tbuckley/cabot-search huggingface dataset:
Neuropeptide Y potentiates specifically the purinergic component of the neural responses in the guinea pig saphenous artery.
Authors: D W Cheung
Journal: Circulation Research (1991)

Contraction of the guinea pig saphenous artery induced by stimulation of perivascular nerves consists of an adrenergic and a purinergic component. Neuropeptide Y (NPY) potentiated the neural responses significantly at low stimulation frequencies but not at high frequencies when the contraction was maximal. After blocking the adrenoceptors with phentolamine, significant potentiation of the purinergic component by NPY could be demonstrated. The potentiating effect of NPY was abolished in the presence of nifedipine. After desensitizing the purinoceptors with alpha,beta-methylene-ATP, there was no potentiation of the remaining adrenergic component by NPY. NPY also has no effect on contractions induced by exogenous norepinephrine but potentiates those induced by alpha,beta-methylene-ATP. These results suggest that NPY potentiates neurally induced contraction in the guinea pig saphenous artery by a specific action on the purinergic response.
Double blind, controlled trial of 4-aminosalicylic acid and prednisolone enemas in distal ulcerative colitis.
Authors: L J O'Donnell, A S Arvind, P Hoang, D Cameron, I C Talbot, D P Jewell, J E Lennard-Jones, M J Farthing
Journal: Gut (1992)

Corticosteroid or 5-aminosalicylic acid enemas are the treatment of choice for distal ulcerative colitis but up to one third of patients may be unresponsive. As an alternative therapy might be advantageous, the efficacy of six weeks9 treatment with 2 g 4-aminosalicylic acid (4-ASA) (n = 24) and 20 mg prednisolone enemas (n = 21) were compared in a double blind, randomised trial in patients with acute distal (less than 30 cm from the anus) ulcerative colitis. Baseline demography and clinical severity were similar in both groups. Five of 24 patients receiving 4-ASA and 4 of 21 receiving prednisolone did not complete the trial because of deteriorating symptoms, failure to improve, or side effects. At the time of leaving the trial, 24 hour stool frequency, the presence of blood in the stools, and histological and sigmoidoscopic appearances were similar in both groups. Symptomatic improvement occurred in 17 of 24 patients receiving 4-ASA compared with 11 of 21 receiving prednisolone (chi 2 = 1.62, NS). Complete symptomatic improvement occurred in 9 of 24 patients receiving 4-ASA compared with 5 of 21 receiving prednisolone (chi 2 = 0.98, NS). Histological improvement was seen in 9 of 24 patients on 4-ASA compared with 7 of 21 on prednisolone (chi 2 = 0.08, NS). One patient receiving 4-ASA was considered to have an idiosyncratic reaction to the drug but other side effects were not considered to be drug related. Thus, 4-ASA, previously used in the treatment of tuberculosis (para-aminosalicyclic acid), is as good as prednisolone in the treatment of distal ulcerative colitis and should be considered in patients unresponsive to steroids or in whom steroid treatment is undesirable.
Residential water source and the risk of childhood brain tumors.
Authors: B A Mueller, K Newton, E A Holly, S Preston-Martin
Journal: Environmental Health Perspectives (2001)

