tbuckley/cabot-search huggingface dataset:
Is There an Association Between the Occurrence of Neutropenia and Neuropathy in Patients with Metastatic Colorectal Cancer Treated with Folfox?
Authors: Jelena Spasic, Nemanja Stanic, Fedja Djordjevic, Marija Ristic, Neda Nikolic, Davorin Radosavljevic
Journal: Annals of Oncology (2013)
Colonoscopy Is Associated With a Reduced Risk for Colon Cancer and Mortality in Patients With Inflammatory Bowel Diseases
Authors: Ashwin N. Ananthakrishnan, Andrew Cagan, Tianxi Cai, Vivian S. Gainer, Stanley Y. Shaw, Susanne Churchill, Elizabeth W. Karlson, Shawn N. Murphy, Isaac Kohane, Katherine P. Liao
Journal: Clinical Gastroenterology and Hepatology (2014)
Ebola and other viral haemorrhagic fevers
Authors: T. E. Fletcher, T. J. G. Brooks, N. J. Beeching
Journal: BMJ (2014)

Be prepared, with new guidance featuring old and well established principles 

The ongoing Ebola outbreak in West Africa is the largest and most complicated that the world has even seen. Since it was first identified in the forested regions of south eastern Guinea in March,1 it has spread to Liberia, Sierra Leone, and Nigeria and has now been declared a “public health emergency of international concern” by the World Health Organization.2

Ebola virus is one of a group of zoonotic viruses that can cause severe disease in humans.3 4 5 Viruses that cause viral haemorrhagic fever include Lassa virus, Crimean-Congo haemorrhagic fever virus, Marburg virus, and emerging ones such as Lujo virus. These viruses are of particular public health importance because of their ability to spread to carers and healthcare workers, the often high case fatality rate, difficulties in their rapid recognition, and the lack of effective specific treatments.3 4 5 6 

The current epidemic is caused by the Zaire strain of Ebola virus, which has a mortality of 50-90% in endemic settings. No licensed cure or vaccine is available, although research is in progress to develop these and two American healthcare workers are reported to have received an experimental monoclonal antibody preparation after acquiring Ebola virus infection in Liberia.7 The keys to case management are early recognition and isolation of cases, use of personal protective equipment, and …
Abstract 5333: A mathematical model for the kinetics of metastasis formation based on SEER data
Authors: Ardith W. El-Kareh, Timothy W. Secomb
Journal: Cancer Research (2014)

Abstract Metastasis is responsible for most cancer mortality, yet many questions remain about how best to describe the kinetics of metastasis formation mathematically. Because the initial step of metastasis is the detachment of cells from a tumor mass, the rate of formation of new metastases is assumed to depend on the size of the original tumor mass. A power-law dependence, rather than linear proportionality, has been assumed, since access to blood vessels and lymphatics becomes more limited as tumor mass increases. Under this assumption, the cumulative distribution of fraction of patients not showing detectable metastases at diagnosis should decrease monotonically as tumor size at detection increases. Using data from the NCI's SEER (Surveillance, Epidemiology, and End Results) 1973-2010 database, it is shown here that this relation in fact shows non-monotonic behavior at larger detection sizes. A mathematical model for tumor growth and metastasis kinetics is developed to show that this implies that proliferation rates and metastatic rates are not independently distributed across the patient population, but rather, show some correlation. The model is further applied to deduce quantitative information about the size-dependence of the rate of metastasis. Kaplan-Meier curves stratified by tumor size, also computed from SEER 1973-2010 data, provide an additional data source for determining model parameters. It is found that accounting for age dependence is necessary for fitting these curves. Two possible age-related effects: a lower lethal tumor burden threshold; and an increased coefficient of metastatic rate due to declining immunity; are considered in the model, and a comparison is made of their ability to describe the observed age-dependence. In sum, the model shows how SEER data can be used to deduce information about the kinetics of metastasis formation, and is expected to have application in optimization of the treatment of metastatic tumors as well as screening schedules. Citation Format: Ardith W. El-Kareh, Timothy W. Secomb. A mathematical model for the kinetics of metastasis formation based on SEER data. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5333. doi:10.1158/1538-7445.AM2014-5333
Sacral nerve stimulation in neuropathic constipation
Authors: U. Khan, J. Mason, P. Hungin, J. Varma, Y. Yiannakou
Journal: Gut (2011)

