tbuckley/cabot-search huggingface dataset:
Multicenter Investigation of the Opioid Antagonist Nalmefene in the Treatment of Pathological Gambling
Authors: Jon E. Grant, Marc N. Potenza, Eric Hollander, Renee Cunningham-Williams, Tommi Nurminen, Gerard Smits, Antero Kallio
Journal: American Journal of Psychiatry (2006)

OBJECTIVE: Pathological gambling is a disabling disorder experienced by approximately 1%–2% of adults and for which there are few empirically validated treatments. The authors examined the efficacy and tolerability of the opioid antagonist nalmefene in the treatment of adults with pathological gambling. METHOD: A 16-week, randomized, dose-ranging, double-blind, placebo-controlled trial was conducted at 15 outpatient treatment centers across the United States between March 2002 and April 2003. Two hundred seven persons with DSM-IV pathological gambling were randomly assigned to receive nalmefene (25 mg/day, 50 mg/day, or 100 mg/day) or placebo. Scores on the primary outcome measure (Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling) were analyzed by using a linear mixed-effects model. RESULTS: Estimated regression coefficients showed that the 25 mg/day and 50 mg/day nalmefene groups had significantly different scores on the Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling, compared to the placebo group. A total of 59.2% of the subjects who received 25 mg/day of nalmefene were rated as “much improved” or “very much improved” at the last evaluation, compared to 34.0% of those who received placebo. Adverse experiences included nausea, dizziness, and insomnia. CONCLUSIONS: Subjects who received nalmefene had a statistically significant reduction in severity of pathological gambling. Low-dose nalmefene (25 mg/day) appeared efficacious and was associated with few adverse events. Higher doses (50 mg/day and 100 mg/day) resulted in intolerable side effects.
Law on infant foods inhibits the marketing of complementary foods for infants, furthering undernutrition in India
Authors: V. Rao
Journal: BMJ (2012)

Data continue to show stubbornly high rates of undernutrition in children in India. Almost two in five (38.4%) children under 3 years old are stunted, 19.1% wasted, and 45.9% underweight.1 Every third malnourished child in the world is from India, says the current Unicef website on India.2 India has one of the highest levels of child malnutrition in the world, more than in most countries in sub-Saharan Africa.3

The multiple causes of child undernutrition are well documented—poverty, sex inequality, poor cultural practices, and poor governance. But another important cause not articulated strongly enough is market related. At present the Indian market completely lacks affordable complementary foods for infants from poor families or for poor children during or recovering from illness. Just over half (55.8%) of children aged 6-9 months in India receive complementary foods.1 This is one of the main causes of acute undernutrition among …
Amino acid metabolism during prolonged starvation
Authors: Philip Felig, Oliver E. Owen, John Wahren, George F. Cahill
Journal: Journal of Clinical Investigation (1969)

Plasma concentration, splanchnic and renal exchange, and urinary excretion of 20 amino acids were studied in obese subjects during prolonged (5-6 wk) starvation. Splanchnic amino acid uptake was also investigated in postabsorptive and briefly (36-48 hr) fasted subjects.A transient increase in plasma valine, leucine, isoleucine, methionine, and alpha-aminobutyrate was noted during the 1st wk of starvation. A delayed, progressive increase in glycine, threonine, and serine occurred after the 1st 5 days. 13 of the amino acids ultimately decreased in starvation, but the magnitude of this diminution was greatest for alanine which decreased most rapidly during the 1st week of fasting. In all subjects alanine was extracted by the splanchnic circulation to a greater extent than all other amino acids combined. Brief fasting resulted in an increased arterio-hepatic venous difference for alanine due to increased fractional extraction. After 5-6 wk of starvation, a marked falloff in splanchnic alanine uptake was attributable to the decreased arterial concentration. Prolonged fasting resulted in increased glycine utilization by the kidney and in net renal uptake of alanine. It is concluded that the marked decrease in plasma alanine is due to augmented and preferential splanchnic utilization of this amino acid in early starvation resulting in substrate depletion. Maintenance of the hypoalaninemia ultimately serves to diminish splanchnic uptake of this key glycogenic amino acid and is thus an important component of the regulatory mechanism whereby hepatic gluconeogenesis is diminished and protein catabolism is minimized in prolonged fasting. The altered renal extraction of glycine and alanine is not due to increased urinary excretion but may be secondary to the increased rate of renal gluconeogenesis observed in prolonged starvation.
Case–Control Study of Overweight, Obesity, and Colorectal Cancer Risk, Overall and by Tumor Microsatellite Instability Status
Authors: Peter T. Campbell, Elizabeth T. Jacobs, Cornelia M. Ulrich, Jane C. Figueiredo, Jenny N. Poynter, John R. McLaughlin, Robert W. Haile, Eric J. Jacobs, Polly A. Newcomb, John D. Potter, Loïc Le Marchand, Roger C. Green, Patrick Parfrey, H. Banfield Younghusband, Michelle Cotterchio, Steven Gallinger, Mark A. Jenkins, John L. Hopper, John A. Baron, Stephen N. Thibodeau, Noralane M. Lindor, Paul J. Limburg, María Elena Martínez
Journal: JNCI Journal of the National Cancer Institute (2010)

