tbuckley/cabot-search huggingface dataset:
Auditory System Development: Primary Auditory Neurons and Their Targets
Authors: Edwin W. Rubel, Bernd Fritzsch
Journal: Annual Review of Neuroscience (2002)

The neurons of the cochlear ganglion transmit acoustic information between the inner ear and the brain. These placodally derived neurons must produce a topographically precise pattern of connections in both the inner ear and the brain. In this review, we consider the current state of knowledge concerning the development of these neurons, their peripheral and central connections, and their influences on peripheral and central target cells. Relatively little is known about the cellular and molecular regulation of migration or the establishment of precise topographic connection to the hair cells or cochlear nucleus (CN) neurons. Studies of mice with neurotrophin deletions are beginning to yield increasing understanding of variations in ganglion cell survival and resulting innervation patterns, however. Finally, existing evidence suggests that while ganglion cells have little influence on the differentiation of their hair cell targets, quite the opposite is true in the brain. Ganglion cell innervation and synaptic activity are essential for normal development of neurons in the cochlear nucleus.
Site-Specific Intracoronary Heparin Delivery in Humans After Balloon Angioplasty
Authors: Edoardo Camenzind, Willem H. Bakker, Ambroos Reijs, Ingeborg M. van Geijlswijk, Eric Boersma, Michael J. B. Kutryk, Eric P. Krenning, Jos R. T. C. Roelandt, Patrick W. Serruys
Journal: Circulation (1997)

Background Demonstration and quantification of site-specific intracoronary administration of compounds has been confined thus far to the experimental animal laboratory. The aim of this study was to describe a scintigraphic method to demonstrate site-specific intracoronary drug delivery in humans. The methods allow on-line visualization and off-line quantification of site-specifically infused γ-emitting compounds. Methods and Results In 12 patients after balloon angioplasty, 99m Tc-labeled heparin was administered at the site of dilatation by use of a coil balloon. Both the infusion period and the washout period after the end of infusion were monitored with a γ-camera. A curve of counts per pixel as a function of time was derived that showed an accumulation phase during infusion followed by a washout phase after the end of infusion. Both phases were fitted by regression analysis and showed a linear accumulation pattern and a biexponential washout pattern. After correction for background counts, 99m Tc decay, and body attenuation, peak heparin amount and regional bioavailability were calculated. Peak amount was defined as the initial point of the slow washout component of the biexponential curve (elimination component), and regional bioavailability was defined as the area under the curve of accumulation and washout phase. Half-life and retention time, defined as seven half-lives, were obtained by use of the elimination component after correction for 99m Tc decay. Mean peak delivered amount was 45±44 IU (236±228 μg), corresponding to an efficiency of delivery ranging from 1% to 8% of the totally infused dose. Total regionally bioavailable heparin reached 244±194 IU·h (1.28±1.01 mg·h). Retention time varied from 12 to 90 hours (mean, 50:33±22:50 hours:minutes). Conclusions Site-specific intracoronary heparin delivery after angioplasty by means of the coil balloon was demonstrated in humans, and regional pharmacokinetics was quantified by use of a radioisotopic technique.
Endobronchial nocardial infection.
Authors: D I Fielding, W A Oliver
Journal: Thorax (1994)

