tbuckley/cabot-search huggingface dataset:
Multicenter Phase II Study of Capecitabine in Paclitaxel-Refractory Metastatic Breast Cancer
Authors: Joanne L. Blum, Stephen E. Jones, Aman U. Buzdar, Patricia Mucci LoRusso, Irene Kuter, Charles Vogel, Bruno Osterwalder, Hans-Ulrich Burger, Cheryl Stoner Brown, Tom Griffin
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Capecitabine is a novel, oral, selectively tumor-activated fluoropyrimidine carbamate. This large multicenter phase II trial tested the efficacy and safety of twice-daily oral capecitabine at 2,510 mg/m 2 /d given for 2 weeks followed by a 1-week rest period and repeated in 3-week cycles, in patients with paclitaxel-refractory metastatic breast cancer. PATIENTS AND METHODS: Patients were to have received at least two but not more than three prior chemotherapeutic regimens, one of which had to have contained paclitaxel given for metastatic disease. One hundred sixty-three patients were entered onto the study at 25 centers, and 162 patients received capecitabine. One hundred thirty-five patients had bidimensionally measurable disease, and 27 patients had assessable disease. RESULTS: The overall response rate was 20% (95% confidence interval, 14% to 28%). All responding patients were resistant to or had failed paclitaxel, and all had received an anthracycline. Three complete responses were seen, with complete response durations of 106, 109, and 194+ days. Median duration of response was 8.1 months, median survival time was 12.8 months, and the median time to disease progression was 93 days. The most common treatment-related adverse events were hand-foot syndrome, diarrhea, nausea, vomiting, and fatigue. Diarrhea (14%) and hand-foot syndrome (10%) were the only treatment-related adverse events that occurred with grade 3 or 4 intensity in more than 10% of patients. CONCLUSION: Capecitabine is an active drug in the treatment of paclitaxel-refractory metastatic breast cancer. It has a favorable toxicity profile with the added advantage of being an oral drug administered at home.
Vemurafenib and Cobimetinib Potently Inhibit Ps6 Signaling in Brafv600 Mutation–Positive Locally Advanced or Metastatic Melanoma from Brim7 Study
Authors: Y. Yan, G. McArthur, T. Gajewski, I. Puzanov, O. Hamid, R. Gonzalez, Y. Wang, S. Lu, M. Wongchenko, N.W. Choong, A. Ribas
Journal: Annals of Oncology (2014)
Extracellular Vesicles in Renal Diseases
Authors: Uta Erdbrügger, Thu H. Le
Journal: Journal of the American Society of Nephrology (2015)

Extracellular vesicles from the urine and circulation have gained significant interest as potential diagnostic biomarkers in renal diseases. Urinary extracellular vesicles contain proteins from all sections of the nephron, whereas most studied circulating extracellular vesicles are derived from platelets, immune cells, and the endothelium. In addition to their diagnostic role as markers of kidney and vascular damage, extracellular vesicles may have functional significance in renal health and disease by facilitating communication between cells and protecting against kidney injury and bacterial infection in the urinary tract. However, the current understanding of extracellular vesicles has derived mostly from studies with very small numbers of patients or in vitro data. Moreover, accurate assessment of these vesicles remains a challenge, in part because of a lack of consensus in the methodologies to measure extracellular vesicles and the inability of most techniques to capture the entire size range of these vesicles. However, newer techniques and standardized protocols to improve the detection of extracellular vesicles are in development. A clearer understanding of the composition and biology of extracellular vesicles will provide insights into their pathophysiologic, diagnostic, and therapeutic roles.
Ozone, Fine Particulate Matter, and Chronic Lower Respiratory Disease Mortality in the United States
Authors: Yongping Hao, Lina Balluz, Heather Strosnider, Xiao Jun Wen, Chaoyang Li, Judith R. Qualters
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Short-term effects of air pollution exposure on respiratory disease mortality are well established. However, few studies have examined the effects of long-term exposure, and among those that have, results are inconsistent.
Differences in cerebrospinal fluid penetration of corticosteroids: possible relationship to the prevention of meningeal leukemia.
Authors: F M Balis, C M Lester, G P Chrousos, R L Heideman, D G Poplack
Journal: Journal of Clinical Oncology (1987)

