tbuckley/cabot-search huggingface dataset:
Clinical Trial to Assess the Relative Efficacy of Fluorouracil and Leucovorin, Fluorouracil and Levamisole, and Fluorouracil, Leucovorin, and Levamisole in Patients With Dukes' B and C Carcinoma of the Colon: Results From National Surgical Adjuvant Breast and Bowel Project C-04
Authors: Norman Wolmark, Howard Rockette, Eleftherios Mamounas, Judy Jones, Sam Wieand, D.L. Wickerham, Harry D. Bear, James N. Atkins, Nikolay V. Dimitrov, Andrew G. Glass, Edwin R. Fisher, Bernard Fisher
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To compare the efficacy of leucovorin-modulated fluorouracil (FU+LV) with that of fluorouracil and levamisole (FU+LEV) or with the combination of FU+LV and levamisole (FU+LV+LEV). PATIENTS AND METHODS: Between July 1989 and December 1990, 2,151 patients with Dukes' B (stage II) and Dukes' C (stage III) carcinoma of the colon were entered onto National Surgical Adjuvant Breast and Bowl Project protocol C-04. Patients were randomly assigned to receive FU+LV (weekly regimen), FU + LEV, or the combination of FU+LV+LEV. The average time on study was 86 months. RESULTS: A pairwise comparison between patients treated with FU+LV or FU+LEV disclosed a prolongation in disease-free survival (DFS) in favor of the FU+LV group (65% v 60%; P = .04); there was a small prolongation in overall survival that was of borderline significance (74% v 70%; P = .07). There was no difference in the pairwise comparison between patients who received FU+LV or FU+LV+LEV for either DFS (65% v 64%; P = .67) or overall survival (74% v 73%; P = .99). There was no interaction between Dukes' stage and the effect of treatment. CONCLUSION: In patients with Dukes' B and C carcinoma of the colon, treatment with FU+LV seems to confer a small DFS advantage and a borderline prolongation in overall survival when compared with treatment with FU+LEV. The addition of LEV to FU+LV does not provide any additional benefit over and above that achieved with FU+LV. These findings support the use of adjuvant FU+LV as an acceptable therapeutic standard in patients with Dukes' B and C carcinoma of the colon.
Genetic and Environmental Influences on the Developmental Course of Attention-Deficit/Hyperactivity Disorder Symptoms From Childhood to Adolescence
Authors: Jean-Baptiste Pingault, Essi Viding, Cédric Galéra, Corina U. Greven, Yao Zheng, Robert Plomin, Frühling Rijsdijk
Journal: JAMA Psychiatry (2015)

Attention-deficit/hyperactivity disorder (ADHD) is conceptualized as a neurodevelopmental disorder that is strongly heritable. However, to our knowledge, no study to date has examined the genetic and environmental influences explaining interindividual differences in the developmental course of ADHD symptoms from childhood to adolescence (ie, systematic decreases or increases with age). The reason ADHD symptoms persist in some children but decline in others is an important concern, with implications for prognosis and interventions.To assess the proportional impact of genes and the environment on interindividual differences in the developmental course of ADHD symptom domains of hyperactivity/impulsivity and inattention between ages 8 and 16 years.A prospective sample of 8395 twin pairs from the Twins Early Development Study, recruited from population records of births in England and Wales between January 1, 1994, and December 31, 1996. Data collection at age 8 years took place between November 2002 and November 2004; data collection at age 16 years took place between February 2011 and January 2013.Both DSM-IV ADHD symptom subscales were rated 4 times by participants' mothers.Estimates from latent growth curve models indicated that the developmental course of hyperactivity/impulsivity symptoms followed a sharp linear decrease (mean score of 6.0 at age 8 years to 2.9 at age 16 years). Interindividual differences in the linear change in hyperactivity/impulsivity were under strong additive genetic influences (81%; 95% CI, 73%-88%). More than half of the genetic variation was specific to the developmental course and not shared with the baseline level of hyperactivity/impulsivity. The linear decrease in inattention symptoms was less pronounced (mean score of 5.8 at age 8 years to 4.9 at age 16 years). Nonadditive genetic influences accounted for a substantial amount of variation in the developmental course of inattention symptoms (54%; 95% CI, 8%-76%), with more than half being specific to the developmental course.The large genetic influences on the developmental course of ADHD symptoms are mostly specific and independent of those that account for variation in the baseline level of symptoms. Different sets of genes may be associated with the developmental course vs the baseline level of ADHD symptoms and explain why some children remit from ADHD, whereas others persist. Recent longitudinal imaging data indicate that the maintenance or increase in symptoms is underpinned by atypical trajectories of cortical development. This may reflect a specific genetic liability, distinct from that which contributes to baseline ADHD symptoms, and warrants closer follow-up.
The effect of a pleural diseases clinic on pleural effusion admission rates
Authors: Sujoy Saikia, Kay Rowe, Helen E. Davies
Journal: European Respiratory Journal (2012)