<h3>Abstract</h3> Coronavirus-19 (COVID-19) mortality in hospitalized patients is strongly associated with old age, nursing home residence, male sex and obesity, with a more controversial association with ethnicity and chronic diseases, in particular diabetes mellitus. Further complicating the evaluation of the independent impacts of these risk factors is the failure to control for frailty in published studies thus far. <h3>Aim</h3> To determine the independent risk factors for mortality in patients confirmed to have COVID-19 needing hospital admission and to evaluate the independence of these risk factors after adjusting for body mass index (BMI) and frailty. <h3>Methods</h3> This observational study retrospectively reviewed hospital electronic medical records of 466 consecutive patients admitted to Croydon University Hospital confirmed positive by rapid PCR test from 11<sup>th</sup> March to 9<sup>th</sup> April 2020. Statistical analysis was performed by multiple unconditional and univariate logistic regression. <h3>Results</h3> After multivariate analysis, male sex [OR 1.44 (CI 0.92-2.40)], age per year [OR 1.07 (CI 1.05-1.09)], morbid obesity (BMI &gt; 40 kg/m<sup>2</sup> vs BMI 18.5-24.9 kg/m<sup>2</sup>) [OR 14.8 (CI 5.25-41.8)], and nursing home residence (OR 3.01 (CI 1.56-5.79) were independently associated with COVID-19 mortality with no statistically significant association found with chronic diseases or ethnicity. BMI was associated with mortality throughout its range from underweight to morbidly obese OR 1.07(1.03-1.11) per kg/m<sup>2</sup> increase, p=0.0002 In the non-nursing home population, after adjusting for age and sex, the OR for type 2 diabetes mellitus (T2DM) as a risk factor was 1.64 (CI 1.03-2.61, p = 0.03) attenuated to 1.30 (CI 0.78-2.18)) after controlling for BMI.; the association of mortality with male sex was strengthened [OR 1.66 (CI 0.96-2.87)] and that for ethnic minority patients was weakened [South Asians [from OR 1.30 (CI 0.67-2.53)) to OR 1.21 (CI 0.60-2.46)]; Afro Caribbean [from OR 1.24 (CI 0.65-2.34) to OR 1.16 (CI 0.58-2.30)]. There was a borderline but potentially large protective effect (p= 0.09) of anticoagulation drug use prior to admission [OR 0.56 (CI 0.28-1.11)]. <h3>Conclusion</h3> No significant effect of ethnicity and chronic diseases as independent risk factors on COVID-19 mortality was found whereas male sex, high BMI, old age, and frailty were found to be independent risk factors. BMI was related to mortality risk throughout its range from underweight to severely obese. It is likely that chronic diseases are epiphenomena of the effects of ageing and visceral adiposity on the immune system. Routine prophylactic treatment with anticoagulant drugs in the high risk COVID-19 population warrants further prompt investigation.
Cardiac Resynchronization Therapy Restores Sympathovagal Balance in the Failing Heart by Differential Remodeling of Cholinergic Signaling
Authors: Deeptankar DeMazumder, David A. Kass, Brian O’Rourke, Gordon F. Tomaselli
Journal: Circulation Research (2015)

Rationale: Cardiac resynchronization therapy (CRT) is the only heart failure (HF) therapy documented to improve left ventricular function and reduce mortality. The underlying mechanisms are incompletely understood. Although β-adrenergic signaling has been studied extensively, the effect of CRT on cholinergic signaling is unexplored. Objective: We hypothesized that remodeling of cholinergic signaling plays an important role in the aberrant calcium signaling and depressed contractile and β-adrenergic responsiveness in dyssynchronous HF that are restored by CRT. Methods and Results: Canine tachypaced dyssynchronous HF and CRT models were generated to interrogate responses specific to dyssynchronous versus resynchronized ventricular contraction during hemodynamic decompensation. Echocardiographic, electrocardiographic, and invasive hemodynamic data were collected from normal controls, dyssynchronous HF and CRT models. Left ventricular tissue was used for biochemical analyses and functional measurements (calcium transient, sarcomere shortening) from isolated myocytes (n=42–104 myocytes per model; 6–9 hearts per model). Human left ventricular myocardium was obtained for biochemical analyses from explanted failing (n=18) and nonfailing (n=7) hearts. The M2 subtype of muscarinic acetylcholine receptors was upregulated in human and canine HF compared with nonfailing controls. CRT attenuated the increased M2 subtype of muscarinic acetylcholine receptor expression and Gαi coupling and enhanced M3 subtype of muscarinic acetylcholine receptor expression in association with enhanced calcium cycling, sarcomere shortening, and β-adrenergic responsiveness. Despite model-dependent remodeling, cholinergic stimulation completely abolished isoproterenol-induced triggered activity in both dyssynchronous HF and CRT myocytes. Conclusions: Remodeling of cholinergic signaling is a critical pathological component of human and canine HF. Differential remodeling of cholinergic signaling represents a novel mechanism for enhancing sympathovagal balance with CRT and may identify new targets for treatment of systolic HF.
A double blind controlled trial of methylprednisolone infusions in systemic lupus erythematosus using individualised outcome assessment.
Authors: J C Edwards, M L Snaith, D A Isenberg
Journal: Annals of the Rheumatic Diseases (1987)

