackisch, Manfred Kaufmann
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To assess the toxicity and efficacy of preoperative chemotherapy with doxorubicin and docetaxel in patients with primary operable breast cancer. PATIENTS AND METHODS: Forty-two patients with histologically confirmed primary breast cancer tumors of at least 2 cm in diameter received doxorubicin (50 mg/m 2 intravenously [IV] over 15 minutes) and docetaxel (75 mg/m 2 IV over 1 hour) every 14 (24 patients) or 21 (18 patients) days for four cycles. RESULTS: The median size of the primary tumor decreased significantly, from 4 cm (range, 2 to 10 cm) to 2 cm (range, 0 to 5 cm) on physical examination and from 3.4 cm (range, 1 to 8 cm) to 1.8 cm (range, 0 to 4 cm) on sonography (P &lt; .001). The overall response rate as assessed by physical examination was 93%, and complete remission of the primary tumor occurred in 33% of patients. The remission rate as assessed by sonographic measurement was 67%. Two patients (5%) had histologically confirmed complete responses. Sonography was more reliable than palpation in predicting histologically determined response. No grade 4 toxicity was noted, and grade 3 toxicity was reported with alopecia (95%), lethargy (17%), loss of appetite (10%), stomatitis (7%), leukopenia (5%), skin desquamation (5%), infection (5%), motor neuropathy (2%), and nausea (2%). The 3-week schedule was associated with less toxicity than the 2-week schedule. CONCLUSION: Preoperative combination chemotherapy with doxorubicin and docetaxel is highly effective and feasible in primary operable breast cancer.
Effects of frusemide on human airway epithelium
Authors: AM Wood, AT Dinh Xuan, TW Higenbottam, A Lockhart
Journal: European Respiratory Journal (1990)

<h3>Introduction</h3> Opioid overdoses claim tens of thousands of lives every year. Many of these deaths might be prevented if overdose-reversal medications such as naloxone are administered in a timely manner. Drones may help overcome barriers to timely arrival on scene for opioid overdoses. This study analyses the time required for a drone carrying naloxone to traverse various distances, simulating the response time for a drone to the scene of an opioid overdose. For comparison, we used the time required for ambulances to traverse similar distances while responding to the scene of actual or suspected opioid overdoses. <h3>Methods</h3> Fifty flight trials, using a modified Dà-Jiāng Innovations (DJI) ‘Inspire 2’ drone, were conducted across seven distances, and the travel time for the drone was then compared with historical response time data from 200 actual or suspected opioid overdose cases that occurred within Detroit, Michigan. <h3>Results</h3> We determined with 95% certainty that drone arrival times were discernibly quicker than ambulance arrival times at all distances where sufficient data were available to perform statistical comparisons including 0.5 km, 1.0 km, 1.5 km, 2.0 km and 3.0 km. <h3>Conclusion</h3> We have shown that a drone is capable of travelling several ranges of straight-line (ie, ‘as the crow flies’) distance faster than an ambulance. Further exploration into the use of drones to deliver life-saving therapies in urban and rural settings is warranted. Head-to-head prospective trials that consider the practical challenges of medical drone delivery are needed to better understand the viability of incorporating this technology into existing emergency response infrastructure.
Abstract #2307: Expression of hemopexin domain of MMP-9 sensitizes resistant glioblastoma cells to radiation therapy
Authors: Ravesanker Ezhilarasan, Indra Mohanam, Jasti Rao, Sanjeeva Mohanam
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

MMP-9 is a multidomain protease, which consists of a prodomain, a catalytic domain with three fibronectin-like type II modules and a C-terminal hemopexin-like domain (MMP-9-PEX). These domains play distinct roles in terms of proteolytic activity, substrate binding and interaction with the tissue inhibitors of matrix metalloproteinases. Our previous study has shown that endogenous expression of MMP-9-PEX significantly decreased the invasive capacity and angiogenic potential of human glioblastoma cells. Resistance of glioblastoma multiforme to radiotherapy poses a major clinical challenge. In this study we investigated the effects of adenovirus-mediated expression of MMP-9-PEX expression on radioresistant glioblastoma cells. We treated human glioblastoma cells with low dose fractionated irradiation and established radioresistant sublines. Parental and radioresistant glioblastoma cells were infected with the different MOIs of the control and MMP-9-PEX expressing adenoviral particles and were evaluated for cell survival, induction of apoptosis, radiosensitivity, invasion and angiogenic capabilities. Our data show that MMP-9-PEX significantly increases the radio- and chemosensitivity of resistant glioblastoma cells. Furthermore, MMP-9-PEX transduction enhanced the induction of apoptosis and it also downregulated the invasive and angiogenic capabilities in radioresistant glioblastoma cells. Taken together, our results suggest that adenovirus-mediated MMP-9-PEX expression significantly sensitizes human glioblastoma cells to ionizing radiation and it supports the use of MMP-9-PEX for targeting radioresistant cancers.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2307.
The Elephant in the Delivery Room
Authors: Neil Marlow
Journal: New England Journal of Medicine (2015)

