tbuckley/cabot-search huggingface dataset:
Late effects of intensive treatment for acute myeloid leukemia and myelodysplasia in childhood.
Authors: R J Liesner, A D Leiper, I M Hann, J M Chessells
Journal: Journal of Clinical Oncology (1994)

PURPOSE To perform a comprehensive assessment of the late effects of short-term intensive chemotherapy for childhood acute myeloid leukemia (AML) and myelodysplasia, and compare the sequelae of intensive chemotherapy alone with those of total-body irradiation (TBI). PATIENTS AND METHODS Of 33 survivors studied, 26 (group A) received intensive chemotherapy including anthracyclines, one also received busulfan, cyclophosphamide (Bu/Cy), and bone marrow transplantation (BMT). Seven patients (group B) received chemotherapy, TBI, and BMT. Hearing, sight, growth, and endocrine, renal, and cardiac function were assessed. RESULTS The mean height standard deviation score of 25 nontransplanted group A patients was +0.67 at diagnosis, -0.11 following treatment (P = .016), and +0.34 7 years later (P &gt; .05), indicating no long-term growth impairment. The patients had normal gonadal function and the girls had normal uterine size and ovarian volume. The Bu/Cy patient had primary ovarian failure. Four group B children required growth hormone and four sex steroids for growth or gonadal failure. The girls had reduced uterine size and ovarian volume. Three had thyroid dysfunction and six had cataracts. Abnormalities of renal function were found in both groups and hearing loss in group A only. The mean cardiac shortening fraction was significantly reduced at 29.2% in group A and 28.6% in group B compared with 36% in normal subjects. Two group A patients have developed cardiac failure. CONCLUSION Chemotherapy and TBI before BMT for AML has resulted in growth failure, gonadal and thyroid damage, and cataracts in most children, whereas chemotherapy alone caused cardiac, renal, and hearing abnormalities only.
Prevalence of comorbidities in subjects with airflow obstruction in Japan
Authors: Hisamitsu Omori, Ayumi Onoue, Yoshiaki Shinonome, Noritaka Higashi, Wataru Miyazaki, Yasuyuki Ogata, Tohru Tsuda, Hirotsugu Kohrogi, Takahiko Katoh
Journal: European Respiratory Journal (2012)

Background: COPD is one of the leading causes of mortality in Japan. Little is known about the prevalence of comorbid conditions in subjects with COPD in Japan.

Objective: The aim of this study was to examine the prevalence of comorbidities between subjects with and without airflow obstruction (AO).

Methods: This study included 19,340 subjects (11,549 men, 7,791 women), aged 16-96 years, who underwent spirometric lung function tests at a medical check-up held between April 2009 and March 2010 at the Japanese Red Cross Kumamoto Health Care Center, Kumamoto, Japan. Data on medical history and life style information were collected by means of interview questionnaires. All subjects were evaluated by a physician. AO was defined according to Global Institute for Chronic Obstructive Lung Disease (GOLD) criteria (FEV1/FVC<0.7).

Results: In logistic regression models adjusted for age, smoking and BMI, prevalence of subjects with diabetes (odds ratio (OR), 1.28; 95% confidence intervals (95%CI), 1.08-1.51), asthma (OR, 4.09; 95%CI, 3.15-5.31) and lung cancer (OR, 3.84; 95%CI, 1.89-7.80) were significantly higher in subjects with AO compared to subjects without AO in male. In female, prevalence of subjects with hypertension (OR, 1.43; 95%CI, 1.15-1.79), diabetes (OR, 1.40; 95%CI, 1.05-1.86), asthma (OR, 3.22; 95%CI, 2.22-4.67) and lung cancer (OR, 4.52; 95%CI, 1.62-12.62) were significantly higher in subjects with AO compared to subjects without AO. Conclusions: This study documented that numerous comorbidities are frequently associated with AO. Therefore, efforts toward earlier detection of AO and the identification of comorbidities may become an integral part of the core prevention of COPD.
In Vitro Suppression of Normal Granulocytic Stem Cells by Inhibitory Activity Derived From Human Leukemia Cells 23
Authors: Hal E. Broxmeyer, Niels Jacobsen, Jeffrey Kurland, Naomi Mendelsohn, Malcolm A.S. Moore
Journal: JNCI Journal of the National Cancer Institute (1978)

