tbuckley/cabot-search huggingface dataset:
Genetic polymorphism of alpha 1 antytrypsin and glutathione S transferase and lung cancer risk
Authors: Andreea Catana, Radu Popp, Monica Pop, Mihai Porojan, Victor Pop, Adrian Trifa, Felicia Petrisor, Marius Farcas
Journal: European Respiratory Journal (2011)

Background:  Polymorphisms for genes encoding alpha 1 antitrypsin (A1AT) and glutathione S-transferase (GSTM1/GSTT1) might contribute to the variability in individual susceptibility to lung cancer.   Objectives:  This is a cross-sectional, randomized, case control study for the evaluation of the frequency of A1AT (MS, MZ) and GST (GSTM1/GSTT1 null) alleles among patients with lung cancer. The study included 56 cases of lung cancer diagnosed patients (histopathological examination), recruted from the Pneumology Hospital Leon Daniello Cluj and 125 healthy unrelated controls, selected among patients observed in the Internal Medicine Department.   Methods:  A1AT genotyping was carried out using PCR amplification of relevant gene segment was followed by restriction enzyme digestion Taq1. Detection of A1AT gene S and Z alleles was determined through analysis of resulting restriction fragment length polymorphism (RFLP). For GSTM and GSTT genotyping we used Multiplex PCR, followed by gel electrophoresis analysis.   Results:  The molecular analysis identified the MS genotype in 3 (5,4%) patients with lung cancer and 1 (0,8%) of the controls. The heterozigous MZ state was detected neither among cases nor in controls. The prevalence of GSTM null genotype in lung cancer patients was 49,4% compared to 42,8% of controls, also the prevalence of GSTT null genotype in lung cancer patients was 24,5% compared to 18,2% of controls.   Conclusions:  Our findings (positive statistical significance),suggest that heritable A1AT and GST status may influence the risk of lung cancer developement.
Recombinant Technology in the Development of Materials and Systems for Soft‐Tissue Repair
Authors: Alessandra Girotti, Doriana Orbanic, Arturo Ibáñez‐Fonseca, Constancio Gonzalez‐Obeso, José Carlos Rodríguez‐Cabello
Journal: Advanced Healthcare Materials (2015)

The field of biomedicine is constantly investing significant research efforts in order to gain a more in‐depth understanding of the mechanisms that govern the function of body compartments and to develop creative solutions for the repair and regeneration of damaged tissues. The main overall goal is to develop relatively simple systems that are able to mimic naturally occurring constructs and can therefore be used in regenerative medicine. Recombinant technology, which is widely used to obtain new tailored synthetic genes that express polymeric protein‐based structures, now offers a broad range of advantages for that purpose by permitting the tuning of biological and mechanical properties depending on the intended application while simultaneously ensuring adequate biocompatibility and biodegradability of the scaffold formed by the polymers. This Progress Report is focused on recombinant protein‐based materials that resemble naturally occurring proteins of interest for use in soft tissue repair. An overview of recombinant biomaterials derived from elastin, silk, collagen and resilin is given, along with a description of their characteristics and suggested applications. Current endeavors in this field are continuously providing more‐improved materials in comparison with conventional ones. As such, a great effort is being made to put these materials through clinical trials in order to favor their future use.
Role of Hemodynamics in Pulmonary Vascular Remodeling
Authors: MITCHELL D. BOTNEY
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Primary pulmonary hypertension (PPH) is a disease characterized clinically by the progressive increase in pulmonary artery impedance, which ultimately produces right ventricular failure and death. At the time most patients with PPH present to clinical attention, pathologic lesions include pulmonary artery medial hypertrophy, adventitial thickening, and neointimal lesions. Neointimal lesions are new vascular structures composed of smooth muscle cells (SMC) and extracellular matrix located on the lumenal side of the inner elastic lamina or, if the vessel is too small to have an inner elastic lamina, between the endothelium and the medial layer of the vessel. The terms “neointima” and “neointimal lesions” are used interchangeably in this review. Nearly all active remodeling (as defined by extracellular matrix gene expression) in patients with severe pulmonary hypertension occurs in the neointima (1‐5). This observation underscores the importance of understanding how pulmonary vascular neointimal lesions develop but the pathogenesis and natural history of neointimal lesion formation in PPH are poorly understood. On the basis of animal studies, and by analogy to systemic arterial disease, it seems likely that endothelial injury is required (6). Whether injury occurs secondary to infection (7), ingestion of toxins (8), or activation of autoimmunity (9) remains speculative. Although vascular injury appears necessary to initiate remodeling, other factors besides injury are likely required before pulmonary vascular neointimal lesions develop since the pulmonary artery histology in traditional animal models, in which remodeling is initiated by monocrotaline or hypoxic injury, does not develop lesions that resemble the neointimal lesions of PPH. Hemodynamic forces and injury-induced biochemical mediators are important components in mechanisms of systemic vascular remodeling, including atherosclerosis, restenosis after angioplasty, and neointimal lesions following vascular bypass surgery. New studies suggest hemodynamic factors may be as important in the pulmonary vasculature as they are in the systemic vasculature.
A hereditary immunoglobulin A abnormality: absence of light-heavy—chain assembly
Authors: Chaya Moroz, Jacob Amir, Andre De Vries
Journal: Journal of Clinical Investigation (1971)

