tbuckley/cabot-search huggingface dataset:
Detection and treatment of early asthma
Authors: T. Metso, K. Kilpiö, F. Björkstén, K. Kiviranta, T. Haahtela
Journal: Allergy (2000)

Background: We sought answers to two questions: 1) how can mild, early asthma best be detected? 2) how should it be treated and the treatment effect monitored? Methods: Eighty adult patients with early, mostly mild asthma and 30 control subjects were examined by lung‐function and biochemical tests. Patients were randomly assigned to two treatment groups. One group was treated with an inhaled steroid (budesonide) for 6 weeks, and the other first with an inhaled β 2 ‐agonist (terbutaline) for 6 weeks and then with an inhaled steroid for 2 weeks. Results: Treatment with budesonide was effective: symptom scores, PEF, blood eosinophils, and sputum ECP values all improved. Terbutaline was ineffective by these criteria. For the detection of early asthma and for the following treatment effects, sputum and serum ECP assays are useful supplements to lung‐function tests. Conclusions: Treatment of early, mild asthma with an inhaled steroid is effective and worthwhile. Detection of the disease remains a problem, as both lung‐function and biochemical tests have low sensitivities.
Estimation of Percentage of Ethyl Alcohol in the Blood
Authors: H. K. V. Soltau
Journal: BMJ (1936)

104 E~flt('L~~LC~)L N~T~E it13WOD -' ICAL 9. Whilst, of course, it is too early to make any definite claims for neocryl in the therapy of syphilis and trypanosomiasis, we consider that we have produced sufficient evidence to show that the drug is of definite value in the therapy of these diseases, and that a more extensive trial is warranted.
Changes in PgR and Ki-67 in residual tumour and outcome of breast cancer patients treated with neoadjuvant chemotherapy
Authors: E. Montagna, V. Bagnardi, G. Viale, N. Rotmensz, A. Sporchia, G. Cancello, A. Balduzzi, V. Galimberti, P. Veronesi, A. Luini, M.G. Mastropasqua, C. Casadio, C. Sangalli, A. Goldhirsch, M. Colleoni
Journal: Annals of Oncology (2014)
High-resolution computed tomography and pulmonary function in children with common variable immunodeficiency
Authors: L. van Zeggeren, A.A.J.M. van de Ven, S.W.J. Terheggen-Lagro, O.M. Mets, F.J. Beek, J.M. van Montfrans, P.A. de Jong
Journal: European Respiratory Journal (2011)

High-resolution computed tomography (HRCT) may be useful to monitor lung disease in children with common variable immunodeficiency disorder (CVID). We evaluated interobserver agreement and correlation with pulmonary function tests (PFTs) for automated quantification and visual scoring of air trapping and airway wall thickening on HRCT in paediatric CVID patients. In a cohort of 51 children with CVID, HRCT was analysed visually and automated for presence of air trapping and airway wall thickening. PFTs were expressed as % predicted. Disease duration, physician-diagnosed pneumonias and antibiotic prophylaxis were recorded. Interobserver agreement for automated airway wall thickening was good with an intra-class correlation coefficient of 0.88, compared with 0.51 for visual scoring. Presence of air trapping on HRCT correlated significantly with PFTs and disease duration, but was not associated with previous pneumonias. Airway wall thickening did not correlate significantly with PFTs or disease duration and was not associated with previous pneumonias or prophylactic antibiotic use. In children with CVID disorders, HRCT air trapping measurements are significantly correlated with PFTs and disease duration. Quantitative air trapping is a feasible and promising technique for small airway disease quantification that may be applied to monitor (silent) disease progression in CVID.
Upper abdominal surgery: does a lung function test exist to predict early severe postoperative respiratory complications?
Authors: G Barisione, S Rovida, GM Gazzaniga, L Fontana
Journal: European Respiratory Journal (1997)