Twenty one patients with severe systemic lupus erythematosus (SLE) were treated with three daily infusions of either 100 mg or 1 g of methylprednisolone on a randomised double blind basis. Nine patients with unsatisfactory outcome subsequently received the alternative therapy. Patients were rated for improvement on a four point scale using individualised criteria. On three occasions patients improved to 'ideal', on 12 there was 'useful' improvement, on 11 the patient remained static, and on four occasions there was deterioration. There was no significant difference between the clinical states after the two doses. The results suggest that any additional benefit of 1 g of methylprednisolone over 100 mg by repeated infusion in the treatment of active SLE is probably not enough to justify the potential hazards and cost involved.
Phospho-Akt Overexpression in Non–Small Cell Lung Cancer Confers Significant Stage-Independent Survival Disadvantage
Authors: Odile David, James Jett, Helena LeBeau, Grace Dy, Janet Hughes, Mitchell Friedman, Arnold R. Brody
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Akt is a signal transduction protein that plays a central role in inhibiting apoptosis in a variety of cell types including human cancer cells. In cell lines derived from human non–small cell lung cancers (NSCLCs), Akt has been shown to confer chemoresistance by inhibition of apoptosis in response to different chemotherapeutic agents including platinum-based agents, which are often the first-line therapy for NSCLCs. Only 20% to 30% of patients with NSCLC treated with chemotherapy have clinical evidence of response. The purpose of this study is to determine whether or not overexpression of activated Akt [i.e., phosphorylated Akt (pAkt)] is correlated with survival. Experimental Design: We studied tumors from 61 patients with NSCLC in three tissue microarrays. All patients were followed for a period of 10 years or until death. The arrays were studied immunohistochemically with antibodies against pAkt, p53, and Ki-67. Results: There was a statistically significant difference in survival between the 14 patients with strong pAkt staining and the 47 patients with weak to absent pAkt staining both by log-rank (P = 0.0416) and Breslow analysis (P = 0.0446). Difference in survival time with respect to pAkt status was also statistically significant even after accounting for stage at diagnosis (P = 0.004). Neither p53 nor Ki-67 was a statistically significant prognostic factor. Conclusions: Overexpression of pAkt is an independent prognostic factor. Additional studies of human NSCLCs are warranted to drive the development of targeted tumor-specific antineoplastic therapies.
Lysophosphatidylcholine acyltransferase 1 altered phospholipid composition and regulated hepatoma progression
Authors: Yoshifumi Morita, Takanori Sakaguchi, Koji Ikegami, Naoko Goto-Inoue, Takahiro Hayasaka, Vu Thi Hang, Hiroki Tanaka, Takashi Harada, Yasushi Shibasaki, Atsushi Suzuki, Kazuhiko Fukumoto, Keisuke Inaba, Makoto Murakami, Mitsutoshi Setou, Hiroyuki Konno
Journal: Journal of Hepatology (2013)
Can procalcitonin have a role in reducing antibiotic selective pressure?
Authors: S. Pomfret
Journal: Thorax (2010)

This multicentre, prospective, parallel group randomised trial compared the use of a modified previously published procalcitonin-guided algorithm for antibiotic use with the conventional use of local or national guidelines for antibiotic use over seven intensive care units. A total of 307 patients in the procalcitonin group and 314 in the control group were included. In …
Effect of the Tumor Vascular-Damaging Agent, ZD6126, on the Radioresponse of U87 Glioblastoma
Authors: Phyllis R. Wachsberger, Randy Burd, Nichol Marero, Constantine Daskalakis, Anderson Ryan, Peter McCue, Adam P. Dicker
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The effect of ZD6126 on tumor oxygen tension and tumor growth delay in combination with ionizing radiation was examined in the human U87 glioblastoma tumor model. Resistance to ZD6126 treatment was investigated with the nitric oxide synthase inhibitor, l-NG-nitroarginine methyl ester (hydrochloride; l-NAME/active form, l-NNA). Methods: U87 human xenografts were grown in athymic nude mice. ZD6126 was given with or without l-NNA. Tumor oxygen tension was measured using the Oxford Oxylite (Oxford, England) fiberoptic probe system. Tumor volume was determined by direct measurement with calipers and calculated by the formula [(smallest diameter2 × widest diameter)/2]. Results: Multiple doses of ZD6126 treatment (three doses) had a significant effect on tumor growth delay, reducing the average daily tumor growth rate from 29% to 16%. When given 1 hour before radiation, ZD6126 caused an acute increase in hypoxia in U87 tumors, and reduced tumor growth delay compared with that of radiation alone. The combination of ZD6126 given after radiation, either as a single dose or in multiple doses, had greater or similar antitumor activity compared with radiation alone. Twenty-four hours after administration, a single dose of ZD6126 induced little (10 ± 8%) necrosis in U87 xenografts. l-NNA, when given in combination with ZD6126, significantly enhanced the effectiveness of ZD6126 in inducing tumor necrosis. Conclusions: Our observation that ZD6126-induced tumor hypoxia can decrease radiation response when ZD6126 is given prior to radiation indicates the importance of scheduling. Our findings suggest that the optimal therapeutic benefit of ZD6126 plus radiation in human glioblastoma may require multiple dosing in combination with a nitric oxide synthase inhibitor, to be scheduled following radiotherapy.
Case of Catalepsy: Employment of Electro-Magnetism
Authors: W. H. Crowfoot
Journal: BMJ (1846)

