tbuckley/cabot-search huggingface dataset:
Thirteen-megahertz ultrasound probe: its role in diagnosing localized scleroderma
Authors: A. Cosnes, M-C. Anglade, J. Revuz, C. Radier
Journal: British Journal of Dermatology (2003)

Ultrasound imaging has been shown to be useful for the evaluation of systemic and localized scleroderma (LS). However, its specificity and sensitivity have not been studied.To define morphological ultrasound diagnostic criteria in LS and to test their sensitivity and specificity with a 13-MHz ultrasound probe.Forty plaques in 26 consecutive patients with LS were examined and compared blindly with 17 control plaques in 16 patients with skin diseases where LS was in the differential diagnosis. Data were also compared with a normal control group. Five patients were re-evaluated 12-18 months after the first examination.Ultrasound examination disclosed a characteristic dense image resembling a flattened 'yo-yo'. Undulations of the dermis, disorganization, loss of thickness and thickened hyperechoic bands in the hypodermis, and the 'yo-yo' image had a high sensitivity and a high specificity for LS. A 92% sensitivity and a 100% specificity for LS were found when at least four of these five signs were present.Thirteen-megahertz ultrasound is a valuable tool for diagnosing LS. Morphological ultrasound diagnostic criteria had a high specificity and a high sensitivity.
Number needed to treat (NNT): implication in rheumatology clinical practice
Authors: M Osiri
Journal: Annals of the Rheumatic Diseases (2003)

To calculate the number needed to treat (NNT) and number needed to harm (NNH) from the data in rheumatology clinical trials and systematic reviews.The NNTs for the clinically important outcome measures in the rheumatology systematic reviews from the Cochrane Library, issue 2, 2000 and in the original randomised, double blind, controlled trials were calculated. The measure used for calculating the NNT in rheumatoid arthritis (RA) interventions was the American College of Rheumatology 20% improvement or Paulus criteria; in osteoarthritis (OA) interventions, the improvement of pain; and in systemic sclerosis (SSc) interventions, the improvement of Raynaud's phenomenon. The NNH was calculated from the rate of withdrawals due to adverse events from the treatment.The data required for the calculation of the NNT were available in 15 systematic reviews and 11 original articles. For RA interventions, etanercept treatment for six months had the smallest NNT (1.6; 95% confidence interval (CI) 1.4 to 2.0), whereas leflunomide had the largest NNH (9.6; 95% CI 6.8 to 16.7). For OA treatment options, only etodolac and tenoxicam produced significant pain relief compared with placebo (NNT=4.4; 95% CI 2.4 to 24.4 and 3.8; 95% CI 2.5 to 7.3, respectively). For SSc interventions, none were shown to be efficacious in improving Raynaud's phenomenon because the 95% CI of the NNT was infinite.The NNT and NNH are helpful for clinicians, enabling them to translate the results from clinical trials and systematic reviews to use in routine clinical practice. Both NNT and NNH should be accompanied by a limited 95% CI and adjusted for the individual subject's baseline risk.
Tyrosine Metabolism in Patients with Liver Disease*
Authors: Robert J. Levine, Harold O. Conn
Journal: Journal of Clinical Investigation (1967)

Plasma levels of tyrosine were assayed in the fasting state and after oral administration of either tyrosine (tyrosine tolerance test) or phenylalanine (phenlyalanine conversion test) in normal subjects and in patients with hepatitis, biliary obstruction, or cirrhosis. Fasting tyrosine levels tended to be slightly increased in patients with hepatitis and biliary obstruction and markedly increased in patients with cirrhosis.
Randomized Phase II Trial Comparing Nitroglycerin Plus Vinorelbine and Cisplatin With Vinorelbine and Cisplatin Alone in Previously Untreated Stage IIIB/IV Non–Small-Cell Lung Cancer
Authors: Hiroyasu Yasuda, Mutsuo Yamaya, Katsutoshi Nakayama, Takahiko Sasaki, Satoru Ebihara, Akio Kanda, Masanori Asada, Daisuke Inoue, Tomoko Suzuki, Tatsuma Okazaki, Hidenori Takahashi, Motoki Yoshida, Tomohiro Kaneta, Kota Ishizawa, Shinsuke Yamanda, Naoki Tomita, Miyako Yamasaki, Akiko Kikuchi, Hiroshi Kubo, Hidetada Sasaki
Journal: Journal of Clinical Oncology (2006)