Being overweight or obese is an established risk factor for colorectal cancer, more so for men than for women. Approximately 10%-20% of colorectal tumors display microsatellite instability (MSI), defined as the expansion or contraction of small repeated sequences in the DNA of tumor tissue relative to nearby normal tissue. We evaluated associations between overweight or obesity and colorectal cancer risk, overall and by tumor MSI status.
Breast Cancer Subtype Approximated by Estrogen Receptor, Progesterone Receptor, and HER-2 Is Associated With Local and Distant Recurrence After Breast-Conserving Therapy
Authors: Paul L. Nguyen, Alphonse G. Taghian, Matthew S. Katz, Andrzej Niemierko, Rita F. Abi Raad, Whitney L. Boon, Jennifer R. Bellon, Julia S. Wong, Barbara L. Smith, Jay R. Harris
Journal: Journal of Clinical Oncology (2008)

To determine whether breast cancer subtype is associated with outcome after breast-conserving therapy (BCT) consisting of lumpectomy and radiation therapy.We studied 793 consecutive patients with invasive breast cancer who received BCT from July 1998 to December 2001. Among them, 97% had pathologically negative margins of resection, and 90% received adjuvant systemic therapy. No patient received adjuvant trastuzumab. Receptor status was used to approximate subtype: estrogen receptor (ER) or progesterone receptor (PR) positive and human epidermal growth factor receptor 2 negative = luminal A; ER+ or PR+ and HER-2+ = luminal B; ER-and PR -and HER-2+ = HER-2; and ER-and PR -and HER-2-= basal. Competing risks methodology was used to analyze time to local recurrence and distant metastases.Median follow-up was 70 months. The overall 5-year cumulative incidence of local recurrence was 1.8% (95% CI, 1.0 to 3.1); 0.8% (0.3, 2.2) for luminal A, 1.5% (0.2, 10) for luminal B, 8.4% (2.2, 30) for HER-2, and 7.1% (3.0, 16) for basal. On multivariable analysis (MVA) with luminal A as baseline, HER-2 (adjusted hazard ratio [AHR] = 9.2; 95% CI, 1.6 to 51; P = .012) and basal (AHR = 7.1; 95% CI, 1.6 to 31; P = .009) subtypes were associated with increased local recurrence. On MVA, luminal B (AHR = 2.9; 95% CI, 1.3 to 6.5; P = .007) and basal (AHR = 2.3; 95% CI, 1.1 to 5.2; P = .035) were associated with increased distant metastases.Overall, the 5-year local recurrence rate after BCT was low, but varied by subtype as approximated using ER, PR, and HER-2 status. Local recurrence was particularly low for the luminal A subtype, but was less than 10% at 5 years for all subtypes. Although further follow-up is needed, these results may be useful in counseling patients about their anticipated outcome after BCT.
Incidence, Cause, and Comparative Frequency of Sudden Cardiac Death in National Collegiate Athletic Association Athletes
Authors: Kimberly G. Harmon, Irfan M. Asif, Joseph J. Maleszewski, David S. Owens, Jordan M. Prutkin, Jack C. Salerno, Monica L. Zigman, Rachel Ellenbogen, Ashwin L. Rao, Michael J. Ackerman, Jonathan A. Drezner
Journal: Circulation (2015)

