tbuckley/cabot-search huggingface dataset:
Scarring, Disfigurement, and Quality of Life in Long-Term Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Karen E. Kinahan, Lisa K. Sharp, Kristy Seidel, Wendy Leisenring, Aarati Didwania, Mario E. Lacouture, Marilyn Stovall, Anand Haryani, Leslie L. Robison, Kevin R. Krull
Journal: Journal of Clinical Oncology (2012)

Childhood cancer survivors are at increased risk for adverse outcomes and chronic medical conditions. Treatment-related scarring, disfigurement, and persistent hair loss, in addition to their long-term impact on psychological distress or health-related quality of life (HRQOL), have received little attention.Self-reported scarring/disfigurement and persistent hair loss were examined in 14,358 survivors and 4,023 siblings from the Childhood Cancer Survivor Study. Multivariable models were used to examine associations with demographic and cancer treatment. The impact of disfigurement and hair loss on HRQOL (ie, Medical Outcomes Short Form-36) and emotional distress (ie, Brief Symptom Inventory-18) was examined.Survivors reported a significantly higher rate of scarring/disfigurement compared with siblings for head/neck (25.1% v 8.4%), arms/legs (18.2% v 10.2%), and chest/abdomen (38.1% v 9.1%), as well as hair loss (14.0% v 6.3%). In age-, sex-, and race-adjusted models, cranial radiation exposure ≥ 36 Gy increased risk for head/neck disfigurement (relative risk [RR], 2.42; 95% CI, 2.22 to 2.65) and hair loss (RR, 4.24; 95% CI, 3.63 to 4.95). Adjusting for cranial radiation, age, sex, race, education, and marital status, survivor hair loss increased risk of anxiety (RR, 1.60; 95% CI, 1.23 to 2.07), whereas head/neck disfigurement increased risk of depression (RR, 1.19; 95% CI, 1.01 to 1.41). Limitations due to emotional symptoms were associated with head/neck disfigurement (RR, 1.24; 95% CI, 1.10 to 1.41), arm/leg disfigurement (RR, 1.19; 95% CI, 1.05 to 1.35), and hair loss (RR, 1.26; 95% CI, 1.09 to 1.47).Survivors of childhood cancer are at increased risk for disfigurement and persistent hair loss, which is associated with future emotional distress and reduced quality of life. Future studies are needed to better identify and manage functional outcomes in these patients.
Whole-Body Hypothermia for Neonates with Hypoxic–Ischemic Encephalopathy
Authors: Seetha Shankaran, Abbot R. Laptook, Richard A. Ehrenkranz, Jon E. Tyson, Scott A. McDonald, Edward F. Donovan, Avroy A. Fanaroff, W. Kenneth Poole, Linda L. Wright, Rosemary D. Higgins, Neil N. Finer, Waldemar A. Carlo, Shahnaz Duara, William Oh, C. Michael Cotten, David K. Stevenson, Barbara J. Stoll, James A. Lemons, Ronnie Guillet, Alan H. Jobe
Journal: New England Journal of Medicine (2005)

