tbuckley/cabot-search huggingface dataset:
Sleep Disturbance in Acute Schizophrenic Patients
Authors: DAVID J. KUPFER, RICHARD J. WYATT, JIMMY SCOTT, FREDERICK SNYDER
Journal: American Journal of Psychiatry (1970)

Sleep patterns were studied longitudinally in six acute schizophrenic patients throughout most of their hospital stays, ranging from 25 to 224 consecutive nights, and the data were compared with those from 15 normal control subjects. The sleep patterns of these six patients showed unique differences from those of the control subjects as well as from sleep patterns of severely depressed patients and normal subjects under experimental conditions. However, no definitive interpretation of these findings can yet be made; further extensive and systematic case studies are needed to determine whether the sleep disturbances reported here are an inherent aspect of all acute schizophrenic exacerbations.
Controlled trial of intravenous metronidazole as an adjunct to corticosteroids in severe ulcerative colitis.
Authors: R W Chapman, W S Selby, D P Jewell
Journal: Gut (1986)

A prospective double blind controlled trial was undertaken to examine the role of metronidazole as an adjunct to corticosteroids in the management of severe ulcerative colitis. Thirty nine patients with severe ulcerative colitis were randomised on admission to hospital to receive either intravenous metronidazole 500 mg eight hourly (19 patients) or an identical intravenous placebo (20 patients). The two groups were similar with respect to age, sex, and the extent of colitis. In addition all patients received a standard intravenous regimen consisting of methyl prednisolone 16 mg six hourly and parenteral nutrition together with a twice daily hydrocortisone 100 mg enema. Treatment was continued for five days when the patients were formally assessed. Fourteen of 19 patients (74%) receiving metronidazole and 14/20 (70%) receiving placebo were substantially improved, or in remission at the end of five days. Five patients treated with metronidazole and six with placebo had no improvement and all proceeded to urgent colectomy with no operative mortality. There were three late deaths, one in the metronidazole and two in the placebo group. These results do not support the routine use of intravenous metronidazole in the treatment of severe ulcerative colitis.
Chronic effects of omega-3 fatty acids (fish oil) in a rat 5/6 renal ablation model.
Authors: W F Clark, A Parbtani, D J Philbrick, B J Holub, M W Huff
Journal: Journal of the American Society of Nephrology (1991)

It has been proposed that fish oil dietary supplementation in the chronic rat 5/6 renal ablation model may be either protective or toxic. These conflicting hypotheses were tested in rats who underwent renal ablation or sham surgery. Twenty rats received sham surgery, and 40 received 5/6 renal ablation. All rats were fed a regular laboratory diet up to 1 week postsurgery. At that time, one half of the renal ablation group was provided with an isocaloric diet supplemented with 24% MaxEPA (fish oil), 1% safflower oil, and antioxidants. The renal ablation rats developed hypertension, albuminuria, gammaglobulinuria, and a decline in glomerular filtration rate, which was less in the fish oil group compared with that in the regular laboratory diet group at 10 and 20 wk postsurgery. The fish oil renal ablation rats had significantly less glomerulosclerosis than did the regular laboratory diet renal ablation animals, and no more glomerular fibrin deposition than did the sham controls. The renal ablation regular laboratory diet rats had a significant dyslipidemia at 20 wk which was prevented in the fish oil renal ablation cohort. The fish oil renal ablation rats also demonstrated a significant decline in renal tissue arachidonic acid incorporation and a concomitant increase in eicosapentaenoic acid and docosahexaenoic acid incorporation. The mortality of the renal ablation group was greater than that of the sham controls but not significantly different for the fish oil or the regular laboratory diet groups. These results support the hypothesis that the fish oil diet containing specific antioxidant, vitamin E, and essential fatty acid supplementation is protective in the rat remnant nephron model and prevents the evolution of glomerulosclerosis with associated renal functional impairment, while preserving glomerular filtration.
Non-CPAP therapies in obstructive sleep apnoea
Authors: W.J. Randerath, J. Verbraecken, S. Andreas, G. Bettega, A. Boudewyns, E. Hamans, F. Jalbert, J.R. Paoli, B. Sanner, I. Smith, B.A. Stuck, L. Lacassagne, M. Marklund, J.T. Maurer, J.L. Pepin, A. Valipour, T. Verse, I. Fietze
Journal: European Respiratory Journal (2011)

