tbuckley/cabot-search huggingface dataset:
Phase I study of weekly outpatient paclitaxel and concurrent cranial irradiation in adults with astrocytomas.
Authors: M J Glantz, H Choy, C M Kearns, B F Cole, P Mills, E G Zuhowski, S Saris, C H Rhodes, E Stopa, M J Egorin
Journal: Journal of Clinical Oncology (1996)

PURPOSE Astrocytomas are extremely resistant to currently available treatments. Cranial irradiation is a mainstay of frontline therapy, but tumor recurrence is nearly universal. Paclitaxel has shown antitumor efficacy against astrocytoma cell lines, and is a potent radiosensitizer. For these reasons, we conducted a phase I study of weekly paclitaxel and concurrent cranial irradiation in patients with newly diagnosed astrocytomas. PATIENTS AND METHODS Patients with astrocytomas were eligible for this study following initial surgery if they had a Karnofsky performance score (KPS) &gt; or = 60%; normal hematologic, liver, and renal function; and could give informed consent. Beginning on day 1 of treatment, patients received paclitaxel by 3-hour infusion once weekly for 6 weeks, concurrent with standard cranial irradiation. Pharmacokinetic studies were performed on 10 patients. RESULTS Sixty patients were enrolled; 56 were fully assessable. Forty-eight had glioblastomas (GBMs), 10 anaplastic astrocytomas (AAs), and two astrocytomas. Age ranged from 21 to 81 years (median, 55); KPS ranged from 60 to 100 (median, 70). The paclitaxel dose was escalated from 20 mg/m2 to 275 mg/m2. No clinically significant anemia or thrombocytopenia occurred. Only one patient (175 mg/m2) became neutropenic. Sensory neuropathy was dose-limiting. The maximum tolerated dose (MTD) was 250 mg/m2. Paclitaxel pharmacokinetic profiles in study patients were identical to those of previously reported patients with other solid tumors. CONCLUSION The MTD of paclitaxel administered weekly for 6 weeks by 3-hour infusion is 250 mg/m2. Since patients with brain tumors often have preexisting neurologic deficits, we suggest 225 mg/m2 as the optimum dose for phase II trials in this group of patients.
Study of the Carcinogenicity of Large Doses of Dimethylnitramine, N-Nitroso-l-proline, and Sodium Nitrite Administered in Drinking Water to Rats23
Authors: Sidney S. Mirvish, Orhan Bulay, Richard G. Runge, Kashinath Patil
Journal: JNCI Journal of the National Cancer Institute (1980)

Journal Article Study of the Carcinogenicity of Large Doses of Dimethylnitramine, N-Nitroso-l-proline, and Sodium Nitrite Administered in Drinking Water to Rats Get access Sidney S. Mirvish, Sidney S. Mirvish Search for other works by this author on: Oxford Academic PubMed Google Scholar Orhan Bulay, Orhan Bulay Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard G. Runge, Richard G. Runge Search for other works by this author on: Oxford Academic PubMed Google Scholar Kashinath Patil Kashinath Patil Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 64, Issue 6, June 1980, Pages 1435–1442, https://doi.org/10.1093/jnci/64.6.1435 Published: 01 June 1980 Article history Received: 03 July 1979 Accepted: 13 December 1979 Published: 01 June 1980
Alveolar accumulation of hyaluronan and alveolar cellular response in bleomycin-induced alveolitis
Authors: O Nettelbladt, A Scheynius, J Bergh, A Tengblad, R Hällgren
Journal: European Respiratory Journal (1991)

Hyaluronan (HA) accumulating in the alveolar interstitial tissue of rats injured by a single intratracheal instillation of bleomycin has been visualized histologically and assayed. HA was present already by Day 1 after bleomycin treatment, increased to a maximum value on Days 3 and 7 and then declined. A time-dependent relationship between this early connective tissue response and the invasion of inflammatory cells in the alveolar tissue was apparent. The dominating invading cells by Day 1 were granulocytes showing positive staining for the monoclonal antibody OX-42 reflecting the C3b receptor. The numbers of macrophages expressing class II antigens started to increase on Day 1, reaching a maximum on Days 3-7 and then declined. Macrophages were the dominating OX-42+ cells by Day 7. The appearance of W3/13+ cells ("pan-T-lymphocytes") showed a similar pattern to that for the class II expressing macrophages. The number of cells expressing CD4 antigen increased until Day 3 and levelled off on Day 30 whilst the largest number of cells expressing CD8 antigen was seen on Day 30. Few cells expressing B-cell phenotype outside lymph nodules were identified. Alveolar lining epithelial cells, probably epithelial type II cells, expressed class II antigens by Days 3-14. The time-related accumulation of HA and the appearance of T-cells, macrophages and granulocytes expressing signs of activation suggests that these cells may be involved in the early connective tissue response of the lung injured by bleomycin.
Autoradiographic Analysis of Cell Proliferation in Spontaneous Breast Cancer of C3H Mouse. III. The Growth Fraction&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: Mortimer L. Mendelsohn
Journal: JNCI Journal of the National Cancer Institute (1962)