Extracts and conditioned medium of bone marrow and blood cells from patients with acute leukemia were assayed for activity against granulocyte-monocyte colony-forming cells in agar (CFU-C). Cell extracts from 76 of 85 patients reproducibly inhibited colony formation of normal CFU-C by 28–90%. Leukemia cell-derived Inhibitory activity (LIA) was at a maximum In medium conditioned for 3–4 days with leukemia cells. LlA was against CFU-C during S-phase and had no Influence on production of colony-stimulating activity (CSA) by CSA-produclng cells. No evidence of CSA Inactivation was obtained. LlA was thus different from the previously reported PMN-derived Inhibitory activity which only Inhibits CSA production. Most of the crude LIA was lost at 37° C within 5 hours, but 10 minutes of Incubation with CFU-C resulted in maximum inhibition. Size and cell morphology of colonies surviving LIA were not Influenced. Inhibition of CFUC by leukemia cell extract was observed after 6–8 days but not after 14 days of Incubation. Velocity sedimentation experiments demonstrated that this observation was not due to a reversible effect on sensitive CFU-C. Colonies scored after 14 days were derived from CFU-C not sensitive at the time of treatment but were inhibited by multiple additions of leukemia cell extract. Human marrow cells that form granulocyte colonies In fibrin clot diffusion chambers In mice and pre-CFU-C in suspension culture In vitro were not Inhibited by single and multiple additions of leukemia cell extract. Extracts from normal hematopoietic cells did not inhibit exogenously stimulated colony formation. The results suggest that Inhibition was not nonspecifically toxic and may explain suppression of normal hematopoiesis associated with acute leukemia.
Increase of nitrosative stress in patients with eosinophilic pneumonia
Authors: Kanako Furukawa, Hisatoshi Sugiura, Kazuto Matsunaga, Tomohiro Ichikawa, Akira Koarai, Tsunahiko Hirano, Masakazu Ichinose
Journal: European Respiratory Journal (2011)

Background: Exhaled nitric oxide (NO) production is increased in asthma and reflects the degree of airway inflammation. The alveolar NO concentration (Calv) in interstitial pneumonia is reported to be increased compared to that in asthma. However, it remains unknown whether NO production is increased and nitrosative stress occurs in eosinophilic pneumonia (EP).

Objective: We hypothesized that nitrosative stress markers including Calv, inducible type of NO synthase (iNOS), and 3-nitrotyrosine (3-NT), are upregulated in EP.

Methods: Exhaled NO was measured in healthy subjects and in patients with interstitial pneumonia including idiopathic pulmonary fibrosis (IPF), cryptogenic organizing pneumonia, hypersensitivity pneumonitis, sarcoidosis and EP. iNOS expression and 3-NT formation were assessed by immunocytochemistory in BALf cells. The exhaled NO, lung function, and systemic inflammatory markers of the EP patients were investigated after corticosteroid treatment.

Results: The Calv levels in the EP group were significantly higher than those in the healthy subjects and the other interstitial pneumonia groups as well as the fractional exhaled NO (FENO) levels. More iNOS and 3-NT positive cells were observed in the EP group compared to the healthy subject and IPF patient. The Calv levels had significant correlations with both iNOS (p<0.05) and 3-NT positive cells (p<0.01). Corticosteroid treatment significantly reduced both the FENO (p<0.05) and the Calv levels (p<0.01). The magnitude of reduction in the Calv levels had a significant correlation with the peripheral blood eosinophil counts (p<0.05).

Conclusion: These results suggested that nitrosative stress was augmented in EP and may be involved in the pathogenesis.
ALLGEMEINE ÄRZTLICHE GESELLSCHAFT FÜR PSYCHOTHERAPIE, 1926-31
Authors: W. G. ELIASBERG
Journal: American Journal of Psychiatry (1956)

1. The six Congresses of the Allgemeine Äerztliche Gesellschaft für Psychotherapie were open to discussions of the basic principles of psychotherapy; they were guided by clinical, experimental, etiological, and prognostic research which led to some clarification of the indications for the selection of method. 2. Mere professions of creed were more and more excluded. 3. Research into the degree of agreement and the reasons and causes of disagreement of the experts in psychotherapy were encouraged. 4. Humane viewpoints, the true basis and justification of psychotherapy, were stressed in the handling of the traumatic neurotic, the social neurotic, the criminal, the neurotic whom the clergyman may see. 5. A psychotherapy of the psychoses was outlined and weighed critically. 6. Psychotherapeutic research in the various medical branches was encouraged.
Abstract P152: Do Self-reported Race, Socioeconomic Status And Genetic Ancestry Influence Fasting Glucose? Preliminary Results From the Ongoing Bach Prediabetes Study
Authors: James B Meigs, Gavin Miyasoto, Bianca Porneala, Lisa Marceau, John B McKinlay
Journal: Circulation (2012)

