tbuckley/cabot-search huggingface dataset:
Acute bronchitis morbidity in railway and subway train machinists
Authors: Elena Amelchenko, Tatyana Rybina, Oksana Omelyanenko
Journal: European Respiratory Journal (2012)

Background: Upper respiratory tract diseases takes the first place in personified morbidity structure in Minsk (Belarus) subway train machinists.We aimed to reveal the probable reasons for high rate of acute bronchitis (AB) in subway train machinists. Methods: Prospective, longitudinal study included 2 comparable groups: the 1st – 1068 subway train machinists, mean age 33,9±8,9 years, mean length of service 8,84±6,6 years; the 2nd – 1212 railway train machinists, mean age 43,3±6,8 years, mean length of service 12,0±9,9 years. AB personified morbidity was assessed during 2005-2008. Results: AB personified morbidity in the 1st group was higher then in the 2nd group (29,7 cases and 286,4 days per 100 workers vs. 4,87 cases and 46,6 days per 100 workers respectively, p<0,05). Odds ratio(OR)for subway train machinists was 6,1±0,14 (OR±m), 95% confidence interval - [4,68; 7,95], etiological portion - 83,6%.The highest morbidity level in the 1st group was established in the age interval of 30-39 years and length of service range 5-9 years compared with those in other age intervals (37,2 cases per 100 workers, p<0,01). We found statistically reliable morbidity decrease among subway train machinists in summer in comparison with the other seasons (4,78 vs. 8,3 cases per 100 workers, p<0,01). No any correlation has been found between the AB morbidity and age, length of service and season in the 2nd group. Conclusions: AB morbidity risk in subway train machinists could probably be related to the occupational exposure of the biological factor in underground work environment. Biological factor influence in underground could derive from the lack of ultraviolet insolation and large volume of passenger traffic.
Prospective randomized placebo-controlled study of granulocyte-macrophage colony-stimulating factor without stem-cell transplantation after high-dose melphalan in patients with multiple myeloma.
Authors: P Moreau, D Fiere, W R Bezwoda, T Facon, M Attal, J P Laporte, P Colombat, H L Haak, M Monconduit, H Lockhorst, D Girault, J L Harousseau
Journal: Journal of Clinical Oncology (1997)

PURPOSE To evaluate the impact of granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo on the durations of intravenous (IV) antibiotic use, hospitalization, neutropenia, and fever, as well as remission rates, after high-dose melphalan (HDM) without stem-cell transplantation (SCT) in patients with multiple myeloma (MM). PATIENTS AND METHODS One hundred two patients with high-risk MM were randomized 2:1 in a prospective multicenter trial to receive 5 microg/kg/d GM-CSF (69 patients) or placebo (33 patients) starting the day after 140 mg/m2 IV melphalan for up to 21 days. RESULTS GM-CSF significantly reduced neutropenia after HDM (median, 23.5 v 29 days; P = .0468), with a trend to reduce the duration of hospitalization (median, 32 v 38 days; P = .0841). Nevertheless, GM-CSF did not significantly reduce infectious toxicity as regards the number of days with fever (median, 5 v 3; P = .359), the number of days with IV antibiotics (median, 22 v 27; P = .14), or early deaths, with an 11.5% treatment-related mortality rate in the GM-CSF group (eight of 69 v two of 32 patients in the placebo group; P = .686). There was no difference in response rates between the two groups of patients. CONCLUSION GM-CSF after HDM without SCT is feasible and significantly shortens neutropenia with a trend toward reduction of hospitalization duration, but does not significantly reduce the morbidity and mortality of such therapy. Thus, when intensive therapy is indicated, given that the mortality of HDM followed by SCT reported in the literature is less than 5% and patients are discharged at approximately day 15, despite the risk of contamination by clonogenic malignant cells, SCT appears to be preferable to GM-CSF after HDM.
Teichoic acids of group D streptococci with special reference to strains from pig meningitis (Streptococcus suis).
Authors: S D Elliott, M McCarty, R C Lancefield
Journal: The Journal of Experimental Medicine (1977)