<h3>Introduction</h3> The prevalence of constipation is between 43% and 58% in patients with either MS or spinal cord injury (SCI). Neuro-constipation is a very difficult to treat because of poor mobility, poor diet and side effects of long-term medication. Surgical options for intractable neuroconstipation involve prolonged operations with significant complications, and are unacceptable to many patients. In contrast sacral nerve stimulation (SNS) offers a potential minimally invasive and effective alternative. <h3>Methods</h3> Patients with refractory neuropathic constipation were offered temporary SNS (TSNS).Bilateral TSNS was performed under sedation and electrodes placed in the sacral foramen that produced the best peripheral response. The electrodes were removed after a 3 week evaluation period (week 7, 8 and 9 of the study) during which patients completed diaries and questionnaires. Patients with more than 50% improvement of baseline symptoms and recurrence of pre-stimulation symptoms were offered bilateral permanent SNS (PSNS). Paired student t test was used to calculate the changes in outcome measures before and during treatment. <h3>Results</h3> 22 patients recruited in the trial over 2 years. There were 8 men and 14 women with an average age of 51.5 years (range 38–69 years.). 4 patients dropped out and 18 completed the trial. 12 patients (67 %) received a permanent implant. The Global Assessment Score for constipation, PAC-SYM and PAC-QOL scores for these patients improved during treatment (p value &lt;0.05). There was also an improvement in toileting time (p 0.04) and decrease in overall laxative use (p 0.03). 6 of the patients with a permanent implant had a tailed response to long-term stimulation and their symptoms have returned to baseline. Long-term response after PSNS was 33 % (6/18). <h3>Conclusion</h3> Patients with neuropathic constipation have a better response after TSNS than patients with idiopathic constipation. However TSNS has only a 50% positive predictive value for a long-term response. SNS offers a reasonable alternative to invasive surgical procedures in these patients but method of predicting long term response need to be improved.
Patient with pyruvate kinase deficiency developed acute myelogenous leukemia
Authors: Ryuji Leki, Shiro Miwa, Hisaichi Fujii, Shouji Kudoh, Hitoshi Kimura, Fumimaro Takaku
Journal: American Journal of Hematology (1990)

Abstract A 44‐year‐old previously healthy male was diagnosed as anemic and treated at a nearby hospital. A year later, he was admitted to our hospital for precise examination of the progression of refractory anemia. Blood examination showed hemolytic anemia and more detailed examination of this hemolysis revealed pyruvate kinase deficiency. The activity was 15.1% of a normal control. Pyruvate kinase activities of his family members were normal or slightly decreased. Ten months after admission to our hospital, 2% of blast cells with Auer's body in the peripheral blood were noted which increased progressively. The bone marrow contained 17.3% of blast cells with a subsequent diagnosis of acute myelogenous leukemia being made. Although intensive chemotherapy was performed, the patient achieved a brief remission and died 2 years after admission to our hospital.
Inhibition of Cholesterol-Induced Coronary Atherogenesis in the Egg-Producing Hen
Authors: JEREMIAH STAMLER, RUTH PICK, LOUIS N. KATZ
Journal: Circulation (1954)

Mature egg-producing hens, intact or after oviduct ligation, are markedly resistant to cholesterol-induced coronary atherogenesis. This inhibition of coronary atherosclerosis is apparently effected by the endogenous estrogen secretion of these female birds.
Novel Oral Formulation of Paclitaxel Inhibits Neointimal Hyperplasia in a Rat Carotid Artery Injury Model
Authors: Dong-Woon Kim, Jin-Sook Kwon, Young-Gyu Kim, Maeng Sup Kim, Gwan-Sun Lee, Tae-Jin Youn, Myeong-Chan Cho
Journal: Circulation (2004)

