tbuckley/cabot-search huggingface dataset:
Rapid recovery of spermatogenesis after mitoxantrone, vincristine, vinblastine, and prednisone chemotherapy for Hodgkin's disease.
Authors: M L Meistrich, G Wilson, K Mathur, L M Fuller, M A Rodriguez, P McLaughlin, J E Romaguera, F F Cabanillas, C S Ha, L I Lipshultz, F B Hagemeister
Journal: Journal of Clinical Oncology (1997)

Because the effects of mitoxantrone on human male fertility were unknown, we determined prospectively the effects of three courses of mitoxantrone (Novantrone), vincristine (Oncovin), vinblastine, prednisone (NOVP) chemotherapy on the potential for fertility of men with Hodgkin's disease (HD).Semen analyses were performed on 58 patients with stages I-III HD before, during, and after chemotherapy and after the sperm count recovered from the effects of abdominal radiotherapy that was given after chemotherapy.Before the initiation of treatment, 84% of the patients were normospermic. Sperm counts declined significantly within 1 month after the start of NOVP chemotherapy. In the month after chemotherapy, 38% of patients were azoospermic, 52% had counts < 1 million/ mL, and 10% had counts between 1 and 3 million/mL. Between 2.6 and 4.5 months after the completion of chemotherapy, sperm counts recovered rapidly to normospermic levels in 63% of patients. In the remaining patients who were followed up for at least 1 year after standard upper abdominal radiotherapy, counts also recovered to normospermic levels.NOVP chemotherapy, like most other regimens, produced marked temporary effects or spermatogenesis. However, sperm production recovered very rapidly, within 3 to 4 months after the end of NOVP chemotherapy. This pattern was caused by killing differentiating spermatogenic cells, but there was little cytotoxicity or inhibition of stem cells from mitoxantrone or the other drugs. After the combination of NOVP plus abdominal radiotherapy, sperm counts and motility were restored in most patients to pretreatment levels, which were compatible with normal fertility.
Active smoking, COPD and arterial hypertension are independent prognostic factors for complications following Nd:YAG laser resection of central lung cancer
Authors: Bojan Zaric, Branislav Perin, Svetlana Jovanovic, Evica Budisin, Nensi Lalic, Goran Stojanovic
Journal: European Respiratory Journal (2011)

Introduction:  Major aim of this study was to investigate complication rate and identify clinical risk factors for complications following Nd:YAG laser resection in patients with advanced lung cancer.   Patients and methods:  We evaluated medical and bronchoscopy charts of 512 patient who underwent Nd:YAG laser resection as a part of multimodality treatment of lung cancer. Complications after laser resection were defined as: severe hypoxemia, global respiratory failure, arrhythmia requiring treatment, haemoptysis, pneumothorax, pneumomediastinum, pulmonary edema, trachea-esophageal fistulae and death. Risk factors were defined as: acute myocardial infarction within 6 months before treatment, hypertension, chronic arrhythmia, chronic obstructive pulmonary disease (COPD), stabilized cardiomyopathy, previous external beam radiotherapy, previous chemotherapy and previous interventional pulmonology treatment.   Results:  Overall complication rate was 8.4%. Statistically significant risk factors were: age (p=0.001), current smoking status (p=0.012), arterial hypertension (p   Conclusion:  Closer monitoring of patients with identified risk factors is advisable prior and immediately after laser resection. In order to avoid or minimize complications special attention should be directed towards patients who are current smokers (over 60 pack years), over 60 years of age, with arterial hypertension or COPD.
Do exhaled non-invasive inflammatory markers correlate with respiratory symptoms and lung function in a longitudinal study of childhood asthma?
Authors: Charlotte Robroeks, Quirijn Jöbsis, Ger Rijker, Will Wodzig, Aalt Bast, Edward Dompeling
Journal: European Respiratory Journal (2011)

Background: Worldwide the level of asthma control is far from optimal. Asthma management is currently based on symptoms and lung function indices. Non-invasive inflammatory markers like exhaled nitric oxide may have additional value for asthma management. Little longitudinal data are available.