Gestation may represent a window of susceptibility to transplacental effects of environmental exposures, including chemicals in water. The N-nitroso compounds (NNC), a class of chemicals with demonstrated neurocarcinogenic potential, include substances detected in drinking water. We used data from a study of possible risk factors for childhood brain tumors (CBT) to investigate the association of source of residential drinking water during pregnancy and CBT occurrence among offspring. In addition, dipstick measurements were made of nitrates and nitrites in tap water for the subset of women living in the same home they had lived in during their pregnancies. Population-based CBT cases (n = 540) and controls (n = 801) were identified in three regions including Los Angeles County, and the San Francisco Bay Area of California, and the Seattle-Puget Sound area of western Washington state. Overall, we observed no increased risk of CBT in offspring associated with wells as the source of residential water. However, an increased risk of CBT [odds ratio (OR) = 2.6; 95% confidence interval (CI), = 1.3-5.2] was observed in western Washington among offspring of women who relied exclusively on well water, and a decreased risk of CBT (OR = 0.2; 95% CI, 0.1-0.8) was observed in Los Angeles County. Among the small subset of subjects for whom dipstick measurements of tap water were available, the risk of CBT associated with the presence of either measurable nitrite and/or nitrate was 1.1 (95% CI, 0.7-2.0). Given the crude measurement method employed and because measurements often were obtained years after these pregnancies occurred, the relevance of the dipstick findings is unclear. The lack of consistency in our findings related to residential water source does not support the hypothesis of increased risk related to consumption of well water; however, regional differences in well water content may exist, and the increased risk observed in western Washington deserves further evaluation.
Survey on Acute and Chronic Complications in Children and Adolescents With Type 1 Diabetes at Muhimbili National Hospital in Dar es Salaam, Tanzania
Authors: Edna S. Majaliwa, Emanuel Munubhi, Kaushik Ramaiya, Rose Mpembeni, Anna Sanyiwa, Angelika Mohn, Francesco Chiarelli
Journal: Diabetes Care (2007)

OBJECTIVE—The purpose of this study was to assess glycemic control and complications of type 1 diabetes in children and adolescents in Tanzania. RESEARCH DESIGN AND METHODS—This demographic and clinical survey included 99 children aged between 5 and 18 years attending Muhimbili National Hospital Clinic for Diabetes. A structured questionnaire was used for evaluating socioeconomic data and for estimation of the prevalence of acute complications occurring over the last 6 months. The prevalences of retinopathy and diabetic nephropathy were determined by fundus ophthalmoscopy and by microalbuminuria, respectively. RESULTS—All of these children were treated with a conventional insulin regimen. The mean ± SD duration of diabetes was 4.76 ± 3.58 years. Only 1 child (1%) had good glycemic control (A1C &amp;lt;7.5%), 60 children (60.6%) had moderate glycemic control (A1C 7.5–10%), 14 children (14.1%) had poor glycemic control (A1C &amp;gt;10–12.5%), and 24 children (24.2%) had very poor glycemic control (A1C &amp;gt;12.5%). At onset of diabetes, 75% of children presented with diabetic ketoacidosis (DKA); 89 children (89.80%) had at least one episode of DKA, and 55 children (55.67%) had symptomatic hypoglycemic episodes. Microalbuminuria was present in 29 (29.3%) and retinopathy in 22 (22.68%) children. CONCLUSIONS—Although there are some methodological limitations, this survey highlights the difficulties of achieving good metabolic control and the high prevalence of acute and chronic complications in Tanzanian children with type 1 diabetes. These results clearly show that major efforts are needed to improve quality of care in children with type 1 diabetes in Tanzania.
Efficacy and toxicity of the antisense oligonucleotide aprinocarsen directed against protein kinase C-α delivered as a 21-day continuous intravenous infusion in patients with recurrent high-grade astrocytomas
Authors: Stuart A. Grossman, Jane B. Alavi, Jeffrey G. Supko, Kathryn A. Carson, Regina Priet, F. Andrew Dorr, John S. Grundy, Jon T. Holmlund
Journal: Neuro-Oncology (2005)