A new immunoglobulin A abnormality, absence of assembly of alpha-chain and light-chain, was found in an adult female suffering from recurrent upper respiratory infection and tonsillitis since childhood, but otherwise healthy. The IgA abnormality was manifest in her serum by the presence of free alpha-chains, in her saliva by the presence of alpha-chains bound to secretory piece, and in her urine by the presence of free alpha-chains and free light-chains. The serum IgG and IgM were found to be complete, containing both heavy-chains and light-chains. Evidence for this immunoglobulin A abnormality was also found in the proposita's mother and elder son, demonstrating it to be a hereditary disorder. Studies performed with patient's tonsillar cells in short-term culture, using amino acids-(14)C, revealed synthesis and secretion of both free alpha-chains and free light-chains, in addition to synthesis and secretion of normally assembled IgG and IgM.
Euthanasia: Going Dutch?
Authors: Robert G Twycross
Journal: Journal of the Royal Society of Medicine (1996)

My experience in 25 years as a hospice doctor have reinforced my belief that when everything is taken into account--physical, psychological, social and spiritual--euthanasia is not the answer. This belief is enhanced by what I see happening in the Netherlands. However, lest it be thought that I have become hardened and indifferent to suffering let me add that, although firmly opposed to euthanasia, I consider that: (i) a doctor who has never been tempted to kill a patient probably has had limited clinical experience or is not able to empathize with those who suffer (ii) a doctor who leaves a patient to suffer intolerably is morally more reprehensible than the doctor who performs euthanasia A doctor has twin obligations to preserve life and to relieve suffering. Preserving life is increasingly meaningless when a terminally ill patient is close to death, and the emphasis on relieving suffering becomes paramount. Even here, however, the doctor is obliged to achieve his objective with minimum risk to the patient's life. This means that treatment to relieve pain and suffering which coincidentally might bring forward the moment of death by a few hours or days is acceptable (the principle of double effect), but administering a drug such as potassium or curare, with the primary intention of causing death, is not.
Mediastinitis due to Gram-negative bacteria is associated with increased mortality
Authors: H. Charbonneau, J.M. Maillet, M. Faron, O. Mangin, E. Puymirat, P. Le Besnerais, L. Du Puy-Montbrun, P. Achouh, J.L. Diehl, J.-Y. Fagon, J.-L. Mainardi, E. Guerot
Journal: Clinical Microbiology and Infection (2013)
Primary immunodeficiencies: not just paediatric diseases
Authors: Andrew R. Gennery, Steven M. Holland
Journal: European Respiratory Journal (2015)

Primary immune deficiencies, once the sole domain of paediatricians, have come of age, and increasing numbers of childhood survivors, testament to meticulous medical care and the introduction of broad-spectrum antimicrobial prophylaxis, are now reaching early-to-mid adulthood. These patient cohorts are important for a number of reasons: 1) they teach us about the natural history of disease, modified through therapeutic intervention; 2) they highlight patients presenting at the extremes of the spectrum, e.g. with less severe disease, modified by genetics and/or environment; 3) they may offer insights into risks and benefits of earlier intervention in the disease course; and 4) they present a challenge to adult physicians, potentially unfamiliar with hitherto "paediatric" disease and its management. Childhood survivors of chronic granulomatous disease show the importance of expertise in primary immunodeficiencies <http://ow.ly/K09mr>
Measuring Symptoms in Terminal Cancer: Are Pain and Dyspnoea Controlled?
Authors: I Higginson, M McCarthy
Journal: Journal of the Royal Society of Medicine (1989)