The incidence and cause of sudden cardiac death (SCD) in athletes is debated with hypertrophic cardiomyopathy often reported as the most common cause. A database of all National Collegiate Athletic Association deaths (2003-2013) was developed. Additional information and autopsy reports were obtained when possible. Cause of death was adjudicated by an expert panel. There were 4 242 519 athlete-years (AY) and 514 total student athlete deaths. Accidents were the most common cause of death (257, 50%, 1:16 508 AY) followed by medical causes (147, 29%, 1:28 861 AY). The most common medical cause of death was SCD (79, 15%, 1:53 703 AY). Males were at higher risk than females 1:37 790 AY versus 1:121 593 AY (incidence rate ratio, 3.2; 95% confidence interval, 1.9-5.5; P<0.00001), and black athletes were at higher risk than white athletes 1:21491 AY versus 1:68 354 AY (incidence rate ratio, 3.2; 95% confidence interval, 1.9-5.2; P<0.00001). The incidence of SCD in Division 1 male basketball athletes was 1:5200 AY. The most common findings at autopsy were autopsy-negative sudden unexplained death in 16 (25%), and definitive evidence for hypertrophic cardiomyopathy was seen in 5 (8%). Media reports identified more deaths in higher divisions (87%, 61%, and 44%), whereas the percentages from the internal database did not vary (87%, 83%, and 89%). Insurance claims identified only 11% of SCDs. The rate of SCD in National Collegiate Athletic Association athletes is high, with males, black athletes, and basketball players at substantially higher risk. The most common finding at autopsy is autopsy-negative sudden unexplained death. Media reports are more likely to capture high-profile deaths, and insurance claims are not a reliable method for case identification.
Activation of NF-κB Is a Novel Target of <i>KRAS</i>-Induced Endometrial Carcinogenesis
Authors: Yasunari Mizumoto, Satoru Kyo, Tohru Kiyono, Masahiro Takakura, Mitsuhiro Nakamura, Yoshiko Maida, Noriko Mori, Yukiko Bono, Hiroaki Sakurai, Masaki Inoue
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Although the KRAS mutation is one of critical genetic alterations in endometrial carcinogenesis, the downstream targets are not known. Experimental Design: In this study, we investigated the molecular targets of KRAS signals, using tumorigenic cells with oncogenic KRAS mutation established from telomerase reverse transcriptase (TERT)-immortalized endometrial epithelial cells. Results: We first confirmed that the RAF-ERK pathway, but not the PI3K-Akt pathway, was activated in KRAS tumorigenic cells. However, the introduction of constitutively active MAP/ERK kinase into immortalized cells to mimic RAF-ERK activation failed to obtain tumorigenic phenotypes, indicating the existence of other carcinogenic pathways triggered by KRAS. Recent evidence suggestive of linkage with KRAS signals prompted us to examine the involvement of NF-κB in endometrial carcinogenesis. We found that the DNA-binding activity of NF-κB was markedly elevated in KRAS tumorigenic cells compared with TERT-immortalized cells. Furthermore, the ability of NF-κB to activate the target gene promoters significantly increased in KRAS tumorigenic cells. Introduction of a mutant IκB that is resistant to degradation and thereby enhances the inhibitory effect on NF-κB largely abrogated the transformed phenotypes of KRAS tumorigenic cells. Thus, oncogenic KRAS signals contributed to the tumorigenic phenotypes of endometrial cells by activating the transcription function of NF-κB. Conclusions: These findings clearly show that NF-κB activation is a novel target of oncogenic KRAS in endometrial carcinogenesis, implying the potential utility of NF-κB inhibitors for endometrial cancer chemoprevention, especially with KRAS mutation. Clin Cancer Res; 17(6); 1341–50. ©2011 AACR.
Cyclic Decidualization of the Human Endometrium in Reproductive Health and Failure
Authors: Birgit Gellersen, Jan J. Brosens
Journal: Endocrine Reviews (2014)

Decidualization denotes the transformation of endometrial stromal fibroblasts into specialized secretory decidual cells that provide a nutritive and immunoprivileged matrix essential for embryo implantation and placental development. In contrast to most mammals, decidualization of the human endometrium does not require embryo implantation. Instead, this process is driven by the postovulatory rise in progesterone levels and increasing local cAMP production. In response to falling progesterone levels, spontaneous decidualization causes menstrual shedding and cyclic regeneration of the endometrium. A growing body of evidence indicates that the shift from embryonic to maternal control of the decidual process represents a pivotal evolutionary adaptation to the challenge posed by invasive and chromosomally diverse human embryos. This concept is predicated on the ability of decidualizing stromal cells to respond to individual embryos in a manner that either promotes implantation and further development or facilitates early rejection. Furthermore, menstruation and cyclic regeneration involves stem cell recruitment and renders the endometrium intrinsically capable of adapting its decidual response to maximize reproductive success. Here we review the endocrine, paracrine, and autocrine cues that tightly govern this differentiation process. In response to activation of various signaling pathways and genome-wide chromatin remodeling, evolutionarily conserved transcriptional factors gain access to the decidua-specific regulatory circuitry. Once initiated, the decidual process is poised to transit through distinct phenotypic phases that underpin endometrial receptivity, embryo selection, and, ultimately, resolution of pregnancy. We discuss how disorders that subvert the programming, initiation, or progression of decidualization compromise reproductive health and predispose for pregnancy failure.
Macrophage subpopulations in lamina propria of normal and inflamed colon and terminal ileum.
Authors: Y R Mahida, S Patel, P Gionchetti, D Vaux, D P Jewell
Journal: Gut (1989)