To investigate the efficacy and safety of nitroglycerin plus vinorelbine and cisplatin in patients with previously untreated stage IIIB/IV non-small-cell lung cancer (NSCLC) as the experimental arm for the next phase III trial.One hundred twenty patients with stage IIIB/IV NSCLC were randomly assigned to vinorelbine 25 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 on day 1, with transdermally applied nitroglycerin (25 mg/patient daily for 5 days; arm A) or with placebo patch (arm B) every 3 weeks for a maximum of four cycles in a double-blind and controlled trial. Primary efficacy end points were the best confirmed response rate and time to disease progression (TTP).The response rate in arm A (72%; 43 of 60 patients) was significantly higher than that for patients in arm B (42%; 25 of 60 patients; P < .001). Median TTP in arm A was longer than that in arm B (327 v 185 days). No severe adverse effect was recognized for either arm. The rate of grade 1 to 2 headache in arm A (30%; 18 of 60 patients) was significantly higher than that in arm B (2%; one of 60 patients; P < .001, chi(2) test).Use of nitroglycerin combined with vinorelbine and cisplatin may improve overall response and TTP in patients with stage IIIB/IV NSCLC. The arm A regimen is being evaluated in a large phase III trial.
Serum 25-Hydroxyvitamin D: A Predictor of Macrovascular and Microvascular Complications in Patients With Type 2 Diabetes
Authors: Markus Herrmann, David R. Sullivan, Anne-Sophie Veillard, Thomas McCorquodale, Isabella R. Straub, Russell Scott, Markku Laakso, Duncan Topliss, Alicia J. Jenkins, Stefan Blankenberg, Anthony Burton, Anthony C. Keech
Journal: Diabetes Care (2014)

OBJECTIVE People with diabetes frequently develop vascular disease. We investigated the relationship between blood 25-hydroxyvitamin D (25OH-D) concentration and vascular disease risk in type 2 diabetes. RESEARCH DESIGN AND METHODS The relationships between blood 25OH-D concentration at baseline and the incidence of macrovascular (including myocardial infarction and stroke) and microvascular (retinopathy, nephropathy, neuropathy, and amputation) disease were analyzed with Cox proportional hazards models and logistic regression in an observational study of patients in the 5-year Fenofibrate Intervention and Event Lowering in Diabetes trial. RESULTS A total of 50% of the patients had low vitamin D concentrations, as indicated by median blood 25OH-D concentration of 49 nmol/L. These patients with a blood 25OH-D concentration &amp;lt;50 nmol/L had a higher cumulative incidence of macrovascular and microvascular events than those with levels ≥50 nmol/L. Multivariate analysis, stratified by treatment and adjusted for relevant confounders, identified blood 25OH-D concentration as an independent predictor of macrovascular events. A 50 nmol/L difference in blood 25OH-D concentration was associated with a 23% (P = 0.007) change in risk of macrovascular complications during the study, and further adjustments for seasonality, hs-CRP, and physical activity level had little impact. The unadjusted risk of microvascular complications was 18% (P = 0.006) higher during the study, though the excess risk declined to 11–14% and lost significance with adjustment for HbA1c, seasonality, or physical activity. CONCLUSIONS Low blood 25OH-D concentrations are associated with an increased risk of macrovascular and microvascular disease events in type 2 diabetes. However, a causal link remains to be demonstrated.
Loss of constitutive activity of the growth hormone secretagogue receptor in familial short stature
Authors: J. Pantel
Journal: Journal of Clinical Investigation (2006)

The growth hormone (GH) secretagogue receptor (GHSR) was cloned as the target of a family of synthetic molecules endowed with GH release properties. As shown recently through in vitro means, this receptor displays a constitutive activity whose clinical relevance is unknown. Although pharmacological studies have demonstrated that its endogenous ligand — ghrelin — stimulates, through the GHSR, GH secretion and appetite, the physiological importance of the GHSR-dependent pathways remains an open question that gives rise to much controversy. We report the identification of a GHSR missense mutation that segregates with short stature within 2 unrelated families. This mutation, which results in decreased cell-surface expression of the receptor, selectively impairs the constitutive activity of the GHSR, while preserving its ability to respond to ghrelin. This first description, to our knowledge, of a functionally significant GHSR mutation, which unveils the critical importance of the GHSR-associated constitutive activity, discloses an unusual pathogenic mechanism of growth failure in humans.
The action of the C-terminal octapeptide of cholecystokinin and related peptides on pancreatic exocrine secretion
Authors: S. Nakajima
Journal: Gut (1973)