We evaluated the capacity to predict severe respiratory complications (SRCs) following upper abdominal surgery (UAS) by using the results of a respiratory questionnaire and preoperative pulmonary function tests. Lung volumes, flows and transfer factor of the lung for carbon monoxide (TL,CO,sb) were assessed in 361 consecutive adult patients (248 males and 113 females). SRCs were diagnosed 24 h after UAS by clinical examination and chest radiography. Univariate and stepwise multiple logistic regression analyses were performed to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of each single input variable, and to determine which indices best predicted outcome. These patients had a 1% mortality rate and 14% incidence of SRCs, with a male:female ratio of 0.86. The best predictors for SRCs by multiple analysis were: preoperative current hypersecretion of mucus (OR=133; p<0.0001); an increase in residual volume (RV) (OR=3.11; p=0.01); and, to a lesser extent, low percentage of predicted values both of forced expiratory volume in one second (FEV1 % pred) and TL,CO,sb. The algorithm thus obtained (logit theta) was extremely sensitive (84%), specific (99%), and accurate (95%) for preoperative prediction of SRCs. We have found that preoperative current hypersecretion of mucus and pulmonary hyperinflation, and to a lesser extent percentage predicted values both of forced expiratory volume in one second and transfer factor of the lung for carbon monoxide, have a significant predictive capacity for severe respiratory complications following upper abdominal surgery.
Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial
Authors: Sanjit S Jolly, Salim Yusuf, John Cairns, Kari Niemelä, Denis Xavier, Petr Widimsky, Andrzej Budaj, Matti Niemelä, Vicent Valentin, Basil S Lewis, Alvaro Avezum, Philippe Gabriel Steg, Sunil V Rao, Peggy Gao, Rizwan Afzal, Campbell D Joyner, Susan Chrolavicius, Shamir R Mehta
Journal: The Lancet (2011)
Sunitinib Therapy for Melanoma Patients with <i>KIT</i> Mutations
Authors: David R. Minor, Mohammed Kashani-Sabet, Maria Garrido, Steven J. O'Day, Omid Hamid, Boris C. Bastian
Journal: Clinical Cancer Research (2012)

Recent studies have shown activating KIT mutations in melanoma originating from mucosa, acral, or cumulative sun-damaged skin sites. We aimed to assess the predictive role of KIT mutation, amplification, or overexpression for response to treatment with the kinase inhibitor sunitinib.Tumor tissues from 90 patients with stage III or IV acral, mucosal, or cumulative sun-damaged skin melanoma underwent sequencing of KIT, BRAF, NRAS, and GNAQ genes, FISH analysis for KIT amplification, and immunohistochemistry of KIT protein (CD117). Patients with mutations, amplifications, or overexpression of KIT were treated with sunitinib and responses measured by Response Evaluation Criteria in Solid Tumors (RECIST).Eleven percent of the melanomas tested had mutations in KIT, 23% in BRAF, 14% in NRAS, and none in GNAQ. Of 12 patients treated with sunitinib, 10 were evaluable. Of the 4 evaluable patients with KIT mutations, 1 had a complete remission for 15 months and 2 had partial responses (1- and 7-month duration). In contrast, only 1 of the 6 patients with only KIT amplification or overexpression alone had a partial response. In 1 responder with rectal melanoma who later progressed, the recurring tumor had a previously undetected mutation in NRAS, which was found in addition to the persisting mutation in KIT. Interestingly, among patients with manifest stage IV disease, KIT mutations were associated with a significantly shortened survival time (P < 0.0001).Sunitinib may have activity in patients with melanoma and KIT mutations; more study is needed. KIT mutations may represent an adverse prognostic factor in metastatic melanoma.
Sudden Cardiac Death With Apparently Normal Heart
Authors: Sumeet S. Chugh, Karen L. Kelly, Jack L. Titus
Journal: Circulation (2000)

Mechanisms of sudden cardiac death (SCD) in subjects with apparently normal hearts are poorly understood. In survivors, clinical investigations may not establish normal cardiac structure with certainty. Large autopsy series may provide a unique opportunity to confirm structural normalcy of the heart before reviewing a patient's clinical history.We identified and reexamined structurally normal hearts from a 13-year series of archived hearts of patients who had sudden cardiac death. Subsequently, for each patient with a structurally normal heart, a detailed review of the circumstances of death as well as clinical history was performed. Of 270 archived SCD hearts identified, 190 were male and 80 female (mean age 42 years); 256 (95%) had evidence of structural abnormalities and 14 (5%) were structurally normal. In the group with structurally normal hearts (mean age 35 years), SCD was the first manifestation of disease in 7 (50%) of the 14 cases. In 6 cases, substances were identified in serum at postmortem examination without evidence of drug overdose; 2 of these chemicals have known associations with SCD. On analysis of ECGs, preexcitation was found in 2 cases. Comorbid conditions identified were seizure disorder and obesity (2 cases each). In 6 cases, there were no identifiable conditions associated with SCD.In 50% of cases of SCD with structurally normal hearts, sudden death was the first manifestation of disease. An approach combining archived heart examinations with detailed review of the clinical history was effective in elucidating potential SCD mechanisms in 57% of cases.
Brain-Selective Overexpression of Angiotensin (AT <sub>1</sub> ) Receptors Causes Enhanced Cardiovascular Sensitivity in Transgenic Mice
Authors: Eric Lazartigues, Shannon M. Dunlay, Angela K. Loihl, Puspha Sinnayah, Julie A. Lang, Joshua J. Espelund, Curt D. Sigmund, Robin L. Davisson
Journal: Circulation Research (2002)