Background  Patients with pleural effusion are frequently admitted to hospital on the medical intake. Some of these admissions may be predicted and acute admission avoided.  Aim  A weekly specialist pleural diseases clinic was established in May 2011. We assessed whether provision of dedicated clinic time for patients who may require pleural intervention would reduce hospital admission rates of patients with pleural effusion.  Method  A retrospective review of electronic records for patients attending the clinic between 01/06/11-30/11/11. Hospital records were analysed for pleural effusion admission events (ICD10 codes J90/J91) in this period and between 01/06/10–30/11/10.  Results  Table 1.   Conclusion  Development of a pleural clinic is associated with a reduced length of stay for patients admitted with pleural effusion. This could have significant cost-saving implications. However, the number of admissions increased by 219% over the study period. The cause of this rise is not clear.
An analysis of the effectiveness of specific guidelines for the management of ipilimumab-mediated diarrhea/colitis: Prevention of gastrointestinal perforation and/or colectomy
Authors: R. Lin, M. J. Yellin, I. Lowy, A. Safferman, K. Chin, R. Ibrahim
Journal: Journal of Clinical Oncology (2008)

9063 Background: The fully human, anti cytotoxic T lymphocyte antigen-4 monoclonal antibody ipilimumab (ipi) produced durable responses/stable disease in some patients (pts) with advanced melanoma. Ipi is associated with generally mild-moderate immune-related adverse events (irAEs), likely due to ipi's mechanism of action and subsequent reduction in tolerance to self-antigens. In January 2005, diarrhea treatment guidelines (DTGs) were developed in cooperation with external experts - based on clinical experience - and introduced into all clinical trials with ipi (both ongoing and new). The guidelines called for close monitoring for any emergence/change in symptoms and prompt treatment of moderate-severe irAEs with corticosteroids. An analysis was conducted to determine if DTGs were effective in preventing life- threatening complications of diarrhea/colitis such as gastrointestinal (GI) perforation and/or colectomy. Methods: Historical safety data from early Medarex studies (which was mostly prior to implementation of the DTGs) was compared with that from ongoing BMS studies CA184004, -007,-008, and -022 (these studies had full DTG implementation). The GI perforation/colectomy rates, drug-related diarrhea, and serious GI irAEs were examined.Most pts in the early Medarex studies received 3 mg/kg ipi in various regimens while most ptss enrolled in ongoing BMS studies received 10 mg/kg ipi every 3 weeks (Q3W) X 4. Results: After the full implementation of DTGs, preliminary data show a substantial reduction (up to 50%) in GI perforation/colectomy rate despite an increase in ipi dose/exposure administered. Conclusions: Preliminary analysis suggests that DTGs are effective in reducing occurrence of life-threatening GI complications such as perforation/colectomy. Health-care providers should encourage pts to immediately report symptoms suggestive of colitis, utilize DTGs to reduce occurrence of life-threatening irAE GI complications, and adhere to treatment guidelines - appropriately treating moderate-severe GI- related irAEs with steroids to prevent serious complications. Education regarding irAE treatment may help to improve overall pts clinical outcome. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Medarex, Inc. Bristol-Myers Squibb, Medarex, Inc.
Skin and Systemic Disease
Authors: Nigel Stollery
Journal: JAMA (1998)

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Remote districts are still inaccessible five days after second Nepal earthquake
Authors: A. Gulland
Journal: BMJ (2015)

Health officials have been unable to reach health facilities in Nepal’s Dolakha district, five days after it was hit by a second major earthquake.