In view of the high prevalence and the relevant impairment of patients with obstructive sleep apnoea syndrome (OSAS) lots of methods are offered which promise definitive cures for or relevant improvement of OSAS. This report summarises the efficacy of alternative treatment options in OSAS. An interdisciplinary European Respiratory Society task force evaluated the scientific literature according to the standards of evidence-based medicine. Evidence supports the use of mandibular advancement devices in mild to moderate OSAS. Maxillomandibular osteotomy seems to be as efficient as continuous positive airway pressure (CPAP) in patients who refuse conservative treatment. Distraction osteogenesis is usefully applied in congenital micrognathia or midface hypoplasia. There is a trend towards improvment after weight reduction. Positional therapy is clearly inferior to CPAP and long-term compliance is poor. Drugs, nasal dilators and apnoea triggered muscle stimulation cannot be recommended as effective treatments of OSAS at the moment. Nasal surgery, radiofrequency tonsil reduction, tongue base surgery, uvulopalatal flap, laser midline glossectomy, tongue suspension and genioglossus advancement cannot be recommended as single interventions. Uvulopalatopharyngoplasty, pillar implants and hyoid suspension should only be considered in selected patients and potential benefits should be weighed against the risk of long-term side-effects. Multilevel surgery is only a salvage procedure for OSA patients.
Microcirculatory blood flow as a tool to select ICU patients eligible for fluid therapy
Authors: Andrius Pranskunas, Matty Koopmans, Peter M. Koetsier, Vidas Pilvinis, E. Christiaan Boerma
Journal: Intensive Care Medicine (2012)

The aim of this study is to assess the incidence of sublingual microcirculatory flow alterations, according to a predefined arbitrary cutoff value, in patients with "clinical signs of impaired organ perfusion". Secondary endpoints were the changes in microvascular flow index (MFI), "clinical signs of impaired organ perfusion", and stroke volume (SV) after fluid administration, and the differences between groups.Prospective, single-center, observational study in a 22-bed mixed intensive care unit (ICU). Patients ≥18 years with invasive hemodynamic monitoring and "clinical signs of impaired organ perfusion" as the principal reason for fluid administration were included. Before and after fluid challenge, systemic hemodynamics and direct in vivo observation of the sublingual microcirculation with sidestream dark-field imaging were obtained. Microvascular flow index (MFI) <2.6 was predefined as abnormal.N = 50. At baseline, MFI <2.6 was present in 66 % of the patients. In these patients, MFI increased from 2.3 (2-2.5) at baseline to 2.5 (2.1-2.8) after fluid challenge (p = 0.003). This was accompanied by a reduction in the number of "clinical signs of impaired organ perfusion" from 2 (1-2) to 1 (0-2) (p < 0.001). However, in patients with MFI >2.6 at baseline, MFI and clinical signs changed insignificantly [2.8 (2.8-2.9) versus 2.8 (2.7-3), p = 0.45, respectively, 1 (1-2) versus 1 (1-2), p < 0.32]. These changes were not restricted to patients with a rise in SV ≥10 %.These data add to the understanding that noninvasive assessment of microvascular blood flow may help to identify patients eligible for fluid therapy, and to evaluate its effect.
Synergistic influence of phosphorylation and metal ions on tau oligomer formation and coaggregation with α-synuclein at the single molecule level
Authors: Georg Nübling, Benedikt Bader, Johannes Levin, Jenna Hildebrandt, Hans Kretzschmar, Armin Giese
Journal: Molecular Neurodegeneration (2012)

Fibrillar amyloid-like deposits and co-deposits of tau and α-synuclein are found in several common neurodegenerative diseases. Recent evidence indicates that small oligomers are the most relevant toxic aggregate species. While tau fibril formation is well-characterized, factors influencing tau oligomerization and molecular interactions of tau and α-synuclein are not well understood.We used a novel approach applying confocal single-particle fluorescence to investigate the influence of tau phosphorylation and metal ions on tau oligomer formation and its coaggregation with α-synuclein at the level of individual oligomers. We show that Al3+ at physiologically relevant concentrations and tau phosphorylation by GSK-3β exert synergistic effects on the formation of a distinct SDS-resistant tau oligomer species even at nanomolar protein concentration. Moreover, tau phosphorylation and Al3+ as well as Fe3+ enhanced both formation of mixed oligomers and recruitment of α-synuclein in pre-formed tau oligomers.Our findings provide a new perspective on interactions of tau phosphorylation, metal ions, and the formation of potentially toxic oligomer species, and elucidate molecular crosstalks between different aggregation pathways involved in neurodegeneration.
Molecular Basis of Ethnic Differences in Drug Disposition and Response
Authors: Hong-Guang Xie, Richard B Kim, Alastair JJ Wood, C Michael Stein
Journal: The Annual Review of Pharmacology and Toxicology (2001)