Paclitaxel has been shown to inhibit vascular smooth muscle cell migration and proliferation contributing to neointimal formation. This study tested whether novel oral formulations of paclitaxel can prevent neointimal formation in a rat carotid artery injury model.Oral formulations of paclitaxel (0, 5, 7.5, or 10 mg/kg) were administered to 40 rats by gavage for 5 days after injury. The peak plasma levels of paclitaxel administered at 5, 7.5, and 10 mg/kg were 61+/-16, 89+/-22, and 108+/-28 nmol/L, respectively. Treatment effects were assessed 11 days after injury. The angiographic minimum luminal diameters of the oral paclitaxel groups treated at 5, 7.5, and 10 mg/kg were 6.28+/-2.09, 6.97+/-1.79, and 7.97+/-1.57 AU, and these were significantly larger than that of the control group (4.67+/-1.45 AU). The oral paclitaxel groups (5, 7.5, 10 mg/kg; 0.05+/-0.05, 0.04+/-0.03, 0.05+/-0.03 mm2) showed significant neointimal formation reductions versus the control group (0.13+/-0.05 mm2). All rats survived to study completion. Only 2 animals in the 10 mg/kg group experienced weight loss ( approximately 10%) and loose stools between 4 and 6 days after injury. All other animals appeared healthy during the study. For comparison purposes, intraperitoneal formulations of paclitaxel (0 or 2 mg/kg) were administered by injection to 15 rats. We confirmed that the intraperitoneal administration of paclitaxel also effectively inhibited neointimal formation.Oral formulations of paclitaxel provide an effective means of inhibiting proliferative response to vascular injury in the rat. Thus, oral formulations of paclitaxel may prevent human restenosis without significant toxicity.
Hepatitis B Antigen Inhibitor in Human Faeces and Intestinal Mucosa
Authors: M. Piazza, G. D. Stasio, G. Maio, L. A. Marzano
Journal: BMJ (1973)

Hepatitis B antigen (HB Ag) positive sera became negative after in-vivo incubation with homogenates of human faeces or intestinal mucosa. This was found to occur in all sera tested by various methods. These findings suggest the existence in the human intestine of a substance able to inactivate the HB Ag and that it is not an antibody or of the nature of interferon. The presence of an inhibitor could explain why B-type hepatitis is seldom if ever faecally transmitted and also the low oral infectiousness of the B virus.
Adenosine Nucleotide Biosynthesis and AMPK Regulate Adult Life Span and Mediate the Longevity Benefit of Caloric Restriction in Flies
Authors: Drew Stenesen, Jae Myoung Suh, Jin Seo, Kweon Yu, Kyu-Sun Lee, Jong-Seok Kim, Kyung-Jin Min, Jonathan M. Graff
Journal: Cell Metabolism (2013)
Reactive Oxygen Species Regulate Angiogenesis and Tumor Growth through Vascular Endothelial Growth Factor
Authors: Chang Xia, Qiao Meng, Ling-Zhi Liu, Yongyut Rojanasakul, Xin-Ru Wang, Bing-Hua Jiang
Journal: Cancer Research (2007)

Abstract Reactive oxygen species (ROS) are associated with multiple cellular functions such as cell proliferation, differentiation, and apoptosis. However, the direct roles of endogenous ROS production still remain to be elucidated. In this study, we found that high levels of ROS were spontaneously produced by ovarian and prostate cancer cells. This elevated ROS production was inhibited by NADPH oxidase inhibitor diphenylene iodonium (DPI) and mitochondria electron chain inhibitor rotenone in the cells. To further analyze the source of ROS production, we found that ovarian cancer cells have much higher expression of NOX4 NADPH oxidase, and that specific inhibition of NADPH oxidase subunit p47phox diminished ROS production. To analyze the functional relevance of ROS production, we showed that ROS regulated hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF) expression in ovarian cancer cells. Elevated levels of endogenous ROS were required for inducing angiogenesis and tumor growth. NOX4 knockdown in ovarian cancer cells decreased the levels of VEGF and HIF-1α and tumor angiogenesis. This study suggests a new mechanism of higher ROS production in ovarian cancer cells and provides strong evidence that endogenous ROS play an important role for cancer cells to induce angiogenesis and tumor growth. This information may be useful to understand the new mechanism of cancer cells in inducing tumorigenesis and to develop new therapeutic strategy by targeting ROS signaling in human cancer in the future. [Cancer Res 2007;67(22):10823–30]
Normal axonemal structure and function in Kartagener's syndrome: an explicable paradox.
Authors: M Greenstone, A Rutman, D Pavia, D Lawrence, P J Cole
Journal: Thorax (1985)