The aim of this study was to characterise human intestinal macrophages in normal and inflamed ileum and colon. Immunoperoxidase staining with a panel of monoclonal antibodies and histochemical staining for acid phosphatase and non-specific esterase was performed. In the superficial lamina propria, normal colonic macrophages were larger and more strongly positive for acid phosphatase and non-specific esterase than those in normal terminal ileum. There were more macrophages staining with monoclonal antibody RFD1 in the superficial lamina propria of the latter. Studies in inflammatory bowel disease tissue showed the presence of macrophages staining with monoclonal antibodies RFD9 and 3G8 which were rarely present in normal tissue and represented a different pattern from that seen in infectious colitis. Studies on isolated intestinal macrophages confirmed the findings in tissue sections. Subpopulations of intestinal macrophages are likely to have different functional roles. Phenotypic changes during inflammation may be induced by mediators of inflammation or may represent a recently recruited population of cells.
Living related liver transplantation: medical and social aspects of a controversial therapy
Authors: C E Broelsch
Journal: Gut (2002)

There are more than 15 000 patients waiting for a liver transplant in the USA, with an average waiting time of 468 days and a mortality rate as high as 15–20%. Until artificial organs or xenotransplantation becomes a reality, living donor liver transplantation remains the best option for patients with end stage liver disease.
Embolic complications of direct current cardioversion of atrial arrhythmias: association with low intensity of anticoagulation at the time of cardioversion
Authors: Mark M Gallagher, Brian J Hennessy, Nils Edvardsson, Ceara M Hart, Muriel S Shannon, Owen A Obel, Naab M Al-Saady, A.John Camm
Journal: Journal of the American College of Cardiology (2002)
Effects of Depression, Anxiety, Comorbidity, and Antidepressants on Resting-State Heart Rate and Its Variability: An ELSA-Brasil Cohort Baseline Study
Authors: Andrew H. Kemp, Andre R. Brunoni, Itamar S. Santos, Maria A. Nunes, Eduardo M. Dantas, Roberta Carvalho de Figueiredo, Alexandre C. Pereira, Antonio L.P. Ribeiro, José G. Mill, Rodrigo V. Andreão, Julian F. Thayer, Isabela M. Benseñor, Paulo A. Lotufo
Journal: American Journal of Psychiatry (2014)

Objective: Increases in resting-state heart rate and decreases in its variability are associated with substantial morbidity and mortality, yet contradictory findings have been reported for the effects of the mood and anxiety disorders and of antidepressants. The authors investigated heart rate and heart rate variability in a large cohort from Brazil, using propensity score weighting, a relatively novel method, to control for numerous potential confounders. Method: A total of 15,105 participants were recruited in the Brazilian Longitudinal Study of Adult Health. Mood and anxiety disorders were ascertained using the Portuguese version of the Clinical Interview Schedule–Revised. Heart rate and its variability were extracted from 10-minute resting-state electrocardiograms. Regressions weighted by propensity scores were carried out to compare participants with and without depressive or anxiety disorders, as well as users and non-users of antidepressants, on heart rate and heart rate variability. Results: Use of antidepressants was associated with increases in heart rate and decreases in its variability. Effects were most pronounced for the tricyclic antidepressants (Cohen’s d, 0.72–0.81), followed by serotonin and norepinephrine reuptake inhibitors (Cohen’s d, 0.42–0.95) and other antidepressants (Cohen’s d, 0.37–0.40), relative to participants not on antidepressants. Only participants with generalized anxiety disorder showed robust, though small, increases in heart rate and decreases in its variability after propensity score weighting. Conclusions: The findings may, in part, underpin epidemiological findings of increased risk for cardiovascular morbidity and mortality. Many factors that have an adverse impact on cardiac activity were controlled for in this study, highlighting the importance of cardiovascular risk reduction strategies. Further study is needed to examine whether, how, and when such effects contribute to morbidity and mortality.
Outcome of cervical spine surgery in patients with rheumatoid arthritis
Authors: K M van Asselt
Journal: Annals of the Rheumatic Diseases (2001)

