tbuckley/cabot-search huggingface dataset:
Cerebral hemodynamic and metabolic changes in fulminant hepatic failure: A retrospective study
Authors: Shushma Aggarwal, David Kramer, Howard Yonas, Walter Obrist, Yoogoo Kang, Maureen Martin, Raymond Policare
Journal: Hepatology (1994)

The purpose of this retrospective study was to determine cerebral hemodynamic and metabolic changes in comatose patients with fulminant hepatic failure. Computerized tomography of the brain and cerebral blood flow measurements by the xenon-computerized tomography scan or intravenous xenon-133 methods were obtained in 33 patients with fulminant hepatic failure. In a subgroup of 22 patients, arteriojugular venous oxygen content difference and cerebral metabolic rate for oxygen were determined. Carbon dioxide reactivity was tested in 17 patients, and intracranial pressure was recorded by an epidural monitor in 8 patients. Cerebral blood flow and arteriojugular venous oxygen content difference were adjusted to the average arterial carbon dioxide pressure of the sample (32 mm Hg). Adjusted cerebral blood flow varied from 16.5 to 94.7 ml/100 gm/min; 52% of the patients had reduced adjusted cerebral blood flows (less than 33 ml/100 gm/min), whereas 24% had hyperemic values (greater than 50 ml/100 gm/min). Patients with higher adjusted cerebral blood flows showed cerebral swelling on computerized tomography scan (p < 0.002), were in deeper coma (p < 0.05) and had greater mortality (p < 0.002). The adjusted arteriojugular venous oxygen content difference was negatively correlated with adjusted cerebral blood flow (r = -0.61, p < 0.002). The majority of patients with reduced adjusted cerebral blood flows had low adjusted arteriojugular venous oxygen content differences (less than 5 vol%), indicating hyperemia rather than ischemia. The average cerebral metabolic rate for oxygen was 50% of normal (1.6 +/- 0.4 ml/100 gm/min); even patients with low cerebral metabolic rates for oxygen recovered neurologically.(ABSTRACT TRUNCATED AT 250 WORDS)
High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response
Authors: Hui Gao, Joshua M Korn, Stéphane Ferretti, John E Monahan, Youzhen Wang, Mallika Singh, Chao Zhang, Christian Schnell, Guizhi Yang, Yun Zhang, O Alejandro Balbin, Stéphanie Barbe, Hongbo Cai, Fergal Casey, Susmita Chatterjee, Derek Y Chiang, Shannon Chuai, Shawn M Cogan, Scott D Collins, Ernesta Dammassa, Nicolas Ebel, Millicent Embry, John Green, Audrey Kauffmann, Colleen Kowal, Rebecca J Leary, Joseph Lehar, Ying Liang, Alice Loo, Edward Lorenzana, E Robert McDonald, Margaret E McLaughlin, Jason Merkin, Ronald Meyer, Tara L Naylor, Montesa Patawaran, Anupama Reddy, Claudia Röelli, David A Ruddy, Fernando Salangsang, Francesca Santacroce, Angad P Singh, Yan Tang, Walter Tinetto, Sonja Tobler, Roberto Velazquez, Kavitha Venkatesan, Fabian Von Arx, Hui Qin Wang, Zongyao Wang, Marion Wiesmann, Daniel Wyss, Fiona Xu, Hans Bitter, Peter Atadja, Emma Lees, Francesco Hofmann, En Li, Nicholas Keen, Robert Cozens, Michael Rugaard Jensen, Nancy K Pryer, Juliet A Williams, William R Sellers
Journal: Nature Medicine (2015)
On Impetigo Contagiosa, or Porrigo
Authors: W. T. Fox
Journal: BMJ (1864)

JournaLitors, and think only of the blight they are incident- ally permiiitted to fix on us.Bat further, according to miiodern view, these princip7es not only exist exter- na.lly (epidemic and endemic), but also are reproduced in, and emitted from, bodies undergoing disease (con- tagious.)In epidenmic sore-throat (and the same pro- Jbably holds good of several other diseases, for "' a more or less sore throat is a constant concomitant of all the acute specific diseases"), the pharyngeal region atppears to be the site of the local synmptoims; here it is that pathological changre is going on in contact with the air, and hence it is that we should expect con- tagia to be emitted.The samie reasoning applies to the laryngeal region in croupal cases.Now, where the carcase is, there will the vultures be gathered to- g-ether; and thus, not content with neutralising poi- sonous matters external to us, these organisms, in obedience to a splendidly designed schenie, seem, as it were, actually to descend upon the parts whence these poisons would be scattered broadcast, and kill them in the bud.Speculations such as these m-ay be idle a-nd need corroboration, still I hope they are not alto- rether irrelevant or useless; for, if we are enabled to look from these supplemental effects, these lesser evils, patent to the eye of sense, to the higher order of harmony to be seen only by the mental eye of thought, we are induced to teimiper our sorrow with gv,itude; and, while deploring and bearing as pa- tiently as possible the trials and afflictions permitted to vex us here below, our faith.is strengthened in, imay, we are even allowed to enjoy a foresaiadowing of, on 19 August
On the mode of cardioprotection produced by a new bradycardic agent, FR 76830, during ischaemia and after reperfusion in the isolated perfused rat heart: a 31P-NMR study
Authors: T. Ishibashi, T. Matsubara, M. Nakazawa, N. Katsumata, S. Imai
Journal: Cardiovascular Research (1990)

