tbuckley/cabot-search huggingface dataset:
Rapid Diagnosis of Medulloblastoma Molecular Subgroups
Authors: Ed C. Schwalbe, Janet C. Lindsey, Debbie Straughton, Twala L. Hogg, Michael Cole, Hisham Megahed, Sarra L. Ryan, Meryl E. Lusher, Michael D. Taylor, Richard J. Gilbertson, David W. Ellison, Simon Bailey, Steven C. Clifford
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Microarray studies indicate medulloblastoma comprises distinct molecular disease subgroups, which offer potential for improved clinical management. Experimental Design: Minimal mRNA expression signatures diagnostic for the Wnt/Wingless (WNT) and Sonic Hedgehog (SHH) subgroups were developed, validated, and used to assign subgroup affiliation in 173 tumors from four independent cohorts, alongside a systematic investigation of subgroup clinical and molecular characteristics. Results: WNT tumors [12% (21/173)] were diagnosed &amp;gt;5 years of age (peak, 10 years), displayed classic histology, CTNNB1 mutation (19/20), and associated chromosome 6 loss, and have previously been associated with favorable prognosis. SHH cases [24% (42/173)] predominated in infants (&amp;lt;3 years) and showed an age-dependent relationship to desmoplastic/nodular pathology; all infant desmoplastic/nodular cases (previously associated with a good outcome) were SHH-positive, but these relationships broke down in noninfants. PTCH1 mutations were common [34% (11/32)], but PTCH1 exon1c hypermethylation, chromosome 9q and REN (KCTD11) genetic loss were not SHH associated, and SMO or SUFU mutation, PTCH1 exon1a or SUFU hypermethylation did not play a role, indicating novel activating mechanisms in the majority of SHH cases. SHH tumors were associated with an absence of COL1A2 methylation. WNT/SHH-independent medulloblastomas [64% (110/173)] showed all histologies, peaked at 3 and 6 years, and were exclusively associated with chromosome 17p loss. Conclusions: Medulloblastoma subgroups are characterized by distinct genomic, epigenomic and clinicopathologic features, and clinical outcomes. Validated array-independent gene expression assays for the rapid assessment of subgroup affiliation in small biopsies provide a basis for their routine clinical application, in strategies including molecular disease-risk stratification and delivery of targeted therapeutics. Clin Cancer Res; 17(7); 1883–94. ©2011 AACR.
Entecavir therapy for lamivudine‐refractory chronic hepatitis B
Authors: Morris Sherman, Cihan Yurdaydin, Halis Simsek, Marcelo Silva, Yun‐Fan Liaw, Vinod K. Rustgi, Hoel Sette, Naoky Tsai, Daniel J. Tenney, James Vaughan, Bruce Kreter, Robert Hindes
Journal: Hepatology (2008)

In hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients who were refractory to current lamivudine therapy, switching to entecavir was superior to continued lamivudine at week 48 for histologic improvement, viral load reduction by polymerase chain reaction and alanine aminotransferase normalization. We assessed the efficacy, safety, and resistance profile of entecavir through 96 weeks of treatment. A total of 286 patients were randomized and treated with entecavir 1 mg (n = 141) or continued lamivudine 100 mg (n = 145). At week 52, 77 entecavir-treated patients who had a protocol-defined virologic response (HBV branched DNA [bDNA] < 0.7 MEq/mL but HBeAg-positive) continued blinded therapy for up to 96 weeks. Patients were assessed for efficacy, safety, and emerging resistance. Cumulative proportions of all treated patients who achieved confirmed efficacy endpoints were also analyzed. Between week 48 and the end of dosing, the proportions of patients with HBV DNA <300 copies/mL by polymerase chain reaction increased from 21% to 40%, and alanine aminotransferase normalization (≤1× upper limit of normal) increased from 65% to 81%. In the second year, HBeAg seroconversion was achieved by 10% of patients. Of the 77 patients in the second year treatment cohort, entecavir resistance emerged in six patients, and seven experienced virologic breakthrough (five with genotypic resistance acquired before year 2). The safety profile of entecavir in the second year of therapy was consistent with that reported during year 1. Conclusion: Through 96 weeks of treatment, 1 mg entecavir resulted in continued clinical benefit in lamivudine-refractory HBeAg-positive chronic hepatitis B patients with a safety profile comparable to lamivudine. (HEPATOLOGY 2008.)
MODERN EXTRAPLEURAL PNEUMOTHORAX IN THE CHANGING TREATMENT OF TUBERCULOSIS
Authors: J. W. Cutler
Journal: JAMA (1953)