Hypothermia is protective against brain injury after asphyxiation in animal models. However, the safety and effectiveness of hypothermia in term infants with encephalopathy is uncertain. We conducted a randomized trial of hypothermia in infants with a gestational age of at least 36 weeks who were admitted to the hospital at or before six hours of age with either severe acidosis or perinatal complications and resuscitation at birth and who had moderate or severe encephalopathy. Infants were randomly assigned to usual care (control group) or whole-body cooling to an esophageal temperature of 33.5 degrees C for 72 hours, followed by slow rewarming (hypothermia group). Neurodevelopmental outcome was assessed at 18 to 22 months of age. The primary outcome was a combined end point of death or moderate or severe disability. Of 239 eligible infants, 102 were assigned to the hypothermia group and 106 to the control group. Adverse events were similar in the two groups during the 72 hours of cooling. Primary outcome data were available for 205 infants. Death or moderate or severe disability occurred in 45 of 102 infants (44 percent) in the hypothermia group and 64 of 103 infants (62 percent) in the control group (risk ratio, 0.72; 95 percent confidence interval, 0.54 to 0.95; P=0.01). Twenty-four infants (24 percent) in the hypothermia group and 38 (37 percent) in the control group died (risk ratio, 0.68; 95 percent confidence interval, 0.44 to 1.05; P=0.08). There was no increase in major disability among survivors; the rate of cerebral palsy was 15 of 77 (19 percent) in the hypothermia group as compared with 19 of 64 (30 percent) in the control group (risk ratio, 0.68; 95 percent confidence interval, 0.38 to 1.22; P=0.20). Whole-body hypothermia reduces the risk of death or disability in infants with moderate or severe hypoxic-ischemic encephalopathy.
Abstract 3854: Gamma-linolenic Acid (GLA) sensitizes pancreatic cancer cells to gemcitabine
Authors: Ruth Lupu, Robert Busby, Park-Hong Cheol, Ingrid Espinoza
Journal: Cancer Research (2012)

Abstract Pancreatic cancer is the fourth leading cause of cancer deaths in the United States and continues to be a disease with few options for treatment. Current therapeutic regimens for pancreatic cancer often include the nucleoside analog gemcitabine (GEM), but while it has been in use for many years, the overall five year survival rate continues to be about 5%. New therapies are urgently needed to treat this disease. The nutritional supplement gamma-linolenic acid (GLA) is a poly-unsaturated fatty acid (PUFA) of the n-6 PUFA family, and has garnered attention for its cytotoxic effects against tumor cell lines while not affecting normal cells. In this study we look at the effect GLA has on Panc-1 cells and its ability to increase the sensitivity of these cells to treatment with GEM. Through the use of cell viability assays, immunofluorescence, 3-D growth assays, and western blotting, our results show that GLA alone will inhibit growth and induce apoptosis in Panc-1 cells. When GLA is combined with GEM, the results are synergistically enhanced. In addition, our results show that GLA may act through disruption of lipid rafts in the cellular membrane and may activate the extrinsic apoptotic pathway causing cell death. These results suggest that the nutritional supplement GLA could be used in combination with GEM to increase the therapeutic effectiveness of GEM while treating pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3854. doi:1538-7445.AM2012-3854
THE TREATMENT OF CUTANEOUS TUBERCULOSIS WITH DIETHYL DITHIOLISO PHTHALATE. A Preliminary Report.
Authors: J. G. COBURN, G. W. MARSDEN
Journal: British Journal of Dermatology (1960)

Journal Article THE TREATMENT OF CUTANEOUS TUBERCULOSIS WITH DIETHYL DITHIOLISO PHTHALATE. A Preliminary Report. Get access J. G. COBURN, B.Sc., M.D., J. G. COBURN, B.Sc., M.D. Consultant Dermatologist Senior Registrar, Manchester and Salford Hospital for Skin Diseases Search for other works by this author on: Oxford Academic Google Scholar G. W. MARSDEN, M.B., M.R.C.P.E. G. W. MARSDEN, M.B., M.R.C.P.E. Consultant Dermatologist Senior Registrar, Manchester and Salford Hospital for Skin Diseases Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 72, Issue 5, 1 May 1960, Pages 192–194, https://doi.org/10.1111/j.1365-2133.1960.tb13874.x Published: 01 May 1960
Positive inotropy linked with class III antiarrhythmic action: electrophysiological effects of the cardiotonic agent DPI 201-106 in the dog heart in vivo
Authors: E. Mortensen, P. M Tande, N.-E. Kiow, E. S Platou, H. Refsum
Journal: Cardiovascular Research (1990)