Ethnicity is an important demographic variable contributing to interindividual variability in drug metabolism and response. In this rapidly expanding research area many genetic factors that account for the effects of ethnicity on pharmacokinetics, pharmacodynamics, and drug safety have been identified. This review focuses on recent developments that have improved understanding of the molecular mechanisms responsible for such interethnic differences. Genetic variations that may provide a molecular basis for ethnic differences in drug metabolizing enzymes (CYP 2C9, 2C19, 2D6, and 3A4), drug transporter (P-glycoprotein), drug receptors (adrenoceptors), and other functionally important proteins (eNOS and G proteins) are discussed. A better understanding of the molecular basis underlying ethnic differences in drug metabolism, transport, and response will contribute to improved individualization of drug therapy.
Membrane sorting during phagocytosis: selective exclusion of major histocompatibility complex molecules but not complement receptor CR3 during conventional and coiling phagocytosis.
Authors: D L Clemens, M A Horwitz
Journal: The Journal of Experimental Medicine (1992)

We have used immunocytochemical techniques and enzyme cytochemistry to examine the distribution of plasma membrane proteins during coiling phagocytosis of Legionella pneumophila and conventional phagocytosis of Escherichia coli. Whereas class I and class II major histocompatibility complex (MHC) molecules are relatively excluded from nascent phagosomes during conventional and coiling phagocytosis, the CR3 complement receptor persists in nascent phagosomes. The staining pattern for alkaline phosphatase activity resembles that of MHC molecules, with a marked exclusion of phosphatase activity from L. pneumophila coils and nascent phagosomes. The staining pattern for 5'-nucleotidase activity, on the other hand, resembles that of CR3 with intense staining in the inner layers of L. pneumophila coils. These results demonstrate that the cell has the ability to exclude selectively certain membrane proteins from the nascent phagosome during phagocytosis, thereby producing a phagosomal membrane markedly different from the plasma membrane from which it is derived.
Expression of interleukin 1-like cytokine interleukin 33 and its receptor complex (ST2L and IL1RAcP) in human pancreatic myofibroblasts
Authors: A. Nishida, A. Andoh, H. Imaeda, O. Inatomi, H. Shiomi, Y. Fujiyama
Journal: Gut (2009)

Interleukin 33 (IL33) is a cytokine belonging to the IL1 family and it binds to a complex of the ST2L/IL1 receptor accessory protein (IL1RAcP). To define the role of IL33 in fibrogenesis of the pancreas, the expression of IL33, ST2L and IL1RAcP was examined in chronic pancreatitis tissues. The effects of IL33 on the functions of human pancreatic myofibroblasts were also investigated.Tissue samples were obtained surgically. The expression of IL33, ST2L and IL1RAcP was evaluated by standard immunohistochemical procedures. Messenger RNA expression for IL33, ST2L and IL1RAcP was analysed by northern blotting and real-time PCR analyses, and protein expression was assessed by western blotting and ELISA. Cell proliferation and migration were assessed by a (3)H-thymidine incorporation assay and the modified Boyden chamber assay, respectively.IL33, ST2L and IL1RAcP were expressed by alpha-SMA-positive myofibroblasts in the fibrosis of chronic pancreatitis. In human pancreatic myofibroblasts, IL33 was weakly immunoexpressed without any stimuli, and this was markedly enhanced by IL1beta, tumour necrosis factor alpha (TNFalpha) and lipopolysaccharide (LPS) via the mitogen-activated protein kinase (MAPK)-dependent AP-1 activation pathway. ST2L mRNA was weakly detected in unstimulated cells, and IL4 and interferon gamma (IFNgamma) strongly enhanced ST2L expression via STAT6 and STAT1 signalling, respectively. IL33 rapidly induced the phosphorylation of MAPKs and IkappaBalpha, and enhanced the expression of inflammatory mediators (IL6, IL8, IP-10, Gro-alpha, Gro-beta and MCP-1) in IL4- or IFNgamma-pretreated cells. IL33 stimulated the proliferation and migration of pancreatic myofibroblasts.IL33 and its receptor complex (ST2L and IL1RAcP) constitute a novel signalling system which may play an important role in the pathogenesis of chronic pancreatitis.
Non HFE-related haemochromatosis: exclusion of the 1q21 zinc-iron regulated transporter-like (ZIRTL) gene in juvenile haemochromatosis
Authors: Giada Sebastiani, Daniel F. Wallace, Maria Lioumi, Ioannis Goutos, Wayne A. Mitchell, Adrian B. Bomford, A.Paul Dhillon, James S. Dooley, Jiannis Ragoussis, Ann P. Walker
Journal: Journal of Hepatology (2003)
Accuracy of screening for gastric cancer using serum pepsinogen concentrations
Authors: F Kitahara, K Kobayashi, T Sato, Y Kojima, T Araki, M A Fujino
Journal: Gut (1999)