Study objective – The aim was to investigate the effects of a newly synthesised bradycardic agent, FR 76830, on cardiac mechanical function and metabolism during ischaemia and reperfusion. Design – FR 76830 and diltiazem were infused during 15 min before ischaemia. Hearts were then subjected to ischaemia (40 min) followed by reperfusion (40 min). High energy phosphate compounds and myocardial pH were assessed by 31P-NMR. The effects of bradycardia induced by FR 76830 before induction of ischaemia on the metabolic derangement resulting from ischaemia and on functional and metabolic recovery after reperfusion were examined in comparison with diltiazem . Experimental material – Male Wistar rats (about 250 g) were used. Measurements and main results – FR 76830 and diitiazem produced a dose dependent decrease in heart rate before ischaemia. However, the decrease in the double product (heart rate × left ventricular pressure) was observed only with diltiazem. Both FR 76830 and diltiazem attenuated the fall in myocardial pH during early ischaemia and improved the level of ATP during late ischaemia. Diltiazem also produced an improvement in myocardial acidosis during late ischaemia and in the level of ATP during early ischaemia. Conclusions – The importance of bradycardia in protection of the myocardial cells during early ischaemia and in preservation of ATP content during late ischaemia and after reperfusion was shown. However, to produce an improvement in myocardial pH during late ischaemia a decrease in the double product is needed.
Polymorphisms in the Muscarinic Receptor 1 Gene Confer Susceptibility to Asthma in Japanese Subjects
Authors: Yukiko Maeda, Nobuyuki Hizawa, Eisei Jinushi, Ayumi Honda, Daisuke Takahashi, Yoshinobu Fukui, Satoshi Konno, Tadamichi Shimizu, Hiroshi Shimizu, Etsuro Yamaguchi, Masaharu Nishimura
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

The human cholinergic receptor muscarinic-1 (CHRM1) is widely distributed in the lungs. In patients with asthma, CHRM1 may be involved in airway constriction, airway epithelial cell proliferation, and airway inflammation. The CHRM1 gene is located on chromosome 11q13, which is one of the candidate loci for asthma and atopy.To determine the role of the CHRM1 gene polymorphisms in asthma.We studied nine single-nucleotide polymorphisms (-18379G > A, -9697C > T, -6965T > C, -4953A > G, +267A > C, +1353C > T, +3970C > G, +5418C > G, and +5455G > T) in a case-control study using 326 patients with asthma and 333 healthy control subjects. We also examined functional consequences of the -9697C > T and -4953A > G polymorphisms at the regulatory region using an mRNA reporter assay.Two common single-nucleotide polymorphisms (-9697C > T and -4953A > G) were associated with asthma. The odds ratio for the TT homozygotes at the -9697C > T polymorphism was 0.29 compared with the CC homozygotes (95% confidence interval, 0.12-0.73; p = 0.008), and the odds ratio for the GG homozygotes at the -4953A > G polymorphism was 1.86 compared with the AA homozygotes (95% confidence interval, 1.04-3.34; p = 0.038). Haplotype analysis showed that the -9697T/-6965T/-4953A haplotype was associated with a lower risk of asthma (p = 0.00055) and the -9697C/-6965T/-4953G haplotype was associated with an increased risk of asthma (p = 0.020). The -9697T/-4953A haplotype was also associated with lower luciferase activity in vitro compared with the -9697C/-4953G haplotype.This study, together with an in vitro functional study, suggests that the CHRM1 gene is an important susceptibility locus for asthma on chromosome11q13.
Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study
Authors: JB Richards, F Rivadeneira, M Inouye, TM Pastinen, N Soranzo, SG Wilson, T Andrew, M Falchi, R Gwilliam, KR Ahmadi, AM Valdes, P Arp, P Whittaker, DJ Verlaan, M Jhamai, V Kumanduri, M Moorhouse, JB van Meurs, A Hofman, HAP Pols, D Hart, G Zhai, BS Kato, BH Mullin, F Zhang, P Deloukas, AG Uitterlinden, TD Spector
Journal: The Lancet (2008)
Ca <sup>2+</sup> Influx Through Ca <sup>2+</sup> Channels in Rabbit Ventricular Myocytes During Action Potential Clamp
Authors: José L. Puglisi, Weilong Yuan, José W. M. Bassani, Donald M. Bers
Journal: Circulation Research (1999)