Modern drug therapy and resectional surgery are producing dynamic changes in current thinking on the treatment of pulmonary tuberculosis. Pneumothorax, a long-established and flexible procedure, has been virtually abandoned in many institutions, because of possible complications, rather than limited to patients with proper indications. Thoracoplasty is decreasingly resorted to as an independent and definitive form of collapse. Extrapleural pneumothorax is seldom used because of prevailing prejudices. Pneumoperitoneum, an inefficient form of therapy and not without serious complications, is still popular in some quarters. On the other hand, resection is greatly on the increase and has become the treatment of choice with many physicians. The development of streptomycin,<i>p</i>-aminosalicylic acid, and the isoniazid compounds has introduced new problems. Needed surgery is often delayed or neglected, with the hope that the new drugs will obviate all other therapeutic procedures. Overlooked is the fact that collapse or resection, or both, is ultimately
Metastases and the Normalization of Tumour Blood Vessels by ICRF 159: A New Type of Drug Action
Authors: A. W. Le Serve, K. Hellmann
Journal: BMJ (1972)

Profound modification of the structure and arrangement of the blood vessels has been shown in tumours after treatment with ICRF 159. X-ray angiography, carbon black (Pelikan ink) labelling, and intravital staining with lissamine green were used to demonstrate the changes. Alteration of the morphology of the blood vessels at the edge of a tumour may affect the escape of malignant cells and the rate of blood flow (and thus the concentration of anticancer drugs) through the tumour.
Measuring peak flow enhances adherence to monitoring in asthma
Authors: C. A Slader, E. G Belousova, H. K Reddel
Journal: Thorax (2007)

Measuring peak flow enhances adherence to monitoring in asthmaPeak expiratory flow (PEF) monitoring is recommended in the management of moderate to severe asthma, 1 and PEF outcome variables are used in many clinical trials.However, adherence with PEF monitoring is poor, and this is often attributed to the burden of measurement and recording.This analysis examined whether adherence with symptom monitoring was impaired by asking patients also to record PEF measurements.Data were obtained from a randomised double blind study of breathing techniques in adults with poorly controlled asthma.Full details of the clinical trial are reported elsewhere. 2Subjects were non-smokers aged 19- 80 years, using reliever as-needed >4 times/ week and taking inhaled corticosteroids >200 mg/day.Figure 1 shows the study design, with between-visit intervals of 2 or 6 weeks.Throughout the study, 57 subjects used electronic diary spirometers (AM2, Erich Jaeger GmbH, Hoechberg, Germany) twice daily to answer questions about symptom frequency/ intensity and treatment.There were three ''PEF periods'' during which subjects also measured spirometry twice daily.PEF was displayed after each of three manoeuvres followed by the highest PEF.At study visits, data were uploaded and reviewed by the research assistant but physician feedback was not provided.
US panel advises caution over smallpox vaccination
Authors: F. Charatan
Journal: BMJ (2003)

An advisory panel of scientists in a report commissioned by the US Centers for Disease Control and Prevention (CDC) has urged caution in using the smallpox vaccine as a separate WHO report warns against mass vaccination because of the likelihood of a high level of adverse reactions.

After the terrorist attacks of 11 September 2001, US government officials had considered making the vaccine available to anyone who wanted it ( BMJ 2002;324:1176).