The effect of the C-terminal octapeptide of cholecystokinin-pancreozymin (CCK-PZ), caerulein, and the C-terminal tetrapeptide of gastrin on pancreatic secretion of fluid, electrolyte, amylase, and protein was studied in anaesthetized dogs prepared with pancreatic fistulae. Against background stimulation of fluid secretion with submaximal doses of secretin, all the polypeptides produced a qualitatively similar pancreatic response, causing a highly significant increase in amylase, protein, calcium, and zinc concentrations. Magnesium concentration was significantly increased only when the concentration preceding the administration of the peptide was below 100 mu-equiv/l. Octa-CCK-PZ was 13-35 times and 20-56 times more potent than tetragastrin on weight and molar bases, respectively, as a stimulant of amylase secretion. The threshold doses were largest for amylase, lower for calcium, and lowest for zinc. A significant linear correlation was observed between amylase and calcium concentration, zinc and protein concentration, and magnesium and calcium concentration. The peptides produced some increase in secretin-induced volume flow, whereas bicarbonate, chloride, sodium, and potassium concentrations remained unchanged. The direct relation between bicarbonate concentration and flow rate was limited to rates below 1.5 ml/5 minutes. At higher rates bicarbonate and chloride concentration reached a high and low plateau, respectively, although the first five-min sample of pancreatic juice after secretin stimulation exhibited a relatively low bicarbonate and high chloride concentration compared with its voluminous flow. Chloride concentration varied inversely with bicarbonate concentration, the sum of the two anions being constant.
Secreted Protein Acidic and Rich in Cysteine Produced by Human Melanoma Cells Modulates Polymorphonuclear Leukocyte Recruitment and Antitumor Cytotoxic Capacity
Authors: Mariano J. Alvarez, Federico Prada, Edgardo Salvatierra, Alicia I. Bravo, Viviana P. Lutzky, Cecilia Carbone, Fernando J. Pitossi, H. Eduardo Chuluyan, Osvaldo L. Podhajcer
Journal: Cancer Research (2005)

Abstract The expression of secreted protein acidic and rich in cysteine (SPARC) has been associated with the malignant progression of different types of human cancer. SPARC was associated with tumor cell capacity to migrate and invade, although its precise role in tumor progression is still elusive. In the present study, we show that SPARC produced by melanoma cells modulates the antitumor activity of polymorphonuclear leukocytes (PMN). Administration to nude mice of human melanoma cells in which SPARC expression was transiently or stably knocked down by antisense RNA (SPARC-sup cells) promoted PMN recruitment and obliterated tumor growth even when SPARC-sup cells accounted for only 10% of injected malignant cells. In addition, SPARC-sup cells stimulated the in vitro migration and triggered the antimelanoma cytotoxic capacity of human PMN, an effect that was reverted in the presence of SPARC purified from melanoma cells or by reexpressing SPARC in SPARC-sup cells. Leukotrienes, interleukin 8, and growth-related oncogene, in combination with Fas ligand and interleukin 1, mediated SPARC effects. These data indicate that SPARC plays an essential role in tumor evasion from immune surveillance through the inhibition of the antitumor PMN activity.
A Short Nur77-Derived Peptide Converts Bcl-2 from a Protector to a Killer
Authors: Siva Kumar Kolluri, Xiuwen Zhu, Xin Zhou, Bingzhen Lin, Ya Chen, Kai Sun, Xuefei Tian, James Town, Xihua Cao, Feng Lin, Dayong Zhai, Shinichi Kitada, Frederick Luciano, Edmond O'Donnell, Yu Cao, Feng He, Jialing Lin, John C. Reed, Arnold C. Satterthwait, Xiao-kun Zhang
Journal: Cancer Cell (2008)
Do we “drive” dyspnoea?
Authors: Anna L. Hudson, Pierantonio Laveneziana
Journal: European Respiratory Journal (2015)