In 2000, the Journal published the first in a series of articles documenting rates of survival and neurodevelopmental impairment among children born at extremely low gestational ages (from 22 to 25 weeks of gestation) in the British Isles.1 Survival rates were low, and approximately half the children who survived had impairments at follow-up in the third year after birth. This article received responses that ranged from "You are obviously no good at looking after babies born at low gestations" to "Why even provide care for such babies?" A series of articles followed that compared these results with additional, competing data . . .
Bedside Assessment of Quadriceps Muscle by Ultrasound after Admission for Acute Exacerbations of Chronic Respiratory Disease
Authors: Neil J. Greening, Theresa C. Harvey-Dunstan, Emma J. Chaplin, Emma E. Vincent, Mike D. Morgan, Sally J. Singh, Michael C. Steiner
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Hospitalization represents a major event for the patient with chronic respiratory disease. There is a high risk of readmission, which over the longer term may be related more closely to the underlying condition of the patient, such as skeletal muscle dysfunction.Objectives: We assessed the risk of hospital readmission at 1 year, including measures of lower limb muscle as part of a larger clinical trial.Methods: Patients hospitalized with an exacerbation of chronic respiratory disease underwent measures of muscle function including quadriceps ultrasound. Independent factors influencing time to hospital readmission or death were identified. Patients were classified into four quartiles based on quadriceps size and compared.Measurements and Main Results: One hundred and ninety-one patients (mean age, 71.6 [SD, 9.1] yr) were recruited. One hundred and thirty (68%) were either readmitted or died. Factors associated with readmission or death were age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01–1.08; P = 0.015), Medical Research Council (MRC) dyspnea grade (OR, 4.57; 95% CI, 2.62–7.95; P < 0.001), home oxygen use (OR, 12.4; 95% CI, 4.53–33.77; P < 0.001), quadriceps (rectus femoris) cross-sectional area (Qcsa) (OR, 0.34; 95% CI, 0.17–0.65; P = 0.001), and hospitalization in the previous year (OR, 4.82; 95% CI, 2.42–9.58; P < 0.001). In the multivariate analyses, home oxygen use (OR, 4.80; 95% CI, 1.68–13.69; P = 0.003), MRC dyspnea grade (OR, 2.57; 95% CI, 1.44–4.59; P = 0.001), Qcsa (OR, 0.46; 95% CI, 0.22–0.95; P = 0.035), and previous hospitalization (OR, 3.04; 95% CI, 1.47–6.29; P = 0.003) were independently associated with readmission or death. Patients with the smallest muscle spent more days in hospital than those with largest muscle (28.1 [SD, 33.9] vs. 12.2 [SD, 23.5] d; P = 0.007).Conclusions: Smaller quadriceps muscle size, as measured by ultrasound in the acute care setting, is an independent risk factor for unscheduled readmission or death, which may have value both in clinical practice and for risk stratification.
<i>Helicobacter pylori</i> strain genotyping based on the amplification and sequencing of cagA gene
Authors: Daniella Garcia, Maria del Pilar Delgado, Andres Quiroga, Maria Mercedes Bravo, Carlos A. Jaramillo
Journal: Clinical Cancer Research (2010)