The disposition of the synthetic corticosteroids, dexamethasone and prednisolone, in CSF was evaluated following bolus intravenous (IV) and intrathecal (IT) injection in a nonhuman primate model. Steroid concentration in plasma and CSF was measured with a radioimmunoassay following celite column chromatography. The CSF to plasma ratios of dexamethasone and prednisolone following IV bolus administration were 0.15 +/- 0.02 and 0.08 +/- 0.03, respectively. Although peak levels of the two steroids in the CSF reached equally potent levels when administered systemically in equipotent doses, the half-life of prednisolone in the CSF was shorter. In addition, there was a significant difference in the plasma protein binding of the two steroids, which may account for the differences in their CSF pharmacokinetics. Dexamethasone was 70% protein bound over a wide concentration range, while the protein binding of prednisolone was concentration dependent, ranging from 60% at 10 mumol/L to 95% at 0.5 mumol/L and below. After the initial distribution phase in plasma, CSF concentrations of dexamethasone and prednisolone approximated free plasma concentrations, indicating that penetration into the CSF was limited primarily by protein binding. At the plasma concentrations achieved following oral administration of standard doses of prednisone in children, the prednisolone (the active metabolite) is greater than 90% protein bound. The proportionally higher free plasma levels of dexamethasone result in greater penetration into the CSF. These findings may explain the lower rates of meningeal leukemia observed in children receiving dexamethasone instead of prednisone for the treatment of acute lymphoblastic leukemia (ALL).
Unilateral treatment with lung volume reduction coils in patients with severe emphysema
Authors: Harald Trautmann
Journal: European Respiratory Journal (2013)

Rationale:  Bronchoscopic Lung Volume Reduction Coil treatment has been successfully used in multiple European studies to improve pulmonary function, exercise capacity and quality of life in bilaterally-treated patients. Unilateral use of LVRC has thus far not been reported in a commercial setting.   Aim : To evaluate whether unilateral LVRC can provide meaningful clinical improvement in severe emphysema patients.   Methods:  We selected patients in a severe condition (mean FEV1 0.662L, mean FVC 1.394L, mean RV 314.78%, mean 6MWT 136.25m) and treated the most severely damaged lobe as evidenced by visual CT analysis. Follow-up tests were conducted approximately 3 months following unilateral treatment. Ten LVRC were placed in one lobe.  Results:  The most remarkable improvements were in 6MWT (mean +57.5m) and dyspnea (mean mMRC -1.06 points from a baseline average of 3+). 6MWT was evaluable in 8 treated patients. One patient experienced 0m 6MWT improvement from a 140m baseline; the mean improvement in the other 7 patients was 65.75m, which is highly significant in this low exercise tolerance group. Mean improvement in FEV1 was +0.24L, and RV% predicted was -27%. We consider these improvements clinically significant, and are encouraged by the patients’ high satisfaction with the procedure and results. We intend to offer the bilateral treatment to these patients as their condition warrants, and may consider suggesting bilateral treatment to patients who did not improve as we would have expected following the first treatment.
CRAC channel inhibition by RP3128 ameliorates airway hyper-reactivity in antigen sensitized mice and guinea pigs
Authors: Kasiviswanath Routhu, Babu Govindrajulu, Sridhar Veeraraghavan, Srikant Viswanadha, Swaroop Vakkalanka
Journal: European Respiratory Journal (2014)

Introduction 

Calcium release activated calcium (CRAC) channel inhibitors have a potent role in treatment of respiratory disorders. RP3128 is a novel CRAC channel inhibitor exhibiting nanomolar potency against ICRAC and immune-modulatory activity across relevant pre-clinical assays. The objective of the current study was to explore and elucidate the anti-asthmatic properties of RP3128 in allergen-challenged mice and guinea pigs.

Methods 

Suppression of antigen-induced asthmatic responses upon oral administration of RP3128 in Balb/c mice and guinea pigs were determined. Changes in ASM reactivity in response to RP3128 in vitro were tested using an organ-bath method.