CASt OP CATALEPSY.5-4-?4 appreciable difference between the two sides in front, * both affording good resonance, slightly defective per- lapps under the left clavicle; evident dulness over the superior scapular region of the left side.-Auscultation:Respiration healthy over the entire right side; of slightly diminished intensity, with increased reson- ance of voice and cough, uinder the left clavicle; cavernous respiration, voice" and cough with large moist crackling over the supra-spinous fossa of the left scapula; around this spot and throughout the remainider of the lung, the respiration healthy.Trealment.-Ablister beneath the left clavicle ; thg mineral acids, with the strup of the iodide of iron.This patient resided in the country, and did not return to the hospital, from which it may be presumed, 444-the.caserapidly terminated unfavourably.Remarks.
Ankylosing spondylitis: an overview
Authors: J Sieper, J Braun, M Rudwaleit, A Boonen, A Zink
Journal: Annals of the Rheumatic Diseases (2002)

Ankylosing spondylitis (AS) is a complex, potentially debilitating disease that is insidious in onset, progressing to radiological sacroiliitis over several years. Patients with symptomatic AS lose productivity owing to work disability and unemployment, have a substantial use of healthcare resources, and reduced quality of life. The pathogenesis of AS is poorly understood. However, immune mediated mechanisms involving human leucocyte antigen (HLA)-B27, inflammatory cellular infiltrates, cytokines (for example, tumour necrosis factor α and interleukin 10), and genetic and environmental factors are thought to have key roles. The detection of sacroiliitis by radiography, magnetic resonance imaging, or computed tomography in the presence of clinical manifestations is diagnostic for AS, although the presence of inflammatory back pain plus at least two other typical features of spondyloarthropathy (for example, enthesitis and uveitis) is highly predictive of early AS. Non-steroidal anti-inflammatory drugs (NSAIDs) effectively relieve inflammatory symptoms and are presently first line drug treatment. However, NSAID treatment has only a symptomatic effect and probably does not alter the disease course. For symptoms refractory to NSAIDs, second line treatments, including corticosteroids and various disease modifying antirheumatic drugs, are employed but are of limited benefit. Emerging biological therapies target the inflammatory processes underlying AS, and thus, may favourably alter the disease process, in addition to providing symptom relief.
Exercise Training Attenuates Age-Associated Diastolic Dysfunction in Rats
Authors: Daniel A. Brenner, Carl S. Apstein, Kurt W. Saupe
Journal: Circulation (2001)

