tbuckley/cabot-search huggingface dataset:
Influence of gender on renal thiazide diuretic receptor density and response.
Authors: Z Chen, D A Vaughn, D D Fanestil
Journal: Journal of the American Society of Nephrology (1994)

The influence of gender and gonadectomy on (1) the density of the renal thiazide-sensitive ion transporter, as quantitated by the ability of renal membranes to bind (3H)metolazone, and (2) the changes in the urinary excretion of electrolytes caused by maximal bendroflumethiazide (BFTZ) in Sprague-Dawley rats was determined. The density of the thiazide receptor was twofold higher (P < 0.001) in females than in males. Orchiectomy increased thiazide receptor significantly in one of two studies (P < 0.01). Ovariectomy decreased thiazide receptor by more than 20% (P < 0.01) in both studies. The rates of the urinary excretion of sodium and chloride after BFTZ and the increases in the urinary excretion of sodium, chloride, and ammonium caused by BFTZ were greater in intact females than in intact males; BFTZ decreased the urinary excretion of calcium 50% in intact females, but not in intact males. Regression analysis of the thiazide receptor (in intact and gonadectomized animals) versus the urinary excretion of electrolytes before and after BFTZ yielded a model in which one-third of the variation in thiazide receptor could be related to the change in the excretion of calcium and ammonium produced by BFTZ, raising the possibility that the density of the thiazide receptor might be related to calcium or acid-base homeostasis. It was concluded that the renal excretion of sodium, chloride, calcium, and ammonium are, in part, controlled by gender and sex hormones via their regulation of the renal density of the thiazide diuretic receptor.
Anxiety and dyspnea relation in early stage COPD patients
Authors: Leyla Yilmaz Aydin, Tarkan Ozdemir, Sinem Berik
Journal: European Respiratory Journal (2012)

Introduction: Anxiety is a co-morbid diseases in COPD. Anxiety prevalance in COPD patients is higher than general population. Although the relationship between anxiety and COPD can not be revealed yet, increased anxiety prevalance was associated with increased dyspnea level.  Aim: To determine the rate of anxiety and relationship of anxiety and dyspnea in early stage COPD patients who do not have advanced functional restriction. Method: COPD patients that volunteered to participate the study who admitted to hospital with a reason other than COPD exacerbation was included to this cross-sectional/descriptive study consecutively. Beck anxiety inventory, medical research council (MRC) dyspnea scale applied.  Results: 134 patients with GOLD1-2 COPD included. Mean age was 58,11±10,53. 92,5% of them were male. Active smokers and former smokers were 61,9%; and 38,1%; respectively. 64,9% did not have co-morbid diseases. According to MRC dyspnea scale 33,6% of the patients were in grade 1 and 55,2% were in grade 2. 34,1% of the patients that answered the question “Do you have shortness of breath?” answered as “No” were having MRC grade 2 and 3 dyspnea. 11,2% of 134 participants had mild and 9% had moderate anxiety. In patients with anxiety 89% were having MRC grade≥2.Although there was no statistically significant relationship between shortness of breath and level of anxiety, there was a significant relationship between MRC grade and level of anxiety (p=0,529 and p=0,004, respectively).  Conclusion: MRC scale can be more effective in detection of dyspnea in early stage COPD. All COPD patients with MRC score ≥2 should investigate for anxiety.
Recent Respiratory and Enteric Adenovirus Infection in Children in the Manchester Area
Authors: S J Richmond, D J Wood, A S Bailey
Journal: Journal of the Royal Society of Medicine (1988)

Seventy-three group B adenoviruses (29 type 3 and 44 type 7) identified in a recent community outbreak were analysed with restriction endonucleases. Considerable genetic heterogeneity was identified, particularly amongst the type 3 isolates, but this genome variation could not be correlated with either clinical or epidemiological findings. Group F adenoviruses were found in 132 (4.1%) of 3202 stool specimens from children with gastroenteritis and, after rotaviruses, they were the most common viruses identified. Unlike rotaviruses, these enteric adenoviruses were endemic throughout the 3-year study period and the greatest proportion of infections (47.6%) were found in babies under 6 months old.
Gemcitabine (G) plus cisplatin (C) plus radiotherapy in first-line treatment of locally advanced and metastatic undifferentiated carcinoma of the nasopharyngeal type (UCNT): Preliminary results of a phase II study
Authors: S. Adane, M. Sadouki, F. Mekki, K. Bouzid
Journal: Journal of Clinical Oncology (2004)