“Smallpox is not the only threat to the nation's health, and vaccination is not the only tool for preparedness,” said the panel's chairman, Dr Brian Strom, a …
A Phase I Clinical, Pharmacologic, and Biologic Study of Thrombopoietin and Granulocyte Colony-Stimulating Factor in Children Receiving Ifosfamide, Carboplatin, and Etoposide Chemotherapy for Recurrent or Refractory Solid Tumors: A Children's Oncology Group Experience
Authors: Anne L. Angiolillo, Virginia Davenport, Mary Ann Bonilla, Carmella van de Ven, Janet Ayello, Olga Militano, Langdon L. Miller, Mark Krailo, Gregory Reaman, Mitchell S. Cairo
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Ifosfamide, carboplatin, and etoposide (ICE) are associated with grade III/IV dose-limiting thrombocytopenia. The Children's Oncology Group conducted a phase I dose escalation, pharmacokinetic, and biological study of recombinant human thrombopoietin (rhTPO) after ICE in children with recurrent/refractory solid tumors (CCG-09717) to assess the toxicity and maximum tolerated dose of rhTPO administered at 1.2, 2.4, or 3.6 μg/kg per dose. Experimental Design: Children received ifosfamide 1,800 mg/m2 on days 0 to 4, carboplatin 400 mg/m2 on days 0 to 1, and etoposide 100 mg/m2 on days 0 to 4. rhTPO was administered i.v. on days +4, +6, +8, +10, and +12 at 1.2, 2.4, or 3.6 μg/kg per dose. Results: rhTPO was well tolerated and maximum tolerated dose was not reached. Median time to platelet recovery ≥100,000/μL of rhTPO at 1.2, 2.4, and 3.6 μg/kg/d was 24 days (22-24d), 25 days (23-29d), and 22 days (16-37d), respectively. Patients required a median of 2 days of platelet transfusions (0-7 days). Mean (± SD) rhTPO maximum serum concentrations were 63.3 ± 9.7 and 89.3 ± 15.7 ng/mL and terminal half-lives were 47 ± 13 and 64 ± 42 hours after 2.4 and 3.6 μg/kg/d, respectively. There was a significant increase in colony-forming unit megakaryocyte upon WBC count recovery. Conclusions: rhTPO was well tolerated. Time to hematologic recovery and median number of platelet transfusions seem to be improved compared with historical controls receiving ICE + granulocyte colony-stimulating factor (CCG-0894).
Spirit of collaboration needs fostering
Authors: F. Woods, P. Golightly, A. Lee, S. Wills
Journal: BMJ (2001)

EDITOR—Brassey et al in their paper describe the ATTRACT project in Wales, which received 193 queries from general practitioners in a period of 13 months.1 Many of these entailed therapeutics. But we regret Brassey et al's apparent lack of awareness of the United Kingdom Medicines Information service.

Medicines Information, formerly Drug Information, began in 1966. Most general hospitals in the United Kingdom have a centre, receiving enquiries from healthcare professionals in both primary and secondary care on all aspects of …
Diagnosing and Managing Common Food Allergies
Authors: Jennifer J. Schneider Chafen, Sydne J. Newberry, Marc A. Riedl, Dena M. Bravata, Margaret Maglione, Marika J. Suttorp, Vandana Sundaram, Neil M. Paige, Ali Towfigh, Benjamin J. Hulley, Paul G. Shekelle
Journal: JAMA (2010)

There is heightened interest in food allergies but no clear consensus exists regarding the prevalence or most effective diagnostic and management approaches to food allergies.To perform a systematic review of the available evidence on the prevalence, diagnosis, management, and prevention of food allergies.Electronic searches of PubMed, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, and Cochrane Central Register of Controlled Trials. Searches were limited to English-language articles indexed between January 1988 and September 2009.Diagnostic tests were included if they had a prospective, defined study population, used food challenge as a criterion standard, and reported sufficient data to calculate sensitivity and specificity. Systematic reviews and randomized controlled trials (RCTs) for management and prevention outcomes were also used. For foods where anaphylaxis is common, cohort studies with a sample size of more than 100 participants were included.Two investigators independently reviewed all titles and abstracts to identify potentially relevant articles and resolved discrepancies by repeated review and discussion. Quality of systematic reviews and meta-analyses was assessed using the AMSTAR criteria, the quality of diagnostic studies using the QUADAS criteria most relevant to food allergy, and the quality of RCTs using the Jadad criteria.A total of 12,378 citations were identified and 72 citations were included. Food allergy affects more than 1% to 2% but less than 10% of the population. It is unclear if the prevalence of food allergies is increasing. Summary receiver operating characteristic curves comparing skin prick tests (area under the curve [AUC], 0.87; 95% confidence interval [CI], 0.81-0.93) and serum food-specific IgE (AUC, 0.84; 95% CI, 0.78-0.91) to food challenge showed no statistical superiority for either test. Elimination diets are the mainstay of therapy but have been rarely studied. Immunotherapy is promising but data are insufficient to recommend use. In high-risk infants, hydrolyzed formulas may prevent cow's milk allergy but standardized definitions of high risk and hydrolyzed formula do not exist.The evidence for the prevalence and management of food allergy is greatly limited by a lack of uniformity for criteria for making a diagnosis.
Hypercalcaemia associated with tuberculosis.
Authors: A G Need, P J Phillips, F Chiu, H Prisk
Journal: BMJ (1980)

