tbuckley/cabot-search huggingface dataset:
Second-Line Chemotherapy in Relapsing or Refractory Non–Small-Cell Lung Cancer: A Review
Authors: C. Huisman, E.F. Smit, G. Giaccone, P.E. Postmus
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Since the increased use of first-line chemotherapy for non–small-cell lung cancer (NSCLC), second-line chemotherapy may nowadays be considered for a growing group of patients. Guidelines for second-line treatment have to be developed yet. METHODS: We reviewed the published literature on second-line chemotherapy for NSCLC with emphasis on the role of factors such as pretreatment, response to first-line treatment, and length of disease-free-interval. RESULTS: Thirty-four single-agent-studies and 24 multidrug-studies on second-line treatment were identified. Docetaxel has been studied most extensively and is the only agent that has been studied in randomized phase III trials. Different definitions of sensitivity applied by different authors and conflicting results have been reported about the influence of response to prior chemotherapy. CONCLUSION: Since most patients are treated with a platinum-based regimen in the first line, platinum resistance usually is a major consideration for the use of second-line agents. We argue, however, that a more general definition of drug resistance is more appropriate than resistance to platinum only. Criteria to select NSCLC patients for second-line treatment have not been defined yet. This is also important in light of the upcoming necessity to test new drugs in pretreated instead of treated patients. Guidelines for second-line treatment of NSCLC based on clinical information on drug sensitivity to first-line therapy need to be developed.
Medical students' understanding of inhalation therapy & inhalers
Authors: Jae Won Jeong, Chan Sun Park
Journal: European Respiratory Journal (2013)

Background:  Few data is available about the assessment of inhaler technique and knowledge on inhalation therapy among medical students.   Aim : To evaluate the skill and knowledge of medical students in proper use of three kinds of inhalers(metered dose inhaler, turbuhaler, and diskus) and inhalation therapy.   Methods:  We enrolled 78 third-year medical students who are on hospital training course. The participants received 1 hour of video instruction from hospital staff. Six weeks later, we assessed their knowledge and skill regarding inhaler use. They were asked to discriminate each type of three devices and to demonstrate the use of each device using placebo inhalers. Also, they were asked about the prevention and management for local adverse reaction induced by inhaled corticosteroids(ICS). Participants’ inhaler skill was assessed into three levels as good, adequate, and inadequate for each device type.   Results:  Only 23.1% (18/78) of medical students could explain the advantages of inhalation therapy compared to oral route. 93.6% (73/78) of participants could not discriminate all types of inhaler devices. Subjects with good inhaler skill was found in 26.9% for metered dose inhaler, 9.0% for turbuhaler, and 11.5% for diskus. With regards to prevention and treatment option for ICS-related local side effects, only 17.9% (14/78) answered correctly.   Conclusions:  We conclude that large percent of medical students were deficient in knowledge and inhalation skills regarding the inhalers. An educational session with video instruction by hospital staff was not effective in enhancing inhaler technique nor increasing knowledge on inhaler treatment.
Clara cell protein (CC16) in serum and urine after exercise challenge
Authors: Ellen Tufvesson, Henning Svensson, Leif Bjermer
Journal: European Respiratory Journal (2012)

