tbuckley/cabot-search huggingface dataset:
Serum Adipokine Levels in Patients With Ankylosing Spondylitis and Their Relationship to Clinical Parameters and Radiographic Spinal Progression
Authors: Uta Syrbe, Johanna Callhoff, Kristina Conrad, Denis Poddubnyy, Hildrun Haibel, Susann Junker, Klaus W. Frommer, Ulf Müller‐Ladner, Elena Neumann, Joachim Sieper
Journal: Arthritis & Rheumatology (2014)

Adipokines have metabolic and inflammatory functions but can also affect bone metabolism. The purpose of this study was to determine the relationship between serum levels of adiponectin, resistin, and visfatin and markers of inflammation, disease activity, and radiographic spinal progression in patients with ankylosing spondylitis (AS).Levels of adiponectin, resistin, and visfatin in the serum of 86 AS patients and 25 healthy controls were measured by enzyme-linked immunosorbent assay at baseline. Radiographic spinal progression was determined by the scoring of radiographs of the spine obtained at baseline and after 2 years.Mean (±SD) baseline levels of resistin and visfatin were significantly higher in AS patients than in healthy controls (11.6 ± 10.6 ng/ml versus 6.6 ± 3.2 ng/ml [P = 0.01] for resistin, and 20.9 ± 48.3 ng/ml versus 3.4 ± 2.6 ng/ml [P = 0.001] for visfatin). Adipokine serum levels did not correlate with disease activity or functional indices. Only resistin serum levels correlated with markers of inflammation. Baseline levels of visfatin, but not resistin or adiponectin, were significantly higher in patients with worsening of the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) by ≥2 units after 2 years (n = 19) as compared to patients without mSASSS worsening (37.7 ± 57.8 ng/ml versus 16.1 ± 44.6 ng/ml; P = 0.029) and in patients with syndesmophyte formation/progression (n = 22) as compared to patients without such progression (37.1 ± 55.3 ng/ml versus 15.3 ± 44.8 ng/ml; P = 0.023). Visfatin levels of >8 ng/ml at baseline were predictive of subsequent radiographic spinal progression (adjusted odds ratio 3.6 for mSASSS progression and 5.4 for syndesmophyte formation/progression).Serum levels of resistin and visfatin are elevated in AS patients. Elevated visfatin levels at baseline are predictive of subsequent progression of radiographic damage in AS patients.
Adaptation of cough reflex with different types of stimulation
Authors: AH Morice, KS Higgins, WW Yeo
Journal: European Respiratory Journal (1992)

Inhalation cough challenge has become an accepted method of investigating antitussive agents. It is, therefore, important to examine the degree of tachyphylaxis seen with repeated cough challenge. In addition, different types of challenge may reveal important differences in the neuronal pathways involved in the cough reflex. Citric acid, distilled water and capsaicin were examined to determine adaptation of the cough response during acute and long-term inhalation studies in healthy subjects. To study acute tachyphylaxis two separate one minute continuous inhalation challenges (n = 13) were performed. Long-term tachyphylaxis (n = 10) was examined using citric acid and capsaicin inhalation at 10 min intervals for 40 min, and at 4 and 6 h. Cross-tachyphylaxis to citric acid and capsaicin was examined in a separate randomized crossover study (n = 10). Highly significant adaptation occurred between the first and last 10 s of the one minute challenge with citric acid (90-100%) and distilled water (74-84%), but was less pronounced with capsaicin (37-49%, at 2 microM). Cough during the whole of the second test was significantly reduced for citric acid (50%). During long-term challenge cough was attenuated over 40 min both with citric acid (100 mM, p less than 0.05; 300 mM, p less than 0.001; 1 M, p less than 0.001) and with capsaicin (3 microM, p less than 0.01; 10, 30, 100 microM, p less than 0.001 each). With higher doses, tachyphylaxis was still present at 180 min with both citric acid (300 mM, p less than 0.05) and capsaicin (100 microM, p less than 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)
Lorazepam in cancer patients treated with cisplatin: a drug having antiemetic, amnesic, and anxiolytic effects.
Authors: J Laszlo, R A Clark, D C Hanson, L Tyson, L Crumpler, R Gralla
Journal: Journal of Clinical Oncology (1985)