Aim: To study the relationship between non-invasive inflammatory markers and conventional parameters, during stable periods and during exacerbations.

Methods: 40 Children with asthma (aged 5-16yrs), visited the outpatient clinic every two months during one year. In addition, 4 extra visits were planned during an exacerbation. Every visit the asthma control questionnaire (ACQ) was assessed, lung function was performed and non-invasive inflammatory markers (FeNO, and nitrate, 8-isoprostane, interleukin-5 and tumor necrosis factor-alpha in exhaled breath condensate) were measured.

Results: 16 Of the 40 children experienced an asthma exacerbation. No significant correlations were founds between non-invasive inflammatory markers and conventional parameters (Spearman, p>0.05).

View this table:

Correlations between conventional parameters and non-invasive inflammatory markers in childhood asthma





Conclusions: This study showed that exhaled non-invasive inflammatory markers provide additional information about childhood asthma compared to conventional parameters.
The chitinase-like protein YKL-40 is elevated in children with severe asthma
Authors: Anna James, Björn Nordlund, Jon Konradsen, Lovisa Johansson, Marri Verhoek, Rolf Boot, Sven-Erik Dahlén, Gunilla Hedlin
Journal: European Respiratory Journal (2011)

Background:  Chitinase family proteins are associated with airway inflammation in adults, yet it is unknown whether levels are altered in children with asthma. Our aim was to examine chitotriosidase (CHIT1) and YKL-40 (CHI3L1) as potential biomarkers of airway inflammation in children, taking into account possible effects of genetic variation.   Methods:  Blood samples were obtained from children aged 6-18 with controlled (n=39) and severe (n=57) asthma, described in Konradsen et al. (Pediatric Allergy Immunology 2011;22:9-18). Serum chitotriosidase activity and YKL-40 levels were analysed in a subset of patients and compared to 41 healthy children. DNA samples were genotyped for a null 24bp duplication in CHIT1 and the CHI3L1 promoter SNP Rs4950928.   Results:  YKL-40 levels were significantly greater in severe asthmatics compared to healthy children, whereas chitotriosidase activity was no different in asthmatics compared to controls. Genetic variation affected both YKL-40 levels and chitotriosidase activity. The CHI3L1 Rs4950928 CC allele was associated with greater levels of serum YKL-40 (24.3 (16.7-29.6)) than the CG allele (19.4 (14.9-23.3), p=0.008). Children lacking the 24bp duplication in CHIT1 showed greater chitotriosidase activity (68.0 (56.6-89.7)) than those heterozygous for the duplication (35.6 (26.9-41.8), p   Conclusions:  These results suggest that serum YKL-40 is a genetically influenced, potential new biomarker of airway inflammation in children.
The clinical dynamic changes and prognosis analysis in patients with cryptogenic organizing pneumonia
Authors: Xin Zhang
Journal: European Respiratory Journal (2011)