Hypercalcaemia associated with tuberculosisHypercalcaemia has been known to be associated with tuberculosis since 1931 and has recently been reported to occur commonly.'The hypercalcaemia is generally asymnptomatic and mild.We describe a case with symptoms and also report a study of the prevalence of hypercalcaemia in 89 tuberculous patients. Case reportA 25-year-old man presented with a history of rigors, night sweats, and productive cough for two weeks.He smoked 10 cigarettes a day, drank alcohol socially, and took no medication.On examination he was feverish (38-6'C), chest radiography confirmed the signs of right upper lobe con- solidation and collapse,, and his sputum grew Mycobacterium tuberculosis.Biochemical analyses (Technicon SMAC) showed hypercalcaemia (plasma calcium concentration 2-72 mmol/I (10-9 mg/l00 ml)) and hypoalbumi- naemia (serum albumin 27 g/l).He was given rifampicin 600 mg, isoniazid 300 mg, pyridoxine 6 mg, ethambutol 1500 mg, and streptomycin 1 g daily.After 19 days he became drowsy, polyuric, dehydrated, and his plasma calcium concentration was 3 33 mmol/l (13.3 mg/100 ml).The results of serum and urine electrophoresis and thyroid function tests were unremark- able and serum parathyroid hormone was undetectable.He was given phosphate by mouth and forced fluids, and he rapidly became more conscious.The plasma calcium concentration became normal by 12 weeks and remained normal two years later.
Muscular Dystrophy, Alveolar Hypoventilation, and Papilledema
Authors: William M. McCormack
Journal: JAMA (1966)

The importance of chronic respiratory disorders with hypercapnia in the differential diagnosis of papilledema was seen in a patient with progressive muscular dystrophy which resulted in alveolar hypoventilation, hypercapnia, and severe retinopathy including papilledema. Improved ventilation resulted in the return of the bloodgas levels toward normal and resolution of the retinopathy. Postmortem examination revealed a normal central nervous system. The papilledema could be ascribed to the respiratory insufficiency with carbon-dioxide retention.
In vivo studies of GABAergic effects in experimental hepatic encephalopathy
Authors: David Rzepczynski, Leslie Zieve, Sandra Lindblad, Darlene Lafontaine
Journal: Hepatology (1986)

The GABAergic agonist, muscimol, and antagonists, picrotoxin and bicuculline, have been studied in rats with chronic portacaval shunts and in rats developing hepatic encephalopathy after massive ischemic necrosis due to hepatic artery ligation within 48 hr of a portacaval shunt. After the chronic portacaval shunt and to a lesser extent in normal rats intraventricular muscimol resulted in chewing and eating behavior, ataxia and loss of balance that lasted 2 to 3 hr. Lethargy, stupor and coma did not occur. Intraventricular saline had no effect. Bicuculline i.p. lessened the effects of the muscimol. In rats developing hepatic encephalopathy, intraventricular muscimol shortened the time to precoma and coma by approximately 40%. Bicuculline i.p. counteracted this effect of muscimol significantly. However, neither bicuculline nor picrotoxin given alone altered the times to precoma (Stage III), coma (Stage IV) or death. While hepatic encephalopathy in this experimental model is susceptible to GABAergic effects, its natural progression does not appear to be due to GABA.
Prediction of rodent nongenotoxic carcinogenesis: evaluation of biochemical and tissue changes in rodents following exposure to nine nongenotoxic NTP carcinogens.
Authors: Clifford R Elcombe, Jenny Odum, John R Foster, Susan Stone, Susan Hasmall, Anthony R Soames, Ian Kimber, John Ashby
Journal: Environmental Health Perspectives (2002)