There currently is no pharmacologic approach to the problem of anticipatory nausea and vomiting (ANV). Lorazepam (Ativan, Wyeth Laboratories, Philadelphia) is an interesting candidate drug if it could block the recall of the unpleasant events associated with chemotherapy, especially if it also has antiemetic properties. Since ANV is a conditioned (learned) response, it may well depend on a memory imprint of the stimulus. This pilot study was designed to use intravenous lorazepam given before and after cisplatin infusion in 32 patients, and to make detailed measurements of nausea, vomiting, recent memory, anxiety, and sedation as well as toxicity. Satisfactory responses occurred in about 70%, as rated separately both by investigator and patient. Forty-six percent did not even recall receiving chemotherapy, regardless of whether or not they vomited; 80% had no significant anxiety after chemotherapy. Adverse reactions included some cases of perceptual disturbance, urinary incontinence, diarrhea, hypotension, and one case of severe transient amnesia. No long-term adverse effects were noted.
Prognostic Assessment of Coronary Artery Bypass Patients With 64-Slice Computed Tomography Angiography
Authors: Gary R. Small, Yeung Yam, Li Chen, Osman Ahmed, Mouaz Al-Mallah, Daniel S. Berman, Victor Y. Cheng, Kavitha Chinnaiyan, Gilbert Raff, Todd C. Villines, Stephan Achenbach, Matthew J. Budoff, Filippo Cademartiri, Tracy Q. Callister, Hyuk-Jae Chang, Augustin Delago, Allison Dunning, Martin Hadamitzky, Jorg Hausleiter, Philipp Kaufmann, Fay Lin, Erica Maffei, James K. Min, Leslee J. Shaw, Benjamin J.W. Chow
Journal: Journal of the American College of Cardiology (2011)
Total Body Irradiation, Thiotepa, and Cyclophosphamide as a Conditioning Regimen for Children With Acute Lymphoblastic Leukemia in First or Second Remission Undergoing Bone Marrow Transplantation With HLA-Identical Siblings
Authors: Marco Zecca, Andrea Pession, Chiara Messina, Federico Bonetti, Claudio Favre, Arcangelo Prete, Simone Cesaro, Fulvio Porta, Ida Mazzarino, Giovanna Giorgiani, Roberto Rondelli, Franco Locatelli
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Allogeneic hematopoietic stem-cell transplantation (HSCT) from HLA-identical siblings can be used to treat children with acute lymphoblastic leukemia (ALL). However, a significant proportion of patients with ALL who undergo HSCT relapse. For this reason, we prospectively evaluated a preparative regimen that included total body irradiation (TBI), thiotepa (TT), and cyclophosphamide (CY) in patients with high-risk ALL in first complete remission (CR) and in children with ALL in second CR. PATIENTS AND METHODS: Forty children (median age, 9 years; range, 1 to 18 years) with ALL in first or second CR who underwent allogeneic HSCT from HLA-identical siblings were conditioned with a combination of fractionated TBI, TT (10 mg/kg), and CY (120 mg/kg over 2 days). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine administered intravenously at a dose of 1 to 3 mg/kg/d for the first 21 days and subsequently orally at a dose of 6 mg/kg/d. RESULTS: All assessable patients were engrafted, with a median time of 11 and 24 days for neutrophil and platelet recovery, respectively. The preparative regimen was well tolerated. Only one patient died as a result of regimen-related causes. Eight patients relapsed at a median time of 8 months after transplantation (range, 3 to 9 months), and this determined a cumulative probability of relapse of 23%. Twenty-six of 40 patients (65%) are alive and in complete hematologic remission, with a median observation time of 36 months (range, 14 to 57 months), which results in a disease-free survival (DFS) at 3 years of 65%. The 13 patients who underwent transplantation in first CR had a DFS of 85%, whereas the 27 patients who underwent HSCT in second CR had a DFS of 56%. CONCLUSION: These data suggest that TT is an effective cytotoxic drug that can be safely added to the classical TBI-CY regimen. Because of its cell cycle–independent action, good CNS diffusion, and limited extramedullary toxicity, TT may contribute to increasing the percentage of children with ALL who are successfully cured with allogeneic BMT.
Systematic reviews in health care: Systematic reviews of evaluations of prognostic variables
Authors: D. G Altman
Journal: BMJ (2001)

This is the last in a series of four articles 

Prognostic studies include clinical studies of variables predictive of future events as well as epidemiological studies of aetiological risk factors. As multiple similar studies accumulate it becomes increasingly important to identify and evaluate all of the relevant studies to develop a more reliable overall assessment. For prognostic studies this is not straightforward.