Background:  Cryptogenic organizing pneumonia (COP) is a common subtype of idiopathic interstitial pneumonia (IIP), which has a multivariate clinical feature.   Objectives:  To characterize the clinical dynamic changes and to identify predictive factors for relapse of patients with COP.   Methods:  73 COP patients were diagnosed in our hospital from Jan 1,1998 to Oct 1, 2009 and followed up until March 31, 2010.   Results:  1) 78.5% (57/73) Patients with subacute onset responded well to steroid. Most patients showed significant improvement during the first three months. 2) Consolidation, ground glass opacity and reticular shadow were three most common abnormal patterns on CT scan during the early stage of the disease. Ground glass opacity (GGO) could progress into consolidation, later, in turn, inverted into GGO and then resolved completely after corticosteroid treatment. Consolidation and ground glass opacity showed rapid and significant resolution after the treatment. Reticular shadow resolved slowly. 4) 23.3% (17/73) patients went through relapses. 70.6% (12/17) relapses occurred during the first year after the treatment when the steroid is stopped or tapering (≤10mg/d).   Conclusions:  1) COP runs a benign course and shows a significant improvement on pulmonary function test and Chest CT in response to steroids. 2) Relapses occur frequently when steroid is tapered ≤10mg/d or stopped, mostly during the first year. Relapses do not affect the outcome. 3) Deceased diffusing capacity and hypoxemia maybe important predictors of the relapses and tapering too fast may increase the risk of relapse.
Biologic Analysis of Fetal MRC Rat Lung Epithelial Cells Treated With 3-Methylcholanthrene in Culture: Premalignant and Malignant Stages2
Authors: Katsuhiko Indo
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Biologic Analysis of Fetal MRC Rat Lung Epithelial Cells Treated With 3-Methylcholanthrene in Culture: Premalignant and Malignant Stages Get access Katsuhiko Indo Katsuhiko Indo Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 2, February 1977, Pages 351–360, https://doi.org/10.1093/jnci/58.2.351 Published: 01 February 1977 Article history Received: 12 March 1976 Accepted: 25 May 1976 Published: 01 February 1977
The muscarinic M3 receptor regulates allergen-induced airway remodeling in mice
Authors: Loes Kistemaker, Sophie Bos, Machteld Hylkema, Pieter Hiemstra, Jurgen Wess, Herman Meurs, Huib Kerstjens, Reinoud Gosens
Journal: European Respiratory Journal (2013)

RATIONALE  Asthma is a chronic obstructive airway disease, characterized by inflammation and remodeling. Acetylcholine (ACh) contributes to asthma symptoms by inducing bronchoconstriction via the muscarinic M 3  receptor. Recent evidence suggests that ACh also regulates airway inflammation and remodeling. Therefore, we studied the contribution of the M 3  receptor to allergen-induced inflammation and remodeling using M 3  receptor subtype deficient (M 3 R -/- ) mice. Wild type (WT), M 1 R -/-  and M 2 R -/-  mice were used as controls.  METHODS  Female C57Bl/6 mice (n=8-10) were sensitized and challenged with ovalbumin (twice weekly, for 4 weeks). Control animals were challenged with saline. Lungs were collected for analyses.  RESULTS  Allergen exposure induced goblet cell metaplasia, airway smooth muscle thickening, pulmonary vascular smooth muscle remodeling and increased deposition of collagen I and fibronectin in the airway wall of WT mice. These effects were partly to fully prevented in M 3 R -/-  mice, whereas M 1 R -/-  and M 2 R -/-  mice responded similar to WT mice. In addition, airway smooth muscle mass and pulmonary vascular smooth muscle mass were lower in saline-challenged M 3 R -/-  mice compared to WT mice. Interestingly, allergen-induced airway inflammation, measured as eosinophil infiltration and cytokine release (IL-4, IL-5, IL-13 and IL-17), was similar in all strains.  CONCLUSION  Our data indicate that ACh contributes to allergen-induced remodeling and smooth muscle mass via the M 3  receptor, and not via M 1  or M 2  receptors. Surprisingly, no role for individual muscarinic receptor subtypes in allergic inflammation was observed, suggesting that the role of ACh in remodeling is independent of the allergic inflammatory response.
Chemotherapy Dose-Intensification for Pediatric Patients With Ewing's Family of Tumors and Desmoplastic Small Round-Cell Tumors: A Feasibility Study at St. Jude Children's Research Hospital
Authors: Neyssa M. Marina, Alberto S. Pappo, David M. Parham, Alvida M. Cain, Bhaskar N. Rao, Catherine A. Poquette, Charles B. Pratt, Carol Greenwald, William H. Meyer
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To evaluate the feasibility of dose-intensification for patients with Ewing's family of tumors (EFT) and desmoplastic small round-cell tumors. PATIENTS AND METHODS: From February 1992 to June 1996, we treated 53 consecutive patients on our Ewing's protocol. Induction comprised three cycles of ifosfamide/etoposide on days 1 to 3 and cyclophosphamide (CTX)/doxorubicin on day 5, followed by granulocyte colony-stimulating factor. Local control using surgery and/or radiotherapy started at week 9 along with vincristine/dactinomycin. Maintenance included four alternating cycles of ifosfamide/ etoposide and doxorubicin/CTX, with randomization to one of two CTX dose levels to determine the feasibility of dose-intensification during maintenance. RESULTS: Patients had a median age of 13.4 years (range, 4.5 to 24.9 years); 34 patients were male and 43 patients were white. Nineteen patients presented with metastatic disease, 29 had tumors greater than 8 cm in diameter, and 26 had primary bone tumors. These patients received 155 induction cycles, 91% of which resulted in grade 4 neutropenia, 68% in febrile neutropenia, and 68% in grade 3 to 4 thrombocytopenia. During maintenance, grade 4 neutropenia and grade 3 to 4 thrombocytopenia occurred in 81% and 85% of cycles, respectively. Thirty-five patients (66%) completed all therapy, only 13 without significant delays; three developed secondary myeloid malignancies. The toxicity and time to therapy completion were similar in both CTX arms. Estimated 3-year survival and event-free survival were 72% ± 8% and 60% ± 9%, respectively. CONCLUSION: Although intensifying therapy seems feasible for 25% of patients on this study, toxicity was considerable. Therefore, the noninvestigational use of dose-intensification in patients with EFT should await assessment of its impact on disease-free survival.
Methacholine hyperresponsiveness in adults born extremely preterm
Authors: Maria Vollsæter, Hege Clemm, Ola Røksund, Trond Markestad, Thomas Halvorsen
Journal: European Respiratory Journal (2013)

