tbuckley/cabot-search huggingface dataset:
Comparison of liposomal doxorubicin versus conventional anthracyclines: A meta-analysis.
Authors: S. M. Rafiyath, G. Lamba, P. Singh, M. Rasul, D. Liu
Journal: Journal of Clinical Oncology (2010)

e13128 Background: Liposomal formulations of anthracyclines have similar efficacies and favorable toxicity profile when compared with conventional anthracyclines in elderly, high-risk cardiac patients and prior patients with prior use of anthracylines. In this study, we performed a meta-analysis to evaluate the adverse effects and quantify the relative safety profile of the liposomal and conventional anthracyclines. Methods: We conducted a broad search strategy of major electronic databases. We performed a meta-analysis of adverse effects on randomized controlled trials comparing liposomal formulation and conventional anthracyclines on different tumors. The primary outcome was the adverse effects including CHF, hematologic toxicity, Palmar-plantar erythrodysthesias, alopecia, nausea, and vomiting. The odds ratios of the adverse effects were calculated separately and the overall odds ratio of the pooled data was calculated. We use the fixed effect model for the meta-analysis and compared it with the random effect model. Results: We identified nine randomized controlled trials comparing liposomal formulations and conventional anthracyclines. The study included 2,220 patients of which 1,112 patients were treated with liposomal formulations and 1,108 were treated with conventional anthracyclines. We found that the liposomal formulations have low incidence of CHF (OR 0.34, 95% CI, 0.24-0.47), alopecia (OR 0.36, 95% CI, 0.29-0.43), neutropenia (OR 0.65, 95% CI, 0.53-0.80), neutropenic fever (OR 0.90, 95% CI, 0.68-1.20), anemia (OR 0.89, 95% CI, 0.71-1.125), thrombocytopenia (OR 0.87, 95% CI, 0.61-1.25) and higher incidence of palmar-plantar erythrodysthesias (OR 3.14, 95% CI, 2.30-4.29). Conclusions: Liposomal doxorubicin and pegylated liposomal doxorubicin demonstrated favorable toxicity profiles with better cardiac safety and less myelosuppression, alopecia, nausea, and vomiting compared with the conventional antracyclines. No significant financial relationships to disclose.
Ultrasonographic diagnosis of hepatic fibrosis or cirrhosis
Authors: Christophe Aubé, Frédéric Oberti, Nouri Korali, Marc-Antoine Namour, Didier Loisel, Jean-Yves Tanguy, Emmanuelle Valsesia, Christophe Pilette, Marie Christine Rousselet, Pierre Bedossa, Hervé Rifflet, Moussa Y Maïga, Dominique Penneau-Fontbonne, Christine Caron, Paul Calès
Journal: Journal of Hepatology (1999)
Phase I Study of Continuous-Infusion L-S,R-Buthionine Sulfoximine With Intravenous Melphalan
Authors: H. H. Bailey, G. Ripple, K. D. Tutsch, R. Z. Arzoomanian, D. Alberti, C. Feierabend, D. Mahvi, J. Schink, M. Pomplun, R. T. Mulcahy, G. Wilding
Journal: JNCI Journal of the National Cancer Institute (1997)

Background : Increased intracellular glutathione has long been associated with tumor cell resistance to various cytotoxic agents. An inhibitor of glutathione biosynthesis, l -S,Rbuthionine sulfoximine (BSO), has been shown to enhance the cytotoxicity of chemotherapeutic agents in vitro and in vivo . We performed a phase I study of BSO administered with the anticancer drug melphalan to determine the combination's safety/tolerability and to determine clinically whether BSO produced the desired biochemical end point of glutathione depletion (<10% of pretreatment value). Methods : Twenty-one patients with advanced cancers received an initial 30-minute infusion of BSO totaling 3.0 g/m 2 and immediately received a continuous infusion of BSO on one of the following schedules: 1) 0.75 g/m 2 per hour for 24 hours (four patients); 2) the same dose rate for 48 hours (four patients); 3) the same dose rate for 72 hours (10 patients); or 4) 1.5 g/m 2 per hour for 48 hours (three patients). During week 1, the patients received BSO alone; during weeks 2 or 3, they received BSO plus melphalan (15 mg/m 2 ); thereafter, the patients received BSO plus melphalan every 4 weeks. Glutathione concentrations in peripheral blood lymphocytes were determined for all patients; in 10 patients on three of the administration schedules, these measurements were made in multiple sections from tumor biopsy specimens taken before, during, and after continuous-infusion BSO. Results : Continuous-infusion BSO alone produced minimal toxic effects, although BSO plus melphalan produced occasional severe myelosuppression (grade 4) and frequent lowgrade nausea/vomiting (grade 1–2). This treatment also produced consistent, profound glutathione depletion (<10% of pretreatment value). The degree of glutathione depletion in peripheral lymphocytes was considerably less than that observed in tumor sections. Conclusions : Continuous-infusion BSO is relatively nontoxic and results in depletion of tumor glutathione.
Tracking Chemotherapy's Effects on Secondary Cancers
Authors: V. Brower
Journal: JNCI Journal of the National Cancer Institute (2013)