Results 

Oral administration of RP3128 to sensitized mice resulted in attenuation of methacholine induced airway hyperresponsivness manifested by dose-dependent reduction in PenH (∼50% @ 3 mg/kg) values as well as eosinophil count (ED50 = 1.9 mg/kg). RP3128 significantly reduced basal (71%) and histamine (86%) or methacholine (87%) induced sRaw values in sensitized guinea pigs. Besides, RP3128 caused a near complete inhibition of ENO levels as well as reduction in serum (IL-4, IL-13, and TNFα) and BALF (IL-4, IL-5, IL-13, and TNFα) cytokines (50-95%). Additionally, contraction amplitude of isolated tracheal or pulmonary smooth muscle in response to cumulative doses of acetylcholine or histamine was significantly reduced in RP3128 treated animals compared to saline control group.

Conclusions 

Data demonstrate the anti-inflammatory and airway remodelling properties of RP3128 upon administration at a low dose thereby indicating the therapeutic potential of this molecule in respiratory disorders.
Randomized Trial of Neoadjuvant Cisplatin, Vincristine, Bleomycin, and Radical Hysterectomy Versus Radiation Therapy for Bulky Stage IB and IIA Cervical Cancer
Authors: Ting-Chang Chang, Chyong-Huey Lai, Ji-Hong Hong, Suei Hsueh, Kuan-Gen Huang, Hung-Hsueh Chou, Chih-Jen Tseng, Chien-Sheng Tsai, Joseph T. Chang, Cheng-Tao Lin, Huei-Hsin Chang, Pei-Jung Chao, Koon-Kwan Ng, Simon Guo-Jeng Tang, Yung-Kwei Soong
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To compare the efficacy of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy with that of radiotherapy (R/T) for bulky early-stage cervical cancer. PATIENTS AND METHODS: Women with previously untreated bulky (primary tumor ≥ 4 cm) stage IB or IIA non–small-cell carcinoma of the uterine cervix were randomly assigned to receive either cisplatin 50 mg/m 2 and vincristine 1 mg/m 2 for 1 day and bleomycin 25 mg/m 2 for 3 days for three cycles followed by radical hysterectomy (NAC arm) or receive primary pelvic radiotherapy only (R/T arm). The ratio of patient allocation was 6:4 for the NAC and R/T arms. Women with enlarged para-aortic lymph nodes on image study were ineligible unless results of cytologic or histologic studies were negative. RESULTS: Of the 124 eligible patients, 68 in the NAC arm and 52 in the R/T arm could be evaluated. The median duration of follow-up was 39 months. Thirty-one percent of patients in the NAC arm and 27% in the R/T arm had relapse or persistent diseases after treatment, and 21% in each group died of disease. Estimated cumulative survival rates at 2 years were 81% for the NAC arm and 84% for the R/T arm; the 5-year rates were 70% and 61%, respectively. There were no significant differences in disease-free survival and overall survival. CONCLUSION: NAC followed by radical hysterectomy and primary R/T showed similar efficacy for bulky stage IB or IIA cervical cancer. Further study to identify patient subgroups better suited for either treatment modality and to evaluate the concurrent use of cisplatin and radiation without routine hysterectomy is necessary.
Prevention of recurrent menstrual psychosis by an oral contraceptive
Authors: A R Felthous, D B Robinson, R W Conroy
Journal: American Journal of Psychiatry (1980)

A 21-year-old unmarried female, with a history of periodic psychotic behavior, was admitted to the hospital after exhibiting overt psychotic symptoms. Several months of hospital observtion and a review of her earlier psychotic episodes suggested that the patient's psychotic behavior was associated with the onset of menses. The symptoms disappeared after oral contraceptives were administered on a regular basis. The patient experienced her 1st psychotic episode 1 year after menache. Several episodes during the intervening years required hospitalization. One of these episodes occurred during a period of prolonged menstrual flow. The patient's menstrual cycles were frequently irregular. During the present hospitalization the patient exhibited psychotic symptoms at the onset of 3 of her 4 menstrual cycles. She became agitated and delusional and exhibited dissociated thought patterns and autonomic symptoms. Despite the use of high doses of antipsychotic drugs, the symptoms persisted until the menstrual flow stopped 7 days later. After the 3rd episode the patient did not menstruate for 2 months. 69 days after the onset of her last menstrual flow the patient was given Provera to induce menstruation. 5 days later the menstrual flow began and Ortho-Novum 1/50 was administered. During the next 6 months she took the contraceptive regularly and remained free of any overt symptoms. The mechanism by which oral contraceptives prevent menstrual psychosis is unknown. Perhaps the estrogen decreases monoamine oxidase activity which in turn alters the level of norepinephine at the synapses.
Second Ear Stapedectomy
Authors: R J Sergeant, P V Wadsworth
Journal: Journal of the Royal Society of Medicine (1980)