Introduction: Bronchial hyperresponsiveness (BHR) has repeatedly been reported in children born extremely preterm (EP). We followed survivors of EP birth from adolescence to adulthood and measured their BHR to methacholine.

Methods: A population based cohort of 48 (94%) of 51 survivors born at gestational age ≤ 28 weeks or birthweight ≤ 1000 gram in 1982-85 performed methacholine provocation test (PD20) at 18 and 25 years of age, together with 46 matched control subjects born at term. Mild bronchopulmonary dysplasia (BPD) was diagnosed if supplemental oxygen was required at ≥ 28 postnatal days and moderate/severe (M/S) BPD if still required at postmenstrual age ≥ 36 weeks. BHR was defined by PD20 ≤ 8 µmol methacholine. A dose-response slope was estimated as the ratio between % decline in FEV1 and administered dose of methacholine.

Results: At 18 years of age, 41/51 (80%) preterm survivors and 46 control subjects were tested. Twelve (26%) controls tested positive compared to 4 (40%) non BPD, 13 (65%) mild BPD and 7 (64%) M/S BPD subjects (p=0.001 case vs. control). At 25 years of age, 37 (73%) preterms and 36 (78%) controls were retested; positive tests obtained from 6 (17%) controls compared to 5 (56%), 10 (59%) and 4 (36%) EP born subjects according to BPD status as above (p=0.004). Dose response slope at follow-up was not significantly influenced by a neonatal BPD at age 25, nor did development over time differ significantly between subgroups (test of interaction, p=0.198).

Conclusion: BHR after extreme preterm birth persists to adulthood, although with a numerical tendency for improvement in those with the most severe neonatal BPD who were also those with the most severe BHR in adolescence.
Dystrophic epidermolysis bullosa.
Authors: V.N. SEHGAL, V.L. REGE, S.K. GHOSH, S.M. KAMAT
Journal: British Journal of Dermatology (1977)