The characteristics of pepsinogen screening for gastric cancer were investigated to establish a suitable cut off point for identifying gastric cancer, using endoscopic diagnosis as the yardstick.Serum pepsinogen concentrations were measured in 5113 subjects who were also screened for gastric cancer by endoscopy. The cut off point for pepsinogen was determined using receiver operator characteristics curves.The most suitable cut off point was a pepsinogen I concentration of less than 70 ng/ml and a ratio of pepsinogen I to pepsinogen II of less than 3. 0. Using this cut off point, the sensitivity and specificity of pepsinogen screening for gastric cancer were 84.6% and 73.5% respectively. All cases of gastric cancer in patients with severe atrophic gastritis were detected. However, two of four cases of gastric cancer in patients with mild atrophic gastritis were overlooked. In subjects with mild atrophic gastritis, when gastric cancer arises within the fundic gland region, the size of the lesion determines whether it is possible to detect cancer by serum pepsinogen screening.Pepsinogen screening has many advantages, including its suitability for combination with other screening methods because it is simple and inexpensive.
Endothelin activation of an inwardly rectifying K+ current in atrial cells.
Authors: D Kim
Journal: Circulation Research (1991)

Various tissues including heart express specific binding sites for endothelin. Endothelins have been reported to increase the force of contraction of cardiac muscle, presumably via specific receptors. Specific binding of endothelin to atrial tissue is particularly high. In spontaneously contracting rat atrial cells used in this study, all three isoforms of endothelin (endothelin-1, endothelin-2, and endothelin-3) decreased the rate of beating and caused an increase in inwardly rectifying K+ current in voltage-clamped whole cells. Endothelin-3 was the most potent isoform, and its effects on beating rate and K+ current were present at a concentration as low as 100 pM (Kd, approximately 1 nM). the atrial cells did not have the hyperpolarization-activated current (the pacemaker current), If. In excised inside-out patches, all three isoforms of endothelin activated a population of K+ channels with kinetic properties identical to those of acetylcholine (muscarinic)-activated K+ channels, and this was GTP dependent. Endothelin failed to decrease the beating rate or to elicit the K+ current in pertussis toxin-treated cells. These results indicate that endothelin has a potent negatively chronotropic effect by activation of the inwardly rectifying, muscarinic K+ channel and therefore could be an important regulator of heart function.
Radiation Field Design in the ACOSOG Z0011 (Alliance) Trial
Authors: Reshma Jagsi, Manjeet Chadha, Janaki Moni, Karla Ballman, Fran Laurie, Thomas A. Buchholz, Armando Giuliano, Bruce G. Haffty
Journal: Journal of Clinical Oncology (2014)

ACOSOG Z0011 established that axillary lymph node dissection (ALND) is unnecessary in patients with breast cancer with one to two positive sentinel lymph nodes (SLNs) who undergo lumpectomy, radiotherapy (RT), and systemic therapy. We sought to ascertain RT coverage of the regional nodes in that trial.We evaluated case report forms completed 18 months after enrollment. From 2012 to 2013, we collected all available detailed RT records for central review.Among 605 patients with completed case report forms, 89% received whole-breast RT. Of these, 89 (15%) were recorded as also receiving treatment to the supraclavicular region. Detailed RT records were obtained for 228 patients, of whom 185 (81.1%) received tangent-only treatment. Among 142 with sufficient records to evaluate tangent height, high tangents (cranial tangent border ≤ 2 cm from humeral head) were used in 50% of patients (33 of 66) randomly assigned to ALND and 52.6% (40 of 76) randomly assigned to SLND. Of the 228 patients with records reviewed, 43 (18.9%) received directed regional nodal RT using ≥ three fields: 22 in the ALND arm and 21 in the SLND arm. Those receiving directed nodal RT had greater nodal involvement (P < .001) than those who did not. Overall, there was no significant difference between treatment arms in the use of protocol-prohibited nodal fields.Most patients treated in Z0011 received tangential RT alone, and some received no RT at all. Some patients received directed nodal irradiation via a third field. Further research is necessary to determine the optimal RT approach in patients with low-volume axillary disease treated with SLND alone.
Hemoptysis in a teenager: A rare case of bronchiectasis in autoimmune polyendocrinopathy type I syndrome
Authors: Salvatore Talamo, Gianfranco Pancosta, Roberto Giaffreda, Stefania Maria Tozzoli, Mattia Toma
Journal: European Respiratory Journal (2014)