A long-term follow up of a personal series of 79 second ear stapedectomies indicates that the procedure can be undertaken with minimal complications. No bilateral dead ears or vestibular disasters have occurred. The results were satisfactory in 87.5% of ears, and bilaterally symmetrical hearing with an air-bone gap of 30 dB or less was achieved in 24% of patients. Whilst the established dictum that only one ear should be operated upon should not be abandoned, the results reported in this paper may encourage the more experienced to operate on the second ear at a later date in carefully selected cases.
Does pulmonary rehabilitation reduce blood pressure in COPD
Authors: Djeya P. Kaliaraju, Jane L. Canavan, Samantha S.C. Kon, Claire M. Nolan, Sarah E. Jones, Amy L. Clark, William D.-C. Man
Journal: European Respiratory Journal (2013)

Introduction 

Cardiovascular disease (CVD) is a common cause of mortality in patients with chronic obstructive pulmonary disease (COPD). Arterial stiffness (AS) is a marker of cardiovascular risk, and is increased in COPD. Two small studies of selected COPD patients have recently identified beneficial exercise training effects on AS probably secondary to reduction in blood pressure (BP) (Vivodtzev 2009, Gale 2011). We hypothesised that an unrecognised benefit of pulmonary rehabilitation (PR) is modification of CVD risk by reduction of BP.

Aims and objectives 

To determine the effect of PR on blood pressure in unselected COPD patients.

Methods 

Systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR) at rest, incremental shuttle walk (ISW) and chronic respiratory disease questionnaire (CRQ) were prospectively measured in 550 consecutive COPD patients referred to an 8 week outpatient PR programme. Pre and post-PR data was analysed using paired t-tests or Wilcoxon signed rank tests. Mann Whitney tests were used to assess the effect of PR in a subset of patients with CVD.

Results 

Data was available in 418 completers. Despite clinically significant improvement in exercise capacity and quality of life with PR, there was no significant change in SBP, mean difference (95%CI) 0.66 (-1.15,2.48) mmHg, or DBP -1.12 (-2.29,0.05) mmHg. Mean resting HR was significantly reduced (p=0.03) but the magnitude of change was minimal -1.3 (-2.4,-0.2) bpm. Subset analysis of patients with known CVD or those with a clinically significant improvement in ISW (ΔISW>47.5m) also showed no meaningful clinical significant change in BP/HR with PR.

Conclusion 

There is no clinically significant reduction in resting BP or HR after an 8 week PR programme.
Addressing the Effects of Climate on Health
Authors: M. J. Friedrich
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Validation of a visual analogue score (LRTI-VAS) in non-CF bronchiectasis
Authors: Josje Altenburg, Kim Wortel, Tjip Van der Werf, Wim Boersma
Journal: European Respiratory Journal (2014)