Involvement of the large intestine in a long standing case of dystrophic epidermolysis bullosa was characterized by recurrent episodes of diarrhoea synchronizing with exacerbation ofthe skin lesions. The radiological investigations revealed two narrow segments, one each in the descending and transverse colon, with ulcer craters in the lower part of the former. The haustra from the distal half of the transverse colon to the sigmoid colon were lost.
A phase I-II trial of induction chemotherapy with carboplatin and fluorouracil in locally advanced head and neck squamous cell carcinoma: a report from the UCL-Oncology Group, Belgium.
Authors: V Grégoire, M Beauduin, Y Humblet, M Hamoir, J Longueville, F Majois, F M Remacle, F Rousseau, E Salamon, A Wambersie
Journal: Journal of Clinical Oncology (1991)

Eighty-three patients (median age, 56 years and Karnofsky performance status greater than or equal to 70) were treated with carboplatin (Carbo) and fluorouracil (5Fu) for stage III and IV head and neck squamous cell carcinoma (HNSCC). 5Fu (1 g/m2/d) was administered from day 1 to 4 by continuous infusion. Carbo was given on day 1 and, in order to evaluate its maximum-tolerated dose (MTD), the dose level was progressively increased from 250 mg/m2 to 450 mg/m2. The effectiveness of this association and its potential role in local control were also evaluated. Three patients received Carbo at a dose of 250 mg/m2, 13 received 300 mg/m2, one received 330 mg/m2, 12 received 350 mg/m2, six received 375 mg/m2, 26 received 400 mg/m2, 18 received 420 mg/m2, and four received 450 mg/m2. Two (13 of 83) or three courses (64 of 83), repeated every 4 weeks, were administered. The overall (primary tumor and node) response and complete response (CR) rates were 33% and 14%, respectively. For primary tumor, the response rate (RR) was 57% with 32% CR and 18% pathologic complete response (PCR); the RR was higher for patients with oropharyngeal tumor (76%, P = .037) and for patients treated with Carbo greater than or equal to 350 mg/m2 (65%, P = .02); the tumor size (T1 + T2 v T3 + T4) was a good prognostic factor for RR (90% v 46%, P = .001), CR (65% v 20%, P less than .001), and PCR (45% v 8%, P less than .001). For nodes, the RR was 33% with 11% CR. Grade 3-4 neutropenia and thrombocytopenia were experienced by 17% and 28% of the patients treated with 420 mg/m2 of Carbo and by 50% of the patients treated with 450 mg/m2. The MTD can be fixed at 420 mg/m2 and the proposed dose at 400 mg/m2. Thirty-eight patients were treated with surgery plus radiotherapy, 33 with radiotherapy alone, and seven with surgery alone. The median follow-up is 12 months. The 18-month disease-free survival (DFS) is 78% for overall complete responders and 39% for the others (P = .04). There is no primary tumor recurrence among the 12 patients with a primary tumor PCR treated by radiotherapy alone for tumor control (median follow-up, 17.3 months). The association of Carbo-5Fu is a safe induction chemotherapy regimen for HNSCC. The proposed dose of Carbo for future treatment is 400 mg/m2.(ABSTRACT TRUNCATED AT 400 WORDS)
Inhibition of JNK Sensitizes Hypoxic Colon Cancer Cells to DNA-Damaging Agents
Authors: Irina A. Vasilevskaya, Muthu Selvakumaran, Lucia Cabal Hierro, Sara R. Goldstein, Jeffrey D. Winkler, Peter J. O'Dwyer
Journal: Clinical Cancer Research (2015)