Protein kinase C alpha (PKC-α) is a cytoplasmic serine threonine kinase involved in regulating cell differentiation and proliferation. Aprinocarsen is an antisense oligonucleotide against PKC-α that reduces PKC-α in human cell lines and inhibits a human glioblastoma tumor cell line in athymic mice. In this phase 2 study, aprinocarsen was administered to patients with recurrent high-grade gliomas by continuous intravenous infusion (2.0 mg/kg/day for 21 days per month). Twenty-one patients entered this trial. Their median age was 46 years (range, 28-68 years), median Karnofsky performance status was 80 (range, 60-100), median tumor volume was 58 cm3 (range, 16-254 cm3), and histology included glioblastoma multiforme (n = 16), anaplastic oligodendroglioma (n = 4), and anaplastic astrocytoma (n = 1). The number of prior chemotherapy regimens included none (n = 3), one (n = 10), and two (n = 8). No tumor responses were observed. Patients on this therapy rapidly developed symptoms of increased intracranial pressure with increased edema, enhancement, and mass effect on neuroimaging. The median time to progression was 36 days, and median survival was 3.4 months. The observed toxicities were mild, reversible, and uncommon (grade 3 thrombocytopenia [n = 3] and grade 4 AST [n = 1]), and no coagulopathy or CNS bleed-ing resulted from this therapy. Plasma concentrations of aprinocarsen during the infusion exhibited significant interpatient variability (mean = 1.06 μg/ml; range, 0.34-6.08 μg/ml). This is the first study to use an antisense oligonucleotide or a specific PKC-α inhibitor in patients with high-grade gliomas. No clinical benefit was seen. The rapid deterioration seen in these patients could result from tumor growth or an effect of aprinocarsen on blood-brain barrier integrity.
n-3 Fatty Acids, Ventricular Arrhythmia–Related Events, and Fatal Myocardial Infarction in Postmyocardial Infarction Patients With Diabetes
Authors: Daan Kromhout, Johanna M. Geleijnse, Janette de Goede, Linda M. Oude Griep, Barbara J.M. Mulder, Menko-Jan de Boer, Jaap W. Deckers, Eric Boersma, Peter L. Zock, Erik J. Giltay
Journal: Diabetes Care (2011)

OBJECTIVE We carried out a secondary analysis in high-risk patients with a previous myocardial infarction (MI) and diabetes in the Alpha Omega Trial. We tested the hypothesis that in these patients an increased intake of the n-3 fatty acids eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and α-linolenic acid (ALA) will reduce the incidence of ventricular arrhythmias and fatal MI. RESEARCH DESIGN AND METHODS A subgroup of 1,014 post-MI patients with diabetes aged 60–80 years was randomly allocated to receive one of four trial margarines, three with an additional amount of n-3 fatty acids and one placebo for 40 months. The end points were ventricular arrhythmia–related events and fatal MI. The data were analyzed according to the intention-to-treat principle, using multivariable Cox proportional hazards models. RESULTS The patients consumed on average 18.6 g of margarine per day, which resulted in an additional intake of 223 mg EPA plus 149 mg DHA and/or 1.9 g ALA in the active treatment groups. During follow-up, 29 patients developed a ventricular arrhythmia–related events and 27 had a fatal MI. Compared with placebo patients, the EPA-DHA plus ALA group experienced less ventricular arrhythmia–related events (hazard ratio 0.16; 95% CI 0.04–0.69). These n-3 fatty acids also reduced the combined end-point ventricular arrhythmia–related events and fatal MI (0.28; 0.11–0.71). CONCLUSIONS Our results suggest that low-dose supplementation of n-3 fatty acids exerts a protective effect against ventricular arrhythmia–related events in post-MI patients with diabetes.
Nature, Classification, and Nomenclature of Kidney Tumors Induced in the Rat by Dimethylnitrosamine&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J. L. Riopelle, G. Jasmin
Journal: JNCI Journal of the National Cancer Institute (1969)