Immunoelectrophoresis revealed in phenol extracts from S. faecalis and S. faecium a mixture of free and lipid-bound teichoic acids, both reactive with Group D antisera. In phenol extracts from S. suis only lipid-bound teichoic acid, also reactive with Group D antiserum, was seen. This difference probably accounts for the low yield of Group D antigen from S. suis as compared with S. faecalis and S. faecium when heating at pH 2 is used for extraction. When phenol is used good yields are obtained from S. suis as well as from S. faecalis and S. faecium. Lipoteichoic acids from S. faecalis and S. faecium have a backbone structure the same as or similar to that of Group A streptococcal teichoic acid. Lipoteichoic acid from S. suis has a structure differing from that of S. faecalis and S. faecium, e.g., possibly in the attachment of its glucosyl substituents. Precipitation reactions between S. suis lipoteichoic acid and Group D antisera were specifically inhibited by glucose. Reactions between S. bovis phenol extracts and some Group D antisera were also specifically inhibited by glucose, but extracts from S. faecalis and S. faecium were not. This may indicate a monosaccharide glucosyl substituent in teichoic acid from S. suis and S. bovis instead of the di- or trisaccharide previously postulated as the glucosyl substituent in the teichoic acid of S. faecalis.
Science, medicine, and the future: Role of molecular cell biology in understanding disease
Authors: J. Savill
Journal: BMJ (1997)

<h3>Abstract</h3> Molecular techniques have revolutionised our knowledge of cell and tissue function in both health and disease. We already have new and powerful treatments based on an understanding of communication between cells by messenger molecules called cytokines. Furthermore, there is great therapeutic promise in defining molecules which regulate cell adhesion, motility, proliferation, survival, and death. Rational manipulation of cell and tissue function for therapeutic ends may be much closer than you think.
Nocturnal Risk of Gout Attacks
Authors: Hyon K. Choi, Jingbo Niu, Tuhina Neogi, Clara A. Chen, Christine Chaisson, David Hunter, Yuqing Zhang
Journal: Arthritis & Rheumatology (2014)

Several plausible mechanisms and anecdotal descriptions suggest that gout attacks often occur at night, although there are no scientific data supporting this. We undertook this study to evaluate the hypothesis that gout attacks occur more frequently at night. We conducted a case-crossover study to examine the risk of acute gout attacks in relation to the time of the day. Gout patients were prospectively recruited and followed up via the internet for 1 year. Participants were asked about the following information concerning their gout attacks: the date and hour of attack onset, symptoms and signs, medication use, and purported risk factors during the 24- and 48-hour periods prior to the gout attack. We calculated the odds ratios (ORs) of gout attacks (with 95% confidence intervals [95% CIs]) according to three 8-hour time blocks of the day (i.e., 12:00 AM to 7:59 AM, 8:00 AM to 3:59 PM [reference], and 4:00 PM to 11:59 PM) using conditional logistic regression. Our study included 724 gout patients who experienced a total of 1,433 attacks (733, 310, and 390 attacks during the first, second, and third 8-hour time blocks, respectively) over 1 year. The risk of gout flares in the 8-hour overnight time block (12:00 AM to 7:59 AM) was 2.36 times higher than in the daytime (8:00 AM to 3:59 PM) (OR 2.36 [95% CI 2.05-2.73]). The corresponding OR in the evening (4:00 PM to 11:59 PM) was 1.26 (95% CI 1.07-1.48). These associations persisted among those with no alcohol use and in the lowest quintile of purine intake in the 24 hours prior to attack onset. Furthermore, these associations persisted in subgroups according to sex, age group, obesity status, diuretic use, and use of allopurinol, colchicine, and nonsteroidal antiinflammatory drugs. These findings provide the first prospective evidence that the risk of gout attacks during the night and early morning is 2.4 times higher than in the daytime. Further, these data support the purported mechanisms and historical descriptions of the nocturnal onset of gout attacks and may have implications for antigout prophylactic measures.
Carcinogenicity of Diallylnitrosamine Following Intragastric Administration to Syrian Hamsters&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: C J Grandjean, J Althoff, P M Pour
Journal: JNCI Journal of the National Cancer Institute (1985)