We showed previously that in HT29 colon cancer cells, modulation of hypoxia-induced stress signaling affects oxaliplatin cytotoxicity. To further study the significance of hypoxia-induced signaling through JNK, we set out to investigate how modulation of kinase activities influences cellular responses of hypoxic colon cancer cells to cytotoxic drugs.In a panel of cell lines, we investigated effects of pharmacologic and molecular inhibition of JNK on sensitivity to oxaliplatin, SN-38, and 5-FU. Combination studies for the drugs and JNK inhibitor CC-401 were carried out in vitro and in vivo.Hypoxia-induced JNK activation was associated with resistance to oxaliplatin. CC-401 in combination with chemotherapy demonstrates synergism in colon cancer cell lines, although synergy is not always hypoxia specific. A more detailed analysis focused on HT29 and SW620 (responsive), and HCT116 (nonresponsive) lines. In HT29 and SW620 cells, CC-401 treatment results in greater DNA damage in the sensitive cells. In vivo, potentiation of bevacizumab, oxaliplatin, and the combination by JNK inhibition was confirmed in HT29-derived mouse xenografts, in which tumor growth delay was greater in the presence of CC-401. Finally, stable introduction of a dominant negative JNK1, but not JNK2, construct into HT29 cells rendered them more sensitive to oxaliplatin under hypoxia, suggesting differing input of JNK isoforms in cellular responses to chemotherapy.These findings demonstrate that signaling through JNK is a determinant of response to therapy in colon cancer models, and support the testing of JNK inhibition to sensitize colon tumors in the clinic.
Effect of Early Adversity and Childhood Internalizing Symptoms on Brain Structure in Young Men
Authors: Sarah K. G. Jensen, Erin W. Dickie, Deborah H. Schwartz, C. John Evans, Iroise Dumontheil, Tomáš Paus, Edward D. Barker
Journal: JAMA Pediatrics (2015)

Early adversity is an important risk factor that relates to internalizing symptoms and altered brain structure.
Immunoglobulin A: Strategic Defense Initiative at the Mucosal Surface
Authors: B J Underdown, J M Schiff
Journal: Annual Review of Immunology (1986)

IgA is the predominant immunoglobulin in the external secretions of humans. Specific IgA-producing cells home to mucosal epithelia through­ out the body to provide humoral protection as a frontline defense against pathogens borne in aerosols, the environment, and the diet. Much of the recent research on IgA has been directed toward three central questions: (a) What are the factors that account for the localization and regulation of IgA-producing cells at the mucosae; (b) What is the nature of the mechanism that selectively transports secretory IgA to the mucosal lumen; and (c) What are the physiologically important roles of IgA, both in blood and in the exocrine environment. Regulation of IgA production is an extensive topic in itself and will be touched on here only briefly. We concentrate on the fate and function of IgA after synthesis and try to assess which of its experimentally described properties are essential for IgA to contribute to the well-being of the host.
The frequency of REM related OSA among patients with mild OSA and the relation between apnea and daytime sleepiness among these patients
Authors: Hatice Kutbay Özçelik, Muhammed Emin Akkoyunlu, Pinar Bostanli, Mehmet Bayram, Fatmanur Karaköse, Murat Sezer, Levent Kart
Journal: European Respiratory Journal (2012)

Aim: The question if REM related OSA is a specific clinical entity or if it is an early sign of severe sleep disordered breathing as there is high occurrence of REM OSA in mild and moderate cases, recently have attracted the investigators. In this study, we aimed to see the frequency of REM related OSA among patients with mild OSA; and also to evaluate relation between apnea and daytime sleepiness among REM related OSA patients.

Methods: 134 patients with mild OSA (RDI=5-15) among 1267 patients with PSG examination at sleep laboratory of Bezmialem University Hospital between August 2010 and February 2012 were retrospectively evaluated. Patients having REM apnea / Non REM apnea >2 and Non REM apnea <15 are considered as REM related OSA.

Results: 80 of 134 (%59) patients with mild OSA were considered as REM related OSA. When REM related OSA and Non-REM OSA are compared for age, gender, daytime sleepiness, BMI, neck surround and aditional diseases; mean age of REM related OSA group was found only significantly lower. Number of apnea in REM was over 15 at 87.3% of REM related OSA group and over 30 at 39.3% of them. There was no relation between apnea number at REM and daytime sleepiness symptom (p=0,81).

Conclusion: We may consider the result of lower mean age in REM related OSA group as a supporting result for early sign of severe sleep disordered breathing. We consider to follow up this group of patients to answer the question about subject.