Background: Race/ethnic disparities in type 2 diabetes (T2D) may have both biophysical and social determinants that likely arise before T2D diagnosis. We examined the association of self-reported (SR) race/ethnicity, socioeconomic status (SES) and genetic ancestry with levels of fasting glucose (FG) in individuals not known to have T2D. Methods: The Boston Area Community Health (BACH) Prediabetes study is an ongoing epidemiologic survey of community-dwelling residents of inner-city Boston. A stratified random sample of 3,300 subjects are being drawn from the parent BACH cohort study, recruiting approximately equal numbers in pre-specified age (30–79 years), sex and race/ethnicity groups. Fasting blood is collected, including FG, other health and SES information, during an early AM in-home interview. SES is measured as a standardized composite score of income and education. Genetic ancestry informative markers (AIMs, n=63) that discriminate European, African and Native American continental ancestry are currently available on a random subset. We compared FG levels across groups using ANOVA, testing independent associations of SR race/ethnicity SES using multiple linear regression with significant P=&lt; 0.05. Results: Of 2,933 participants recruited, 63% were women and 70% were older than 50 years. Black, Hispanic and white SR race/ethnicity comprised 32%, 33% and 35% of the sample, respectively. The majority had low SES (57%), 35% had moderate SES and 8% had high SES. FG varied significantly by SR race/ethnicity (mean±SD, mg/dL): 113±37 for white, 119±46 for Hispanic and 121±49 for black subjects (P&lt;0.001). FG was inversely associated with SES (low 122±49, medium 113±39, high 106±23, P&lt;0.001). In joint SR race/ethnicity and SES models adjusting for age and sex, both main effects were attenuated but remained associated with FG (SR race/ethnicity P=0.01; SES P&lt;0.001). For the subsample with AIMs data (n=373), predominant AIMs ancestry, defined as the ancestry most likely as predicted by AIMs, was closely linked to SR race/ethnicity. European ancestry was predominant in 100% of 110 SR white respondents, while African ancestry was predominant in 95% of 129 SR black respondents. In 134 SR Hispanics, 43% were predominantly European, 41% African and 16% Native American. FG varied with predominant AIMs ancestry (European 115±45 mg/dL, African 121±53 and Native American 127±67), although not significantly so (P=0.33), likely due to the limited sample size. Conclusions: Both self-reported race/ethnicity and SES are associated with FG in community-based individuals without known T2D, and they share explanatory information reflecting a common effect. A larger sample with AIMs will help disentangle the degree to which FG variation is socially patterned in the community versus a biophysical phenomenon determined in part by genetic ancestry.
Influence of the Vitamin D-binding Protein on the Serum Concentration of 1,25-Dihydroxyvitamin D3
Authors: Roger Bouillon, Frans A. Van Assche, Hugo Van Baelen, Walter Heyns, Pieter De Moor
Journal: Journal of Clinical Investigation (1981)

The influence of the serum binding protein (DBP) for vitamin D and its metabolites on the concentration of its main ligands, 25-hydroxyvitamin D(3) (25-OHD(3)) and 1,25-dihydroxyvitamin D(3) (1,25-[OH](2)D(3)) was studied. The concentration of both 1,25-(OH)(2)D(3) and DBP in normal female subjects (45+/-14 ng/liter and 333+/-58 mg/liter, mean+/-SD, respectively; n = 58) increased during the intake of estro-progestogens (69+/-27 ng/liter and 488+/-90 mg/liter, respectively; n = 29), whereas the 25-OHD(3) concentration remained unchanged. A positive correlation was found between the concentrations of 1,25-(OH)(2)D(3) and DBP in these women. At the end of pregnancy, the total concentrations of 1,25-(OH)(2)D(3) (97+/-26 ng/liter, n = 40) and DBP (616+/-84 mg/liter) are both significantly higher than in nonpregnant females and paired cord serum samples (48+/-11 ng/liter and 266+/-41 mg/liter, respectively). A marked seasonal variation of 25-OHD(3) was observed in pregnant females and their infants, whereas in the same samples the concentrations of both DBP and 1,25-(OH)(2)D(3) remained constant throughout the year. The free 1,25-(OH)(2)D(3) index, calculated as the molar ratio of this steroid and DBP, remains normal in women taking estro-progestogens, however, and this might explain their normal intestinal calcium absorption despite a high total 1,25-(OH)(2)D(3) concentration. In pregnancy the free 1,25-(OH)(2)D(3) index remains normal up to 35 wk of gestation, but during the last weeks of gestation, the free 1,25-(OH)(2)D(3) index increases in both circulations. A highly significant correlation exists between the (total and free) 25-OHD(3) and 1,25-(OH)(2)D(3) concentrations in maternal and cord serum both at 35 and 40 wk of gestation.
Trends in diagnosis and clinical presentation of alpha-1 antitrypsin deficiency within an Irish population
Authors: Catherine O'Connor, Tomas Carroll, Geraldine O'Brien, N.G. McElvaney
Journal: European Respiratory Journal (2012)