Single and multiple intragastric doses of diallylnitrosamine [(DAN) CAS: 16338-97-9] administered to Syrian golden hamsters induced tumors, primarily of the respiratory tract, in which the nasal cavity epithelium was the preferred site. When compared to the effect of DAN after subcutaneous administration at equal doses, the incidence of respiratory tract tumors was lower but that of hepatic tumors was higher, suggesting partial metabolism of DAN in the liver. Comparative metabolic and mutagenesis studies in BD IX rats (which reportedly are refractory to the carcinogenic effects of DAN), in Wistar rats, and in Syrian hamsters showed that a greater proportion of orally administered DAN was exhaled by both rat strains (12-19%) than by hamsters (2-4%). The activity of the microsomal fraction of the hamster liver for metabolizing DAN to allyl alcohol was about 10 times higher than that in rats, whereas no significant species differences were found with the cytosolic fraction. Pretreatment of animals with phenobarbital (PB) or pregnenolone-16 alpha-carbonitrile (PCN) did not influence either microsomal or cytosolic enzyme activities in hamsters, whereas about a tenfold increase in enzyme activities was seen after pretreatment with PB in both rat strains and following PCN in Wistar rats. Moreover, in bacterial mutagenesis assays, hamster liver microsomes were twice as active as those in BD IX rats. The results are discussed in relation to the carcinogenicity of DAN in rats and hamsters.
Primary lymphomas of the central nervous system: patterns of failure and factors that influence survival.
Authors: J S Loeffler, T J Ervin, P Mauch, A Skarin, H J Weinstein, G Canellos, J R Cassady
Journal: Journal of Clinical Oncology (1985)

Primary lymphomas of the CNS are rare tumors accounting for less than 2% of all extranodal non-Hodgkin's lymphomas. The treatment for this disease has been disappointing. Radiation therapy and surgery have produced consistently poor control of this disease, with a median survival of 15 months. We have reviewed ten cases of primary lymphoma of the CNS treated at the Joint Center for Radiation Therapy or Dana-Farber Cancer Institute (Boston) from 1968 to 1981. All patients had biopsy-proven CNS lymphomas without systemic disease at presentation. In our series, control of CNS lymphoma was seen only in patients receiving craniospinal radiation or CNS-penetrating chemotherapy.
Cyst fluid from human autosomal dominant polycystic kidneys promotes cyst formation and expansion by renal epithelial cells in vitro.
Authors: M Ye, M Grant, M Sharma, L Elzinga, S Swan, V E Torres, J J Grantham
Journal: Journal of the American Society of Nephrology (1992)

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive renal enlargement, culminating in renal insufficiency in over one half of affected individuals. The highly variable onset and clinical course of ADPKD may be due to factors extrinsic to the genetically defined renal cysts. In this study, cyst fluid samples from 12 nonazotemic and 18 azotemic ADPKD subjects were examined for in vitro biologic activity that promotes cellular proliferation and the secretion of fluid by renal epithelial monolayers, two pathogenetic mechanisms that have critical roles in the formation and the rate of expansion of renal cysts. Cyst fluid added to culture medium (final concentrations, 1 to 20%) caused Madin-Darby canine kidney cells and human kidney cortex (HKC) cells derived from primary cultures to form cysts in Type I collagen matrix. Cyst fluid stimulated the net transepithelial secretion of fluid by polarized monolayers composed of these same cells. Absolute levels of fluid secretory activity determined by MDCK bioassay were correlated directly with the rate of fluid secretion by HKC cell monolayers and with the extent of cyst formation by MDCK and HKC cells embedded in collagen matrix. The secretory activity of urine was negligible; secretory activity was detectable in the serum of normal and ADPKD subjects, but the levels were much lower than in cyst fluid. cAMP agonists prostaglandins E1 and E2, arginine vasopressin, and 8-Br-cAMP stimulated fluid secretion by MDCK and HKC monolayers, but these substances did not cause HKC cells to form cysts in collagen matrix, whereas cyst fluid did. Among other naturally occurring growth factors and autacoids, only epidermal growth factor and transforming growth factor alpha stimulated cyst formation by HKC cells; however, the capacity of cyst fluid to stimulate fluid secretion was not affected by treatment with antiserum to epidermal growth factor. It was concluded that potent, and possibly unique, substances in the cyst fluids of individuals with ADPKD support and augment biologic processes in renal epithelial cells that may be important in the promotion of progressive cyst expansion.
Results of the United Kingdom Children's Cancer Study Group first Wilms' Tumor Study.
Authors: J Pritchard, J Imeson, J Barnes, S Cotterill, D Gough, H B Marsden, P Morris-Jones, D Pearson
Journal: Journal of Clinical Oncology (1995)