Exercise is known to affect the airway epithelium, giving rise to a release of inflammatory mediators, such as Clara cell protein (CC16). The aim of this study was to investigate the epithelial involvement during exercise, by repeatedly measuring the level of CC16 in serum and urine in asthmatic subject and healthy controls.  Asthmatic subjects (n=18) and healthy controls (n=12) performed an 8 min exercise challenge on a treadmill. Serum was collected before and 1, 5, 10, 15, 20, 30, 45 and 60 min after the challenge. Urine was collected before and 30 and 60 after the challenge. CC16 was measured in serum and urine. Exhaled nitric oxide was measured at 50, 100, 200 and 300 ml/s.  The serum level of CC16 was significantly increased directly after exercise in all subjects with a further increase after an additional 15 minutes. The increase in serum CC16 was more pronounced in asthmatic subjects. In urine, there was a clear increase in CC16 levels in all subjects 30 min after exercise, returning back to baseline after 60 min. No difference between asthmatic subjects and healthy controls could be seen in urine levels of CC16. A decrease in alveolar NO concentration was seen after the exercise challenge.  The CC16 response measured in serum are more pronounced inter- and intra-individually than in urine. The increase in serum CC16 both directly after the test and at a later time point indicates that the CC16 increase in serum may be explained by a combination of leakage followed by active secretion. This could explain the different response between asthmatics and healthy controls with an assumed altered epithelial involvement seen in the asthmatic subjects after exercise provocation.
Targeted Induction of Ceramide Degradation Leads to Improved Systemic Metabolism and Reduced Hepatic Steatosis
Authors: Jonathan Y. Xia, William L. Holland, Christine M. Kusminski, Kai Sun, Ankit X. Sharma, Mackenzie J. Pearson, Angelica J. Sifuentes, Jeffrey G. McDonald, Ruth Gordillo, Philipp E. Scherer
Journal: Cell Metabolism (2015)
‘We'D like to Have a Family’ - Young Women Doctors’ Opinions of Maternity Leave and Part-Time Training
Authors: V J Warren, R E Wakeford
Journal: Journal of the Royal Society of Medicine (1989)

Maternity leave and part-time training should facilitate the integration of the family and professional lives of young women doctors - whom the NHS cannot afford to lose as their numbers rise to half the number of the graduates of UK medical schools. Women doctors' planned professional activity is high, but to what extent do the maternity leave and part-time training arrangements assist them in fulfilling their plans? One hundred and forty-five young women doctors reported their experiences of and views on maternity leave and part-time training. Most had children between 6 and 10 years after qualification, to fit with career development. Seventy-one per cent of the confinements had qualified for maternity leave and pay, but there were complaints about the working of the regulations, particularly in relation to junior hospital doctors' short contracts. When asked to comment about part-time training, most (77%) expressed themselves as broadly in favour - only three actively opposing it. It was perceived as difficult to organize by 20% of respondents, as difficult to undertake by 29%, and as being of low status by 15%. This study concludes that the arrangements for maternity leave need to be improved and that the availability and status of part-time training need enhancing - especially to encourage women doctors to enter careers in hospital medicine.
<i>MSH2</i> Mutation Carriers Are at Higher Risk of Cancer Than <i>MLH1</i> Mutation Carriers: A Study of Hereditary Nonpolyposis Colorectal Cancer Families
Authors: H. F.A. Vasen, A. Stormorken, F. H. Menko, F. M. Nagengast, J. H. Kleibeuker, G. Griffioen, B. G. Taal, P. Moller, J. T. Wijnen
Journal: Journal of Clinical Oncology (2001)

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by the clustering of colorectal cancer, endometrial cancer, and various other cancers. The disease is caused by mutations in DNA-mismatch-repair (MMR) genes, most frequently in MLH1, MSH2, and MSH6. The aims of the present study were to compare the risk of developing colorectal, endometrial, and other cancers between families with the various MMR-gene mutations.Clinical and pathologic data were collected from 138 families with HNPCC. Mutation analyses were performed for all families. Survival analysis was used to calculate the cumulative risk of developing cancer in the various subsets of relatives.Mutations were identified in 79 families: 34 in MLH1, 40 in MSH2, and five in MSH6. The lifetime risk of developing cancer at any site was significantly higher for MSH2 mutation carriers than for MLH1 mutation carriers (P < .01). The risk of developing colorectal or endometrial cancer was higher in MSH2 mutation carriers than in MLH1 mutation carriers, but the difference was not significant (P = .13 and P = .057, respectively). MSH2 mutation carriers were found to have a significantly higher risk of developing cancer of the urinary tract (P < .05). The risk of developing cancer of the ovaries, stomach, and brain was also higher in the MSH2 mutation carriers than in the MLH1 mutation carriers, but the difference was not statistically significant.Pending large prospective studies, the extension of the current surveillance program in MSH2 mutation carriers with the inclusion of the urinary tract should be considered.
A novel missense mutation in GJB2, p.Tyr65His, causes severe Vohwinkel syndrome
Authors: E.A. de Zwart-Storm, M. van Geel, E. Veysey, S. Burge, S. Cooper, P.M. Steijlen, P.E. Martin, M.A.M. van Steensel
Journal: British Journal of Dermatology (2010)