Box 1 summarises the clinical importance of information on prognostic factors. Many of the issues discussed are also relevant to aetiological studies, especially cohort ones. Some features of prognostic studies lead to particular difficulties for the systematic reviewer. Firstly, in most clinical prognostic studies the outcome of primary interest is the time to an event, often death. Meta-analysis of such studies is rather more difficult than that for binary data or continuous measurements. Secondly, in many contexts the prognostic variable of interest is often one of several prognostic variables. When examining a variable of interest researchers should consider other prognostic variables with which it might be correlated. Thirdly, many prognostic factors are continuous variables, for which researchers use a wide variety of methods of analysis.

#### Summary points

Systematic reviews are applicable to all types of research design, and studies of prognostic variables are an important additional area where appropriate methodology should be applied

Prognostic variables should be evaluated in a representative sample of patients assembled at a common point in the course of their disease—ideally they should all have received the same medical treatment or been in a randomised trial

When examined critically, a high proportion of prognostic studies are found to be methodologically poor

Meta-analysis of published data is hampered by difficulties in extraction of data and variation in the characteristics of the study and patients

The poor quality of the published literature is a strong argument in favour …
Taxing sugar should be just one element of a multifaceted campaign
Authors: Michael Craig Watson, John Lloyd
Journal: BMJ (2015)

We agree that sugar sweetened drinks should be taxed,1 but on its own this policy may have little effect and may even be counterproductive.

In addition to fiscal measures, a diverse range of approaches is needed, such as developing personal skills, creating supportive environments, and reorienting health services so that …
Need for a proactive and structured approach to risk analysis when designing phase I trials
Authors: Cornelis A Van den Bogert, Adam F Cohen
Journal: BMJ (2015)

Good news from Emanuel and colleagues1—apparently, phase I clinical drug trials are safe. However, given the very low frequencies of serious adverse events, retrospective associations of trial characteristics with adverse events are of no use for predicting safety problems in future trials. None of these associations would have helped prevent the cytokine storm caused by TGN1412. This drug’s risk …
Treatment of bone metastases with dichloromethylene bisphosphonate.
Authors: G Francini, S Gonnelli, R Petrioli, F Conti, P Paffetti, C Gennari
Journal: Journal of Clinical Oncology (1992)

PURPOSE The study was undertaken to evaluate the effects of dichloromethylene bisphosphonate (Cl2MDP) on osteolytic and osteoblastic bone lesions from a variety of tumoral primary sites and to investigate the in vivo mechanism underlying the action of this drug. PATIENTS AND METHODS Seventy-six patients participated in the current study: 59 had predominantly osteolytic lesions and 17 osteoblastic metastases. Sixteen patients had hypercalcemia. All of the patients received 300 mg of Cl2MDP intravenously (IV) for 7 days and then 200 mg of Cl2MDP intramuscularly (IM) for 14 days. Biochemical parameters were measured in the patients before the start of treatment and 3, 7, 14, and 21 days after beginning treatment. After the withdrawal of parenteral Cl2MDP, 59 patients with predominantly osteolytic lesions were then randomized to receive chemotherapy alone (group A, 29 cases) or chemotherapy plus Cl2MDP given at an oral dose of 1,200 mg/d (group B, 30 cases). RESULTS Serum calcium (Ca), urinary calcium (UCa) phosphate (UPO4), and hydroxyproline (HOP) excretion levels significantly decreased in all patients, whereas no significant changes occurred in serum alkaline phosphatase (AlkPh) and bone Gla-protein (BGP) levels. In 56 patients with painful bone lesions, a progressive analgesic effect was observed mainly between day 7 and day 14. In patients with predominantly osteoblastic metastases, the Cl2MDP treatment led to a more evident hypocalcemia and an increase in both AlkPh and BGP. However, in the majority of these patients the hypocalcemia was corrected by the concurrent use of effective cytotoxic treatments capable of reducing osteoblast stimulation. During 6 months of follow-up, two pathologic fractures occurred in patients of group A, and none occurred in patients of group B. CONCLUSIONS We conclude that Cl2MDP was effective in patients presenting bone metastases with and without hypercalcemia. Care should be taken particularly in those patients with mixed metastases when the sclerotic component is predominant, as the drug may enhance the possibility of hypocalcemia, which is generally corrected by effective cytotoxic drugs. Therefore, Cl2MDP can be considered a valuable support in the treatment of bone metastases.
Scombroid-Fish Poisoning
Authors: N. A. Al-Wabel
Journal: New England Journal of Medicine (1991)