PURPOSE The first United Kingdom Children's Cancer Study Group (UKCCSG) Wilms' Tumor Trial (UKW1) applied treatment regimens stratified by stage and histology in accordance with National Wilms' Tumor Study (NWTS) criteria, seeking to reduce treatment of low-stage, favorable-histology (FH) tumors without impairing survival and to improve prognosis of stage III and IV (FH) and unfavorable-histology (UH) tumors with more intensive chemotherapy. PATIENTS AND METHODS Three hundred eighty-four consecutively diagnosed patients with Wilms' tumor were recruited from the 20 UKCCSG centers and Oslo, Norway, between January 1980 and June 1986. The regimen for stage I patients was vincristine (Vcr) only, while stage II patients received Vcr and dactinomycin (Act-D). Stage III patients received three-drug therapy and stage IV and UH patients four-drug regimens. Act-D was given as pulsed doses of 1.5 mg/m2 every 3 or every 6 weeks. No lung irradiation was used in stage IV patients. No randomized comparisons were attempted. End points were survival and event-free survival (EFS). RESULTS Survival at 6 years in FH patients was 96% for stage I, 93% for stage II, 83% for stage III, 65% for stage IV, and 50% for UH patients of all stages. CONCLUSION Vcr alone is as effective for stage I FH tumors as the two-drug regimen used in the NWTS and International Society of Pediatric Oncology (SIOP) studies. Fractionation of Act-D is unnecessary. The poorer results for stage IV FH and UH patients compared with the NWTS may be due to treatment differences, such as the use of lung irradiation for stage IV FH patients in NWTS3, and/or to case selection bias.
Specific pulmonary arterial hypertension therapy in COPD patients with severe pulmonary hypertension
Authors: George Calcaianu, Armelle Schuller, Ari Chaouat, Matthieu Canuet, Romain Kessler
Journal: European Respiratory Journal (2014)

Background: The efficacy of specific (PAH) therapy in COPD with severe PH (mPAP>35mmHg) is not known.

Aim: to describe the clinical and pulmonary hemodynamic follow up data after 3 months of specific PAH therapy in COPD with severe PH.

Material and methods: We assessed NYHA class, 6-minute walk distance (6MWD) and pulmonary hemodynamic in a cohort of 37 patients with COPD and severe PH recruited between 2008 and 2013. Patients were evaluated at baseline and after 3 months PAH treatment (n=26).

Results: Patients characteristics were (mean ± SD) age: 70±10 years, body mass index: 27±8 kg/m2,NYHA dyspnea scale: 3±1, 6MWD: 244±105m, PaO2: 51±10 mmHg, FEV1: 55±24%pred, diffusion capacity of CO (DLCO): 30±13% pred,mPAP: 42±8 mmHg, cardiac index (CI): 2.9±0.8 l/min/m2, PVR: 7.6±4.2 Wood units.

Correlations of baseline variables showed that PVR was correlated with FEV1/DLCO(r=0.62, p=0.004) and BNP (r=0.41, p=0.03). CI was inversely correlated with FEV1/DLCO(r=-0.54, p=0.006).

After 3 months of specific PAH treatment, we found an improvement of cardiac index (+0.38 ± 0.61 l/min/m2, p=0.006), a reduction of PVR (mean=-1.8 ± 2.9 Wood units, p=0.018). PaO2 decreased significantly (mean=-2.5 ± 6 mmHg, p=0.046).

Conclusion: Specific PAH treatment improved pulmonary hemodynamic in this series of COPD patients with severe PH but without significant changes of NYHA functional class and 6MWD.

Key words: COPD, severe pulmonary hypertension.
Enzastaurin (LY317615.HCl) inhibits human lung cancer cells in vitro and in vivo: a pharmacodynamic study
Authors: Daniel Chan, Victor Chen, Zhiyong Zhang, Di Zheng, Alexandra Dulude, Barbara Helfrich, Fred Hirsch, Eji Nakajima, Michael Clay, Doreen Ma, Paul Bunn
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