Cervical spine instability in patients with rheumatoid arthritis (RA) may lead to cervical myelopathy or occipital neuralgia, or both. Morbidity and mortality in patients with RA treated with cervical spine surgery during two years of follow up were evaluated.Between 1992 and 1996 55 patients with RA underwent cervical spine surgery because of occipital neuralgia or cervical myelopathy, or both. Patients were classified according to the Ranawat criteria for pain and neurological assessment before operation and three months and two years postoperatively. For occipital neuralgia a successful operation was defined as complete relief of pain and for cervical myelopathy as neurological improvement.Occipital neuralgia was present in 17 patients, cervical myelopathy in 14 patients, and 24 had both. Surgical treatment in the patients with symptoms of occipital neuralgia who were still alive two years after surgery was successful in 18/29 (62%). In the surviving patients with cervical myelopathy neurological improvement of at least one Ranawat class was seen in 16/24 (67%). Postoperative mortality within six weeks was 3/51 (6%). Within two years after the operation 14 /51 (27%) of the patients had died; in most patients the cause of death was not related to surgery. The highest mortality (50%) was found in the group of six patients with quadriparesis and very poor functional capacity (Ranawat IIIB).Cervical spine surgery in patients with RA performed because of occipital neuralgia or cervical myelopathy, or both, is successful in most patients who are alive two years after surgery. However, the mortality rate during these two years is relatively high, which seems to be largely related to the severity of the underlying disease and not to the surgery itself.
Polarographic Oxygen, the Epicardial Electrocardiogram and Muscle Contraction in Experimental Acute Regional Ischemia of the Left Ventricle
Authors: JOHN J. SAYEN, WARNER F. SHELDON, GEORGE PEIRCE, PETER T. KUO
Journal: Circulation Research (1958)

This study is the first attempt to correlate myocardial oxygen availability by the polaro-graphic method with direct electrocardiographic leads and cinematographic records of muscle contraction during experimental acute coronary branch occlusion and narrowing. The comparative insensitivity and slowness of the epicardial electrocardiogram as an index of acute regional ischemia is demonstrated. Special attention is given to the rates of myocardial oxygen change immediately following attainment of a significant degree of coronary obstruction, the effects of pure oxygen inhalation on the experimental situations, and alterations in coronary vein color following release of arterial occlusion.
A Randomized Phase II Trial of Vismodegib versus Placebo with FOLFOX or FOLFIRI and Bevacizumab in Patients with Previously Untreated Metastatic Colorectal Cancer
Authors: Jordan Berlin, Johanna C. Bendell, Lowell L. Hart, Irfan Firdaus, Ira Gore, Robert C. Hermann, Mary F. Mulcahy, Mark M. Zalupski, Howard M. Mackey, Robert L. Yauch, Richard A. Graham, Gordon L. Bray, Jennifer A. Low
Journal: Clinical Cancer Research (2012)

Vismodegib, a Hedgehog pathway inhibitor, has preclinical activity in colorectal cancer (CRC) models. This trial assessed the efficacy, safety, and pharmacokinetics of adding vismodegib to first-line treatment for metastatic CRC (mCRC).Patients were randomized to receive vismodegib (150 mg/day orally) or placebo, in combination with FOLFOX or FOLFIRI chemotherapy plus bevacizumab (5 mg/kg) every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Key secondary objectives included evaluation of predictive biomarkers and pharmacokinetic drug interactions.A total of 199 patients with mCRC were treated on protocol (124 FOLFOX, 75 FOLFIRI). The median PFS hazard ratio (HR) for vismodegib treatment compared with placebo was 1.25 (90% CI: 0.89-1.76; P = 0.28). The overall response rates for placebo-treated and vismodegib-treated patients were 51% (90% CI: 43-60) and 46% (90% CI: 37-55), respectively. No vismodegib-associated benefit was observed in combination with either FOLFOX or FOLFIRI. Increased tumor tissue Hedgehog expression did not predict clinical benefit. Grade 3 to 5 adverse events reported for more than 5% of patients that occurred more frequently in the vismodegib-treated group were fatigue, nausea, asthenia, mucositis, peripheral sensory neuropathy, weight loss, decreased appetite, and dehydration. Vismodegib did not alter the pharmacokinetics of FOLFOX, FOLFIRI, or bevacizumab.Vismodegib does not add to the efficacy of standard therapy for mCRC. Compared with placebo, treatment intensity was lower for all regimen components in vismodegib-treated patients, suggesting that combined toxicity may have contributed to lack of efficacy.