The 12 May earthquake, measuring magnitude 7.3, came just over two weeks after a 7.8 magnitude shock had devastated many towns and villages in the country on 25 April.

Rahul Pradhan, a surveillance medical officer for the World Health Organization, said that health services in Dolakha, one of the districts worst affected by the second earthquake, had already been fragile before the second shock. Of 57 health facilities in the province, including hospitals and primary care centres, 27 were completely damaged in the first earthquake, 18 were partially damaged, and …
A Survey of the Current Methods Used in the UK to Assess Pituitary Function
Authors: Melanie J Davies, Trevor A Howlett
Journal: Journal of the Royal Society of Medicine (1996)

A national survey of the current methods used by specialists to evaluate pituitary function in the UK was performed by postal questionnaire. Seventy-three respondents, of whom 89% were consultants and 80% clinical endocrinologists, returned the questionnaire. Fifty per cent routinely used the insulin stress test (IST) to evaluate the hypothalamo-pituitary-adrenal (HPA) axis, while 50% routinely used tetracosactrin stimulation, there being little overlap between the two groups. This represents a significant change in clinical practice since the last survey in 1988. In those who used ACTH stimulation there was almost an equal split into those who administered the tetracosactrin intramuscularly (45%) or intravenously (47%). Furthermore, either the peak or 60 min cortisol value was used by 71% when interpreting the result of the test, despite the fact that in previous studies only the 30 min cortisol value has been shown to correlate with the IST result. The IST remains the most frequently used method to assess growth hormone reserve in adult subjects. The thyrotrophin-releasing-hormone and gonadotrophin-releasing-hormone tests are still used routinely by approximately a quarter of clinicians. These results provide data that could be used to develop guide-lines for the use of tests to investigate pituitary function.
Use of chemotherapy in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients
Authors: R. A. Saber, S. S. Mohamad
Journal: Journal of Clinical Oncology (2005)

5543 Background: Concomitant chemoradiotherapy (CRTH) hold the promise of better local control than conventional radiotherapy (RTH) for the treatment of advanced head and neck cancers. Also, early and accurate diagnosis of residual/recurrent disease is essential for proper management. Methods: A prospective, study was concluded at radiotherapy department in patients with locally advanced (stage III, IV) squamous cell carcinoma of the head and neck from August 2001 to July 2004 to evaluate the role of concomitant CRTH. Sixty patients were randomised to receive either conventional RTH alone (60–70 Gy over 6–7 weeks) or concomitant CRTH consisting of conventional RTH with cisplatin (30 mg/m2 weekly started on the first day of RTH and then weekly until the end of RTH). CT, 99mTc-MIBI scan and direct endoscopy were performed for all patients before and after completion of radiation treatment. Biopsy and/or two years follow-up clinical, radiological and endoscopic studies were used to exclude the presence of active residual or recurrent disease. Results: The overall response rates were 89% and 71% with concomitant CRTH and conventional RTH respectively (P=0.007). The overall complete response rates were 76% with CRTH and 43% with RTH alone (P=0.001). The two-year rates of locoregional control were 87% and 69% with concomitant CRTH and conventional RTH respectively (P=0.008). Grade III mucositis was seen in 47% and 28% of patients with CRTH and RTH alone respectively (P=0.01). Although there was no statistical difference between the two imaging techniques in the detection of the primary disease (P=0.1), CT was superior to 99mTc-MIBI in the detection of regional lymph node metastases (sensitivity: 94% vs 88%; P=0.03). However, in comparison with CT, we found scintigraphic method have a higher sensitivity (100% vs 88%; P=0.01) and specificity (93% vs 69%; P=0.005) in differentiating viable tumor from post-treatment fibrosis. Conclusions: Concomitant CRTH is more reliable than the conventional RTH to reduce locoregional failure rates with organ preservation. 99mTc-MIBI imaging was found to be more sensitive than CT in differentiating active residual/recurrent disease from post-treatment fibrosis. No significant financial relationships to disclose.
Branched-chain Amino Acid Nitrogen Transfer to Alanine In Vivo in Dogs
Authors: E. Ben Galim, K. Hruska, D. M. Bier, D. E. Matthews, M. W. Haymond
Journal: Journal of Clinical Investigation (1980)