Journal Article A novel missense mutation in GJB2, p.Tyr65His, causes severe Vohwinkel syndrome Get access E.A. de Zwart‐Storm, E.A. de Zwart‐Storm Department of DermatologyGROW – School for Oncology and Developmental Biology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, the NetherlandsDepartment of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, U.K. Correspondence: Eugene A. de Zwart‐Storm. E‐mail: ea.de.zwart.storm@mumc.nl Search for other works by this author on: Oxford Academic Google Scholar M. van Geel, M. van Geel Department of DermatologyGROW – School for Oncology and Developmental Biology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar E. Veysey, E. Veysey Department of Dermatology, Churchill Hospital, Oxford, U.K. Search for other works by this author on: Oxford Academic Google Scholar S. Burge, S. Burge Department of Dermatology, Churchill Hospital, Oxford, U.K. Search for other works by this author on: Oxford Academic Google Scholar S. Cooper, S. Cooper Department of Dermatology, Churchill Hospital, Oxford, U.K. Search for other works by this author on: Oxford Academic Google Scholar P.M. Steijlen, P.M. Steijlen Department of DermatologyGROW – School for Oncology and Developmental Biology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar P.E. Martin, P.E. Martin Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.A.M. van Steensel M.A.M. van Steensel Department of DermatologyGROW – School for Oncology and Developmental Biology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 1, 1 January 2011, Pages 197–199, https://doi.org/10.1111/j.1365-2133.2010.10058.x Published: 01 January 2011
Clinical and economic outcomes following 52-week add-on omalizumab
Authors: Lorna Marie West, Caroline Gouder, Stephen Montefort
Journal: European Respiratory Journal (2013)

Background:  Preliminary NICE appraisal does not recommend omalizumab within its marketing authorisation for treating severe persistent allergic asthma since current benefits do not lower incremental cost-effectiveness ratios to acceptable levels.   Objective:  The aim of this study was to assess clinical and economic outcomes following a 52-week omalizumab treatment.   Methods:  Outcome variables were compared 52 weeks prior and post initiation of omalizumab in 13 adults with severe persistent allergic asthma. These included: Asthma Control Test (ACT) score; number of exacerbations; number/duration and cost of asthma-related hospitalisations; oral corticosteroid (OCS) courses; number and cost of a) medicines during hospital-stay, b) unscheduled doctor visits and c) days off work. Student9s  t -test was used for statistical analysis with a  p     Results:  There was an improvement in ACT by 47% ( p  =  p  = .03), hospitalisations (25%  p  = .75) and duration (66%  p  = .39), OCS courses (63%  p  = .002), doctor visits (36%  p  = .26) and days off work (84%  p  = .07). Total costs per hospitalisations (€11,274.12 vs €3,843.45), doctor visits (€4,920 vs €1,056), medicines during hospital-stay (€1,742.46 vs €436.53) and days off work (€3,827 vs €602) decreased after starting omalizumab. Total annual cost for omalizumab in this cohort was €226,061.55.   Conclusion:  Omalizumab significantly improved asthma control with a resultant substantial increase in cost. A limitation is the small cohort. Further studies need to assess indirect long-term costs, such as management of side effects of long-term steroids.   Reference:  NICE. Appraisal consultation document 2012.
Host and viral factors predicting severity of rhinovirus-associated wheeze
Authors: Giulia Cangiano, Elena Proietti, Marie Noelle Krönig, Elisabeth Kieninger, Meri Gorgievski, Maria Teresa Barbani, Laurent Kaiser, Caroline Tapparel, Marco Polo Alves, Nicolas Regamey
Journal: European Respiratory Journal (2012)