If tumors consist of mixtures of non-growing cells plus cells proliferating at a uniform rate, it is possible to estimate the growth fraction (proliferating cells/total cells) by an autoradiographic method. The method is based on the labeling of a random sample of proliferating cells and requires the parenteral injection of tritiated thymidine several cell generations before the fixation of the tumors. The incidence of labeling in the total population is then determined as labeled cells/100 cells. The corresponding incidence in the proliferating population is given by labeled mitoses/100 mitoses. The ratio of these indexes reduces to a time-dependent estimate of growth fraction. Primary tumors from C3H mice given injections 5 days before killing gave a mean of 0.61 for this estimate. Based on similar data from serially removed autotransplanted tumors, or on doubling times of 1 week for tumor volume, 0.61 at 5 days is equivalent to a growth fraction of 0.40 at the outset. Within the limits of the model, the results suggest that only 40 percent of these tumor cells are actively involved in the mitotic cycle at any one time. Other possible models of tumor growth were considered in order to evaluate the effects of variation in growth rate. In those cases in which the duration of either mitosis or deoxyribonucleic acid (DNA) synthesis are proportional to generation times, the growth-fraction method remains valid in spite of variations in generation time. On the other hand, when the durations of mitosis and DNA synthesis are relatively constant but generation times vary extensively, there may be an aberrant reduction in the measured growth fraction. Models for several types of variation were examined, and hypothetical growth fractions were calculated for several published distributions of cell generation times.
Prevalence and predictors of arrhythmia in patients with obstructive sleep apnea (OSA)
Authors: Ahmed BaHammam, Nader Alasousi, Munir Sharif, Ahmad Hesi
Journal: European Respiratory Journal (2011)

Background:  Very limited number of studies has addressed cardiac arrhythmias in OSA patients.   Objectives:  To estimate the prevalence and types of arrhythmias in OSA patients and to try to detect predictors for arrhythmia in this group of patients.   Methods:  In this case-control study, polysomnography (PSG) of all patients with and without OSA were reviewed by physicians who were blinded to the existing sleep disorder for the presence of arrhythmia.   Results:  The study comprised 257 OSA patients and 99 non-OSA patients (control group). OSA patients had a mean age 47.9±13.5 years, body mass index of 35.7±9.5 kg/m 2 , apnea hypopnea index (AHI) of 42.4±36.9/hr, and males represented 60.7% of the group. The prevalence of arrhythmia in OSA patients was higher than that in the non-OSA group (24.5% vs. 12.1%, p = 0.01). Among OSA patients, premature atrial contraction was present in 10.1%, premature ventricular contraction in 16.3% and atrial fibrillation in 4 patients (1.6%). OSA patients with arrhythmias were significantly older (53.5±15.3 years vs. 46±12.4 years; p 2 vs. 34.9±9.5 kg/m 2 ; p   Conclusions:  Arrhythmia was more prevalent among OSA patients with longer periods of hypoxemia and those with ischemic heart disease.
Cardiovascular comorbidity and mortality in patients with chronic obstructive pulmonary disease
Authors: Plamen Pavlov, Yavor Ivanov, Pavlina Glogovska, Tsania Popova, Elena Borisova, Venzislav Nozharov
Journal: European Respiratory Journal (2012)