Study objective – The aim was to investigate whether the positive inotrope DPI 201-106 prolongs ventricular monophasic action potential duration and refractoriness in vivo without affecting conduction, thus possessing class III antiarrhythmic characteristics in vivo. Design – Electrophysiological and haemodynamic effects of DPI 201-106 (0.5, 1.0, and 2.0 mg·kg−1 intravenously) were studied at spontaneous heart rate and at three different paced cycle lengths (353, 300, and 261 ms). The following were recorded: monophasic action potentials from right ventricular endocardium; intracardiac conduction times by His bundle electrocardiography; refractoriness by programmed electrical stimulation; and left ventricular (LV) pressures. Subjects – Seven mongrel dogs of either sex, weighing 14-24 kg, were studied under sodium pentobarbitone anaesthesia. Measurements and main results – DPI 201-106 prolonged ventricular monophasic action potential duration and refractoriness dose dependently and most effectively at long cycle lengths, with no effect on intracardiic conduction times. DPI 201-106 increased LV dP/dtmax, while LV systolic and end diastolic pressures were unchanged both during spontaneous and paced heart rate. DPI 201-106 decreased spontaneous heart rate. Conclusions – Prolonged monophasic action potential duration and increased refractoriness, with no effect on conduction, indicate class III antiarrhythmic action of DPI 201-106 in vivo.
Comment on: Torres-Mejía et al. Moderate-Intensity Physical Activity Ameliorates the Breast Cancer Risk in Diabetic Women. Diabetes Care 2012;35:2500–2502
Authors: Dongfeng Zhang, Yili Wu, Wenjie Jiang, Xiubo Jiang
Journal: Diabetes Care (2013)

We read with great interest the article by Torres-Mejia et al. (1) showing that moderate-intensity physical activity can substantially ameliorate the increased risk of breast cancer (BC) in diabetic women. In addition, higher serum levels of C-peptide, IGF-1, and IGF-1 binding protein 3 (IGFBP3) were found to increase BC risk in premenopausal women. The finding is important because there is little evidence on physical activity and BC risk in diabetic women. In this letter, we would like to draw attention to several aspects.

First, compared with the least active women, a …
Chest Compression Rates During Cardiopulmonary Resuscitation Are Suboptimal
Authors: Benjamin S. Abella, Nathan Sandbo, Peter Vassilatos, Jason P. Alvarado, Nicholas O’Hearn, Herbert N. Wigder, Paul Hoffman, Kathleen Tynus, Terry L. Vanden Hoek, Lance B. Becker
Journal: Circulation (2005)

Recent data highlight a vital link between well-performed cardiopulmonary resuscitation (CPR) and survival after cardiac arrest; however, the quality of CPR as actually performed by trained healthcare providers is largely unknown. We sought to measure in-hospital chest compression rates and to determine compliance with published international guidelines.We developed and validated a handheld recording device to measure chest compression rate as a surrogate for CPR quality. A prospective observational study of adult cardiac arrests was performed at 3 hospitals from April 2002 to October 2003. Resuscitations were witnessed by trained observers using a customized personal digital assistant programmed to store the exact time of each chest compression, allowing offline calculation of compression rates at serial time points. In 97 arrests, data from 813 minutes during which chest compressions were delivered were analyzed in 30-second time segments. In 36.9% of the total number of segments, compression rates were <80 compressions per minute (cpm), and 21.7% had rates <70 cpm. Higher chest compression rates were significantly correlated with initial return of spontaneous circulation (mean chest compression rates for initial survivors and nonsurvivors, 90+/-17 and 79+/-18 cpm, respectively; P=0.0033).In-hospital chest compression rates were below published resuscitation recommendations, and suboptimal compression rates in our study correlated with poor return of spontaneous circulation. CPR quality is likely a critical determinant of survival after cardiac arrest, suggesting the need for routine measurement, monitoring, and feedback systems during actual resuscitation.
Long-Term Results of the Randomized Phase III Trial EORTC 18991 of Adjuvant Therapy With Pegylated Interferon Alfa-2b Versus Observation in Resected Stage III Melanoma
Authors: Alexander M.M. Eggermont, Stefan Suciu, Alessandro Testori, Mario Santinami, Wim H.J. Kruit, Jeremy Marsden, Cornelis J.A. Punt, François Salès, Reinhard Dummer, Caroline Robert, Dirk Schadendorf, Poulam M. Patel, Gaetan de Schaetzen, Alan Spatz, Ulrich Keilholz
Journal: Journal of Clinical Oncology (2012)