Abstract —Ca 2+ influx via Ca 2+ current ( I Ca ) during the action potential (AP) was determined at 25°C and 35°C in isolated rabbit ventricular myocytes using AP clamp. Contaminating currents through Na + and K + channels were eliminated by using Na + - and K + -free solutions, respectively. DIDS (0.2 mmol/L) was used to block Ca 2+ -activated chloride current ( I Cl(Ca) ). When the sarcoplasmic reticulum (SR) was depleted of Ca 2+ by preexposure to 10 mmol/L caffeine, total Ca 2+ entry via I Ca during the AP was ≈12 μmol/L cytosol (at both 25°C and 35°C). Similar Ca 2+ influx at 35°C and 25°C resulted from a combination of higher and faster peak I Ca , offset by more rapid I Ca inactivation at 35°C. During repeated AP clamps, the SR gradually fills with Ca 2+ , and consequent SR Ca 2+ release accelerates I Ca inactivation during the AP. During APs and contractions in steady state, total Ca 2+ influx via I Ca was reduced by ≈50% but was again unaltered by temperature (5.6±0.2 μmol/L cytosol at 25°C, 6.0±0.2 μmol/L cytosol at 35°C). Thus, SR Ca 2+ release is responsible for sufficient I Ca inactivation to cut total Ca 2+ influx in half. However, because of the kinetic differences in I Ca , the amount of Ca 2+ influx during the first 10 ms, which presumably triggers SR Ca 2+ release, is much greater at 35°C. I Ca during a first pulse, given just after the SR was emptied with caffeine, was subtracted from I Ca during each of 9 subsequent pulses, which loaded the SR. These difference currents reflect I Ca inactivation due to SR Ca 2+ release and thus indicate the time course of local [Ca 2+ ] in the subsarcolemmal space near Ca 2+ channels produced by SR Ca 2+ release (eg, maximal at 20 ms after the AP activation at 35°C). Furthermore, the rate of change of this difference current may reflect the rate of SR Ca 2+ release as sensed by L-type Ca 2+ channels. These results suggest that peak SR Ca 2+ release occurs within 2.5 or 5 ms of AP upstroke at 35°C and 25°C, respectively. I Cl(Ca) might also indicate local [Ca 2+ ], and at 35°C in the absence of DIDS (when I Cl(Ca) is prominent), peak I Cl(Ca) also occurred at a time comparable to the peak I Ca difference current. We conclude that SR Ca 2+ release decreases the Ca 2+ influx during the AP by ≈50% (at both 25°C and 35°C) and that changes in I Ca (and I Cl(Ca) ), which depend on SR Ca 2+ release, provide information about local subsarcolemmal [Ca 2+ ]. The full text of this article is available at http://www.circresaha.org.
NICE issues new guidance on urinary incontinence in women
Authors: Adrian O'Dowd
Journal: BMJ (2006)

Doctors in England and Wales have been given new guidance to improve the care and treatment of millions of women who have urinary incontinence.

But surgeons should have specific competences before they perform surgery in cases of urinary incontinence, says the guidance, which was issued this week by the clinical standards body the National Institute for Health and Clinical Excellence (NICE).

The guidelines on how to manage urinary incontinence in women contain around 100 recommendations and advise on diagnosis, treatment, and training in this area, which NICE says …
Effect of hindlimb isolation procedure on isogravimetric capillary pressure and transcapillary fluid dynamics in dogs.
Authors: R A Brace, A C Guyton
Journal: Circulation Research (1976)

We measured isogravimetric capillary pressure (Pci) and plasma colloid osmotic pressure (pip) in isolated dog hindlimbs. A very rapid isolation technique and a perfusion technique involving no weight change were developed in order to compare the effects of different isolation procedures. Also, a "previous isolation procedure" (PIP) was used to approximate isolation procedures previously reported; this procedure included (A) anesthesia for 1 to 1 1/2 hours before limb isolation, (B) 1/2 hour of denervation before isolation, and (C) perfusion after isolation for 1/2 hour at an arterial pressure of 100 mm Hg and a venous pressure of 6 mm Hg. These different procedures altered average (+/- SE) capillary pressure and fluid dynamics in the hindlimb as shown in the foly pressure in the intact resting dog hindlimb may be 8 mm Hg below plasma colloid osmotic pressure, or about 9 mm Hg, and that many reported values have been heavily influenced by the isolation technique.
Bacterial arthritis in an English health district: a 10 year review.
Authors: C Cooper, M I Cawley
Journal: Annals of the Rheumatic Diseases (1986)