Certain chemotherapies, including anthracyclines for breast cancer and topoisomerase inhibitors for leukemia, raise the risk of secondary cancers, particularly acute myeloid leukemia (AML). The treatments kill cancer cells by damaging DNA but may also cause hidden, latent damage to the DNA of normal cells, which may eventually cause new cancers. New research indicates that cancer patients receiving chemotherapy are nearly five times as likely as the general population to be diagnosed with treatment-related AML (t-AML), a risk especially high in the first 5 years after treatment with alkylating drugs (or radiation) but that may develop up to 10 years afterward. “As well as finding significant variation in AML rates over 30 years, we found that chemotherapy alone may raise the risk of secondary cancers, which we previously thought applied only to radiation,” said Lindsay Morton, Ph.D., primary author of the study (Blood, Feb. 14, 2013) and investigator at the National Cancer Institute’s division of cancer epidemiology and genetics. Among 426,068 study patients drawn from the Surveillance, Epidemiology, and End Results (SEER) database, treatment for non-Hodgkin lymphoma accounted for the greatest increase in AML, followed by myeloma. “We also found that since 2000, treatment-related secondary cancers increased among esophageal, cervical, and prostate cancer patients, and since the 1990s, in bone,joint and endometrial cancers,” said Morton. Risk of t-AML, which is extremely difficult to treat, or other secondary cancers should be calculated into all treatment decisions, Morton said. “This is the first research since the 1980s to document treatment changes and risk of AML over time in a large cohort of patients,” said Margaret Tucker, M.D., director of the human genetics program and acting director of the division of cancer epidemiology and genetics at NCI. Documenting substantial changes that are likely to be related to the evolution of various treatments over time, the new study is more powerful than previous studies because of the number of surviving patients, Tucker said. “In breast cancer, melphalan, known to be cancer causing, was widely used in the 1970s, followed by cyclophosphamide in the early 1980s. That was replaced in the 1990s by anthracyclines,” Morton observed. “The corresponding risks of secondary cancers were highest in the 1970s with melphalan, then fell in the 1980s with cyclophosphamide, and rose again in the 1990s with anthracyclines,” she added. Patients with multiple myeloma and certain thyroid cancers remain at high risk for t-AML, probably because of ongoing use of melphalan for aggressive disease and anthracyclines, respectively. The U.S. has 12 million adult and 363,000 childhood cancer survivors, and these figures could increase to 20 million and 460,000, respectively, by 2020, said Les Robison, Ph.D., chair of the department of
Left ventricular hypertrophy associated with chronic cocaine abuse.
Authors: M E Brickner, J E Willard, E J Eichhorn, J Black, P A Grayburn
Journal: Circulation (1991)