Aim.To determine the prevalence of cardiovascular diseases (CVDs) and cardiovascular mortality in patients with chronic obstructive pulmonary disease (COPD).  Material.COPD patients (n=3571) were checked if they had CVDs (CAD – coronary artery disease, HF - heart failure, AH - arterial hypertension, CCP – chronic cor pulmonale, CVD - cerebrovascular disease) and mortality. Of these, 2642 (74%) were male and 929 (26%) women, aged 65.4 (SD ± 9.7), and FEV1 = 49.8 (SD ± 18.9)% pred.The risk for CVDs (OR - Add Ratio) was compared with that of 150 controls.  Results. Among COPD patients 84.5% had CVDs: 59% (GOLD I), 74% (GOLD II), 86% (GOLD III) and 99% (GOLD IV) (r=0.35, p=0.0001); OR=1.96. Correlation was found between age and prevalence of CVDs: 48.7% (40-49yrs), 71.6% (50-59yrs), 85% (60-69yrs) and 96.9% (> 70yrs) (r=0.38, p=0.0001).  Patients with COPD had a higher prevalence of CVDs and cardiovascular risk: CAD (66%; OR = 1.8), HF (74%; OR = 1.9), AH (45%; OR = 1.2), CCP (46%; OR = 3.8) and CVD (33.3%; OR = 1.6). In 33% of COPD deaths cardiovascular causes of death were found: 36.7% myocardial infarction, 33.3% pulmonary embolism, 12% HF and 18% of CVD.  Conclusion.The study found an increased risk and mortality from cardiovascular diseases, especially in adult patients with severe COPD.
Effects of gefitinib (G) on bone metatases (BMs) in non-small cell lung cancer patients
Authors: D. Garfield, G. Zampa, J. Cadranel, D. W. Bell, M. Moscato, N. Normanno
Journal: Journal of Clinical Oncology (2006)

17147 Background: Selected pts with advanced NSCLC might have particular benefit from EGFR tyrosine kinase (TK) inhibitor treatment. We have identified 4 NSCLC pts with BMs who had major responses to G. Methods: Pts characteristics: Pt 1, 62 y/o female, never-smoker (ns), NSCLC, brain and BMs with bone pain; pt 2, 51 y/o male, former smoker (fs), ADC and BMs; pt 3, 51 y/o male, ns, ADC and BMs; pt 4, 50 y/o male, fs, ADC, pleural effusion, BMs and bone pain. Pts 1 and 4 had mixed osteolytic-sclerotic BMs; pts 2 and 3 had osteolytic BMs. Pts were treated with 250 mg/day of G; the dose was increased to 375 mg/day in pt 1 for maximum CNS control. Pts 1 and 4 received G as first-line therapy, pts 2 and 3 as second-line following failure of platinum-containing therapy. Pts 1–3 also received zoledronic acid. Results: Pts 1 and 4 experienced significant decrease in bone pain with G, within hours in pt 1 and by day 3 in pt 4. Pts 1–3 developed rash. Objective regression of primary tumor was observed in all 4 pts. After 3 months of G the bone scan did not change in pt 1 but many lesions became more sclerotic. Bone scans became negative after one year of treatment in pts 2 and 3. Pt 2 had resection of the primary tumor with no recurrence, 26+ months (mos) from diagnosis, 9+ mos from surgery. Pt 1 has had disease control for 7+ mos, pt 3 for 15+ mos. Pt 1 had CNS regression with G. Pt 3 was found to have asymptomatic CNS mets at 6 mos of G, received whole-brain radiation, and remains on G at &gt;1 year. Pt 4 died 6 weeks after starting G from unrelated causes but showed dramatic BMs response by PET. Tumor tissue was available for molecular analyses for pts 2 and 4, who respectively showed EGFR-TK domain G719C mutation in exon 18 and L858R mutation in exon 21. Both mutations have been previously described in NSCLC patients responding to G. Conclusions: G may be effective in the treatment of BMs in some NSCLC patients. [Table: see text]
CytotoxiC Activity of Methylene Bis-nucleotides: Brief Communication
Authors: M. Y. Feldman, Henny Balabanova, Isidro Martinez
Journal: JNCI Journal of the National Cancer Institute (1978)

New facts relating to the mechanism of cytotoxic and antitumor activity of formaldehyde-treated RNA and its hydrolysates have been revealed. Synthetic methylene bis-nucleotides and, in particular, methylene bis-nucleosides have a cytotoxic effect on cultured human adenocarcinoma cells (line HCCL). The cytotoxic effect of methylene bis-derivatives of the guanine series was most pronounced. In addition, methylene bis-nucleotides were dephosphorylated in the cell culture medium. Chromosome aberrations were induced by alkaline hydrolysate of dialyzed formaldehyde-treated RNA in which 39% of purine nucleotides were modified to methylene bis-derivative.
Comparison between theophylline and an adenosine non-blocking xanthine in acute asthma
Authors: JS Vilsvik, CG Persson, T Amundsen, E Brenna, T Naustdal, U Syvertsen, L Storstein, AG Kallen, G Eriksson, S Holte
Journal: European Respiratory Journal (1990)