Background  Rhinovirus (RV) is a common cause of wheeze in childhood. Personal history of atopy, presence of siblings and day care attendance are known risk factors for severe RV-associated wheezing but objective markers predicting disease severity are lacking. We aimed at identifying such markers in a cohort of preschool children hospitalized for RV-associated wheezing.  Methods  Direct immunofluorescence for RV and other viruses was performed on nasopharyngeal aspirates (NPA) within the first 24 hours of hospitalisation of children aged 0-6 years. RV load, interferons (γ and λs) and cytokines (IL-4, 6, 8, 13, IP-10) were quantified by RT-PCR and ELISA and related to clinical parameters.  Results  Within a 4-years period (2007- 2011), we included 126 children (median (range) age: 1.66 (0.40-5.81) years). Presence of RV was confirmed by RT-PCR in all NPA samples. RV load was inversely related to age (r=-0.22, p=0.02) and correlated with the pro-inflammatory cytokines IL-8 (r=0.23, p=0.01) and IL-6 (r=0.35, p=0.001). There was no relationship between RV load or any IFNs cytokine level and clinical outcome parameters (clinical severity scores, length of hospitalisation and duration of oxygen therapy). Post-hoc analysis revealed a trend towards higher IL-6 levels of children with prolonged oxygen need (>1 vs. ≤1 days): (135 (5-789) vs.16 (5-244) pg/ml, p=0.07).  Conclusions  In our cohort, RV load and related antiviral and pro-inflammatory responses were not associated with disease severity. This may be due to the wide age-range of subjects studied. Whether IL-6 levels in NPA may help to predict clinical outcome in subgroups of children with RV-associated wheezing illnesses needs to be evaluated in further studies.
Immunologic Control of the Ascites Form of Murine Adenocarcinoma 755. II. Tumor Immunity Associated With a Friend-Moloney-Rauscher-Type Virus 2
Authors: Jeffrey J. Collins, Gary Roloson, Darrow E. Haagensen, Peter J. Fischinger, Samuel A. Wells, Walter Holder, Dani P. Bolognesi
Journal: JNCI Journal of the National Cancer Institute (1978)

We demonstrated that ADV, a murine C-type virus associated with tumor cells of the ascites form of adenocarcinoma 755 (AD755a), was closely related to the Friend and Rauscher murine leukemia agents, and we explored the role of virus-related antigens in the serum transfer rejection process. The syngeneic mouse anti-AD755a antiserum which was capable of transferring specific tumor immunity could neutralize ADV, Friend murine leukemia virus (F-MuLV), and Rauscher murine leukemia virus (R-MuLV) infectivity, as well as demonstrate group-specific reactivity for the major envelope glycoprotein (gp71) of murine leukemia virus (MuLV) in radioimmunoassay. The neutralizing activity appeared to be mainly type-specific for F-MuLV-R-MuLV-type viruses. The serum could also lyse mouse cells producing F-MuLV, but absorption studies with purified viruses and viral components indicated that this reactivity was only partially directed toward virus structural proteins. Similar absorptions revealed that the immune transfer capacity of the serum could not be removed by antigens present in the intact virus preparations. However, absorption with F-MuLV-infected cells, but not cells expressing AKR MuLV or mammary tumor virus antigens, could eliminate the protective capacity of the anti-AD755a serum. Nevertheless, direct immunization of C57BL/6 mice with F-MuLV could induce immunity to AD755a cells. These results suggested that the AD755a cells expressed at least two types of virus-related antigens: 1) virus structural antigens that were involved in the induction of specific tumor immunity subsequent to direct immunization and 2) virus-related cell-surface antigens that were primarily responsible for the induction of antibodies mediating the protective capacity of the anti-AD755a serum seen upon passive transfer.
Thyroid Enlargement in Lake Erie Coho Salmon
Authors: John J. Black, C. Lenore Simpson
Journal: JNCI Journal of the National Cancer Institute (1974)

Pennsylvania, New York, and Ohio introduced stocks of coho salmon, Oncorhynchus kisutch, into Lake Erie. Of 117 mature salmon examined during the 1972 spawning migration, 44% had grossly enlarged thyroids. Microscopic examination of the thyroids revealed marked hyperplasia. Local invasion was not considered evidence of neoplasia because of the diffuse nature of the normal fish thyroid. The presence of intravascular thyroid cells in one enlarged gland raised the possibility of superimposed carcinoma in some fish
Molecular characterization of mycobacterium tuberculosis resistant to fluoroquinolones, distributed in Saratov region
Authors: Tatiana Morozova, Tatiana Salina
Journal: European Respiratory Journal (2012)