BACKGROUND This study was performed to determine whether chronic cocaine abuse is associated with left ventricular hypertrophy in humans. METHODS AND RESULTS A consecutive series of 40 chronic cocaine abusers 23-44 years old who were enrolled in an inpatient drug rehabilitation program were considered for the study. Subjects with elevated resting blood pressure (n = 4) or a history of hypertension (n = 3) were excluded. Technically adequate two-dimensional echocardiograms were obtained in 30 cocaine abusers and 30 age- and race-matched normal control subjects. All subjects were men, and the groups were similar with regard to resting blood pressure, height, weight, and body surface area. All echocardiograms were read in blinded fashion, and left ventricular mass was calculated by the area-length method. Left ventricular cavity dimensions and wall motion were normal in all subjects. Left ventricular mass index was higher in the cocaine group (103 +/- 24 versus 77 +/- 14 g/m2, p = 0.0001). Posterior wall thickness was increased (1.2 cm or more) in 13 cocaine abusers (43%) compared with four controls (p = 0.0099). CONCLUSIONS Chronic cocaine abuse is associated with increased left ventricular mass index and wall thickness. Left ventricular hypertrophy may provide a substrate facilitating the development of myocardial ischemia and/or arrhythmias in cocaine abusers.
Critical role of phospholipase Cγ2 in integrin and Fc receptor-mediated neutrophil functions and the effector phase of autoimmune arthritis
Authors: Zoltán Jakus, Edina Simon, David Frommhold, Markus Sperandio, Attila Mócsai
Journal: The Journal of Experimental Medicine (2009)

β2 integrins and Fcγ receptors are critically involved in neutrophil activation at the site of inflammation. Both receptor types trigger a receptor-proximal tyrosine phosphorylation cascade through Src family kinases and Syk, but further downstream signaling events are poorly understood. We show that phospholipase C (PLC) γ2 is phosphorylated downstream of Src family kinases and Syk during integrin or Fc receptor-mediated activation of neutrophils. PLCγ2−/− neutrophils are completely defective in β2 integrin or Fcγ receptor-mediated functional responses such as respiratory burst, degranulation, or cell spreading in vitro and show reduced adhesion/spreading in inflamed capillary venules in vivo. However, PLCγ2−/− neutrophils respond normally to various other agonists, including chemokines, bacterial formyl peptides, Toll-like receptor ligands, or proinflammatory cytokines, and migrate normally both in vitro and in vivo. To confirm the in vivo relevance of these observations, the effect of the PLCγ2−/− mutation was tested in the K/B×N serum transfer arthritis model, which is known to require β2 integrins, Fcγ receptors, and neutrophils. PLCγ2 deficiency completely protected mice from clinical signs and histological features of arthritis as well as from arthritis-induced loss of articular function. These results identify PLCγ2 as a critical player of integrin and Fc receptor-mediated neutrophil functions and the neutrophil-mediated effector phase of autoimmune arthritis.
Pathologic Nodal Staging Scores in Patients Treated with Radical Prostatectomy: A Postoperative Decision Tool
Authors: Luis A. Kluth, Firas Abdollah, Evanguelos Xylinas, Malte Rieken, Harun Fajkovic, Maxine Sun, Pierre I. Karakiewicz, Christian Seitz, Paul Schramek, Michael P. Herman, Andreas Becker, Wolfgang Loidl, Karl Pummer, Alessandro Nonis, Richard K. Lee, Yair Lotan, Douglas S. Scherr, Daniel Seiler, Felix K.-H. Chun, Markus Graefen, Ashutosh Tewari, Mithat Gönen, Francesco Montorsi, Shahrokh F. Shariat, Alberto Briganti
Journal: European Urology (2013)
Molecular evidence of type 2 mosaicism in Gorlin syndrome
Authors: A. Torrelo, A. Hernández-Martín, E. Bueno, I. Colmenero, I. Rivera, L. Requena, R. Happle, R. González-Sarmiento
Journal: British Journal of Dermatology (2013)

We present a 12‐year‐old girl with a family history of Gorlin syndrome who had unilateral, segmentally arranged basaloid skin tumours present since birth, ipsilateral, palmoplantar pits of rather large size distributed along Blaschko lines, and an ipsilateral odontogenic keratocyst. The patient and her father were heterozygous for a germline mutation in the form of a single‐base substitution in exon 18 of the PTCH1 gene. In the patient's lesional skin, a microdeletion in exon 3 of PTCH1 was detected, giving rise to a truncated protein. This additional mutation was ruled out in the contralateral skin and in blood lymphocytes, thus confirming its mosaic state. In this way we provide for the first time molecular proof of a type 2 segmental involvement of this autosomal dominant trait.
Incidence and predictive factors of first episode of spontaneous bacterial peritonitis in cirrhosis with ascites: Relevance of ascitic fluid protein concentration
Authors: Josep Llach, Antoni Rimola, Miquel Navasa, Pere Ginès, Joan M. Salmerón, Angels Ginès, Vicente Arroyo, Joan Rodés
Journal: Hepatology (1992)