Scombroid fish Poisoning:As presented in this review, Histamine Poisoning is known as Scombroid Poisoning and in general it is occured by consuming the members of Scombridae family.On this subject have been carried out on bacteria species which caused Scombroid fish poisoning and the semptomps of poisoning and treatment methods have been determined.
Impairments in Dark Adaptation Are Associated with Age-Related Macular Degeneration Severity and Reticular Pseudodrusen
Authors: Jason Flamendorf, Elvira Agrón, Wai T Wong, Darby Thompson, Henry E Wiley, E Lauren Doss, Shaza Al-Holou, Frederick L Ferris, Emily Y Chew, Catherine Cukras
Journal: Ophthalmology (2015)
Ultrasound guided transthoracic tru-cut biopsy and FNAC lung: An Indian study
Authors: Debajyoti Bhattacharyya, M.S. Barthwal, C.D.S Katoch, Anand Arora
Journal: European Respiratory Journal (2012)

Introduction: Pulmonary lesions located in close proximity to thoracic wall may be sampled either by tru-cut biopsy or by fine needle aspiration cytology (FNAC) of lung using 18-20 gauge needles under ultrasound guidance.  Aims and objectives: To assess the utility and safety of ultrasound guided transthoracic tru-cut biopsy and FNAC lung in the evaluation of peripherally located pulmonary lesions.  Methods: All patients with peripheral lung lesions who underwent tru-cut biopsy or FNAC of lung under USG guidance between January 2008 and January 2012 in a tertiary care hospital were included in the study. Patients were observed for one hour following the procedure and a chest x-ray was performed after that to look for any pneumothorax.  Results: 57 patients (39 males and 18 females) underwent the above procedure during the period of study. Mean age of patients was 51.3 years (range: 25-79 years). 42 patients underwent tru-cut biopsy of lung and 15 cases underwent FNAC of lung. Mean tumour sizes were 60.2 ± 29.3 mm. Histological/cytological examination provided the diagnosis in 53 cases: lung cancer – 40, other malignant tumours – 3, benign tumours – 2, granuloma – 6, and organizing pneumonia – 2. Adenocarcinoma (22 cases) was the most common lung cancer detected. In three cases the diagnosis was inconclusive. Complications were observed in five patients: mild haemoptysis which improved spontaneously – 2, subcutaneous emphysema – 1 (improved without any intervention), and pneumothorax in two patients, one of whom required tube thoracostomy.  Conclusions: USG guided tru –cut biopsy/FNAC of lung gives a high diagnostic yield in peripheral lung lesions. Complication rate of the procedure is low.
Phase I Trial of Docetaxel With Estramustine in Androgen-Independent Prostate Cancer
Authors: Daniel P. Petrylak, Robert B. Macarthur, John O'Connor, Gary Shelton, Timothy Judge, Joshua Balog, Charles Pfaff, Emilia Bagiella, Daniel Heitjan, Robert Fine, Nancy Zuech, Ihor Sawczuk, Mitchell Benson, Carl A. Olsson
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To evaluate the toxicity, efficacy, and pharmacokinetics of docetaxel when combined with oral estramustine and dexamethasone in a phase I study in patients with progressive metastatic androgen-independent prostate cancer. PATIENTS AND METHODS: Thirty-four men were stratified into minimally pretreated (MPT) and extensively pretreated (EPT) groups. Estramustine 280 mg PO tid was administered 1 hour before or 2 hours after meals on days 1 through 5, with escalated doses of docetaxel from 40 to 80 mg/m 2 on day 2. Treatment was repeated every 21 days. RESULTS: Thirty-four patients were assessable for toxicity and 33 for response. In the MPT patients, dose-limiting myelosuppression was reached at 80 mg/m 2 , with six patients experiencing grade 3/4 granulocytopenia. In EPT patients, escalation above 70 mg/m 2 was not attempted. Fourteen MPT (70%) and six EPT (50%) patients had a ≥ 50% decline in serum PSA on two consecutive measurements taken at least 2 weeks apart. The overall 50% PSA response rate was 63% (95% confidence interval [CI], 28% to 81%). Of the 18 patients with bidimensionally measurable disease, five (28%; 95% CI, 11% to 54%) achieved a partial response. At the time of entry onto the study, 15 patients required narcotic analgesics for bone pain; after treatment, eight (53%) discontinued their pain medications. The area under the curve for docetaxel increased linearly from 40 to 70 mg/m 2 . At 80 mg/m 2 , the measured area under the curve was 8.37 (standard deviation, 0.724), which was significantly higher than the previously reported values. CONCLUSION: The recommended phase II dose of docetaxel combined with estramustine is 70 mg/m 2 in MPT patients and 60 mg/m 2 in EPT patients. This combination is active in men with androgen-independent prostate cancer.
Abstract 10481: Predictors of Bleeding Events in Patients Treated With Prasugrel or Clopidogrel: Insights From the TRITON-TIMI 38 Trial
Authors: Willibald Hochholzer, Stephen D Wiviott, Charles F Contant, Jianping Guo, Robert P Giugliano, Elliott M Antman, Eugene Braunwald
Journal: Circulation (2010)