Background  Quality of life in patients with non-cystic fibrosis (non-CF) bronchiectasis is largely defined by respiratory symptoms. To date no disease specific tool for symptom measurement in this patient group was available. We developed the Lower Respiratory Tract Infections Visual Analogue Scale (LRTI-VAS) in order to quickly and conveniently quantify symptoms in non-CF bronchiectasis. This study aimed to validate LRTI-VAS for use in non-CF bronchiectasis.  Methods  This study included out-patients from our department of pulmonary medicine with radiologically proven bronchiectasis and no evidence of CF. Results of LRTI-VAS were compared to other markers of disease activity (lung function parameters, oxygen saturation and three health-related quality of life questionnaires (SF-36, SGRQ and LCQ) and validity, reliability and responsiveness were assessed.  Results  30 stable and 30 exacerbating participants completed LRTI-VAS. When testing for repeatability on two separate occasions, no statistically significant difference between total scores was found (1.4 (SD 5.3), p= 0.16). Internal consistency was high across items (Cronbach9s alpha 0.86). Correlation with SGRQ-, SF36- and LCQ total scores was high. Following antibiotic treatment, mean (SD) LRTI-VAS total score improved from 18.1 (SD 9.9) to 26.1 (SD 6.6) (p   Conclusion  LRTI-VAS showed excellent validity, reliability and responsiveness to change and is therefore a reliable tool for symptom measurement in non-CF bronchiectasis.
Possible Role of Mucosal Damage in Stomach Carcinogenesis With N-Methyl-N'-Nitro-N-Nitrosoguanidine in the Rat2
Authors: Yoshiki Tabuchi, Toshio Ogino, Takao Mitsuno, Taketoshi Sugiyama
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Possible Role of Mucosal Damage in Stomach Carcinogenesis With N-Methyl-N'-Nitro-N-Nitrosoguanidine in the Rat Get access Yoshiki Tabuchi, Yoshiki Tabuchi 3Department of Pathology, Kobe University School of Medicine, Ikuta-ku, Kobe, Japan4Department of Surgery, Kobe University School of Medicine Search for other works by this author on: Oxford Academic PubMed Google Scholar Toshio Ogino, Toshio Ogino 3Department of Pathology, Kobe University School of Medicine, Ikuta-ku, Kobe, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Takao Mitsuno, Takao Mitsuno 4Department of Surgery, Kobe University School of Medicine Search for other works by this author on: Oxford Academic PubMed Google Scholar Taketoshi Sugiyama Taketoshi Sugiyama 3Department of Pathology, Kobe University School of Medicine, Ikuta-ku, Kobe, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 5, May 1974, Pages 1589–1594, https://doi.org/10.1093/jnci/52.5.1589 Published: 01 May 1974 Article history Received: 19 November 1973 Accepted: 04 February 1974 Published: 01 May 1974
Authors’ reply to Steele and colleagues
Authors: William Hamilton, Steve Hajioff, John Graham, Mia Schmidt-Hansen
Journal: BMJ (2015)

In response to Steele and colleagues,1 2 half of patients with colorectal cancer did not meet the criteria for urgent referral under the previous guidance. These patients, with “low risk, but not no risk symptoms” did badly, with longer times to diagnosis,3 more emergency admissions,4 and higher mortality.3 The 2015 National Institute for Health and Care Excellence (NICE) guidance sought to improve this.1

The …
The relationship between exhaled nitric oxide measurements and subsequent asthma control in a cohort of children followed over 12-months
Authors: Rebecca Cutts, Steve Turner
Journal: European Respiratory Journal (2011)

Introduction:  Exhaled nitric oxide (FE NO ) may be a useful biomarker for childhood asthma control but clinical studies have been disappointing. The aims of the present observational study was to relate FE NO  values with later asthma control and to derive clinically useful FE NO  cut off values.   Methods:  Children with stable asthma were recruited. Exhaled NO was measured at two month intervals when the Childhood Asthma Control Test (CACT) was also completed.   Results:  Forty nine children with stable asthma were recruited in whom 252 FE NO  measurements were made. Exhaled NO was inversely related to CACT after two months (rho -0.22, p=0.005, n=158) and four months (rho -0.23, p=0.009, n=127) but not six months (rho -0.12, p=0.256, n=93). There were 121 2-month periods when asthma remained well controlled (mean initial FE NO  20.9ppb [95%CI 17.6, 23.5]), 12 when control was gained (35.0ppb [22.1, 55.3]), 8 when good control was lost (28.3ppb [12.4, 64.7]) and 15 when control remained poor (19.0ppb [95%CI 13.2, 27.4]); the difference in FE NO  between remain controlled and became controlled was significant (p=0.022). Exhaled NO of >46ppb had sensitivity of 63% and specificity of 77% for predicting future loss of asthma control (AUC 0.61). Exhaled NO of >22ppb had a sensitivity of 65% and specificity of 58% for a future reduction in CACT of 3 points (AUC 0.65).   Conclusions:  Increased FE NO  is associated with reduced asthma control over the following four months. In this population of stable asthmatic children, increased FE NO  lacked precision for predicting future changes in asthma control. Exhaled NO might be useful in predicting ongoing well-controlled asthma.