Abstract Relevance: H. pylori presence has been described as a high risk factor of suffering gastric cancer, which is the fourth most common cancer in Colombia. Some studies [1, 2]; point out that when a genotypic characterization of different strains of this microorganism is carried out, more than one genotype can be found in the same patient can be found. Purpose: To characterize different H.pylori cagA genotypes that occur in the same patient sample (biopsy) applying molecular and bioinformatic techniques. Methods: cagA positive strains (n=35) from Instituto Nacional de Cancerología (Bogotá-Colombia), bank s samples were included as study material. Tissue DNA was extracted and used to amplify the 3’ region of the cagA gene by PCR [3]. The NTC11637 H. pylori strain was included as a positive control. PCR products were visualized in 2% agarose gels and the amplified fragments were purified using a commercial kit. As a final stage, a precipitation based on ethanol and EDTA was done and reaction products were sequenced. The obtained sequences were edited and submitted to a bioinformatic analysis using AASA, a program designed to characterize the EPIYA phosphorylation motifs localized in the C-terminal of the CagA protein by Rothstain, Yañez and Vivas (Los Andes University Thesis, 2008). Results: The molecular and bioinformatic approach described allowed strain characterization. The applied strategy leads to verify the presence of the A, B and C EPIYA motifs in different combinations. ABC group was the most frequent motif found (48%). These results match those of previous reports in Colombia, nevertheless it is important to remark that amplicons with different molecular sizes can have the same EPIYA motif and that amplicons with similar sizes can have different EPIYA motifs. Conclusions: The current strategy demonstrated to be useful in the identification and posterior characterization of more than one genotype of the different H. pylori strains present in the same biopsy sample. This molecular and bioinformatics approach combined with other techniques seems to be a good alternative to establish if an infection by H. pylori is the result of a coinfection or a microevolution process. References: 1. Aras, R.A., et al., Natural variation in populations of persistently colonizing bacteria affect human host cell phenotype. The Journal of infectious diseases, 2003. 188(4): p. 486-496. 2. Panayotopoulou, E., et al., Strategy to characterize the number and type of repeating EPIYA phosphorylation motifs in the carboxyl terminus of CagA protein in Helicobacter pylori clinical isolates?†. Journal of Clinical Microbiology, 2007. 45(2): p. 488-495. 3. Yamaoka, Y., et al., Relationship between the cagA 3'repeat region of Helicobacter pylori, gastric histology, and susceptibility to low pH. Gastroenterology, 1999. 117(2): p. 342-349.
Late-breaking abstract: Inhibition of Pim1 kinase augments the anti-viral response to rhinovirus infection
Authors: Maaike de Vries, Nicole Bedke, Natalie P. Smithers, Peter H. Howarth, Martijn C. Nawijn, Donna E. Davies
Journal: European Respiratory Journal (2014)

Asthma is a chronic inflammatory disease characterized by reversible airflow obstruction and bronchial hyperreactivity. Asthmatic patients frequently suffer from exacerbations, mainly triggered by viral infections, and therapeutic options are limited. The anti-viral response in asthmatic patients is compromised and factors augmenting this response could offer new therapeutic approaches. Here, we hypothesized that Pim1 kinase, known to stabilize SOCS-proteins that interfere with interferon signalling, could be such a new therapeutic target.  Air-liquid interface (ALI) cultures of primary bronchial epithelial cells (PBEC) were exposed to rhinovirus (RV16) without or with pharmacological inhibition of Pim1 kinase. Viral replication and viral load were measured by qPCR and HeLa cell titration assay. Anti-viral responses were measured by analysing IFN-β, IL-29, IP-10 and RANTES expression. Protein levels of SOCS-3 and p-STAT1 were determined by Western Blotting.  Inhibition of Pim1 kinase significantly reduced viral replication in ALI cultures of healthy volunteers, which was accompanied by an increase in anti-viral responses 12 hours after RV16 infection. Although no difference in SOCS-3 levels were detectable, STAT1 phosphorylation was higher in RV16-infected PBECs when Pim1 kinase activity was inhibited. A comparable reduction in viral infection and increase in anti-viral responses was observed in ALI cultures of severe asthmatics.  In conclusion, our data suggest that Pim1 kinase facilitates viral replication by suppressing anti-viral signalling. The therapeutic potential of Pim1 kinase inhibition for treatment of viral-induced asthma exacerbations should be further explored.
Anti-inflammatory effects of targeted lung denervation in patients with COPD
Authors: Loes E.M. Kistemaker, Dirk-Jan Slebos, Herman Meurs, Huib A.M. Kerstjens, Reinoud Gosens
Journal: European Respiratory Journal (2015)

Acetylcholine is the primary parasympathetic neurotransmitter in the airways and induces bronchoconstriction via binding with M3 receptors. Cholinergic tone is increased in patients with chronic obstructive pulmonary disease (COPD) and this is the major reversible component of airflow obstruction in the disease [1]. Accordingly, treatment with anticholinergics is an effective bronchodilator therapy for patients with COPD [2]. Recent evidence from animal models of COPD revealed that acetylcholine also promotes airway inflammation and remodelling, which can be inhibited by anticholinergic intervention [3]. Such an anti-inflammatory effect of anticholinergic intervention could be clinically relevant. It has not been previously demonstrated in patients with COPD. Targeted lung denervation attenuates airway inflammation in patients with COPD <http://ow.ly/QzLbD>
Abstract P058: Impact of Comorbid Hypertension and Obesity on Glycemic Control in Adults with Type 2 Diabetes Mellitus from a National Representative US Population
Authors: Shih-Yin Chen, Chien-Chia Chuang, Sophia Wu, Nicole Quon
Journal: Circulation (2013)