5618 Background: In our experience, G is efficient (44%) in third-line monotherapy of recurrent metastatic nasopharynx carcinoma after first-line 5-fluorouracil + C and second-line anthracyclines + taxanes (ASCO 2002 abstract #3034). In this prospective, phase II study, we used G + C in neoadjuvant setting before radiotherapy in first-line treatment of patients (pts) with locally advanced and metastatic UCNT. The primary endpoint was toxicity and the secondary endpoints of this study included objective response and pathological response. Methods: Chemonaive pts with histologically (WHO type 3) proven stage III and IV TNM/UICC 1997, and an ECOG performance status (PS) 0–2 received G 1250 mg/m2 over a 30-minute infusion on days (D) 1 and 8 and C 70 mg/m2 on D1, every 3 weeks. Four to 6 weeks after the third cycle of induction chemotherapy, curative intent radiotherapy was given on nasopharynx (70–72 Gys) and on cervical nodes (50 Gys). Four weeks after radiotherapy, 2 cycles of G + C were given. Follow-up was performed 4 weeks after the third cycle by clinical evaluation, CT scan of nasopharynx, and nasofibroscopy with biopsy. Results: To date, 12 pts (11 men) with a median age of 45 years (range 22–65) and a PS 0 (2 pts), PS 1 (7 pts) and PS 2 (2 pts) have been enrolled. Seven pts had stage IVA, 3 pts had stage IVC, and 2 pts had stage III. A total of 43 cycles have been completed with a median of 3.6 cycles (range 2–4). All pts were evaluable for toxicity. No WHO grade 3/4 toxicity occurred. The most commonly reported hematologic event was grade 2 neutropenia (4%) and thrombocytopenia (2%). The most common nonhematologic event was grade 2 asthenia (12%) and nausea/vomiting (9%) Of the 10 patients evaluable for response, there were 5 complete response (all pathological complete response with 50% pf pCR) and 3 partial responses for an overall response rate of 80%. One pt reported stable disease, and 1 progressed. Conclusions: Based on this preliminary results, G + C appears to be very effective and well tolerated for chemonaive pts with UCNT. No significant financial relationships to disclose.
Dendritic cells loaded with wild-type p53 peptides induce T cell immunity and disease stabilization in patients with advanced breast cancer
Authors: I. M. Svane, A. E. Pedersen, H. E. Johnsen, D. Nielsen, C. Kamby, K. Nikolajsen, S. Ottesen, M. Zocca, J. S. Johansen, M. H. Claesson
Journal: Journal of Clinical Oncology (2006)

2577 Background: p53 mutations and over-expression are found in up to 30% of breast cancers and are associated with poor prognosis following conventional therapy. Peptides derived from over-expressed p53 protein are presented by class I MHC molecules and may act as tumor-associated epitopes and thereby as target for vaccination. Due to the diversity of p53 mutations, immunogenic peptides representing wild-type sequences are preferable as basis for a broad-spectrum p53-targeting cancer vaccine. Furthermore, single amino acid modified p53 peptides can increase HLA-A2 binding capacity and induction of p53-specific cytotoxic T cells. Methods: In a phase I-II trial a total of 32 HLA-A2+ patients with progressive advanced breast cancer were treated with autologous dendritic cells (DC) loaded with six HLA-A2 binding peptides: 3 wild-type [p53 65–73 RMPEAAPPV, p53 264–272 LLGRNSFEV, p53 187–197 GLAPPQHLIRV], 3 modified [p53 149–157 SLPPPGTRV, p53 139–147 KLCPVQLWV, p53 103–111 YLGSYGFRL]. Each patient received up to 10 sc vaccinations with 5x10 6 p53-peptide loaded DC with 1–2 weeks interval. Concomitantly, 6 MIU/m 2 IL-2 was administered s.c. Results: Clinical benefit, mainly as SD or minor regression was obtained in 12 out of 32 patients. Using ELISPOT assay vaccine induced p53 peptide specific T cells were demonstrated in 7/11 of the analyzed response patients but only in 4/14 patients with continued progression, in contrast, 2 patients in this group had reduction of pre-existing reactivity. In most cases T cells specific for several of the six p53 peptides were found and no single p53-epitope was predominant. SD was associated with cessation of serum LDH rise and reduction in serum IL-6 level. In addition more response patients had significant p53 tumor expression. T cell immunity was further explored by dextramer technology and CD107 cytotoxicity assay, and serum YKL-40 was measured and compared to clinical response. Conclusions: A significant fraction of breast cancer patients with progressive disease obtained disease stabilization during treatment with p53-peptide loaded DCs. Induction of p53 specific immunity and changes in disease markers support the clinical results. No significant financial relationships to disclose.
Glutathione reverses the growth abnormalities of skin fibroblasts from insulin-dependent diabetic patients with nephropathy.
Authors: A Morocutti, M Sethi, A Hayward, A Lee, G Viberti
Journal: Journal of the American Society of Nephrology (1998)