The symptoms of 86 patients referred to a district terminal care support team were rated throughout care using a standardized schedule. Pain was the most common main symptom at referral, occurring in 35 (41%) of the patients. The assessment scores for pain showed significant improvements after one week of care (P&lt;0.01) and there was a further improvement into the week of death. However, towards death, 18 (21%) patients developed dyspnoea as their main symptom, and this became the most severe symptom at death. The symptom assessment scores for patients with dyspnoea showed no change over time, suggesting that existing methods to control dyspnoea are ineffective and that new interventions are needed.
Questioning causal involvement of telomeres in aging
Authors: Mirre J.P. Simons
Journal: Ageing Research Reviews (2015)

Multiple studies have demonstrated that telomere length predicts mortality and that telomeres shorten with age. Although rarely acknowledged these associations do not dictate causality. I review telomerase knockout and overexpression studies and find little support that telomeres cause aging. In addition, the causality hypothesis assumes that there is a critical telomere length at which senescence is induced. This generates the prediction that variance in telomere length decreases with age. In contrast, using meta-analysis of human data, I find no such decline. Inferring the causal involvement of telomeres in aging from current knowledge is therefore speculative and could hinder scientific progress.
A molecular analysis of quinolone-resistant haemophilus influenzae: Validation of the mutations in quinolone resistance-determining regions
Authors: Hisashi Shoji, Tetsuro Shirakura, Takahiro Takuma, Kazuo Tanaka, Kunihiko Fukuchi, Yoshihito Niki
Journal: European Respiratory Journal (2013)

The mechanism of quinolone-resistance is considered to be amino acid mutations in the type II topoisomerase. We validated the genetic mechanisms of quinolone resistance in Haemophilus influenzae. We obtained 29 H. influenzae strains from a nationwide surveillance program in Japan (including 11 quinolone-resistant strains [moxifloxacin: MFLX or levofloxacin MIC � 2 mg/ml]). We analyzed the sequences of the Quinolone Resistance-Determining Regions (QRDRs) in GyrA, GyrB, ParC and ParE. Furthermore, we induced resistance in susceptible strains by exposing them to quinolone, and investigated the relationship between mutations in the QRDRs and the MICs. Five amino acid substitutions in GyrA (at Ser84 and Asp88) and ParC (at Gly82, Ser84 and Glu88) were found to be closely related to the MICs. The strains with a MFLX MIC of 0.125e1 and 2e4 mg/ml had one and two mutations, respectively. The strains with a MFLX MIC of � 8 mg/ml had three or more mutations. The strains with induced resistance with MFLX MICs of 0.5e1 and � 2 mg/ml also had one and two mutations, respectively. We confirmed that these five mutations strongly contribute to quinolone resistance and found that the degree of resistance is related to the number of the mutations. In addition, the three strains of 18 susceptible strains (16.7%) also had a single mutation. These strains may therefore be in the initial stage of quinolone resistance. Currently, the frequency of quinolone-resistant H. influenzae is still low. However, as has occurred with b-lactams, an increase in quinolone use may lead to more quinolone-resistant strains.
P-106 Pembrolizumab (MK-3475) versus paclitaxel as second-line therapy for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: Randomized, open-label, phase 3 KEYNOTE-061 study
Authors: A. Ohtsu, J. Tabernero, Y.-J. Bang, C. Fuchs, L. Sun, Z. Wang, I. Csiki, M. Koshiji, E. Van Cutsem
Journal: Annals of Oncology (2015)
A Review of Wavelet Transform Time–Frequency Methods for NIRS-Based Analysis of Cerebral Autoregulation
Authors: Paul S. Addison
Journal: IEEE Reviews in Biomedical Engineering (2015)

Near-infrared spectroscopy (NIRS) has been proposed as a suitable technique for the analysis of cerebral autoregulation as it provides a simpler acquisition methodology and more artifact-free signal. A number of sophisticated wavelet transform methods have recently emerged to quantify the cerebral autoregulation mechanism using NIRS and blood pressure signals. These provide an enhanced partitioning of signal information via the time-frequency plane, which facilitates improved extraction of the components of interest. This area is reviewed, and enhancements to this form of analysis are suggested.
Separation of Two Distinct Tumor-Associated Antibodies in the Serum of Melanoma Patients
Authors: M. G. Lewis, T. M. Phillips
Journal: JNCI Journal of the National Cancer Institute (1972)