Purpose Adjuvant pegylated interferon alfa-2b (PEG-IFN-α-2b) was approved for treatment of resected stage III melanoma in 2011. Here, we present long-term follow-up results of this pivotal trial. Patients and Methods In all, 1,256 patients with resected stage III melanoma were randomly assigned to observation (n = 629) or PEG-IFN-α-2b (n = 627) for an intended duration of 5 years. Stratification factors were microscopic (N1) versus macroscopic (N2) nodal involvement, number of positive nodes, ulceration and tumor thickness, sex, and center. Recurrence-free survival (RFS; primary end point), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed for the intent-to-treat population. Results At 7.6 years median follow-up, 384 recurrences or deaths had occurred with PEG-IFN-α-2b versus 406 in the observation group (hazard ratio [HR], 0.87; 95% CI, 0.76 to 1.00; P = .055); 7-year RFS rate was 39.1% versus 34.6%. There was no difference in OS (P = .57). In stage III-N1 ulcerated melanoma, RFS (HR, 0.72; 99% CI, 0.46 to 1.13; P = .06), DMFS (HR, 0.65; 99% CI, 0.41 to 1.04; P = .02), and OS (HR, 0.59; 99% CI, 0.35 to 0.97; P = .006) were prolonged with PEG-IFN-α-2b. PEG-IFN-α-2b was discontinued for toxicity in 37% of patients. Conclusion Adjuvant PEG-IFN-α-2b for stage III melanoma had a positive impact on RFS, which was marginally significant and slightly diminished versus the benefit seen at prior follow-up (median, 3.8 years). No significant increase in DMFS or OS was noted in the overall population. Patients with ulcerated melanoma and lower disease burden had the greatest benefit.
Clinical Spectrum Associated with Hepatocyte Nuclear Factor-1β Mutations
Authors: Christine Bellanné-Chantelot, Dominique Chauveau, Jean-François Gautier, Danièle Dubois-Laforgue, Séverine Clauin, Sandrine Beaufils, Jean-Marie Wilhelm, Christian Boitard, Laure-Hélène Noël, Gilberto Velho, José Timsit
Journal: Annals of Internal Medicine (2004)

Background: Maturity-onset diabetes of the young type 5 (MODY5), a type of dominantly inherited diabetes mellitus and nephropathy, has been associated with mutations of the hepatocyte nuclear factor-1β (HNF-1β) gene, mostly generating truncated protein. Various phenotypes, including urogenital malformations, are related to HNF-1β mutations. Objective: To describe clinical and genetic findings in 13 patients with 8 novel HNF-1β mutations. Design: Multicenter, descriptive study. Setting: 2 departments of diabetes, 1 department of internal medicine, and 1 department of nephrology. Participants: 8 probands with diabetes diagnosed before 40 years of age and nondiabetic kidney disease who were selected independent of their family history of diabetes, and 5 offspring. Measurements: Characteristics of diabetes, renal function and structure, genital tract abnormalities, pancreas structure, insulin secretion, exocrine pancreas function, and liver test results. Results: All mutations, including 5 missense changes, were found in the DNA-binding domain. Cosegregation of the mutation and MODY5 phenotype was observed in 4 families. Occurrence of a de novo mutation was demonstrated in 2 families. Diabetes was present in 10 of 13 mutation carriers. It was clinically overt in 5 participants and found by screening at age 19 to 38 years in 5 participants. Pancreas atrophy was observed in 5 of 6 probands, and pancreas exocrine insufficiency was observed in 6 of 7 probands. Renal involvement, consisting of structural changes and slowly progressive renal failure, was recognized in 9 patients at 18 to 41 years of age. Dysplastic kidneys were found by ultrasonography in 3 fetuses who subsequently showed transient neonatal renal failure. Genital tract abnormalities were present in 5 probands and liver enzyme levels were abnormal in 11 of 13 patients. Limitations: Since the study was small and not population-based, it could not estimate the prevalence of MODY5. Other phenotypes might be associated with HNF-1β mutations. Conclusions: Maturity-onset diabetes of the young type 5 encompasses a wide clinical spectrum. Analysis for mutations of HNF-1β is warranted, even without a family history of diabetes, in nonobese patients with diabetes and slowly progressive nondiabetic nephropathy, particularly when pancreatic atrophy or genital abnormalities are present.
MOLLUSCUM CONTAGIOSUM AND SARCOIDOSIS:.
Authors: M. GANPULE, MAURICE GARRETTS
Journal: British Journal of Dermatology (1971)