Oxidative stress has been proposed as a possible pathogenic factor for diabetic complications. It is relevant in determining cell replicative capacity and life span, and in vitro antioxidant treatment is able to reverse the impaired proliferative activity of different cell types. It was recently demonstrated that cultured skin fibroblasts from insulin-dependent diabetic patients with nephropathy age prematurely and have a shorter life cell cycle. To test whether the growth phenotype of cells from patients with diabetic nephropathy was related to a lack of protection from oxidative stress, the effect of reduced glutathione (GSH) on cultured skin fibroblasts from 13 insulin-dependent diabetes mellitus (IDDM) patients with nephropathy (DN), 10 IDDM patients without kidney disease (D), and 10 nondiabetic control subjects (C), in normal (5 mM) glucose (NG) and high (22 mM) glucose (HG) medium was studied. After 6 to 8 passages, fibroblasts from DN showed impaired growth both in NG (mean +/- SD fold increase over baseline counts in DN 1.17 +/- 0.6 versus D 1.7 +/- 0.5 versus C 1.95 +/- 0.8; P = 0.04 by ANOVA) and in HG (mean +/- SD fold increase over baseline counts DN 1.16 +/- 0.41 versus D 1.89 +/- 0.66 versus C 2.24 +/- 0.9; P = 0.003 by ANOVA). GSH prevented the growth abnormalities of cells from DN restoring it to values similar to that of the other two groups (mean +/- SD fold increase over baseline counts NG +/- GSH: DN 1.68 +/- 0.9 versus D 1.78 +/- 0.49 versus C 1.99 +/- 0.7, P = 0.6; and in HG + GSH: DN 1.66 +/- 0.69 versus D 1.87 +/- 0.75 versus C 2.2 +/- 0.9, P = 0.3). Growth rates were not affected by the addition of GSH in fibroblasts from D and C. The treatment of fibroblasts from D and C with the inhibitor of the gamma-glutamylcysteine synthetase activity, L-buthionine-S,R-sulfoximine, resulted in growth impairment, and the addition to the culture medium of another antioxidant, superoxide dismutase, corrected the growth abnormalities in fibroblasts from DN. The impaired growth of cultured fibroblasts from IDDM patients with nephropathy is prevented by GSH and superoxide dismutase and is independent of prevailing glucose concentrations. This suggests that oxidative stress is an important mechanism of intrinsic cell dysfunction in these patients.
A phase I trial of recombinant human tumor necrosis factor and interferon-gamma: effects of combination cytokine administration in vivo.
Authors: G D Demetri, D R Spriggs, M L Sherman, K A Arthur, K Imamura, D W Kufe
Journal: Journal of Clinical Oncology (1989)

The combination of tumor necrosis factor (TNF) and interferon-gamma has synergistic bioactivity in numerous preclinical model systems. We have tested this potential synergism in vivo by administration of both cytokines to patients with advanced cancer using overlapping 24-hour continuous intravenous (IV) infusions in a phase I trial. Thirty-six patients were treated with a fixed dose of interferon-gamma (200 micrograms/m2/d) with interpatient dose escalation of TNF (from 5 to 205 micrograms/m2/d). The dose-limiting toxicity at the maximal-tolerated dose (MTD) of TNF (205 micrograms/m2) with interferon-gamma was hypotension. Other toxicities noted included an influenza-like syndrome, transient decreases in circulating leukocyte and platelet counts, subclinical evidence of disseminated intravascular coagulation, and the sporadic occurrence of acute pulmonary toxicity. The recommended phase II dose for this combination schedule is TNF, 136 micrograms/m2, with interferon-gamma, 200 micrograms/m2. The addition of interferon-gamma to TNF resulted in a greater than three-fold increase in toxicity compared with TNF administered as a single agent, supporting the hypothesis that the combination of these cytokines may induce synergistic effects in vivo.
Natural history of prostate cancer in a large cohort of untreated patients in the United Kingdom
Authors: M. W. Kattan, J. Cuzick, P. T. Scardino
Journal: Journal of Clinical Oncology (2005)