Alpha-1 Antitrypsin Deficiency (AATD) is an autosomal co-dominant genetic disorder associated with a substantially increased risk for the development of chronic obstructive pulmonary disease (COPD) and liver disease. AATD is a notoriously under-diagnosed and under-recognized condition. ATS/ERS guidelines recommend testing of all individuals with COPD and poorly controlled asthma. The objective of the study was to investigate the diagnostic experiences of ZZ AATD individuals in Ireland.

A total of 50 ZZ AATD individuals completed a questionnaire at an Alpha-1 Clinic in relation to their diagnostic experiences and clinical presentation.

The mean age of symptom on set was 36.7 years +/- 1.7 (range 4-60); mean age of diagnosis was 42.9 years +/- 1.6 (range 4-68). The interval between onset of symptom and diagnosis was 6.2 years. The mean number of physicians seen prior to a diagnosis was 2.6 +/- 0.3 (range 1-13). Symptomatically screened ZZ individuals mean age of symptom on set was 36.2 years+/- 2.0 (range 4-60): mean age of diagnosis was 44.3 years +/- 1.9 (range 4-68). The interval between onset of symptom and diagnosis was 8.1 years. The number of physicians seen prior to a diagnosis was 3.1 +/-0.3 (range 1-13). Family screened ZZ individuals mean age of symptom onset was 37.63 +/- 3.0 (range 21-51); mean age of diagnosis was 38.5 +/- 2.8 (range 21-53). The interval between onset of symptoms 0.9 years. The mean number of physicians seen prior to a diagnosis was 1.2 +/- 0.2 (range 1-3).

Our results further underline the need for increased awareness and early detection of symptomatic AATD individuals in the Irish population, especially among the COPD popluation.
Induction of cytochrome P450 (CYP3A4) by gefitinib in non-small cell lung cancer (NSCLC) patients
Authors: Y. Fujisaka, N. Yamamoto, H. Nokihara, I. Sekine, H. Kunitoh, Y. Ohe, T. Tamura, N. Saijo
Journal: Journal of Clinical Oncology (2005)

3027 Background: Cytochrome P450 (CYP3A4) is an enzyme responsible for the metabolism of a wide variety of chemicals, including anti-cancer agents. Gefitinib is also metabolized by CYP3A4. We previously reported a significant correlation between CYP3A4 activity and the urinary cortisol metabolite, 6beta-hydroxycortisol (6beta-OHF) after cortisol administration (Yamamoto, et al. JCO 2000). The aim of the present study was to assess the change in CYP3A4 activity by Gefitinib. Methods: We prospectively evaluated the changes in urinary 6beta-OHF, free-cortisol (FC), 6beta-OHF/FC ratio and the plasma trough concentration of gefitinib before treatment, on day 15 and day 29 in patients receiving gefitinib. A 300mg of hydrocortisone was administered in several patients, and the total amount of 24-hour urinary 6beta-OHF was measured on the same days. Results: Fifty one patients with NSCLC were entered onto this study. Twenty-one of them were received hydrocortisone. The 6beta-OHF/FC ratio before treatment, on day 15, and 29 was 7.41+/-4.63, 7.31+/-4.21 and 12.60+/-10.02 (mean+/-SD) respectively. 6beta-OHF/FC ratio on day 29 was significantly higher than both before treatment and on day 15 (p=0.001), suggesting the induction of CYP3A4. However, the trough concentration of gefitinib in plasma did not change significantly between day 15 and day 29 (245.1+/-108.2ng/ml, 253.0+/-100.8ng/ml; p=0.506). The total 24-hour urinary 6β-OHF content after cortisol administration was 8.22+/-4.67, 8.19+/-4.26 and 7.64+/-4.17mg/day, before treatment, on day 15 and day 29 respectively, and the values did not change significantly. The overall response rate was 29.4%. Grade 3 liver enzyme elevation was observed in 3 patients and Grade 3 skin eruption in 1 patient. Conclusion: Induction of CYP3A4 by gefitinib was suggested. In combination chemotherapy consisting of gefitinib and other anti-cancer agents metabolized by CYP3A4, we need to evaluate whether there is a drug-drug interaction. No significant financial relationships to disclose.
Our surgical experience of 302 patients with bronchiectasis during last 20-year period
Authors: Turgut Isitmangil, Nurettin Yiyit, Akin Yildizhan, Fatih Candas, Rauf Gorur, Haluk Sasmaz, Habil Tunc, Saban Sebit, Oryal Erdik
Journal: European Respiratory Journal (2013)