Data indicates a very low incidence of lung disease in patients with autoimmune polyendocrinopathytype I syndrome called Autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED). It is an autosomal recessive disease caused by mutations in the AIRE gene involved in the education process that involves thymic lymphocyte and causes a defect in the maturation of regulatory T cells to peripheral antigens. This causes high susceptibility to autoimmune manifestations in relation to various organs, endocrine or not. The sporadic but severe respiratory manifestations (9 cases out of 110 reported) seem related to the detection of autoantibodies against a potassium channel regulator expressed in the bronchial epithelium: in 7 out of the 9 cases with pulmonary manifestations these autoantibodies were detected, and in only 4 cases,bronchiectasis has been reported. The 16-year-old teenager under study, showed sequential analysis of the entire gene AIRE with 2 molecular defects: mutation W78R, peculiar of Apulian patients (southern Italy) with APECED and, in combination with this, the deletion of 2 codons (22 and 23) located in the first exon of the gene included in the HSR domain protein, not yet described in the literature. The patient9s parents, asymptomatical, were both carriers of the same mutation W78R; the father was also carrier of the deletion cod22 and 23. The occurrence of hemoptysis required the execution of a CT scan that showed the presence of cylindrical bronchiectasis and of a otolaryngology control which confirmed a sinusitis, undetected until that date. BAL allowed us to identify a bacterial colonization of bronchiectasis with Pseudomonas aeruginosa.
Inhibition of Vascular Smooth Muscle Cell Proliferation by Sodium Salicylate Mediated by Upregulation of p21 <sup>Waf1</sup> and p27 <sup>Kip1</sup>
Authors: Diego E. Marra, Tommaso Simoncini, James K. Liao
Journal: Circulation (2000)

Background —Salicylates may have direct vascular effects by mechanisms that are independent of platelet inhibition. Methods and Results —We investigated the effect of salicylates on vascular smooth muscle cell (SMC) proliferation in response to platelet-derived growth factor (PDGF) in vitro. Salicylate concentrations of 5 and 10 mmol/L inhibited serum- or PDGF-induced SMC cell count and [ 3 H]thymidine incorporation by 62% and 81%, respectively. There was no evidence of cellular toxicity or apoptosis as determined by trypan blue exclusion and FACS analyses. Because cell cycle progression is regulated by hyperphosphorylation of the retinoblastoma (Rb) protein, we examined the effects of salicylate on Rb hyperphosphorylation. Treatment with salicylate, but not indomethacin, inhibited nuclear factor-κB activation and completely abolished Rb hyperphosphorylation in PDGF-treated SMCs. This effect was associated with a decrease in cyclin-dependent kinase (Cdk)-2 and, to a lesser extent, Cdk-6, but not Cdk-4 activity, without changes in Cdk-2, -4, and -6 and cyclin D and E protein levels. Because Cdk-2 activity is regulated by the Cdk inhibitors p21 Waf1 and p27 Kip1 , we studied the effects of salicylate on p21 Waf1 and p27 Kip1 expression. Treatment with salicylate prevented PDGF-induced downregulation of p21 Waf1 and p27 Kip1 but not of the Cdk-4/-6 inhibitor p16 Ink4 . Conclusions —These findings indicate that high doses of salicylates inhibit SMC proliferation by cell cycle arrest at the G 1 -S phase and suggest a beneficial role for high-dose salicylates in the treatment of vascular proliferative disorders.
PRIOR CORONARY ARTERY BYPASS GRAFT PATIENTS TREATED WITH PRIMARY PERCUTANEOUS CORONARY INTERVENTION HAVE HIGHER LONG-TERM ADVERSE EVENT RATES
Authors: Vrijraj S. Rathod, Daniel A. Jones, Krishnaraj Rathod, Sean M. Gallagher, Saidi Mohiddin, Ajay Jain, Charles Knight, Anthony Mathur, Andrew Wragg
Journal: Journal of the American College of Cardiology (2012)