Summary.— A case of molluscum contagiosum associated with sarcoidosis is presented and the literature on profuse lesions of molluscum conlagiosum is reviewed. It is postulated that failure of immune mechanisms is a predisposing factor in this case.
Vitamin D binding protein gene polymorphisms and baseline vitamin D levels as predictors of antiviral response in chronic hepatitis C
Authors: Edmondo Falleti, Davide Bitetto, Carlo Fabris, Giovanna Fattovich, Annarosa Cussigh, Sara Cmet, Elisa Ceriani, Ezio Fornasiere, Michela Pasino, Donatella Ieluzzi, Mario Pirisi, Pierluigi Toniutto
Journal: Hepatology (2012)

Vitamin D deficiency seems to predict the unsuccessful achievement of sustained viral response (SVR) after antiviral treatment in hepatitis C virus (HCV) difficult-to-treat genotypes. Vitamin D binding protein (GC) gene polymorphisms are known to influence vitamin D levels. This study was performed to assess whether the interaction between basal circulating vitamin D and the GC polymorphism plays a role in influencing the rate of antiviral responses in patients affected by chronic hepatitis C. In all, 206 HCV patients treated with a combination therapy of pegylated (PEG)-interferon plus ribavirin were retrospectively evaluated. GC rs7041 G>T, GC rs4588 C>A, and IL-28B rs12979860 C>T polymorphisms were genotyped. Frequencies of GC rs7041 G>T and rs4588 C>A polymorphisms were: G/G = 64 (31.1%), G/T = 100 (48.5%), T/T = 42 (20.4%) and C/C = 108 (52.4%), C/A = 84 (40.8%), A/A = 14 (6.8%). Patients were divided into those carrying ≥3 major alleles (wildtype [WT]+: G-C/G-C, G-C/T-C, G-C/G-A, N = 100) and the remaining (WT−: G-C/T-A, T-A/T-C, T-A/T-A, T-C/T-C, N = 106). Four groups were identified: vitamin D ≤20 ng/mL and WT−, vitamin D ≤20 and WT+, vitamin D >20 and WT−, vitamin D >20 and WT+. In difficult-to-treat HCV genotypes the proportion of patients achieving SVR significantly increased with a linear trend from the first to the last group: 6/25 (24.0%), 9/24 (37.5%), 12/29 (41.4%), 19/29 (65.5%) (P = 0.003). At multivariate analysis, having basal vitamin D >20 ng/mL plus the carriage of GC WT+ was found to be an independent predictor of SVR (odds ratio 4.52, P = 0.015). Conclusion: In difficult-to-treat HCV genotypes, simultaneous pretreatment normal serum vitamin D levels and the carriage of GC-globulin WT isoform strongly predicts the achievement of SVR after PEG-interferon plus ribavirin antiviral therapy. (HEPATOLOGY 2012;56:1641–1650)
High-Mobility Group A1 Proteins Regulate p53-Mediated Transcription of <i>Bcl-2</i> Gene
Authors: Francesco Esposito, Mara Tornincasa, Paolo Chieffi, Ivana De Martino, Giovanna Maria Pierantoni, Alfredo Fusco
Journal: Cancer Research (2010)