To investigate the long–term probability of the appearance of the first episode of spontaneous bacterial peritonitis in cirrhosis with ascites and to identify predictors of this complication, we closely followed throughout their illness 127 patients consecutively admitted to our unit for the treatment of an episode of ascites without prior spontaneous bacterial peritonitis (follow–up period: 21 ± 22 mo). Thirteen patients (10%) had the first spontaneous bacterial peritonitis episode during follow–up. The appearance probability of this complication is 11% at 1 yr and 15% at 3 yr. Thirty–three variables obtained at admission (including clinical data, standard liver and kidney function test results, ascitic fluid protein concentrations and hemodynamic parameters) were analyzed in relation to their value in predicting spontaneous bacterial peritonitis development. In univariate analysis (Kaplan–Meier curves) five variables reached statistical significance (p &lt; 0.05) as predictive factors for the development of the first spontaneous bacterial peritonitis episode. These five variables were poor nutritional status, increased serum bilirubin levels, increased serum AST levels, decreased prothrombin activity and reduced total protein concentration in ascitic fluid. When these five variables were introduced in a multivariate analysis, only the ascitic fluid protein concentration was found to correlate independently with spontaneous bacterial peritonitis development (p = 0.002). The probability of first spontaneous bacterial peritonitis after 3 yr of follow–up was 24% and 4% in patients with ascitic fluid protein content lower than 1 gm/dl and greater than or equal to 1 gm/dl, respectively. We concluded that the most important predictor of the development of the first spontaneous bacterial peritonitis episode in cirrhosis with ascites is the total protein concentration in ascitic fluid. (Hepatology 1992;16:724-727.)
Performance of activities of daily living and inspiratory muscle force in patients with COPD
Authors: Eloisa Regueiro, Renata Basso, Mauricio Jamami, Dirceu Costa, Valéria Pires Di Lorenzo
Journal: European Respiratory Journal (2011)

Background:  Patients with COPD often experience a decline in exercise tolerance, resulting in disability in the performance of activities of daily living (ADL). Inspiratory muscle weakness is commonly observed in these patients and contributes to dyspnea, fatigue and reduced exercise capacity. However it is unclear if inspiratory muscle weakness decreases the performance during ADL.   Aim:  To assess the correlation between inspiratory muscle force and performance during a standardized protocol of ADL.   Methods:  18 patients (FEV1 47±16%pred; MIP 52±20cmH2O) performed different activities during 30 minutes approximately. A portable metabolic system was used to assess VE, VO2 and MET during different ADL such as wake up and making bed, taking shower and washing one9s back, putting on clothes, brushing teeth and combing hair, lifting and lowering containers on a shelf at eye level, lifting and lowering containers on a shelf above the scapular waist and hanging. The Borg scale was used to verify dyspnea and fatigue.   Results:  There was no significant correlation (r=0.2, p=0,08) between MIP and performance indicators (VE, VO2), dyspnea and fatigue observed during this protocol of ADL.   Conclusion:  Performance during this specific protocol, which is representative of some daily life tasks was not related to the MIP. Preliminary data suggest that ventilatory and metabolic responses had no influence of inspiratory muscle capacity during this standardized protocol of ADL in patients with COPD.
British Thoracic Society national pleural procedures audit 2010
Authors: C. Hooper, N. Maskell
Journal: Thorax (2011)

In this report, we detail the results of the 2010 BTS national pleural procedures audit, to which 58 hospitals covering a collective population of more than 20 million patients contributed data regarding local pleural procedure practice and training policies and the process and complications associated with a total of 824 chest drain insertions. The results highlight a promising increase in the use of real time ultrasound guidance for pleural procedures but also deficiencies in pre-procedure consent practice and a significant rate of avoidable minor complications such as drain fall-out and procedure related pain. Action points for improvement to local pleural procedure practice are suggested.
Neonatal pemphigus vulgaris associated with mild oral pemphigus vulgaris in the mother during pregnancy
Authors: None Chowdhury, None Natarajan
Journal: British Journal of Dermatology (1998)