Two antibody/antigen reactions, previously described in human malignant melanoma, were studied by cross-absorption, immunofluorescence, and immunodiffusion techniques. Two different melanoma cell suspensions and their autologous positive sera were used to separate antibodies in the sera so that the common antibody against cytoplasmic contents was absorbed out, thus leaving a patient-specific antibody directed against the individual cell surface membrane. This further confirms the relative specificity of the antibody/antigen reaction in human malignant melanoma and offers a method for study of the relationship between these 2 antibodies and circulating antigen in the natural history of this tumor.
Dipstick Haematuria: Its Association with Smoking and Nonsteroidal Anti-Inflammatory Drugs
Authors: J Philip Britton, Anthony C Dowell, Peter Whelan
Journal: Journal of the Royal Society of Medicine (1990)

Of 1015 men over the age of 60, 125 (12.3%) were found to have dipstick haematuria on a single test. Analysis of smoking history revealed a 1.6 fold increased incidence of dipstick haematuria in current smokers as compared with ex-smokers and non-smokers. The relationship with bladder cancer and smoking is discussed. Several commonly used drugs, including nonsteroidal anti-inflammatory preparations, have been implicated as a cause of urinary tract bleeding. In this study of 1015 men over the age of 60, no association was found between the presence of dipstick haematuria and the intake of aspirin, other nonsteroidal anti-inflammatory drugs or warfarin.
Late-breaking abstract: Smoking is associated with higher incidence of parapneumonic effusion in community-acquired pneumonia
Authors: Rosanel Amaro, Jacobo Sellarés, Juan A Riesco, Catia Cillloniz, Emilia Abad, Antoni Torres
Journal: European Respiratory Journal (2014)

Rationale:  Smoking is associated with higher risk of developing community-acquired pneumonia (CAP), although it is not clear the association of smoking with pulmonary complications, including parapneumonic effusion (PPE). The objective of the study was to assess the influence of smoking on the incidence of PPE in patients with different baseline disorders.   Methods:  We conducted a single-centre cohort study of 3779 consecutively collected patients diagnosed with community-acquired pneumonia. We assessed clinical, radiographic and pleural-fluid chemistry and microbiological variables. Patients were classified according to their smoking status.   Measurements and main results:  958 patients (25%) were current smokers at the diagnosis of CAP. The incidence of parapneumonic effusion was higher in smokers compared to non-smokers patients (13% vs 10%, p    Conclusions:  Smoking is associated with higher incidence of PPE in patients with CAP and with higher pleural inflammatory markers. Association with empyema/complicated PPE could not be demonstrated in the present study.
Reduction of lung injury and fibrosis by human embrionic stem cells in a mouse model of silica-induced lung fibrosis
Authors: Paola Spitalieri, Maria Chiara Quitadamo, Augusto Orlandi, Lorenzo Guerra, Emiliano Giardina, Valeria Casavola, Cesare Saltini, Giuseppe Novelli, Federica Sangiuolo
Journal: European Respiratory Journal (2011)

We assessed the ability of human embryonic stem cells (HUES-3) to differentiate into functioning alveolar type II cells (ATIICs), engraft into damaged lungs and ameliorate pulmonary fibrosis, thereby reducing mortality, in a mouse model of silica-induced pulmonary inflammation and fibrosis.  Nude mice (Charles River, Italy) were intranasally administered either silica oxide powder (99.9% Alfa Aesar) intranasally (5mg/mL, 50 μl/mice/day) or saline for 15 days followed by intratracheal 2.5×106 HUES-3-ATIICs (n=50, HUES-3-ATIICs treated) or saline (n=50, Sham treated). Ten silica treated mice were instilled mature fibroblasts.  In vitro differentiated HUES-3-ATIICs displayed an alveolar phenotype (multilamellar body, SP-B, SP-C and ZO-1 expression and CFTR-mediated chloride ion transport). After transplantation into silica-damaged mice, HUES-3-ATIICs were capable of engraftment as they showed persistence of human SP-C and of human DNA and effectively reduced inflammation and fibrosis. HUES-3-ATIICs treated mice showed reduced expression of IL-6, TNF-α, MIP-2 and TGF-β and of collagen marker Col1-α1 (p  In conclusion, the data show that HUES-3-ATIICs intratracheal instillation can reduce silica-induced lung injury and fibrosis in the mouse model of silica-induced lung fibrosis, indicating stem cell therapy as a viable approach for pulmonary fibrosis treatment.
Combined liver radiation and chemotherapy for palliation of hepatic metastases from colorectal cancer.
Authors: M Mohiuddin, E Chen, N Ahmad
Journal: Journal of Clinical Oncology (1996)