We studied nine presumed nongenotoxic rodent carcinogens, as defined by the U.S. National Toxicology Program (NTP), to determine their ability to induce acute or subacute biochemical and tissue changes that may act as useful predictors of nongenotoxic rodent carcinogenesis. The chemicals selected included six liver carcinogens (two of which are peroxisome proliferators), three thyroid gland carcinogens, and four kidney carcinogens. We administered the chemicals (diethylhexyl phthalate, cinnamyl anthranilate, chlorendic acid, 1,4-dichlorobenzene, monuron, ethylene thiourea, diethyl thiourea, trimethyl thiourea, and d-limonene to the same strains of mice and rats used in the original NTP bioassays (nine chemicals to rats and seven to mice). Selected tissues (liver, thyroid gland, and kidney) were collected from groups of animals at 7, 28, and 90 days for evaluation. Tissue changes selected for study were monitored for all of the test groups, irrespective of the specificity of the carcinogenic responses observed in those tissues. This allowed us to assess both the carcinogen specificity and the carcinogen sensitivity of the events being monitored. We studied relative weight, cell labeling indices, and pathologic changes such as hypertrophy in all tissues; a range of cytochrome P450 enzymes and palmitoyl coenzyme A oxidase in the liver; changes in the levels of plasma total triiodothyronine, total thyroxine, and thyroid-stimulating hormone (TSH) as markers of thyroid gland function; and hyaline droplet formation, tubular basophilia, and the formation of granular casts in the kidney. There were no single measurements that alerted specifically to the carcinogenicity of the agents to the rodent liver, thyroid gland, or kidney. However, in the majority of cases, the chemical induction of cancer in a tissue was preceded by a range of biochemical/morphologic changes, most of which were moderately specific for a carcinogenic outcome, and some of which were highly specific for it (e.g., increases in TSH in the thyroid gland and increases in relative liver weight in the mouse). The only measurements that failed to correlate usefully with carcinogenicity were the induction of liver enzymes (with the exception of the enzymes associated with peroxisome proliferation). Most of the useful markers were evident at the early times studied (7 days and 28 days), but no overall best time for the measurement of all markers was identified. The judicious choice of markers and evaluation times can aid the detection of potential nongenotoxic rodent carcinogens.
Nitric Oxide Synthase Gene Transfer Restores Activity of Circulating Angiogenic Cells From Patients With Coronary Artery Disease
Authors: Michael R Ward, Kathleen A Thompson, Kathryn Isaac, Jonathan Vecchiarelli, Qiuwang Zhang, Duncan J Stewart, Michael JB Kutryk
Journal: Molecular Therapy (2011)

Circulating angiogenic cells (CACs), represent a potential new therapeutic tool for the treatment of cardiovascular diseases, but their regenerative function is impaired in patients with coronary artery disease (CAD) and cardiac risk factors. The objective of this study is to assess the effect of lentiviral overexpression of endothelial nitric oxide synthase (eNOS) on the activity of CACs from patients with CAD and cardiac risk factors. In vitro and in vivo assays were employed to evaluate the regenerative capacity of the cells compared to CACs derived from healthy volunteers. Lentiviral eNOS transduction of cells from CAD patients significantly improved chemotactic migration compared with sham transduction, and increased the ability of CACs to induce angiogenic tube formation when cocultured with human umbilical vein endothelial cells (HUVECs) on Matrigel. In addition, eNOS transduction restored the ability of patient-derived CACs to enhance neovascularization and improve ischemic hind limb perfusion, approaching the efficacy of cells from healthy donors. These data indicate that CAC dysfunction seen in high-risk patients can be partially reversed by eNOS overexpression, suggesting that ex vivo gene delivery may improve the efficacy of autologous cell therapy for cardiovascular disease. Circulating angiogenic cells (CACs), represent a potential new therapeutic tool for the treatment of cardiovascular diseases, but their regenerative function is impaired in patients with coronary artery disease (CAD) and cardiac risk factors. The objective of this study is to assess the effect of lentiviral overexpression of endothelial nitric oxide synthase (eNOS) on the activity of CACs from patients with CAD and cardiac risk factors. In vitro and in vivo assays were employed to evaluate the regenerative capacity of the cells compared to CACs derived from healthy volunteers. Lentiviral eNOS transduction of cells from CAD patients significantly improved chemotactic migration compared with sham transduction, and increased the ability of CACs to induce angiogenic tube formation when cocultured with human umbilical vein endothelial cells (HUVECs) on Matrigel. In addition, eNOS transduction restored the ability of patient-derived CACs to enhance neovascularization and improve ischemic hind limb perfusion, approaching the efficacy of cells from healthy donors. These data indicate that CAC dysfunction seen in high-risk patients can be partially reversed by eNOS overexpression, suggesting that ex vivo gene delivery may improve the efficacy of autologous cell therapy for cardiovascular disease.