Introduction: The balance between risk (bleeding) and benefit (ischemia protection) in choosing the intensity of dual antiplatelet therapy is a key consideration in therapeutic decision making. The...
A major failure of scientific governance
Authors: Richard Smith, Fiona Godlee
Journal: BMJ (2015)

Public inquiry is needed to learn from an egregious case

Today The BMJ retracts a 1989 paper by R K Chandra,1 2 a Canadian scientist who recently lost a libel case against the Canadian Broadcasting Corporation (CBC). The broadcaster had accused him in television programmes of scientific fraud and financial deception.3 4 Chandra has had one other paper retracted,5 but it seems probable that many of his published studies are fraudulent. This long running and still unresolved saga raises serious questions about the governance of science and calls for a comprehensive response.

The BMJ started the process that led to the Canadian programmes when in 2000 it asked Chandra’s university, the Memorial University of Newfoundland, to investigate a study submitted to the journal that the editors thought might be fraudulent.3

Unknown to The BMJ editors, the university had already done an investigation in 1994-95, which concluded that “scientific misconduct had been committed by Dr Chandra.” The allegations had been made by the university’s professor of paediatrics. The investigating committee faced great difficulties. It noted that “no raw data (or files) of any kind were exhibited”; it could not “identify anyone who did or remembers a significant amount of the work”; and “the coauthors of the papers had little or very likely nothing to …
Netrin-1 Promotes Medulloblastoma Cell Invasiveness and Angiogenesis, and Demonstrates Elevated Expression in Tumor Tissue and Urine of Patients with Pediatric Medulloblastoma
Authors: Tomoshige Akino, Xuezhe Han, Hironao Nakayama, Brendan McNeish, David Zurakowski, Akiko Mammoto, Michael Klagsbrun, Edward Smith
Journal: Cancer Research (2014)

Abstract Invasion and dissemination of medulloblastoma within the central nervous system is the principal factor predicting medulloblastoma treatment failure and death. Netrin-1 is an axon guidance factor implicated in tumor and vascular biology, including in invasive behaviors. We found that exogenous netrin-1 stimulated invasion of human medulloblastoma cells and endothelial cells in contrast to VEGF-A, which promoted invasion of endothelial cells but not medulloblastoma cells. Furthermore, medulloblastoma cells expressed endogenous netrin-1 along with its receptors, neogenin and UNC5B. Blockades in endogenous netrin-1, neogenin, or UNC5B reduced medulloblastoma invasiveness. Neogenin blockade inhibited netrin-1–induced endothelial cells tube formation and recruitment of endothelial cells into Matrigel plugs, two hallmarks of angiogenesis. In patients with pediatric medulloblastoma, netrin-1 mRNA levels were increased 1.7-fold in medulloblastoma tumor specimens compared with control specimens from the same patient. Immunohistochemical analyses showed that netrin-1 was elevated in medulloblastoma tumors versus cerebellum controls. Notably, urinary levels of netrin-1 were 9-fold higher in patients with medulloblastoma compared with control individuals. Moreover, urinary netrin-1 levels were higher in patients with invasive medulloblastoma compared with patients with noninvasive medulloblastoma. Finally, we noted that urinary netrin-1 levels diminished after medulloblastoma resection in patients. Our results suggest netrin-1 is a candidate biomarker capable of detecting an invasive, disseminated phenotype in patients with medulloblastoma and predicting their disease status. Cancer Res; 74(14); 3716–26. ©2014 AACR.