Dimethylnitrosamine-induced kidney tumors of the rat occur as simple epithelial growths, sarcoma-like productions, or complexes of epithelial and sarcomatoid tissues. It is still undecided in the literature if they belong to a single histogenetic group, or if they originate from two or several cell lines. In our opinion, there are, on one hand, purely epithelial tumors seemingly derived from hyperplastic nephrons and, on the other hand, sarcomatoid tumors, which can be separated into three subgroups. Neoplasms of the first subgroup grow rapidly, occasionally invading neighboring perirenal structures. Their basic tissue is composed of large cells, resembles early renal blastema, and can differentiate into immature smooth or striated muscle or mesenchyme. It mimics early kidney organogenesis by clumping around tubules resembling collecting ducts, but fails to differentiate into primitive nephric tubules. Adult nephric components often present in it give no evidence of in situ genesis. Tumors of the second subgroup reach only moderate size and are chiefly characterized by centrally located, maturing periductal cell clumps that eventually transform into smooth muscle or undergo fibrosis. Dysplastic epithelial islands occasionally found in them seem to originate from preexisting tubules. Tumors of the third subgroup attain only minor size and are essentially composed of an outer zone of small spindle cells and a fibrosing center. All subgroups seem to proceed from the same line of interstitial cells. The generic name “stromal nephroma” is proposed for the whole group, with appropriate labeling of the subgroups.
Genome Alteration Print (GAP): a tool to visualize and mine complex cancer genomic profiles obtained by SNP arrays
Authors: Tatiana Popova, Elodie Manié, Dominique Stoppa-Lyonnet, Guillem Rigaill, Emmanuel Barillot, Marc Henri Stern
Journal: Genome biology (2009)

Abstract We describe a method for automatic detection of absolute segmental copy numbers and genotype status in complex cancer genome profiles measured with single-nucleotide polymorphism (SNP) arrays. The method is based on pattern recognition of segmented and smoothed copy number and allelic imbalance profiles. Assignments were verified by DNA indexes of primary tumors and karyotypes of cell lines. The method performs well even for poor-quality data, low tumor content, and highly rearranged tumor genomes.
Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study
Authors: Maarten J Titulaer, Lindsey McCracken, Iñigo Gabilondo, Thaís Armangué, Carol Glaser, Takahiro Iizuka, Lawrence S Honig, Susanne M Benseler, Izumi Kawachi, Eugenia Martinez-Hernandez, Esther Aguilar, Núria Gresa-Arribas, Nicole Ryan-Florance, Abiguei Torrents, Albert Saiz, Myrna R Rosenfeld, Rita Balice-Gordon, Francesc Graus, Josep Dalmau
Journal: The Lancet Neurology (2013)
Phenolic glycolipid-1 of Mycobacterium leprae binds complement component C3 in serum and mediates phagocytosis by human monocytes.
Authors: L S Schlesinger, M A Horwitz
Journal: The Journal of Experimental Medicine (1991)

Previous studies from this laboratory have demonstrated that Mycobacterium leprae, an obligate intracellular bacterial parasite, enters human mononuclear phagocytes via complement receptors on these host cells and bacterium-bound C3. The present study investigates the role of M. leprae surface molecules in C3 fixation and phagocytosis. By enzyme-linked immunosorbent assay, C3 binds selectively to phenolic glycolipid-1 (PGL-1), a major surface molecule of the leprosy bacillus. C3 fixation to PGL-1 is serum concentration dependent and is abolished in heat-inactivated serum or serum containing ethylenediaminetetraacetic acid. C3 fixation is also abolished in serum containing ethyleneglycol-bis (beta-aminoethyl ether)N,N,N'-tetraacetic acid and MgCl2 indicating that isolated PGL-1 fixes C3 via the classical complement pathway. The capacity of PGL-1 to fix C3 is dependent upon its terminal trisaccharide since sequential removal of monosaccharide units of the trisaccharide results in a stepwise reduction in C3 fixation. Deacylation of PGL-1 also abolishes C3 fixation. C3 fixes to the trisaccharide of PGL-1 that is chemically linked to bovine serum albumin via the chemical carrier, 8-methoxycarbonyloctanol. PGL-1 mediates C3 fixation to polystyrene microspheres, and PGL-1 and C3 together mediate ingestion of polystyrene microspheres by human monocytes, wherein these inert test particles reside in membrane-bound phagosomes. Thus, complement receptors on mononuclear phagocytes, complement component C3, and PGL-1 comprise a three-component receptor-ligand-acceptor molecule system for mediating phagocytosis of M. leprae.
Pulmonary infiltrates in non-HIV immunocompromised patients: a diagnostic approach using non-invasive and bronchoscopic procedures
Authors: A Rano
Journal: Thorax (2001)