Ubiquitin-specific protease (USP) 2 participates in glucose metabolism in peripheral tissues such as the liver and skeletal muscle. However, the glucoregulatory role of USP2 in the central nervous system is not well known. In this study, we focus on USP2 in the ventromedial hypothalamus (VMH), which has dominant control over systemic glucose homeostasis. ISH using a <i>Usp2</i>-specific probe showed that <i>Usp2</i> mRNA is present in VMH neurons, as well as other glucoregulatory nuclei, in the hypothalamus of male mice. Administration of a USP2-selective inhibitor, ML364 (20 ng/head), into the VMH elicited a rapid increase in the circulating glucose level in male mice, suggesting USP2 has a suppressive role on glucose mobilization. ML364 treatment also increased serum norepinephrine concentration, while it negligibly affected serum levels of insulin and corticosterone. ML364 perturbated mitochondrial oxidative phosphorylation in neural SH-SY5Y cells, and subsequently promoted the phosphorylation of AMP-activated protein kinase (AMPK). Consistent with these findings, hypothalamic ML364 treatment stimulated AMPKα phosphorylation in the VMH. Inhibition of hypothalamic AMPK prevented ML364 from increasing serum norepinephrine and blood glucose. Removal of ROS restored the ML364-evoked mitochondrial dysfunction in SH-SY5Y cells and impeded the ML364-induced hypothalamic AMPKα phosphorylation, as well as prevented the elevation of serum norepinephrine and blood glucose levels in male mice. These results indicate hypothalamic USP2 attenuates perturbations in blood glucose levels by modifying the ROS–AMPK–sympathetic nerve axis. <b>Significance statement:</b> Under normal conditions (excluding hyperglycemia or hypoglycemia), blood glucose levels are maintained at a constant level. In this study, we used a mouse model to identify a hypothalamic protease controlling blood glucose levels. Pharmacological inhibition of ubiquitin-specific protease (USP) 2 in the ventromedial hypothalamus (VMH) caused a deviation in blood glucose levels under a non-stressed condition, indicating that USP2 determines the set point of the blood glucose level. Modification of sympathetic nervous activity accounts for the USP2-mediated glucoregulation. Mechanistically, USP2 mitigates the accumulation of ROS in the VMH, resulting in attenuation of the phosphorylation of AMP-activated protein kinase (AMPK). Based on these findings, we uncovered a novel glucoregulatory axis consisting of hypothalamic USP2, ROS, AMPK, and the sympathetic nervous system.
A novel KIR-associated function: evidence that CpG DNA uptake and shuttling to early endosomes is mediated by KIR3DL2
Authors: Simona Sivori, Michela Falco, Simona Carlomagno, Elisa Romeo, Cristiana Soldani, Armand Bensussan, Antonella Viola, Lorenzo Moretta, Alessandro Moretta
Journal: Blood (2010)
Blood, Urine, and Breath Levels After Rapid Intravenous Infusion of Ethanol
Authors: J. W. Dundee, J. W. D. Knox, M. Isaac
Journal: BMJ (1970)

A re-evaluation of alcohol as an intravenous anaesthetic provided an opportunity of studying the changes in venous blood, urine, and breath levels under controlled conditions. Twelve volunteer patients were given 0·8 g./kg. in 8% w/v solution over four to six minutes. Despite standardization of technique there was a great variation in the peak urinary concentration and also some variation in the time at which urinary level exceeded that of blood, but this latter always occurred within 30 minutes of infusion. From one hour after infusion there was a constant mean rate of decline of both venous and urinary concentrations. While urinary/venous blood ratios varied greatly they remained fairly constant in each individual patient. The average ratio (1·35) was similar to that of other published papers. With a modification of gearing (58:1 to 67:1) the standard Ethanographe gave good correlation of breath with venous blood concentrations at low levels when patients were able to operate the machine themselves. At high levels, however, with a two-minute period of rebreathing in the unconscious patient, the correlation was poor.
Effects of zinc, iron and copper deficiencies on cadmium in tissues of Japanese quail.
Authors: M R Fox, S H Tao, C L Stone, B E Fry
Journal: Environmental Health Perspectives (1984)