To investigate the contribution of branched-chain amino acids as a nitrogen source for alanine in vivo, dogs were infused with l-[15N]leucine, l-[U-14C]leucine, l-[2,3,3,3-2H4]alanine, and d-[6,6-2H2]-glucose. 14C and 15N isotopic equilibrium in plasma leucine, and deuterium enrichment in arterial and femoral plasma glucose and alanine were achieved within 3 h of initiation of the respective isotope infusion in all animals. The average flux of leucine determined by [15N]leucine was 5.4 μmol·kg−1·min−1, whereas using [14C]leucine it was 3.7 μmol·kg−1·min−1. Turnover rates for alanine and glucose were 11.0 and 17.2 μmol·kg−1·min−1, respectively.
Antitumor Activity of Deoxyribonucleic Acid Fraction From &lt;italic&gt;Mycobacterium bovis&lt;/italic&gt; BCG. I. Isolation, Physicochemical Characterization, and Antitumor Activity&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: T Tokunaga, H Yamamoto, S Shimada, H Abe, T Fukuda, Y Fujisawa, Y Furutani, O Yano, T Kataoka, T Sudo
Journal: JNCI Journal of the National Cancer Institute (1984)

A fraction extracted from Mycobacterium bovis strain BCG, which was composed of 70.0% DNA, 28.0% RNA, 1.3% protein, 0.20% glucose, and 0.1% lipid and of no detectable amounts of cell wall components such as alpha, epsilon-diaminopimelic acid and hexosamine, was found to possess strong antitumor activity. Repeated intralesional injection of this fraction, designated MY-1, without attachment to oil or a single intralesional injection of MY-1 emulsified in mineral oil caused the IMC carcinoma of CDF1 mice and line 10 tumor of strain 2 guinea pigs to regress and/or prevented metastasis very effectively. MY-1 after digestion with RNase, which contained 97.0% single-stranded DNA with a guanine-cytosine content of 69.8%, was more effective than undigested MY-1 against IMC and line 10 tumor, while MY-1 digested with DNase, which contained 97.0% RNA, had reduced activity, suggesting that the DNA from BCG possessed strong antitumor activity under certain conditions. Details of the extraction procedures and physicochemical characterization of MY-1 were also described.
Abstract 16222: The Effect of Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy on Mitral Regurgitation
Authors: Jacob C Townsend, William H Spencer, Valerian Fernandes, Eric R Powers, Robert A Leonardi, Chetan A Patel, Daniel H Steinberg, David Gregg, Christopher D Nielsen
Journal: Circulation (2011)

Introduction: Hypertrophic Obstructive Cardiomyopathy (HOCM) is associated with systolic anterior motion of the mitral valve, frequently leading to mitral regurgitation (MR). We hypothesized that a...
Late-breaking abstract: A novel and short-term mouse model of chronic obstructive pulmonary disease
Authors: Masahiro Onishi, Osamu Hataji, Ayshwarya-Lakshmi Chelakkot-Govindalayathil, Corina N. D'Alessandro-Gabazza, Kentaro Fujiwara, Masaaki Toda, Tetsu Kobayashi, Esteban C. Gabazza, Osamu Taguchi
Journal: European Respiratory Journal (2014)