Enprofylline, a drug without adenosine antagonism and theophylline, a potent adenosine antagonist, were compared, double-blind, randomized, in acute asthma (n = 33). The drugs were given intravenously as loading over 10 min followed by maintenance infusion for 24 h. Mean final plasma levels were very high with enprofylline (14 mg.l), and larger than calculated with theophylline (16 mg.l). Seven patients had maximum levels of enprofylline ranging between 16 and 42 mg.l. Extreme plasma levels of enprofylline were not associated with any theophylline-like central nervous system excitatory effects related to seizure-inducing ability. Some irregularities in the heart rhythm did not raise clinical problems and no significant difference between enprofylline and theophylline was recorded. At 1 h patients on enprofylline (mean plasma level: 5.7 mg.l) and theophylline (12.2 mg.l) had improved their peak expiratory flow rates by 31% and 15% (p less than 0.05), respectively. The improvement in lung function after 24 hours did not differ between treatments suggesting that the high levels of enprofylline were supramaximal for its anti-asthma effects in this situation. In conclusion, with enprofylline it is demonstrated that an adenosine non-blocking xanthine derivative may lack CNS-excitatory effects, but be more potent than theophylline in the treatment of acute asthma.
Can impulse oscillometry and body plethysmography differentiate response to two salbutamol doses
Authors: Rahul Kodgule, Nitin Vanjare, Shweta Rasam, Satish Bhosale, Yogesh Gupta, Sundeep Salvi
Journal: European Respiratory Journal (2013)

Background: Whether sensitive lung function tests like Impulse Oscillometry (IOS) & Body Plethysmography (BP) can differentiate response between two doses of bronchodilator is not known.

Aim: To study the effect of 100 and 400 mcg of salbutamol on IOS & BP parameters?Methods: In this ongoing study, 9 asthma & 10 COPD patients were randomized to receive either 100 mcg or 400 mcg of inhaled salbutamol in a cross-over manner. IOS to study resistances at 5 Hz, 20 Hz and 5-20 Hz (R5, R20 and R5-20), BP to study specific airway conductances sGawtot & sGaweff & spirometry to study FEV1 & FEF25-75 was done before and 30 min after drug administration. Within group & between group changes were analyzed by paired t-test & independent t-test respectively.Results: The mean percent changes (MPC) for each drug are shown in Table 1.

View this table:

Table 1: Mean percent change (MPC) in asthma





All individual responses were statistically significant (p value<0.5) but 400 mcg of salbutamol did not produce better response than 100 mcg. R5, R20, R5-20 & FEF25-75% showed maximum differentiation between two doses.Conclusion: This ongoing study suggests that FEF25-75%, R5, R20 & R5-20 may differentiate between response to low & high doses of bronchodilator.
Association of psoriasis with stroke and myocardial infarction: meta‐analysis of cohort studies
Authors: T. Xu, Y.‐H. Zhang
Journal: British Journal of Dermatology (2012)

Background Psoriasis is a common, chronic, relapsing, inflammatory skin disorder. Observational studies suggest an association between psoriasis and the incidence of stroke or myocardial infarction (MI). However, whether psoriasis is an independent risk factor for these two vascular events remains controversial. Objectives To evaluate the association of psoriasis with stroke and MI by conducting a meta‐analysis of cohort studies. Methods Cohort studies were searched in MEDLINE (Pubmed), EMBASE and Cochrane Library from their inception to March 2012. Stroke and MI were considered as a composite endpoint. Two authors independently extracted information on the characteristics of the study participants, follow‐up range and control for potential confounding factors. A random‐effects model was used to calculate the overall combined risk estimates. Results Seven cohort studies were included in the meta‐analysis. On the basis of cohort characteristics, five of them were considered good quality and two were fair. The overall combined relative risk for psoriasis and composite vascular endpoint was 1·2 (95% confidence interval 1·1–1·31). Subgroup analysis maintained this significance with respect to stroke and MI individually. Sensitivity analysis and 'trim and fill' method yielded similar results. No evidence of publication bias was observed. Conclusions This meta‐analysis of cohort studies suggests that psoriasis significantly increases the risk of stroke and MI. The increase is probably independent of conventional cardiovascular risk factors.
Expiratory vocal cord dysfunction - symptom presentation and co-morbidities
Authors: Siobhan Lillie, Stephen Fowler
Journal: European Respiratory Journal (2013)