We have previously described a mechanism through which the high-mobility group A1 (HMGA1) proteins inhibit p53-mediated apoptosis by delocalizing the p53 proapoptotic activator homeodomain-interacting protein kinase 2 from the nucleus to the cytoplasm. By this mechanism, HMGA1 modulates the transcription of p53 target genes such as Mdm2, p21(waf1), and Bax, inhibiting apoptosis. Here, we report that HMGA1 antagonizes the p53-mediated transcriptional repression of another apoptosis-related gene, Bcl-2, suggesting a novel mechanism by which HMGA1 counteracts apoptosis. Moreover, HMGA1 overexpression promotes the reduction of Brn-3a binding to the Bcl-2 promoter, thereby blocking the Brn-3a corepressor function on Bcl-2 expression following p53 activation. Consistently, a significant direct correlation between HMGA1 and Bcl-2 overexpression has been observed in human breast carcinomas harboring wild-type p53. Therefore, this study suggests a novel mechanism, based on Bcl-2 induction, by which HMGA1 overexpression contributes to the escape from apoptosis leading to neoplastic transformation.
Acute ischaemic colitis in a female long distance runner.
Authors: M Heer, F Repond, A Hany, H Sulser, O Kehl, K Jager
Journal: Gut (1987)

A 34 year old female long distance runner is reported with bloody diarrhoea. Colonoscopy revealed patchy haemorrhagic mucosal lesions throughout the colon. The most extensive lesions were found in the sigmoid colon. Histologic examination disclosed mucosal haemorrhage, dilated capillaries, patchy fibrosis and superficial erosions. Additional findings in this patient were haemorrhagic gastritis, microscopic haematuria and rhabdomyolysis. The only medication taken by the patient was oral contraceptives. We conclude that ischaemic colitis is one of the possible mechanisms leading to gastrointestinal blood loss in competitive runners.
Gene Expression Profile of Papillary Thyroid Cancer: Sources of Variability and Diagnostic Implications
Authors: Barbara Jarząb, Małgorzata Wiench, Krzysztof Fujarewicz, Krzysztof Simek, Michał Jarząb, Małgorzata Oczko-Wojciechowska, Jan Włoch, Agnieszka Czarniecka, Ewa Chmielik, Dariusz Lange, Agnieszka Pawlaczek, Sylwia Szpak, Elżbieta Gubała, Andrzej Świerniak
Journal: Cancer Research (2005)

Abstract The study looked for an optimal set of genes differentiating between papillary thyroid cancer (PTC) and normal thyroid tissue and assessed the sources of variability in gene expression profiles. The analysis was done by oligonucleotide microarrays (GeneChip HG-U133A) in 50 tissue samples taken intraoperatively from 33 patients (23 PTC patients and 10 patients with other thyroid disease). In the initial group of 16 PTC and 16 normal samples, we assessed the sources of variability in the gene expression profile by singular value decomposition which specified three major patterns of variability. The first and the most distinct mode grouped transcripts differentiating between tumor and normal tissues. Two consecutive modes contained a large proportion of immunity-related genes. To generate a multigene classifier for tumor-normal difference, we used support vector machines-based technique (recursive feature replacement). It included the following 19 genes: DPP4, GJB3, ST14, SERPINA1, LRP4, MET, EVA1, SPUVE, LGALS3, HBB, MKRN2, MRC2, IGSF1, KIAA0830, RXRG, P4HA2, CDH3, IL13RA1, and MTMR4, and correctly discriminated 17 of 18 additional PTC/normal thyroid samples and all 16 samples published in a previous microarray study. Selected novel genes (LRP4, EVA1, TMPRSS4, QPCT, and SLC34A2) were confirmed by Q-PCR.Our results prove that the gene expression signal of PTC is easily detectable even when cancer cells do not prevail over tumor stroma. We indicate and separate the confounding variability related to the immune response. Finally, we propose a potent molecular classifier able to discriminate between PTC and nonmalignant thyroid in more than 90% of investigated samples.