COPD is considered the major growing cause of mortality and morbidity worldwide, and it is going to become the third most common cause of death by 2020. Presently, there are about 200 million people suffering from some degree of COPD in the entire world. Animal models are very important to get insights into the pathogenesis of COPD. However, the currently available cigarette smoke-induced COPD models usually take a long time to develop and are reversible after stopping the stimuli. The need of a new model is compelling. In the present study we focus on the role of matrix metalloproteinases in the pathogenesis of COPD and hypothesized that overexpression of MMP-2 in lungs would allow the development of COPD in a short term after cigarette smoke inhalation. We developed a novel MMP-2 transgenic mouse that can express high level of the human MMP-2 in the lungs. COPD was induced by inhalation of cigarette smoking extract (CSE) for two weeks in wild type (WT/CSE) C57BL/6 and human MMP-2 transgenic mice (MMP-2/CSE). Mice that inhaled saline (WT/SAL & MMP-2/SAL) were used as control groups. The MMP-2 transgenic mice expressed high levels of MMP-2 in the lungs. They showed no phenotype in unstressed conditions. MMP-2/CSE showed significant emphysematous changes in the lungs compared to WT/CSE and MMP-2/SAL groups after 2-week inhalation of CSE. The lung of MMP-2/CSE mice showed significantly increased infiltration of inflammatory cells and increased level of inflammatory cytokines compared to control mice. This novel mouse model of COPD will be a very useful tool for evaluating the mechanistic pathways and for the development of novel therapies in cigarette smoke-associated COPD.
Screening for Iron Deficiency Anemia and Iron Supplementation in Pregnant Women to Improve Maternal Health and Birth Outcomes: U.S. Preventive Services Task Force Recommendation Statement
Authors: Albert L. Siu
Journal: Annals of Internal Medicine (2015)

Update of the 2006 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for iron deficiency anemia.The USPSTF reviewed the evidence on the association between change in iron status as a result of intervention (oral supplementation or treatment) in pregnant women and adolescents and improvement in maternal and infant health outcomes.This recommendation applies to pregnant women and adolescents living in the United States who do not have symptoms of iron deficiency anemia. It does not address pregnant women who are malnourished, have symptoms of iron deficiency anemia, or have special hematologic conditions or nutritional needs that may increase their need for iron.The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for iron deficiency anemia in pregnant women to prevent adverse maternal health and birth outcomes. (I statement). The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of routine iron supplementation for pregnant women to prevent adverse maternal health and birth outcomes. (I statement).
Molecular epidemiology of HPV infection using a clinical array methodology in 2952 women in Greece
Authors: S. Tsiodras, A. Hatzakis, A. Spathis, N. Margari, C. Meristoudis, A. Chranioti, M. Kyrgiou, J. Panayiotides, D. Kassanos, G. Petrikkos, M. Nasioutziki, A. Loufopoulos, E. Paraskevaidis, P. Karakitsos
Journal: Clinical Microbiology and Infection (2011)
Gating Deficit Heritability and Correlation With Increased Clinical Severity in Schizophrenia Patients With Positive Family History
Authors: Tiffany A. Greenwood, Gregory A. Light, Neal R. Swerdlow, Monica E. Calkins, Michael F. Green, Raquel E. Gur, Ruben C. Gur, Laura C. Lazzeroni, Keith H. Nuechterlein, Ann Olincy, Allen D. Radant, Larry J. Seidman, Larry J. Siever, Jeremy M. Silverman, William S. Stone, Catherine A. Sugar, Debby W. Tsuang, Ming T. Tsuang, Bruce I. Turetsky, Robert Freedman, David L. Braff
Journal: American Journal of Psychiatry (2015)

Objective: The Consortium on the Genetics of Schizophrenia Family Study evaluated 12 primary and other supplementary neurocognitive and neurophysiological endophenotypes in schizophrenia probands and their families. Previous analyses of prepulse inhibition (PPI) and P50 gating measures in this sample revealed heritability estimates that were lower than expected based on earlier family studies. Here the authors investigated whether gating measures were more heritable in multiply affected families with a positive family history compared with families with only a single affected proband (singleton). Method: A total of 296 nuclear families consisting of a schizophrenia proband, at least one unaffected sibling, and both parents underwent a comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives. Among the families, 97 were multiply affected, and 96 were singletons. Results: Both PPI and P50 gating displayed substantially increased heritability in the 97 multiply affected families (47% and 36%, respectively) compared with estimates derived from the entire sample of 296 families (29% and 20%, respectively). However, no evidence for heritability was observed for either measure in the 96 singleton families. Schizophrenia probands derived from the multiply affected families also displayed a significantly increased severity of clinical symptoms compared with those from singleton families. Conclusions: PPI and P50 gating measures demonstrate substantially increased heritability in schizophrenia families with a higher genetic vulnerability for illness, providing further support for the commonality of genes underlying both schizophrenia and gating measures.