<h3>BACKGROUND</h3> The development of pulmonary infiltrates is a frequent life threatening complication in immunocompromised patients, requiring early diagnosis and specific treatment. In the present study non-invasive and bronchoscopic diagnostic techniques were applied in patients with different non-HIV immunocompromised conditions to determine the aetiology of the pulmonary infiltrates and to evaluate the impact of these methods on therapeutic decisions and outcome in this population. <h3>METHODS</h3> The non-invasive diagnostic methods included serological tests, blood antigen detection, and blood, nasopharyngeal wash (NPW), sputum and tracheobronchial aspirate (TBAS) cultures. Bronchoscopic techniques included fibrobronchial aspirate (FBAS), protected specimen brush (PSB), and bronchoalveolar lavage (BAL). Two hundred consecutive episodes of pulmonary infiltrates were prospectively evaluated during a 30 month period in 52 solid organ transplant recipients, 53 haematopoietic stem cell transplant (HSCT) recipients, 68 patients with haematological malignancies, and 27 patients requiring chronic treatment with corticosteroids and/or immunosuppressive drugs. <h3>RESULTS</h3> An aetiological diagnosis was obtained in 162 (81%) of the 200 patients. The aetiology of the pulmonary infiltrates was infectious in 125 (77%) and non-infectious in 37 (23%); 38 (19%) remained undiagnosed. The main infectious aetiologies were bacterial (48/125, 24%), fungal (33/125, 17%), and viral (20/125, 10%), and the most frequent pathogens were <i>Aspergillus fumigatus</i> (n=29),<i>Staphylococcus aureus</i> (n=17), and<i>Pseudomonas aeruginosa</i> (n=12). Among the non-infectious aetiologies, pulmonary oedema (16/37, 43%) and diffuse alveolar haemorrhage (10/37, 27%) were the most common causes. Non-invasive techniques led to the diagnosis of pulmonary infiltrates in 41% of the cases in which they were used; specifically, the diagnostic yield of blood cultures was 30/191 (16%); sputum cultures 27/88 (31%); NPW 9/50 (18%); and TBAS 35/55 (65%). Bronchoscopic techniques led to the diagnosis of pulmonary infiltrates in 59% of the cases in which they were used: FBAS 16/28 (57%), BAL 68/135 (51%), and PSB 30/125 (24%). The results obtained with the different techniques led to a change in antibiotic treatment in 93 cases (46%). Although changes in treatment did not have an impact on the overall mortality, patients with pulmonary infiltrates of an infectious aetiology in whom the change was made during the first 7 days had a better outcome (29% mortality) than those in whom treatment was changed later (71% mortality; p=0.001). <h3>CONCLUSIONS</h3> Non-invasive and bronchoscopic procedures are useful techniques for the diagnosis of pulmonary infiltrates in immunocompromised patients. Bronchial aspirates (FBAS and TBAS) and BAL have the highest diagnostic yield and impact on therapeutic decisions.
Role of Type 1 IFNs in Antiglioma Immunosurveillance—Using Mouse Studies to Guide Examination of Novel Prognostic Markers in Humans
Authors: Mitsugu Fujita, Michael E. Scheurer, Stacy A. Decker, Heather A. McDonald, Gary Kohanbash, Edward R. Kastenhuber, Hisashi Kato, Melissa L. Bondy, John R. Ohlfest, Hideho Okada
Journal: Clinical Cancer Research (2010)