Electromyography (EMG) measures neural drive, and is routinely used to investigate movement control and pathophysiology in human subjects. The electrical signals recorded from a muscle indicate the recruitment and discharge of spinal motor neurones by voluntary and reflex activation. EMG recordings are typically made with surface electrodes placed on the skin over the muscle of interest, or intramuscular needle or wire electrodes inserted into the muscle of interest. There are advantages and disadvantages of both techniques [1] but the disadvantages are somewhat amplified for EMG recordings from the respiratory muscles. As many respiratory muscles are small and located close to one other, often in layers of muscle with different functions ( e.g. the external and internal intercostal muscles), surface recordings are easily contaminated by activity from neighbouring muscles. Intramuscular recordings are more selective but the risks associated with needle use are more serious for the respiratory muscles because of the underlying lung. In saying that, inspiratory muscle surface EMG recordings are possible [2, 3] and electrode position can be optimised for the diaphragm [4] for some protocols. With intramuscular electrodes, the risk of pneumothorax can be minimised by using ultrasound to visualise the muscle and lung and estimate maximal insertion depth prior to recordings [5], and on-line audio and visual feedback of EMG activity during recordings [6]. Changes between neural drive and dyspnoea were determined during exercise in severe COPD patients by measuring EMGdi <http://ow.ly/FCAs3>
Combining Chemotherapy With Biological Response Modifiers in Treatment of Cancer
Authors: M. S. Mitchell
Journal: JNCI Journal of the National Cancer Institute (1988)

Combinations of chemotherapeutic agents with various biological response modifiers (“biomodulators”) in the treatment of cancer are now being tested. Since most (though not all) chemotherapy is immunosuppressive, the schedules by which the chemotherapeutic agents and the biomodulators are combined are of critical importance. This review summarizes the effects of chemotherapy on immunity and suggests the most logical ways in which these categories of drugs might be combined with biomodulators. Specific examples are also provided of combination therapies that have proved useful or that are of significant potential utility. An understanding of the types of action and the mechanisms of action of specific chemotherapeutic agents and specific biomodulators may help to achieve additive effects (possibly synergism) with these combinations. At the very least, that understanding will avoid the hazard of one modality's negating the effects of the other. [J Natl Cancer last 1988;80:1445–1450
Treatment of latent infection with Mycobacterium tuberculosis: update 2010
Authors: C C Leung, H L Rieder, C Lange, W W Yew
Journal: European Respiratory Journal (2010)

Much remains unknown about latent infection with Mycobacterium tuberculosis . Existing immunodiagnostic tools for this condition have various limitations, most importantly in their ability to predict disease. Randomised controlled trials have established protective efficacy of isoniazid therapy for 6–12 months among non-HIV-infected and HIV-infected subjects. While efficacy may reach 90%, acceptance and adherence to prolonged therapy are less than desired. Rifampicin plus pyrazinamide for 2 months, though efficacious, has been associated with excess hepatotoxicity in non-HIV-infected persons. Isoniazid plus rifampicin for 3 months has proven efficacy, but adverse effects may be more frequent than isoniazid or rifampicin monotherapy. Rifampicin monotherapy for 3–4 months is well tolerated, but efficacy data are currently limited, and concerns remain over possible selection of rifampicin-resistant mutants. For contacts of patients with multidrug-resistant tuberculosis, expert opinions differ on whether to treat with at least two drugs or just a fluoroquinolone, and for how long. With the existing diagnostic and treatment tools, efficacy of preventive therapy does not necessarily translate into field effectiveness. A targeted approach is required to maximise cost-effectiveness. Each geographic region needs to set its own priority after taking into account available scientific data and local circumstances.
Association of Vitiligo With Tumor Response in Patients With Metastatic Melanoma Treated With Pembrolizumab
Authors: Camille Hua, Lise Boussemart, Christine Mateus, Emilie Routier, Céline Boutros, Hugo Cazenave, Roxane Viollet, Marina Thomas, Séverine Roy, Naima Benannoune, Gorana Tomasic, Jean-Charles Soria, Stéphane Champiat, Matthieu Texier, Emilie Lanoy, Caroline Robert
Journal: JAMA Dermatology (2015)