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a concerning epidemic, and sub-optimal glycemic control could lead to higher risk of complications and needs for additional care. Hypertension and obesity are common comorbid conditions, yet their impact on glycemic control has not been quantified. We hypothesize that comorbid hypertension and/or obesity are associated with a higher likelihood of uncontrolled glycemic level. METHODS: Data from a nationally representative sample of US population participating in the National Health and Nutrition Examination Survey (NHANES) 2003-2010 were analyzed in a cross-sectional retrospective observational study. Adults aged 20 years or older with self-reported diabetes and anti-diabetes medication use were included. Pregnant women were excluded. T2DM was defined by excluding diabetes patients who were diagnosed before age 30 and took only insulin. Uncontrolled hypertension was defined as blood pressure of ≥130 mmHg (systolic) or ≥80 mmHg (diastolic) based on American Diabetes Association’s guidance for hypertension in diabetes patients. Obesity was determined if body mass index ≥30 kg/m 2 . Uncontrolled glycemic level was defined as HbA1c ≥7%. We estimated the prevalence of uncontrolled hypertension and obesity among T2DM patients. Rates of uncontrolled glycemic level were reported and compared by uncontrolled hypertension and/or obesity status using Chi-square tests. Population weights were applied to account for multi-stage sampling design to produce nationally representative estimates. RESULTS: After applying the population weights to the 2,203 respondents with T2DM, findings from these respondents were extrapolated to an estimated 15.4 million T2DM patients in the US (prevalence of T2DM=7.4%), of which 61.1% were obese. Among US T2DM patients, the prevalence of uncontrolled hypertension was 52.6%. Among US T2DM patients, the prevalence of patients who had uncontrolled hypertension and who were obese was 31.2%. No statistically significant differences were found in uncontrolled glycemic level rates between those with and without uncontrolled hypertension (44.0% vs. 41.0%; p=0.31). Obese patients had a statistically significant higher rate of uncontrolled glycemic level than non-obese (44.5% vs. 37.9%; p=0.03). T2DM patients with comorbid uncontrolled hypertension and obesity had a statistically significant higher rate of uncontrolled glycemic level than the rest of the T2DM patients (47.1% vs. 40.0%; p=0.02). CONCLUSIONS: Prevalence of uncontrolled hypertension and obesity was high in US adults with T2DM. Obese patients, especially those who had uncontrolled blood pressure, had sub-optimal glycemic control. Interventions targeting these patients should be considered.
A Theory of Postoperative Fatigue
Authors: Peter Salmon, George M Hall
Journal: Journal of the Royal Society of Medicine (1997)

The concept of fatigue has entered medicine from other disciplines in which the term refers to weakening of a material by demands put upon it. Its application to the behavioural and subjective changes that characterize postoperative convalescence has led to the assumption that these changes reflect the physiological and metabolic consequences of surgery. Because evidence does not support this view, we outline a new theory in which postoperative fatigue is the product of physiological, psychological and cultural factors. This theory leads to novel predictions that can be tested in future clinical research. Of particular interest will be the evaluation of systematic attempts to change patient and staff expectations about postoperative convalescence.
Simple aspiration versus intercostal tube drainage for spontaneous pneumothorax in patients with normal lungs
Authors: J Harvey, R J Prescott
Journal: BMJ (1994)

patients starting second line drug treatment who require faster correction of their anaemia than would be achieved by the modifying effect on the disease of such drugs.We thank Cilag for providing the human recombinant erythropoietin and matching placebo; metrologists Anne Thomson (Glasgow), Frances McEvoy (Belfast), and Gwynneth Clarke (Eastbourne); Dorothy McKnight for help with computing; and Professor R D Sturrock and Drs A Zoma and Max Field for allowing us to include their patients in the study.
Learning Disabilities: An Overview
Authors: LLOYD J. THOMPSON
Journal: American Journal of Psychiatry (1973)

The expression learning disabilities is widely used and easily understood, but it may be applied to various handicaps. The author discusses the details of one particular handicap—reading disability—with implications that apply to the whole group in general. He emphasizes the concept that the fundamental basis of specific reading disability or dyslexia is usually found in inherent maturational lags rather than in   or environmental influences. Although developmental lags do produce   the author states the objections to the use of such terms as brain damage and minimal  dysfunction, which connote  pathology. The concept of developmental lags is more accurate and more constructive.