Bronchiectasis is an uncommon disease defined by localized, irreversible dilation of part of the bronchial tree caused by destruction of the muscle and elastic tissue. In our study, it was aimed to evaluate 302 patients with 304 surgical interventions for bronchiectasis in our clinic between January 1993 and December 2012.  Out of all patients 288 were male and 14 were female and mean age was 23.57 (14-71). The most common complaints were cough and sputum expectoration. Left lung of 8 patients and right lung of one patient were entirely bronchiectasic (destroyed lung). In other 293 patients, 124 of bronchiectasic lesions were in the right lung and 241 were in the left lung. In two patients there was bilateral bronchiectasis.  These 304 surgical operations were done with thoracotomy in 297 surgical interventions and with VATS in 7 interventions. Right middle lobectomy in 5 patients and wedge resection in two patients were performed with VATS. Two patients with bilateral bronchiectasis were operated in different sessions. Eight left pneumonectomies, one right pneumonectomy, 1 right upper bilobectomy, 7 right lower bilobectomies, 230 lobectomies, 26 lingulectomies, 28 segmentectomies and 64 wedge resections were performed with thoracotomy. Rethoracotomy was performed in four patients for postoperative complications. One patient who had left pneumonectomy died in postoperative period.  Surgery is an important adjunct to therapy in patients with advanced or complicated bronchiectasis.
Modulation of Fluorouracil by Leucovorin in Patients With Advanced Colorectal Cancer: An Updated Meta-Analysis
Authors: P Thirion, S Michiels, J P Pignon, M Buyse, A C Braud, R W Carlson, M O'Connell, P Sargent, P Piedbois
Journal: Journal of Clinical Oncology (2004)

The modulation of fluorouracil (FU) by folinic acid (leucovorin [LV]) has been shown to be effective in terms of tumor response rate in patients with advanced colorectal cancer, but a meta-analysis of nine trials previously published by our group failed to demonstrate a statistically significant survival difference between FU and FU-LV. We present an update of the meta-analysis, with a longer follow-up and the inclusion of 10 newer trials.Analyses are based on individual data from 3,300 patients randomized in 19 trials on an intent-to-treat basis. Two trials had multiple comparisons, leading to a total of 21 pair-wise comparisons. FU doses were similar in both arms in 10 pair-wise comparisons, 15% to 33% higher in the FU-alone arm in six comparisons, and more than 66% higher in five comparisons.Overall analysis showed a two-fold increase in tumor response rates (11% for FU-LV v 21% for FU-LV v 11% for FU [corrected] alone; odds ratio, 0.53; 95% CI, 0.44 to 0.63; P <.0001) and a small but statistically significant overall survival benefit for FU-LV over FU alone (median survival, 11.7 v 10.5 months, respectively; hazards ratio, 0.90; 95% CI, 0.87 to 0.94; P =.004), which were primarily seen in the first year. We observed a significant interaction between treatment benefit and dose of FU, with tumor response and overall survival advantages of FU-LV over FU-alone being restricted to trials in which a similar dose of FU was prescribed in both arms.This updated analysis demonstrates, on a large data set, that FU-LV improves both response rate and overall survival compared with FU alone and that this benefit is consistent across various prognostic factors.
Adverse Effects of Androgen Deprivation Therapy: Defining the Problem and Promoting Health Among Men with Prostate Cancer
Authors: Philip J. Saylor, Matthew R. Smith
Journal: Journal of the National Comprehensive Cancer Network (2010)

Androgen deprivation therapy (ADT) plays a central role in the management of men with locally advanced, recurrent, and metastatic prostate cancer. Because most men diagnosed with prostate cancer will die of something other than their cancer, treatment-related adverse effects are highly relevant to their long-term health. Benefits of ADT in each clinical setting must be weighed against ADT-related adverse effects. ADT is detrimental to several metabolic end points and to bone health. ADT has been prospectively shown to cause decreased lean muscle mass, increased fat mass, weight gain, increased cholesterol and triglycerides, insulin resistance, and loss of bone mineral density. In population-based analyses it has been associated with an increased incidence of diabetes, clinical fractures, and cardiovascular disease. Data-driven recommendations for managing these adverse effects are needed. Currently the authors advocate the use of adapted practice guidelines developed to prevent diabetes, fractures, and coronary heart disease in the general population.