Aim: To study the spectrum of mutations of gena gyrA M. tuberculosis, coding for drug-resistance to fluoroquinolones, in the Saratov region.  Methods: We examined 47 samples of sputum patients with active pulmonary tuberculosis. Detection of Mycobacterium tuberculosis (MBT) and determine their drug susceptibility to fluoroquinolones was performed using biological microchips. The results of the reaction were evaluated with the use of hardware-software complex Chipdetektor-01. Technology research, a set of reagents and equipment were developed by staff of the Institute of Molecular Biology (Biochip-IMB, Moscow).  Results: DNA M. tuberculosis were found in 39 (83%) patients. Mutations in the gene gyrA were identified in 22 (56,4%) samples, of which - in 13 (59%) found the mutation in codon 95 Ser (AGC) -> Thr (ACC) due to the natural polymorphism of the gene and do not lead to the development of drug resistance. In 9 (41%) samples identified mutations in 91 (33,3%), 94 (44,4%), 90 (22,2%) codons that encode resistance to fluoroquinolones. Primary drug resistance is set in 5 (12,8%) patients. In 4 cases revealed secondary drug resistance in patients, which received 90-120 doses antibacterial drugs. Of these, 3 cases have double mutations in gyrA /Asp94->Gly + Ala90->Val /; /Asp94->Ala + Ala90->Gly_a; Asp94->Gly + Ala90>Val/and in 1 patient was found a combination of four mutations. Conclusion: In the Saratov region primary resistance to fluoroquinolones at the level of genetic mutations was set in 12,8% cases. Was found the increase in the number of mutations among MBT strains isolated from patients receiving prolonged treatment with anti-TB drugs.
Epidemiologic Comparison of Breast Cancer Patients With Early and Late Onset of Malignancy and General Population Controls&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: T J Craig, G W Comstock, P B Geiser
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Epidemiologic Comparison of Breast Cancer Patients With Early and Late Onset of Malignancy and General Population Controls Get access Thomas J. Craig, M.D., Thomas J. Craig, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar George W. Comstock, M.D., George W. Comstock, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Patricia B. Geiser, R.N. Patricia B. Geiser, R.N. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 6, December 1974, Pages 1577–1581, https://doi.org/10.1093/jnci/53.6.1577 Published: 01 December 1974 Article history Received: 26 April 1974 Accepted: 20 August 1974 Published: 01 December 1974
Short and long-term outcomes after the first episode of non-invasive ventilation (NIV) for an acute exacerbation of COPD (AECOPD) on a general ward
Authors: K.H.M. Walraven, M. van Vliet, J.A. van Noord
Journal: European Respiratory Journal (2012)

Background NIV is an evidence based treatment for acute respiratory acidosis due to an AECOPD. However, less data exist on long-term prognosis after the first episode of NIV.

Aim To investigate the short and long-term outcomes after the first episode of NIV for AECOPD.

Method A retrospective, observational, cohort study of 183 patients admitted to the hospital between 2008-2011 for an acute respiratory acidosis due to AECOPD treated with NIV on a general ward. Potential prognostic factors were recorded.

Results During a 3-year period 275 admissions involving 183 patients were analysed. Included were 72 (39%) men and 111 (61%) women, with a mean age of 70 years (range 45-93y) and a mean FEV1 of 33% (range 12-74%). 34 (19%) patients were readmitted for NIV with an average of 3 admissions (range 1-9).

Success rate of NIV was 76% (211 of 275 episodes). In 24% (64 episodes) NIV failed: 32 patients died during NIV (all prior Do-Not-Intubate patients), 7 did not tolerate NIV and died (all prior DNI patients), 16 needed invasive ventilation at the ICU (2 died), 9 died because of a non-respiratory cause.

In-hospital mortality during the first admission was 21%. The mortality rate at 1 and 2 years was 48% and 53%, respectively. The cause of death was COPD in 70%, cardiovascular in 6%, miscellaneous in 24%.

Multivariate logistic regression analysis showed that higher age, persistent hypercapnia and domiciliary oxygen use were associated with bad prognosis. The parameters of severity of the first NIV episode were not prognostic.

Conclusion Success rate of NIV on a general ward is high (76%), but survival after 1 and 2 years is poor.