Experiments with young Japanese quail were conducted to determine whether combined moderate deficiencies of zinc, iron and copper would cause greater uptake and tissue retention of cadmium than the single deficiencies. Birds were fed the experimental diets containing 62 ppb cadmium from hatching to 16 days of age. On day 9 each bird received a dose of 109CdCl2 in its diet. On day 10, the duodenal and jejunal-ileal tissues contained large amounts of cadmium, and there were many significant effects of treatment on cadmium-109 retention in the livers and kidneys. At day 16, zinc deficiency caused increased cadmium in the liver, whereas iron and copper deficiencies each caused increased cadmium in the kidneys. Combined deficiencies had little or no greater effect than single deficiencies and in some cases the combined effect was less than that of a single deficiency.
Persistent Endothelial Dysfunction in Humans after Diesel Exhaust Inhalation
Authors: Håkan Törnqvist, Nicholas L. Mills, Manuel Gonzalez, Mark R. Miller, Simon D. Robinson, Ian L. Megson, William MacNee, Ken Donaldson, Stefan Söderberg, David E. Newby, Thomas Sandström, Anders Blomberg
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Exposure to combustion-derived air pollution is associated with an early (1-2 h) and sustained (24 h) rise in cardiovascular morbidity and mortality. We have previously demonstrated that inhalation of diesel exhaust causes an immediate (within 2 h) impairment of vascular and endothelial function in humans.To investigate the vascular and systemic effects of diesel exhaust in humans 24 hours after inhalation.Fifteen healthy men were exposed to diesel exhaust (particulate concentration, 300 microg/m(3)) or filtered air for 1 hour in a double-blind, randomized, crossover study. Twenty-four hours after exposure, bilateral forearm blood flow, and inflammatory and fibrinolytic markers were measured before and during unilateral intrabrachial bradykinin (100-1,000 pmol/min), acetylcholine (5-20 microg/min), sodium nitroprusside (2-8 microg/min), and verapamil (10-100 microg/min) infusions.Resting forearm blood flow, blood pressure, and basal fibrinolytic markers were similar 24 hours after either exposure. Diesel exhaust increased plasma cytokine concentrations (tumor necrosis factor-alpha and interleukin-6, p < 0.05 for both) but appeared to reduce acetylcholine (p = 0.01), and bradykinin (p = 0.08) induced forearm vasodilatation. In contrast, there were no differences in either endothelium-independent (sodium nitroprusside and verapamil) vasodilatation or bradykinin-induced acute plasma tissue plasminogen activator release.Twenty-four hours after diesel exposure, there is a selective and persistent impairment of endothelium-dependent vasodilatation that occurs in the presence of mild systemic inflammation. These findings suggest that combustion-derived air pollution may have important systemic and adverse vascular effects for at least 24 hours after exposure.
Upper Airway Sampling
Authors: THOMAS FRISCHER, EUGENIO BARALDI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The role of airway inflammation in asthmatic disease has mainly been determined from studies in the adult population. Data from these patients have demonstrated an association between the concentration of inflammatory cells and markers in samples from the lower airways and airway responsiveness and the clinical severity of asthma. Airway inflammation is therefore a useful marker of disease activity. There is less information concerning airway inflammation in young children, in whom the asthma phenotype is thought to be more heterogeneous and in whom access to the lower airways is a major obstacle. The upper airway, specifically the nasal epithelium, shares many properties with the lower airway. Moreover, it is easily accessible and nasal lavage (NAL) procedures are well tolerated even by infants as young as 4 wk old. In comparison with serum analysis, measurements of inflammatory markers can generally be assumed to reflect airway pathology more directly. Therefore, the determination of inflammatory markers in the nasal epithelium fluid would be attractive for both clinical and epidemiological purposes. The response of the upper airway to allergens in individuals with hay fever (1), response to viral infection (2, 3), and response to different exogenous harmful substances, such as ozone (4), passive smoking, or particles (5) have been studied extensively. This article focuses on methodological considerations for the use of upper airway sampling in the relatively neglected field of pediatric asthma. In particular, we address the extent to which nasal samples can provide information on lower airway inflammation.