4512 Purpose: The natural history of prostate cancer managed without immediate aggressive therapy is not well understood. Prior studies have lacked baseline PSA, Gleason grade, adequate sample size, or long term followup. We studied a large and well characterized group of men with clinically localized prostate cancer managed without curative intent to determine predictors of long-term outcomes. Methods: We reviewed cancer registries in 6 regions of the United Kingdom to identify men diagnosed with prostate cancer from 1990 to 1996. Registry records and chart reviews were conducted to identify men who at the time of diagnosis were age 30 - 75 years, and who met the following inclusion criteria: baseline serum PSA level < 100 ng/ml, cT1–3NxM0, survived 6 months without evidence of metastasis and no definitive local therapy. Clinical staging was centrally reviewed and assigned based on a description of the digital rectal exam. Pathological materials from the diagnostic procedure (biopsy or TURP) were collected and centrally reviewed to confirm the diagnosis and assigned primary and secondary Gleason grades. Outcomes were determined from medical records and cancer registry data. Death certificates were reviewed to assign cause of death. Cox models were constructed and nomograms developed to predict time-to-progression and death from prostate cancer using pretreatment PSA, clinical stage, and Gleason grade. Results: Of 2446 eligible men, 30% were treated with hormonal therapy within 6 months of diagnosis. The median followup was 88.9 months (interquartile range 60–107). In a competing risks analysis, 30% of the patients have died of prostate cancer and 30% of other causes within 12 years. For men who did not die of another cause, the probability of metastases, death from prostate cancer, or additional therapy within 12 years was 90%. Conclusions: In the largest cohort of conservatively managed patients to date that includes baseline PSA and reviewed Gleason grade, clinically localized prostate cancer managed conservatively resulted in a high rate of progression or secondary treatment within 12 years. We developed models to predict the risk of death and progression for individual patients from their baseline characteristics. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Oncovance Board Member
Hemodialysis vascular access morbidity.
Authors: H I Feldman, S Kobrin, A Wasserstein
Journal: Journal of the American Society of Nephrology (1996)

Complications associated with hemodialysis vascular access represent one of the most important sources of morbidity among ESRD patients in the United States today. In this study, new data on the magnitude and growth of vascular access-related hospitalization in the United States is presented, demonstrating that the costs of this morbidity will soon exceed $1 billion per yr. This study also reviews published literature on the morbidity associated specifically with native arteriovenous fistulae, polytetrafluoroethylene bridge grafts, and permanent central venous catheters. Next, new information on the changing patterns of vascular access type in the United States is presented, demonstrating the continuing evolution of medical practice away from the use of arteriovenous fistulae in favor of more reliance on synthetic bridge grafts. Based on these data, a discussion is provided of the tradeoffs among the most commonly available modalities of vascular access today. Although radial arteriovenous fistulae continue to represent the optimal access modality, the appropriate roles for brachial arteriovenous fistulae, synthetic bridge grafts, and central venous catheters are less certain because of inadequate data on the long-term function of the first and the high rates of complications associated with the latter two. To reduce vascular access-related morbidity, strategies must be developed not only to prevent and detect appropriately early synthetic vascular access dysfunction, but to better identify the patients in a whom radial arteriovenous fistula is a viable clinical option.
Comparison of two physiotherapic methods in bronchiectasis: Active cycle breathing technique (ACBT) and oscillating physiotherapy device
Authors: Hamid Reza Khoddami Vishteh, Fariba Ghorbani, Masoomeh Masoudnia, Saied Mahmoudian, Shadi Shafaghi, Katayoun Najafizadeh
Journal: European Respiratory Journal (2011)

Background: Because of existence of various physiotherapeutic methods, selecting an effective and capable one is a major problem for the most of bronchiectasis patients. The aim of this study was comparison of two physiotherapeutic methods.

Materials and methods: In this cross-sectional study, 29 known bronchiectasis patients were selected. Each patient performed active cycle breathing technique (ACBT) method in one day and an oscillating physiotherapy device (RC-cornet®) method in the following day under supervision of a physiotherapist. Each physiotherapy session lasted for maximum of 30 minute and all expectorated sputum were collected for volume measurement. In addition, patients responded to 7 questions about each method satisfaction. Paired t test and McNemar test were used for comparison between two methods.

Results: The mean age of patients was 30 year and 16 (55%) were male. There were no significant differences between two methods in sputum volume (ACBT, 17.5±4 ml; RC-cornet, 18.6±4 ml, P=0.729). In addition, there were no significant differences between two methods in terms of understanding performing the method, expectorated sputum amount, time consuming, tedious, need of additional training session and overall satisfaction (P>0.05). However, patients believed that they can do physiotherapy with RC-cornet® method at home lonely than ACBT method (25 vs. 15, P=0.022).