We report a neonate with immunofluorescence-proven pemphigus vulgaris. The condition presented at birth with widespread skin erosions and ulceration of the oral mucosa. Histopathological and immunofluorescence studies confirmed pemphigus vulgaris. The mother had mild oral pemphigus vulgaris treated during pregnancy with topical corticosteroids. All the neonate's skin erosions had crust formation at day 2 but healed completely within 2 weeks.
Surgery for early stage small cell lung cancer
Authors: Ulrik Sartipy
Journal: Thorax (2012)

Surgery for early stage small cell lung cancerIn this database study from the USA, survival following surgical treatment for stage I and II small cell lung cancer (SCLC) was investigated.The Surveillance, Epidemiology and End Results (SEER) database, sponsored by the National Cancer Institute, covers almost one third of the US population and captures 98% of all cancer cases in the surveyed areas.All patients between 1988 and 2007 with stage I or II SCLC were retrieved from the SEER database together with information regarding demographics, stage of disease, radiotherapy, resection as the treatment and survival.If available, pathological staging was used, otherwise patients were staged clinically.Three thousand five hundred and sixty six patients were included, and 25% underwent surgery, primarily lobectomy.The unadjusted median survival in the surgical group was 34 months compared with 16 months in patients who did not undergo surgery.The multivariable adjusted Cox regression model showed that patients with stage I or II SCLC who underwent surgery had better survival compared with patients who did not have surgery (HR 0.45, 95% CI 0.39 to 0.51).This survival advantage was persistent in a number of subgroup analyses.Limitations recognised by the authors were lack of information regarding concurrent diseases and chemotherapy.Consequently it cannot be ruled out that patients who were recommended surgery were healthier than the patients in the non-surgical group, and it is also possible that chemotherapy was more common in patients who underwent surgery, which may have influenced the prognosis.Keeping these weaknesses in mind, this study is nevertheless a valuable addition to the growing literature providing evidence for a survival benefit from surgical treatment in stage I or II SCLC.
O6-methylguanine DNA-methyltransferase methylation status can change between first surgery for newly diagnosed glioblastoma and second surgery for recurrence: clinical implications
Authors: A. A. Brandes, E. Franceschi, A. Tosoni, S. Bartolini, A. Bacci, R. Agati, C. Ghimenton, S. Turazzi, A. Talacchi, M. Skrap, G. Marucci, L. Volpin, L. Morandi, S. Pizzolitto, M. Gardiman, A. Andreoli, F. Calbucci, M. Ermani
Journal: Neuro-Oncology (2010)

O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation status is a prognostic factor in newly diagnosed glioblastoma patients. However, it is not yet clear whether, and if so how, MGMT methylation status may change. Moreover, it is unknown whether the prognostic role of this epigenetic feature is retained during the disease course. A retrospective analysis was made using a database of 614 glioblastoma patients treated prospectively from January 2000 to August 2008. We evaluated only patients who met the following inclusion criteria: age ≥18 years; performance status 0-2; histological diagnosis of glioblastoma at both first and second surgery for recurrence; postoperative treatment consisting of: (i) radiotherapy (RT) followed by adjuvant temozolomide (TMZ) until 2005 and (ii) TMZ concurrent with and adjuvant to RT after 2005; a time interval ≥3 months between first and second surgery. MGMT status was evaluated at first and second surgery in all 44 patients (M:F 32:12, median age: 49 years, range: 27–67 years). In 38 patients (86.4%), MGMT promoter status was assessable at both first and second surgery. MGMT methylation status, changed in 14 patients (37%) of second surgery samples and more frequently in methylated than in unmethylated patients (61.5% vs 24%, P = .03). The median survival was significantly influenced only by MGMT methylation status determined at first surgery (P = .04). Significant changes in MGMT methylation status during the course of GBM occur more frequently in MGMT methylated than unmethylated cases. MGMT methylation status determined at first surgery appears to be of prognostic value; however, it is not predictive of outcome following second surgery.