Bacterial arthritis continues to present a difficult clinical and therapeutic problem, necessitating prompt diagnosis and intensive therapy. This study comprises a 10 year review of the condition in an English health district, with particular reference to aetiology, presentation, treatment, and outcome. Although the causative organisms remain qualitatively unchanged, increasing numbers of patients are elderly, immunosuppressed, or have underlying arthropathy. Factors which influence outcome include age, causative organism, joint involved, and delay in diagnosis. Attention is drawn to the notably poor outcome of hip infections in the elderly.
Intravenous immunoglobulin in autoimmune chronic urticaria
Authors: None O'donnell, None Barr, None Kobza Black, None Francis, None Kermani, None Niimi, None Barlow, None Winkelmann, None Greaves
Journal: British Journal of Dermatology (1998)

Histamine releasing autoantibodies play a central role in the pathogenesis of chronic urticaria (CU) in approximately 30% of affected patients. We investigated the therapeutic effect of high‐dose intravenous immunoglobulin (IVIG) on disease activity in patients with severe CU of autoimmune aetiology. Autoimmune urticaria was diagnosed by the development of a weal‐and‐flare reaction to the intradermal injection of autologous serum and by serum‐induced histamine release from the basophil leucocytes of healthy donors in vitro. Ten patients with severe, autoimmune CU, poorly responsive to conventional treatment, were treated with IVIG 0.4 g/kg per day for 5 days. The outcome on cutaneous wealing and itch was monitored using urticaria activity scores, visual analogue scales and autologous intradermal serum tests. Clinical benefit was noted in nine of 10 patients; three patients continue in prolonged complete remissions (3 years follow‐up), two had temporary complete remissions, and symptoms in four patients improved subsequent to treatment. There was significant improvement in the urticaria activity scores and visual analogue scores at 2 (P< 0.01) and 6 weeks (P< 0.01) post‐IVIG compared with the baseline values (Wilcoxon matched pairs). The diminution in urticarial activity in the majority of patients corresponded with a reduced weal‐and‐flare response to the intradermal injection of autologous post‐treatment serum compared with the pretreatment serum. Minor side‐effects were common, but there were no serious or long‐term adverse effects. IVIG represents a novel therapeutic option in selected patients with recalcitrant CU associated with histamine releasing autoantibodies.
Genome-Wide Linkage Analyses of 12 Endophenotypes for Schizophrenia From the Consortium on the Genetics of Schizophrenia
Authors: Tiffany A. Greenwood, Neal R. Swerdlow, Raquel E. Gur, Kristin S. Cadenhead, Monica E. Calkins, Dorcas J. Dobie, Robert Freedman, Michael F. Green, Ruben C. Gur, Laura C. Lazzeroni, Keith H. Nuechterlein, Ann Olincy, Allen D. Radant, Amrita Ray, Nicholas J. Schork, Larry J. Seidman, Larry J. Siever, Jeremy M. Silverman, William S. Stone, Catherine A. Sugar, Debby W. Tsuang, Ming T. Tsuang, Bruce I. Turetsky, Gregory A. Light, David L. Braff
Journal: American Journal of Psychiatry (2013)

Objective The Consortium on the Genetics of Schizophrenia has undertaken a large multisite study to characterize 12 neurophysiological and neurocognitive endophenotypic measures as a step toward understanding the complex genetic basis of schizophrenia. The authors previously demonstrated the heritability of these endophenotypes; in the present study, genetic linkage was evaluated. Method Each family consisted of a proband with schizophrenia, at least one unaffected sibling, and both parents. A total of 1,286 participants from 296 families were genotyped in two phases, and 1,004 individuals were also assessed for the endophenotypes. Linkage analyses of the 6,055 single-nucleotide polymorphisms that were successfully assayed, 5,760 of which were common to both phases, were conducted using both variance components and pedigree-wide regression methods. Results Linkage analyses of the 12 endophenotypes collectively identified one region meeting genome-wide significance criteria, with a LOD (log of odds) score of 4.0 on chromosome 3p14 for the antisaccade task, and another region on 1p36 nearly meeting genome-wide significance, with a LOD score of 3.5 for emotion recognition. Chromosomal regions meeting genome-wide suggestive criteria with LOD scores >2.2 were identified for spatial processing (2p25 and 16q23), sensorimotor dexterity (2q24 and 2q32), prepulse inhibition (5p15), the California Verbal Learning Test (8q24), the degraded-stimulus Continuous Performance Test (10q26), face memory (10q26 and 12p12), and the Letter-Number Span (14q23). Conclusions Twelve regions meeting genome-wide significant and suggestive criteria for previously identified heritable, schizophrenia-related endophenotypes were observed, and several genes of potential neurobiological interest were identified. Replication and further genomic studies are needed to assess the biological significance of these results.
Fibronectin signaling stimulates BNP gene transcription by inhibiting neuron-restrictive silencer element-dependent repression
Authors: E Ogawa
Journal: Cardiovascular Research (2002)