To examine the physiological importance of brain angiotensin II type 1 (AT1) receptors, we developed a novel transgenic mouse model with rat AT1a receptors targeted selectively to neurons of the central nervous system (CNS). A transgene consisting of 2.8 kb of the rat neuron-specific enolase (NSE) 5' flanking region fused to a cDNA encoding the full open-reading frame of the rat AT1a receptor was constructed and transgenic mice (NSE-AT1a) were generated. Two of six transgenic founder lines exhibited brain-selective expression of the transgene at either moderate or high levels. Immunohistochemistry revealed widespread distribution of AT1 receptors in neurons throughout the CNS. This neuron-targeted overexpression of AT1a receptors resulted in enhanced cardiovascular responsiveness to intracerebroventricular (ICV) angiotensin II (Ang II) injection but not to other central pressor agents, demonstrating functional overexpression of the transgene in NSE-AT1a mice. Interestingly, baseline blood pressure (BP) was not elevated in either transgenic line. However, blockade of central AT1 receptors with ICV losartan caused significant falls in basal BP in NSE-AT1a mice but had no effect in nontransgenic controls. These results suggest that whereas there is an enhanced contribution of central AT1 receptors to the maintenance of baseline BP in NSE-AT1a mice, particularly effective baroreflex buffering prevents hypertension in this model. Used both independently, and in conjunction with mice harboring gene-targeted deletions of AT1a receptors, this new model will permit quantitative and relevant investigations of the role of central AT1a receptors in cardiovascular homeostasis in health and disease.
Activation of Adenyl Cyclase by Glucagon in Cat and Human Heart
Authors: GERALD S. LEVEY, STEPHEN E. EPSTEIN
Journal: Circulation Research (1969)

The purpose of this investigation was to determine the direct effects of glucagon on adenyl cyclase activity in cat and human heart particles and to elucidate the role of the beta receptor in any glucagon-mediated activation of adenyl cyclase. At the peak of its dose-response curve, crystalline glucagon increased the conversion of AT 32 P to cyclic 3', 5'-AM 32 P in particulate fractions of both cat and human heart homogenates by approximately 70%. The activation of adenyl cyclase was dose-related over a concentration ranging from 1 x 10 -7 M to 1 x 10 -5 M. Half maximal activity was observed at 8 x 10 -7 M. DL-propranolol, 1 x 10 -5 M, did not block the activation of adenyl cyclase produced by glucagon, 1 x 10 -6 M or 1 x 10 -5 M. However, the same concentration of propranolol blocked adenyl cyclase activation induced by norepinephrine, 1 x 10 -6 M and 1 x 10 -5 M. Combined maximal doses of glucagon and norepinephrine did not produce additive effects on the activation of adenyl cyclase. The failure of DL-propranolol to block the glucagon-mediated activation of adenyl cyclase suggests that there are at least two receptor sites in myocardial tissue responsible for the activation of adenyl cyclase, one responsive to glucagon and one to norepinephrine. Moreover, since combined maximal doses of glucagon and norepinephrine failed to produce an additive response, it appears that in the heart there is probably only a single adenyl cyclase enzyme responsive to these hormones.
Determinants of Accelerated Progression of Arterial Stiffness in Normotensive Subjects and in Treated Hypertensive Subjects Over a 6-Year Period
Authors: Athanase Benetos, Chris Adamopoulos, Jeanne-Marie Bureau, Mohamed Temmar, Carlos Labat, Kathryn Bean, Frédérique Thomas, Bruno Pannier, Roland Asmar, Mahmoud Zureik, Michel Safar, Louis Guize
Journal: Circulation (2002)