We hypothesized that the type 1 IFNs would play a pivotal role in antiglioma immunosurveillance through promotion of type 1 adaptive immunity and suppression of immunoregulatory cells.
Continuous positive airway pressure delivered by oronasal mask may not be effective for obstructive sleep apnoea: Figure 1–
Authors: Fabíola Schorr, Pedro R. Genta, Marcelo G. Gregório, Naury J. Danzi-Soares, Geraldo Lorenzi-Filho
Journal: European Respiratory Journal (2012)

To the Editors:

Continuous positive airway pressure (CPAP) is considered the gold standard treatment for patients with moderate to severe obstructive sleep apnoea (OSA). The treatment of OSA with CPAP was first conceptualised using a nasal-only interface because the pressure delivered through the nose would be transmitted to the back of the upper airway and would push the palate anteriorly [1]. Since the first description, the CPAP industry has developed a large number of different interfaces in order to improve patient comfort and adherence to treatment. Patients with OSA frequently present nasal obstruction and oronasal interfaces may be used to deliver CPAP. Nasal and oronasal masks are often used interchangeably and the choice of CPAP delivery interface for OSA therapy remains largely based on clinical experience. However, patients with OSA on oronasal mask are less adherent to CPAP for reasons that are not completely understood [2]. One recent randomised trial [3] and a preliminary report [4] suggest that the effectiveness of CPAP for treating OSA is variable when delivered by an oronasal interface. We describe a well-documented patient in whom CPAP was not effective when an oronasal mask was used due to the posterior displacement of the tongue.

A 69-yr-old Japanese–Brazilian, body mass index 26.1 kg·m−2, presented to the outpatient sleep clinic complaining of typical symptoms suggestive of OSA, including loud snoring, witnessed apnoeas and excessive daytime sleepiness. The patient had a positive medical history of systemic hypertension and diabetes mellitus. A standard overnight polysomnography (Alice 5; Philips Respironics, Murrysville, PA, USA) confirmed severe OSA, with apnoea-hypopnoea index (AHI) 76 events per h and lowest oxygen saturation 58%. An in-laboratory manual CPAP titration study was performed with an oronasal mask because of reported oral breathing during sleep. CPAP was …
Therapeutic potential of ketotifen in irritable bowel syndrome (IBS) may involve changes in mast cells at sites beyond the rectum
Authors: M. O'Sullivan
Journal: Gut (2010)

The recent study published in Gut by Klooker and coworkers1 reported very interesting and important findings, but with some contradictions. The authors investigated the effects of treatment with the mast cell stabiliser ketotifen in irritable bowel syndrome (IBS) with three key findings. First, treatment (but not placebo) increased the threshold for discomfort in patients with IBS with documented visceral hypersensitivity. Second, and importantly, ketotifen therapy significantly decreased abdominal pain and other IBS symptoms—an effect that appeared to be reversible on withdrawal of the drug. Third, the mast cell stabiliser did not alter mast cell numbers or mediator release in the rectal biopsy tissue investigated …
Accident Flying Squad
Authors: R. Snook
Journal: BMJ (1972)

This paper describes the organization, evaluation, and costing of an independently financed and operated accident flying squad. 132 accidents involving 302 casualties were attended, six deaths were prevented, medical treatment contributed to the survival of a further four, and the condition or comfort of many other casualties was improved. The calls in which survival was influenced were evenly distributed throughout the three-and-a-half-year survey and seven of the 10 so aided were over 16 and under 30 years of age, all 10 being in the working age group. The time taken to provide the service was not excessive and the expense when compared with the overall saving was very small. The scheme was seen to be equally suitable for basing on hospital or general practice or both, and working as an integrated team with the ambulance service. The use of specialized transport was found to be unnecessary. Other benefits of the scheme included use of the experience of attending accidents to ensure relevant and realistic training for emergency service personnel, and an appreciation of the effect of ambulance design on the patient.