Objective: Brain natriuretic peptide (BNP) is a cardiac hormone mainly synthesized in ventricles and its expression is markedly increased in ventricular hypertrophy that involves the accumulation of extracellular matrix proteins, such as fibronectin (Fn). We recently reported that Fn signaling stimulated BNP secretion accompanied by hypertrophic responses in vitro. Methods: To elucidate the regulatory mechanism for BNP gene transcription, we examined cis-acting elements downstream of Fn signaling in rat ventricular myocytes transfected with either the −1812 human BNP-luciferase reporter gene (−1812hBNP/Luc) or one of several truncated forms. Results: A strong cis-repressor element was identified between −552 and −522 in myocytes plated on uncoated dishes. This region contains a neuron-restrictive silencer element (NRSE)-like element (NRSEBNP) that is 90% homologous with the NRSE consensus sequence. Neuron-restrictive silencer factor (NRSF) is known to bind to NRSE and to silence transcription of genes containing NRSE. Deletion of NRSEBNP and dominant negative NRSF markedly increased the reporter activity in transfected cells, suggesting that the NRSE/NRSF system silences basal BNP gene transcription. When myocytes were cultured on Fn-coated dishes, the reporter activity of −1812hBNP/Luc was increased by ∼600% compared with that on uncoated dishes. Interestingly, truncation from −552 to −522 reduced the Fn-inducible reporter activity. Moreover, deletion of NRSEBNP and dominant negative NRSF also inhibited the Fn-inducible reporter activity. Electrophoretic mobility shift assays showed that Fn signaling inhibited the binding activity of NRSF to NRSEBNP. Conclusion: These results suggest that Fn-induced BNP up-regulation in rat ventricular myocytes is due to inhibition of NRSEBNP-dependent repression of BNP gene transcription.
Artificial disruption of skin barrier prior to irritant patch testing does not improve test design
Authors: K.L. Gebhard, I. Effendy, H. Loffler
Journal: British Journal of Dermatology (2004)

Irritant patch testing is often performed as a 24- or 48-h occlusive patch test with low concentrations of sodium lauryl sulphate (SLS).The aim of this study was to investigate potential ways to shorten this test procedure and obtain precise test results.Thirty-six healthy volunteers underwent irritant patch testing with different pretreatments (PT) of the test fields. Occlusive test chambers were applied on the upper back with SLS 0.5%, 1%, 2% and 5% in large Finn Chambers(R). The patches were removed after 4 and 24 h, respectively, depending on the concentration used. Test fields were pretreated as follows: PT 0, field without any PT (control); PT 1, prick with lancet; PT 2, prick with test stamp; PT 3, scratch with lancet; PT 4, incision with standardized incision instrument (0.1-0.2 mm depth). Skin reactions were evaluated by transepidermal water loss (TEWL), skin erythema and skin hydration and as well by a visual score (VS) at 4, 24 and 72 h.Our data show an obvious distinction between PT 0-2 and PT 3-4 at all measurement methods. The average TEWL values with PT 3-4 were higher than those with PT 0-2, especially on the 4-h course. This distinction may derive from the shape and size of the skin impairment achieved by PT 3-4, leading to a mechanical barrier disruption. However, SLS may infiltrate directly into deeper skin layers supported by capillarity. Consequently, no or little penetration through the epidermis and interaction with its structures occurs, which is responsible for irritant skin reactions. The SLS dose in the upper skin layers is therefore lower at these PTs. The lower remaining dose of SLS also explains this distinction, especially for the VS. Additionally, there are presumed reactions in deeper layers of the epidermis and dermis at PT 3-4.In summary, all data suggest a different reaction pattern from the classical irritant response. Therefore, application without any PT seems to be best suited for irritancy skin testing, especially for visual assessment. PTs prior to irritant patch testing have been shown to be unjustifiable.