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PKCβ is a member of the PKC family of serine-threonine protein kinases which have been implicated in human cancer proliferation, cell cycle progression, angiogenesis and apoptosis. Enzastaurin (LY317615), a selective PKCβ inhibitor, has been shown to inhibit a variety of human tumors including glioblastoma, colon, prostate and lung cancer cell lines in vitro. Elevated phosphorylation and altered PKC expression has been demonstrated in several NSCLC cell lines versus normal lung epithelia cell lines. In this presentation we show that enzastaurin inhibited the growth of 14 NSCLC cell lines with average IC50 of 8.2 µM, ranging 1.5 to 20 µM and 14 SCLC cell lines with average IC50 of 7.0 µM, ranging 3 to 10 µM. The sensitivities toward enzastaurin among the four different NSCLC histologies (adenocarcinomas, squamous, large cell carcinomas or bronchial alveolar carcinoma) are very similar. By western blot analysis, we found that enzastaurin significantly reduced phosphorylation of GSK3β (Ser9), ribosomal protein S6 (Ser240 /244) but not in phospho-AKT(Thr308) in both NSCLC and SCLC cell lines. Using Combination-Index analysis, when enzastaurin was combined with pemetrexed concurrently or pemetrexed followed by enzastaurin sequentially, the interaction is greater than additive. Our in vivo studies showed that enzastaurin by daily BID oral gavages at 38, 75 and 150 mg/kg suppressed human lung xenografts H2122 adenocarcinomas in athymic nude mice, but not in a dose-dependent manner. In conjunction with efficacious studies of enzastaurin in tumor bearing nude mice, plasma pharmacokinetics were evaluated on day 3, 10 or 21 following the start of dosing. The plasma enzastaurin levels for these days were found to be 1180±58.6, 931.3±399 and 1018.7±158 ng/ml for 38 mg/kg dose; 636.5±414, 2093.3±432 and 1830±355 ng/ml for 75 mg/kg dose; 2473.3±169, 2906.7±370 and 5020±790 ng/ml for 150 mg/kg respectively, supporting the observed therapeutic effects of enzastaurin against human lung xenografts. Our preclinical data provided strong evidence that enzastaurin may be effective for the treatment of human lung cancers.
Comparison of referral patterns between a respiratory laboratory in the Republic of Ireland and Western Australia
Authors: Elizabeth Salamon, Maria Stack, Kevin Gain
Journal: European Respiratory Journal (2011)

Background: Respiratory diseases account for 13% of deaths in the Republic of Ireland (ROI), and 8% in Western Australia (WA) each year.

County Cork has a population of 0.5 million and is serviced by Cork University Hospital (CUH), one other public, and one private hospital laboratory. CUH has 815 beds and is the principle teaching hospital.

Located in the city centre, Royal Perth Hospital (RPH) is the largest teaching hospital (855 beds) in WA, which has a population of 2.2 million. This area is also serviced by three other teaching hospitals, and numerous private laboratories.

Aim: To compare test request profiles of two public respiratory laboratories in ROI and WA.

Method: Referrals to each laboratory between 1st November 2009 and 31st October 2010, were reviewed.

Results: CUH performed 5360 tests on 2104 patients, aged 5-90 years. 9% were repeat visits within the time frame. RPH performed 5766 tests on 2336 patients, aged 13-98 years. 14% were repeat visits. The tests offered and diagnoses are presented.

View this table:



Discussion: The number of patients seen, and number of tests per patient were comparable. Specialist nurses at CUH also perform spirometry which is reflected in the reduced number of COPD and cancer patients seen in the laboratory.
Effect of ivacaftor on lung clearance index and FEV1 in subjects with CF who have the G551D-CFTR mutation and mild lung disease
Authors: Felix Ratjen, Helen Sheridan, Po-Shun Lee, Tao Song, Anne Stone, Jane Davies
Journal: European Respiratory Journal (2012)

Objectives:  This study assessed the use of LCI as a more sensitive measure of improvement in lung function in subjects with FEV 1  in the normal range   Methods:  This Phase 2, randomized, double-blind, placebo-controlled, multicenter, crossover study evaluated the effect of ivacaftor on LCI derived from multiple breath washout of SF6 using an open system Innocor device. Key inclusion were age ≥6 years, a  G551D-CFTR  mutation on at least one allele, FEV 1  >90% predicted, and LCI >7.4 (upper limit of normal). Ivacaftor 150 mg or placebo was administered q12h for two 4-week periods with a 4-week washout in between.   Results:  Mean (SD) baseline parameters for the 20 randomised patients were 16.6 (10.9) years for age, 9.0 (1.5) for LCI and 97.2 (10.6) percent predicted for FEV 1 . The treatment effect of ivacaftor for adjusted mean change from baseline in LCI at Day 29 was -2.07 (P=0.0004) whereas the mean change from baseline in FEV 1  was 7.0% (P=0.0117). Treatment difference for the mean change from baseline in sweat chloride was -45.8 mmol/L (P   Conclusions:  In subjects with CF who have mild lung disease, ivacaftor treatment improved ventilation inhomogeneity as measured by LCI and respiratory function as measured by percent predicted FEV 1 . Adverse events were consistent with previous ivacaftor studies and mostly related to manifestations of CF.  Sponsored by Vertex.