PURPOSE To report the effects of boost dose radiation on palliation, survival, and toxicity in patients undergoing palliative treatment for hepatic metastases from colorectal cancers and to assess the potential benefits of higher doses of radiation to partial liver volumes. MATERIALS AND METHODS Forty-five patients with hepatic metastases from colorectal cancers were treated with a course of palliative irradiation. Eligible patients included those with radiographically or histologically proven liver metastases. All patients but one received chemotherapy, either pretreatment (one patient) and/or concurrently with radiation (43 patients) via intravenous or hepatic intraarterial infusion. Patients were divided into two groups based on whether or not boost radiation was given. Thirty-three of the 45 patients (group 1) received whole-liver irradiation at doses that ranged from 8 to 31 Gy at 2.0 to 3.0 Gy per fraction (median dose, 21 Gy). The remaining 12 patients (group 2) received liver irradiation to 20 to 30 Gy followed by a boost dose to the area of dominant disease for a total dose of 33 to 60 Gy. The extent of liver involvement was similar between the two groups. Palliation, overall survival, and toxicity were analyzed with respect to radiation dose. RESULTS There was no increase in acute effects observed in treating partial liver volumes to higher doses in conjunction with systemic chemotherapy. No cases of radiation-induced hepatitis or nephritis were documented. Hematologic toxicity (&gt; or = grade 3) was observed in four patients with thrombocytopenia, three with leukopenia, and two with anemia. Pain was relieved in 71% and hepatomegaly in 59% of group 1 patients, as compared with 100% and 89%, respectively, of group 2 patients. Other symptoms such as nausea, fever, fatigue, and jaundice were palliated in 35% of group 1 and 90% of group 2 patients. The median survival time for group 1 patients was 4 months (range, 1 week to 26 months), which is consistent with that reported in the literature. The median survival time for group 2 patients was 14 months (range, 2 to 32 months) (P=.01). CONCLUSION Standard hepatic irradiation followed by boost radiation to partial liver volumes in combination with chemotherapy is well tolerated without significant acute/late morbidity. Higher radiation doses to partial liver volumes offers improved palliative benefit and may prolong survival without an increase in morbidity.
Sleep quality and other patient‐reported outcomes improve after patients with psoriasis with suboptimal response to other systemic therapies are switched to adalimumab: results from PROGRESS, an open‐label Phase IIIB trial
Authors: B.E. Strober, J.M. Sobell, K.C. Duffin, Y. Bao, A. Guérin, H. Yang, O. Goldblum, M.M. Okun, P.M. Mulani
Journal: British Journal of Dermatology (2012)

Psoriasis is associated with poor health-related quality of life, including sleep impairment.To assess the extent of sleep impairment, the effect of adalimumab on sleep and other patient-reported outcomes, and correlations between changes in these outcomes and sleep quality in patients with psoriasis.Patients in the 16-week, open-label, Phase IIIb PROGRESS trial had chronic plaque psoriasis and suboptimal response to prior therapy (etanercept, methotrexate or narrowband ultraviolet B phototherapy). Adalimumab was self-injected subcutaneously (80 mg at week 0, then 40 mg every other week from week 1). The focus for this analysis was the Medical Outcomes Study Sleep Scale. Other patient-reported outcomes included the Dermatology Life Quality Index (DLQI), Psoriasis Area and Severity Index (PASI), Physician's Global Assessment, a visual analogue scale for psoriasis/psoriatic arthritis (PsA) pain, and the Work Productivity and Activity Index Questionnaire-Specific Health Problems.Patients with psoriasis had impaired sleep at baseline. The degree of sleep impairment was significantly associated with the extent of work productivity for all sleep measures and, for some sleep measures, was associated with DLQI impairment, clinical severity measured by PASI, the presence of PsA, and depression. Adalimumab treatment significantly improved sleep quality by 15% from baseline, as well as DLQI score, pain and work productivity. The improvement in sleep was partially explained (R(2 ) = 0·16, P < 0·001) by improvements in the objectively measured psoriasis signs in PASI.Adalimumab treatment improved sleep outcomes and other patient-reported outcomes including health-related quality of life, work productivity, daily activity and disease-related pain.