Introduction:  Vocal Cord Dysfunction (VCD) is typically characterised as adduction of the vocal cords during inspiration. More rarely however, it can present as excessive adduction of the vocal cords during expiration. Vocal cord dysfunction is diagnosed by detailed case history and flexible nasendoscopy (often with challenge). Patients with VCD often have coexistent medical conditions which may contribute to the presentation.   Methods:  We reviewed clinical data and co-morbidities of six patients diagnosed with expiratory VCD.   Results:  The patients were: 83% female, mean (range) age 60 (40-75) years, body mass index (BMI) 31.3 (25 - 49.8) kg/m 2 . All patients had another confirmed respiratory diagnosis (asthma, COPD, bronchiectasis and/or rhinitis) and four had gastro-oesophageal reflux disease. All six presented with symptoms of laryngeal irritation, globus, cough and a feeling of being choked from the larynx. Four patients reported intermittent dysphonia. Three presented with a dysfunctional breathing pattern and also required specialist respiratory physiotherapist intervention. Two patients had a history of anxiety and required clinical psychology input.   Conclusions:  Expiratory VCD has a lower incidence than inspiratory VCD, but the symptoms described are very similar. Comorbidities such as reflux and anxiety are also common. All patients had another respiratory disease process which may be a contributing factor to expiratory VCD. Glottic narrowing may be a therapeutic response to the other respiratory disease process allowing a certain amount of positive end expiratory pressure to maintain airway patency. Further research is required to investigate the therapeutic response further.
Identification of the skin virome in a boy with widespread human papillomavirus‐2‐positive warts that completely regressed after administration of tetravalent human papillomavirus vaccine
Authors: M.M. Landini, C. Borgogna, A. Peretti, J. Doorbar, H. Griffin, F. Mignone, A. Lai, L. Urbinati, A. Matteelli, M. Gariglio, M. De Andrea
Journal: British Journal of Dermatology (2015)

Funding sources: This work was supported by the Italian Ministry for University and Research – MIUR (FIRB – Futuro in Ricerca 2008 to M.D.A.), Compagnia di San Paolo (grant CSP2012 to M.G.), Associazione Italiana per la Ricerca sul Cancro – AIRC (grant IG 2012 to M.G.) and the European Society of Clinical Microbiology and Infectious Diseases – ESCMID (research grant 2013 to C.B.). Alberto Peretti is supported by a Fellowship from Fondazione Italiana per la Ricerca sul Cancro ‐ FIRC. Conflicts of interest: none declared. Dear Editor, Human papillomavirus (HPV) infections are normally controlled by an intact cell‐mediated and humoral immune system. Therefore patients with cell‐mediated immunodeficiencies – whether primary, secondary or iatrogenic – are all at increased risk of developing extensive, persistent and recurrent warts.1 However, the sequestration of HPV in epithelial cells can provide protection for the virus, resulting in inefficient activation of innate immunity, poor priming of the adaptive response and persistence of infections, even in immunocompetent individuals.2 In addition, genome variations, especially those enhancing viral promoter activities, have been associated with enhanced viral replication and unusual clinical manifestations.3 4 5
Recurrent Clostridium difficile diarrhoea
Authors: L Kyne
Journal: Gut (2001)

Clostridium difficile diarrhoea is a common iatrogenic nosocomial disease. Fortunately, most affected patients respond well to medical therapy that includes discontinuation of the inciting antibiotic and treatment with metronidazole or vancomycin.1 However, despite successful treatment of initial episodes, 15–25% will have recurrence of diarrhoea following withdrawal of specific antibiotic therapy.1 2 Treatment of this form of C difficile disease can be particularly problematic.

Approaches to management include conservative therapy, treatment with specific anti- C difficile antibiotics, use of anion binding resins, therapy with microorganisms (probiotics), and immunoglobulin therapy (table 1).

View this table:

Table 1 
Approach to management of recurrent Clostridium difficile diarrhoea



### CONSERVATIVE THERAPY

Conservative management of recurrent diarrhoea is preferable to retreatment with metronidazole or vancomycin as these agents perpetuate disturbance of the normal intestinal flora predisposing patients to further recurrences.2 However, it is often difficult to withhold antibiotic therapy as many patients with recurrent disease are not able to tolerate ongoing diarrhoea. Persistent or worsening …