Background — In contrast to systolic function, which is relatively well preserved with advancing age, diastolic function declines steadily after age 30. Our goal was to determine whether changes in diastolic function that occur with aging could be reversed with exercise training. Methods and Results — Adult (6-month-old) and old (24-month-old) Fischer 344/BNF1 rats were studied after either 12 weeks of treadmill training or normal sedentary cage life. Three aspects of diastolic function were studied: (1) left ventricular (LV) filling in vivo via Doppler echocardiograph, (2) LV passive compliance, and (3) the degree of ischemia-induced LV stiffening. Maximal exercise capacity was lower in the old rats (18±1 minutes to exhaustion on a standard treadmill) than in the adult rats (25±1 minutes). Training increased exercise capacity by 43% in the old rats and 46% in the adults (to 26±1 and 37±1 minutes, respectively). Echocardiographic indices of LV relaxation were significantly lower in the old rats, but with training, they increased back to the levels seen in the adults. LV stiffness measured in the isolated, perfused hearts was not affected by age or training. Also in the isolated hearts, the LV stiffened more rapidly during low-flow ischemia in the old hearts than in the adults, but training eliminated this age-associated difference in the response to ischemia. Conclusions — Our findings indicate that in rats, some age-associated changes in diastolic function are reversible and thus may not be intrinsic to aging but instead secondary to other processes, such as deconditioning.
Differential Effects of Anti-cytokine Treatment on Bronchoalveolar Hemostasis in Endotoxemic Chimpanzees
Authors: MARCEL LEVI, TOM van der POLL, HUGO ten CATE, BART KUIPERS, BART J. BIEMOND, HENK M. JANSEN, JAN WOUTER ten CATE
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Activation and inhibition of coagulation and fibrinolysis was analyzed in bronchoalveolar lavage (BAL) fluids obtained from endotoxin-challenged chimpanzees. The mediatory role of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) on endotoxin-induced changes in bronchoalveolar coagulation and fibrinolysis was investigated in experiments in which the infusion of endotoxin was combined with the administration of monoclonal anti-TNF-alpha or anti-IL-6 antibodies. Endotoxin infusion elicited a marked increase in bronchoalveolar thrombin generation as measured by levels of prothrombin activation fragment F1+2 and thrombin-antithrombin complexes. Markers for intrinsic pathway activation were not detectable, suggesting that the thrombin generation was mediated by the tissue factor-dependent route. Levels of antithrombin were low before the injection of endotoxin and not detectable hereafter. The administration of anti-IL-6 antibody completely abolished the endotoxin-induced activation of bronchoalveolar coagulation, whereas treatment with anti-TNF-alpha antibody only partly inhibited this effect. Bronchoalveolar fibrinolytic activity, due to urokinase-type plasminogen activator (u-PA), was significantly depressed after endotoxin injection, mainly due to a striking increase in plasminogen activator inhibitor-2 levels in BAL fluid. The endotoxin-induced effects on bronchoalveolar fibrinolysis could be blocked by the simultaneous administration of anti- TNF-alpha antibodies. We conclude that endotoxemia results in the activation of bronchoalveolar coagulation, which is apparently mediated by the tissue factor route of coagulation activation and which may be amplified by consumption of antithrombin III. Bronchoalveolar fibrinolytic activity is significantly abolished by increased levels of mainly PAI-2 after the injection of endotoxin. The endotoxin-induced effects on bronchoalveolar coagulation appears to be mediated by IL-6, whereas TNF-alpha seems to be the pivotal mediator of the endotoxin-induced depression of bronchoalveolar fibrinolysis.
Guidelines for protocol studies in chronic lymphocytic leukemia
Authors: Richard T. Silver, Arthur Sawitsky, Kanti Rai, James F. Holland, Oliver Glidewell
Journal: American Journal of Hematology (1978)

Abstract The treatment of any malignant disease requires appropriate criteria for diagnosis of the disease, appropriate methods for study, and techniques for evaluating response to treatment. In the past five years, there have been a number of proposed guidelines for studies in chronic lymphocytic leukemia (CLL). These submitted guidelines represent a further re‐evaluation of concepts in CLL, and are currently in use by Cancer and Leukemia Group B for protocol studies. It is clear that revisions will continue to be made as new knowledge accumulates. In the meantime, these are submitted for publication for use by other investigators.
Low power interstitial Nd YAG laser photocoagulation in normal and neoplastic rat colon.
Authors: K Matthewson, T Barton, M R Lewin, J P O'Sullivan, T C Northfield, S G Bown
Journal: Gut (1988)

The effects of low power (1-2 Watts), long exposure (30-400 seconds), interstitial Nd YAG laser therapy on dimethylhydrazine induced rat colonic neoplasms and normal rat colon have been studied. After a single exposure with appropriate laser parameters, dimethylhydrazine induced rat colonic neoplasms underwent coagulative necrosis, sloughed off over a four day period, and left an ulcer which healed within 28 days. Inadequate laser energy resulted in incomplete tumour necrosis whilst excessive laser power or energy increased the likelihood of perforation. Treatment of normal colon with 1 Watt for 30 seconds or longer resulted in coagulative damage which healed by granulation. Mean colonic bursting pressures were significantly decreased one hour after treatment with 1 Watt for 75 or 100 seconds compared with untreated colon (p less than 0.05 and p less than 0.001 respectively) but not in colon treated with 1 Watt for 30 or 50 seconds. In animals treated with 1 Watt for 100 seconds mean bursting pressures were significantly lower than untreated animals when the animals were killed two, four, and seven days after lasering (p less than 0.001 in each case) but not in animals killed at 11, 17, or 21 days. The technique may be of value in the treatment of some inoperable colorectal cancers and sessile polyps in man.