Vitiligo is an autoimmune skin disorder that reacts against melanocytes. The association of vitiligo with tumor response in patients with melanoma who undergo immunotherapy has been reported but is still controversial.To prospectively evaluate the appearance of vitiligo in patients receiving pembrolizumab, a monoclonal antibody directed against the programmed death cell receptor.This prospective observational study was conducted from January 1, 2012, through September 24, 2013, in a single tertiary care hospital with a unit dedicated to patients with melanoma. Sixty-seven patients with metastatic melanoma who received pembrolizumab treatment in the context of a phase 1 study were included and screened for the emergence of vitiligo. Data were collected from January 1, 2012, to February 28, 2014, and analyzed from February through December 2014.Objective tumor response with regard to the occurrence of vitiligo in patients receiving pembrolizumab therapy. Correlation between vitiligo occurrence and overall survival was also estimated using the Kaplan-Meier product-limit method and compared with a log-rank test. To prevent guarantee- or lead-time bias, a landmark analysis approach after 12, 16, and 20 weeks of treatment was retained.Of the 67 patients included in the study, 17 (25%) developed vitiligo during pembrolizumab treatment and 50 (75%) did not. An objective (complete or partial) response to treatment was associated with a higher occurrence of vitiligo (12 of 17 [71%] vs 14 of 50 [28%]; P = .002). The time to onset of vitiligo ranged from 52 to 453 (median, 126) days from the start of treatment. Of the 17 patients with vitiligo, 3 (18%) had a complete response, 9 (53%) had a partial response, 3 (18%) had stable disease, and 2 (12%) had progressive disease at the final follow-up. All the patients treated with pembrolizumab who developed vitiligo were alive at the time of analysis, with a median follow-up of 441 days.Vitiligo, a clinically visible immune-related adverse event could be associated with clinical benefit in the context of pembrolizumab treatment.
Phase III Study, V-15-32, of Gefitinib Versus Docetaxel in Previously Treated Japanese Patients With Non–Small-Cell Lung Cancer
Authors: Riichiroh Maruyama, Yutaka Nishiwaki, Tomohide Tamura, Nobuyuki Yamamoto, Masahiro Tsuboi, Kazuhiko Nakagawa, Tetsu Shinkai, Shunichi Negoro, Fumio Imamura, Kenji Eguchi, Koji Takeda, Akira Inoue, Keisuke Tomii, Masao Harada, Noriyuki Masuda, Haiyi Jiang, Yohji Itoh, Yukito Ichinose, Nagahiro Saijo, Masahiro Fukuoka
Journal: Journal of Clinical Oncology (2008)

This phase III study (V-15-32) compared gefitinib (250 mg/d) with docetaxel (60 mg/m(2)) in patients (N = 489) with advanced/metastatic non-small-cell lung cancer (NSCLC) who had failed one or two chemotherapy regimens.The primary objective was to compare overall survival to demonstrate noninferiority for gefitinib relative to docetaxel. An unadjusted Cox regression model was used for the primary analysis.Noninferiority in overall survival was not achieved (hazard ratio [HR], 1.12; 95.24% CI, 0.89 to 1.40) according to the predefined criterion (upper CI limit for HR <or= 1.25); however, no significant difference in overall survival (P = .330) was apparent between treatments. Poststudy, 36% of gefitinib-treated patients received subsequent docetaxel, and 53% of docetaxel-treated patients received subsequent gefitinib. Gefitinib significantly improved objective response rate and quality of life versus docetaxel; progression-free survival, disease control rates, and symptom improvement were similar for the two treatments. Grades 3 to 4 adverse events occurred in 40.6% (gefitinib) and 81.6% (docetaxel) of patients. Incidence of interstitial lung disease was 5.7% (gefitinib) and 2.9% (docetaxel). Four deaths occurred due to adverse events in the gefitinib arm (three deaths as a result of interstitial lung disease, judged to be treatment related; one as a result of pneumonia, not treatment related), and none occurred in the docetaxel arm.Noninferiority in overall survival between gefitinib and docetaxel was not demonstrated according to predefined criteria; however, there was no statistically significant difference in overall survival. Secondary end points showed similar or superior efficacy for gefitinib compared with docetaxel. Gefitinib remains an effective treatment option for previously treated Japanese patients with NSCLC.
Targeted Therapy of Cancer: New Prospects for Antibodies and Immunoconjugates
Authors: R. M. Sharkey, D. M. Goldenberg
Journal: CA A Cancer Journal for Clinicians (2006)

ABSTRACT Immunotherapy of cancer has been explored for over a century, but it is only in the last decade that various antibody-based products have been introduced into the management of patients with diverse cancers. At present, this is one of the most active areas of clinical research, with eight therapeutic products already approved in oncology. Antibodies against tumor-associated markers have been a part of medical practice in immunohistology and in vitro immunoassays for several decades, have even been used as radioconjugates in diagnostic imaging, and are now becoming increasingly recognized as important biological agents for the detection and treatment of cancer. Molecular engineering has improved the prospects for such antibody-based therapeutics, resulting in different constructs and humanized/human antibodies that can be administered frequently. Consequently, a renewed interest in the development of antibodies conjugated with radionuclides, drugs, and toxins has emerged. We review how antibodies and immunoconjugates have influenced cancer detection and therapy, and also describe promising new developments and challenges for broader applications.