Conclusion: Our findings showed that use of RC-cornet® at home is preferred by most of the patients. Since this method was more acceptable and preferable than ACBT for home usage, we highly suggest use of such convenient methods.
Systemic Therapy for Metastatic Colorectal Cancer
Authors: Leonard Saltz
Journal: Journal of the National Comprehensive Cancer Network (2013)

In the treatment of advanced colorectal cancer (CRC), the addition of so-called “targeted” agents to irinotecan- and oxaliplatin-based regimens has resulted in statistically significant—but often clinically modest—improvements in progression-free and overall survival. This is true for the most recent additions to the treatment armamentarium, regorafenib and ziv-aflibercept. In his recent presentation at the NCCN 18th Annual Conference, Leonard Saltz, MD, reviewed the landmark trials establishing targeted agents as effective in metastatic CRC. However, he also noted that statistical significance does not necessarily equal clinical significance, and indicated that clinicians should consider the differential toxicity profiles of the regimens when individualizing treatment.
Consequences of obesity on gas exchange during exercise
Authors: Bohumil Matula, Stanislav Majerník, Plamen Kabaivanov, Daniel Magula, Ján Plutinsky
Journal: European Respiratory Journal (2011)

Obesity produces an increment in total blood volume and cardiac output and a decrease in lung compliance as a result of increased pulmonary blood volume and alveolar collapse in the lung bases.   Aim:  To evaluate gas exchange parameters under incremental exercise in “healthy” obese patients (pts).   Methods:  Analysis of symptom limited incremental cardiopulmonary exercise tests in supine position of 115 pts (36M, 79F) with FEV1,VC and TLCO ≥ 80% predicted (ECCS) and without history of cardiovascular disease. Punctions of arteria radialis were made to evaluate arterial oxygen and carbon dioxide pressure (PaO2, PaCO2) at peak exercise (PE) and to calculate dead-space to tidal volume ratio at PE (VD/VT) and alveolar-arterial oxygen pressure difference (PA-aO2). Slope of heart rate to oxygen uptake (DHR/DVO2 beat. l/min) was determined. Pts were divided into 2 groups: Ob (n=58): Body mass index (BMI) ≥ 30kg/m 2 , N (n=57): BMI  2 .   Results:  Significant differences were found between group Ob and N at PE in PaO2 (83.3 vs 89.1mmHg, p   Conclusion:  Hypervolemia and pulmonary over-perfusion may be an important factor of gas exchange impairment under exercise in obese patients.
Effectiveness of pneumococcal conjugate vaccine against presumed bacterial pneumonia hospitalisation in HIV-uninfected South African children: a case–control study
Authors: Shabir A Madhi, Michelle J Groome, Heather J Zar, Constant N Kapongo, Christine Mulligan, Susan Nzenze, David P Moore, Elizabeth R Zell, Cynthia G Whitney, Jennifer R Verani
Journal: Thorax (2015)

<h3>Introduction</h3> We evaluated pneumococcal conjugate vaccine (PCV) effectiveness against hospitalisation for presumed bacterial pneumonia (PBP) in HIV-uninfected South African children. 7-valent PCV was introduced in April 2009 using a 2+1 schedule (doses at age 6, 14 and 39 weeks), superseded with 13-valent PCV in May 2011. <h3>Methods</h3> A matched case–control study was conducted at three public hospitals (Soweto, Cape Town and KwaZulu-Natal) between April 2009 and August 2012. PBP cases had either WHO defined radiographically confirmed pneumonia or 'other infiltrate' on chest radiograph with C-reactive protein ≥40 mg/L. Hospitalised controls were children admitted with a disease unlikely to be pneumococcal and matched for case age, site and HIV infection status. Age-matched community controls were enrolled from Soweto. Adjusted vaccine effectiveness (aVE) was estimated using conditional logistic regression. <h3>Results</h3> Of 1444 HIV-uninfected enrolled PBP cases, 1326 had ≥1 hospital controls (n=2075). Overall, aVE of an up-to-date PCV schedule was 20.1% (95% CI −9.3% to 41.6%) in children aged ≥8 weeks and 39.2% (95% CI 8.46% to 59.6%) among children 16–103 weeks of age. There were 889 PBP cases in Soweto with hospital controls and ≥1 community control (n=2628). The aVE using community controls was similar compared with hospital controls in Soweto, including 32.1% (95% CI 4.6% to 51.6%) and 38.4% (95% CI 7.7% to 58.8%), respectively, in age group ≥8 weeks and 52.7% (95% CI 25.7% to 69.9%) and 53.8% (95% CI 19.5% to 73.5%), respectively, in age group 16–103 weeks. <h3>Conclusions</h3> PCV implemented using a 2+1 schedule in the routine infant immunisation programme was effective at preventing PBP in HIV-uninfected children. Effectiveness estimates were similar to efficacy measured by earlier randomised controlled trials using different vaccination schedules.