Background — Elastic artery stiffness, a result of arterial aging, is an independent indicator of cardiovascular risk. The aim of the present longitudinal study was to compare the progression of aortic stiffness over a 6-year period in treated hypertensive subjects and normotensive subjects, and to evaluate the determinants of this progression. Methods and Results — Data for the present analysis were gathered from 483 subjects who had 2 health checkups at the Centre d’Investigations Préventives et Cliniques, the first one in 1992–1993 and the second one in 1998–1999. Carotid-femoral pulse wave velocity (PWV) was used to evaluate aortic stiffness in 187 hypertensive subjects who were under treatment at the time of the first visit and throughout the follow-up period, and in 296 subjects who were classified as normotensive during the first visit and who remained treatment-free throughout the follow-up period. In both populations, PWV progression was higher in older subjects. Annual rates of progression in PWV in treated hypertensives were significantly higher than in normotensives. Only treated hypertensives with well-controlled blood pressure levels at the time of both visits had a PWV progression similar to that of normotensives. In treated hypertensives, high heart rate and high creatinine during the first visit were associated with an accelerated progression in PWV. Conclusions — The presence of high blood pressure, high heart rate, and high serum creatinine were the major determinants of accelerated progression of aortic stiffness in treated hypertensives. This is the first longitudinal study to evaluate the determinants of arterial aging over an extended period of time.
NadA, a Novel Vaccine Candidate of <i>Neisseria meningitidis </i>
Authors: Maurizio Comanducci, Stefania Bambini, Brunella Brunelli, Jeannette Adu-Bobie, Beatrice Aricò, Barbara Capecchi, Marzia Monica Giuliani, Vega Masignani, Laura Santini, Silvana Savino, Dan M. Granoff, Dominique A. Caugant, Mariagrazia Pizza, Rino Rappuoli, Marirosa Mora
Journal: The Journal of Experimental Medicine (2002)

Neisseria meningitidis is a human pathogen, which, in spite of antibiotic therapy, is still a major cause of mortality due to sepsis and meningitis. Here we describe NadA, a novel surface antigen of N. meningitidis that is present in 52 out of 53 strains of hypervirulent lineages electrophoretic types (ET) ET37, ET5, and cluster A4. The gene is absent in the hypervirulent lineage III, in N. gonorrhoeae and in the commensal species N. lactamica and N. cinerea. The guanine/cytosine content, lower than the chromosome, suggests acquisition by horizontal gene transfer and subsequent limited evolution to generate three well-conserved alleles. NadA has a predicted molecular structure strikingly similar to a novel class of adhesins (YadA and UspA2), forms high molecular weight oligomers, and binds to epithelial cells in vitro supporting the hypothesis that NadA is important for host cell interaction. NadA induces strong bactericidal antibodies and is protective in the infant rat model suggesting that this protein may represent a novel antigen for a vaccine able to control meningococcal disease caused by three hypervirulent lineages.
Proton spectroscopy of brain glutamine in acute liver failure
Authors: James R. McConnell, Dean L. Antonson, Chin Siong Ong, Wei-Kom Chu, Ira J. Fox, Thomas G. Heffron, Alan N. Langnas, Byers W. Shaw
Journal: Hepatology (1995)

Evidence indicates that the accumulation of glutamine in the brain plays an important role in the pathogenesis and severity of the encephalopathy of acute liver failure (ALF). This study uses in vivo proton magnetic resonance spectroscopy (1H MRS) to assess brain glutamine (GLN) in five cases of acute liver failure. The findings are consistent with prior investigations and suggest that the alpha 1H of the GLN molecule can be used for noninvasive spectroscopic quantitation of brain GLN in patients with ALF.
Pseudoprogression in boron neutron capture therapy for malignant gliomas and meningiomas
Authors: Shin-Ichi Miyatake, Shinji Kawabata, Naosuke Nonoguchi, Kunio Yokoyama, Toshihiko Kuroiwa, Hideki Matsui, Koji Ono
Journal: Neuro-Oncology (2009)

Pseudoprogression has been recognized and widely accepted in the treatment of malignant gliomas, as transient increases in the volume of the enhanced area just after chemoradiotherapy, especially using temozolomide. We experienced a similar phenomenon in the treatment of malignant gliomas and meningiomas using boron neutron capture therapy (BNCT), a cell-selective form of particle radiation. Here, we introduce representative cases and analyze the pathogenesis. Fifty-two cases of malignant glioma and 13 cases of malignant meningioma who were treated by BNCT were reviewed retrospectively mainly via MR images. Eleven of 52 malignant gliomas and 3 of 13 malignant meningiomas showed transient increases of enhanced volume in MR images within 3 months after BNCT. Among these cases, five patients with glioma underwent surgery because of suspicion of relapse. In histology, most of the specimens showed necrosis with small amounts of residual tumor cells. Ki-67 labeling showed decreased positivity compared with previous samples from the individuals. Fluoride-labeled boronophenylalanine PET was applied in four and two cases of malignant gliomas and meningiomas, respectively, at the time of transient increase of lesions. These PET scans showed decreased lesion:normal brain ratios in all cases compared with scans obtained prior to BNCT. With or without surgery, all lesions were decreased or stable in size during observation. Transient increases in enhanced volume in malignant gliomas and meningiomas immediately after BNCT seemed to be pseudoprogression. This pathogenesis was considered as treatment-related intratumoral necrosis in the subacute phase after BNCT.
Tuberculosis elimination: dream or reality? The case of Cyprus
Authors: Constantia Voniatis, Giovanni Battista Migliori, Michael Voniatis, Andreas Georgiou, Lia D’Ambrosio, Rosella Centis, Mario C. Raviglione
Journal: European Respiratory Journal (2014)

To the Editor: 

The World Health Organization (WHO)-recommended strategy of tuberculosis (TB) control has evolved from the DOTS (directly observed treatment, short course) strategy to the Stop TB strategy [1, 2]. By breaking the chain of transmission through rapid diagnosis and effective treatment of infectious TB cases, this strategy allowed the development of national TB programmes and proved to be highly cost-effective [3, 4].

However, in order to accelerate the decline of the TB pandemic, WHO has planned a post-2015 strategy focusing on the concept of TB elimination [5–8]. To reach elimination (defined as fewer than one sputum smear-positive case per million inhabitants), countries should ensure that diagnosis and treatment of latent TB infection (LTBI) supplements detection and treatment of active TB disease [7–10].

A recent survey conducted by the European Respiratory Society (as part of its 2012–2013 Presidential plan) and WHO in Europe has demonstrated that the majority of countries do not have all the interventions in place to reach elimination [11], and stressed the importance of studying model countries able to demonstrate that TB elimination can be reached [12–14].

The aim of the present study was to show the progress achieved by Cyprus towards the elimination targets. Cyprus has been selected because of its solid TB control programme, the quality of surveillance data and health services, and its small population (865 878 in 2012).

The way …
Heated intra-operative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis: pharmacokinetics and tissue distribution
Authors: D. Elias, M. Bonnay, J.M. Puizillou, S. Antoun, S. Demirdjian, A. El Otmany, J.P. Pignon, L. Drouard-Troalen, J.F. Ouellet, M. Ducreux
Journal: Annals of Oncology (2002)

Purpose: This article reports the pharmacokinetics (PK) of heated intra-operative intraperitoneal oxaliplatin and its tolerance profile. Oxaliplatin has demonstrated significant activity in advanced colorectal cancer, and this is the first publication concerning its intraperitoneal administration.Methods: Twenty consecutive patients with peritoneal carcinomatosis (PC) of either gastrointestinal or uniquely peritoneal origin underwent complete cytoreductive surgery followed by intra-operative intraperitoneal chemo-hyperthermia (IPCH) with increasing doses of oxaliplatin. We performed IPCH using an open procedure (skin pulled upwards), at an intraperitoneal temperature of 42–44°C, with 2 l/m2 of 5% dextrose instillate in a closed circuit. The flow-rate was 2 l/min for 30 min. Patients received intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2) just before the IPCH to maximize the effect of oxaliplatin. We treated at least three patients at each of the six intraperitoneal oxaliplatin dose levels (from 260 to 460 mg/m2) before progressing to the next. We analysed intraperitoneal, plasma and tissue samples with atomic absorption spectrophotometry.Results: The mean duration of the entire procedure was 8.4 ± 2.7 h. Half the oxaliplatin dose was absorbed in 30 min at all dose levels. Area under the curve (AUC) and maximal plasma concentration (Cmax) increased with dose. At the highest dose level (460 mg/m2), peritoneal oxaliplatin concentration was 25-fold that in plasma. AUCs following intraperitoneal administration were consistently inferior to historical control AUCs after intravenous oxaliplatin (130 mg/m2). Intratumoral oxaliplatin penetration was high, similar to absorption at the peritoneal surface and 17.8-fold higher than that in non-bathed tissues. Increasing instillate volume to 2.5 l/m2 instead of 2 l/m2 dramatically decreased oxaliplatin concentration and absorption. There were no deaths, nor severe haematological, renal or neurological toxicity, but we observed two fistulas and three deep abscesses.Conclusions: Heated intraperitoneal chemotherapy gives high peritoneal and tumour oxaliplatin concentrations with limited systemic absorption. We recommend an oxaliplatin dose of 460 mg/m2 in 2 l/m2 of 5% dextrose for intraperitoneal chemo-hyperthermia, at a temperature of 42–44°C over 30 min. We may be able to improve these results by increasing the intraperitoneal perfusion duration or by modifying the instillate composition.