tbuckley/cabot-search huggingface dataset:
Preliminary Note ON INVESTIGATIONS UPON ONE THOUSAND CONSECUTIVE CASES OF PERIPHERAL NERVE INJURY
Authors: J. L. F. Burrow
Journal: BMJ (1918)

THE most important preliminary to every communication on nerve injuries is a full statement of the methods em- ployed to obtain the stated results.In reading and criticizing the work of others our chief difficulties arise from a lack of knowledge of the methods that they have employed to arrive at their conclusions.First, to be of practical value, routine observations on cases of nerve injury should be made at regular intervals if possible.Secondly, a system of careful case-taking and charting is necesary.Thirdly, there must be a standardization of methods used so that the successive observations are exactly comparable.In recording sensory changes the commonest mistakes arise from the use of moderately coarse stimuli, which appeal to deep sensation althouglh intended to stimulate the more superficial sense organs.Recent writers have omitted to draw attention to the fact that local temperature changes cause most remarkable variations in sensory functions.Examination in a cold room, andaof a cyanosed, oedematous, or chilled limb, will give many motor,, sensorv, and electrical variations from the healthy state.From observations so made misleading conclusions are drawn unless the observer be experienced enough to recognize and correct the causes of the plhenomena encountered.The methods employed for routine work by us are rougher than we would wish, owing to the large number of patients to be examined and reported upon.Certain patients only are picked out for special observation.These patients are chosen, some because their lesions are definite, and others because of a high degree of intelligence, which facilitates the recording of their sensations, etc. PRELIMINARIES TO EXAMINATION.Attention is directed to the following points in recording the history of the lesion:The nature of the injury.The position of the patient at the time that the injury was received. Immediate effects.After-history, which includes notes on the surgical treatment to date.
The cost-effectiveness of temozolomide in the adjuvant treatment of newly diagnosed glioblastoma in the United States
Authors: A. Messali, J. W. Hay, R. Villacorta
Journal: Neuro-Oncology (2013)

The objective of this work was to determine the cost-effectiveness of temozolomide compared with that of radiotherapy alone in the adjuvant treatment of newly diagnosed glioblastoma. Temozolomide is the only chemotherapeutic agent to have demonstrated a significant survival benefit in a randomized clinical trial. Our analysis builds on earlier work by incorporating caregiver time costs and generic temozolomide availability. It is also the first analysis applicable to the US context.A systematic literature review was conducted to collect relevant data. Transition probabilities were calculated from randomized controlled trial data comparing temozolomide plus radiotherapy with radiotherapy alone. Direct costs were calculated from charges reported by the Mayo Clinic. Utilities were obtained from a previous cost-utility analysis. Using these data, a Markov model with a 1-month cycle length and 5-year time horizon was constructed.The addition of brand Temodar and generic temozolomide to the standard radiotherapy regimen was associated with base-case incremental cost-effectiveness ratios of $102 364 and $8875, respectively, per quality-adjusted life-year. The model was most sensitive to the progression-free survival associated with the use of only radiotherapy.Both the brand and generic base-case estimates are cost-effective under a willingness-to-pay threshold of $150 000 per quality-adjusted life-year. All 1-way sensitivity analyses produced incremental cost-effectiveness ratios below this threshold. We conclude that both the brand Temodar and generic temozolomide are cost-effective treatments for newly diagnosed glioblastoma within the US context. However, assuming that the generic product produces equivalent quality of life and survival benefits, it would be significantly more cost-effective than the brand option.
Evolutionary Rate and Gene Expression Across Different Brain Regions
Authors: Tamir Tuller, Martin Kupiec, Eytan Ruppin
Journal: Genome biology (2008)

The evolutionary rate of a protein is a basic measure of evolution at the molecular level. Previous studies have shown that genes expressed in the brain have significantly lower evolutionary rates than those expressed in somatic tissues.We study the evolutionary rates of genes expressed in 21 different human brain regions. We find that genes highly expressed in the more recent cortical regions of the brain have lower evolutionary rates than genes highly expressed in subcortical regions. This may partially result from the observation that genes that are highly expressed in cortical regions tend to be highly expressed in subcortical regions, and thus their evolution faces a richer set of functional constraints. The frequency of mammal-specific and primate-specific genes is higher in the highly expressed gene sets of subcortical brain regions than in those of cortical brain regions. The basic inverse correlation between evolutionary rate and gene expression is significantly stronger in brain versus nonbrain tissues, and in cortical versus subcortical regions. Extending upon this cortical/subcortical trend, this inverse correlation is generally more marked for tissues that are located higher along the cranial vertical axis during development, giving rise to the possibility that these tissues are also more evolutionarily recent.We find that cortically expressed genes are more conserved than subcortical ones, and that gene expression levels exert stronger constraints on sequence evolution in cortical versus subcortical regions. Taken together, these findings suggest that cortically expressed genes are under stronger selective pressure than subcortically expressed genes.
Stereotactic brachytherapy of low-grade cerebral glioma after tumor resection
Authors: B. Suchorska, M. Ruge, H. Treuer, V. Sturm, J. Voges
Journal: Neuro-Oncology (2011)

The purpose of this study was to assess the impact of stereotactic brachytherapy (SBT) on survival time and outcome when applied after resection of low-grade glioma (LGG) of World Health Organization grade II. From January 1982 through December 2006 we treated 1024 patients who had glioma with stereotactic implantation of iodine-125 seeds and SBT in accordance with a prospective protocol. For the present analysis, we selected 95 of 277 patients with LGG, in whom SBT was applied to treat progressive (43 patients) or recurrent (52 patients) tumor after resection. At 24 months after seed implantation, the tumor response rate was 35.9%, and the tumor control rate was 97.3%. The median progression-free-survival (PFS) duration after SBT was 52.7 ± 7.1 months. Five-year and 10-year PFS probabilities were 43.4% and 10.7%, respectively. Malignant tumor transformation, the diagnosis “astrocytoma,” and tumor volume >20 mL were significantly associated with reduced PFS. Tumor progression or relapse after SBT (53 of 95 patients) was treated with tumor resection, a second SBT, chemotherapy, and/or radiotherapy. The median overall survival duration (from the first diagnosis of LGG until the patient's last contact) was 245.0 ± 4.9 months. Patients still under observation after seed implantation had a median follow-up time of 156.4 ± 55.7 months. Perioperative transient morbidity was 1.1%, and the frequency of permanent morbidity caused by SBT was 3.3%. In conclusion, SBT of recurrent or progressive LGG after resection located in functionally critical brain areas has high local efficacy and comparably low morbidity. Referred to individually adopted glioma treatment concepts SBT provides a reasonably long PFS, thus improving overall survival. In selected patients, SBT can lead to delays in the application of chemotherapy and/or radiotherapy.
Differential induction of transcription factors that regulate the interleukin 2 gene during anergy induction and restimulation.
Authors: C Go, J Miller
Journal: The Journal of Experimental Medicine (1992)

T cell activation requires two distinct signals. The first is delivered through the antigen-specific T cell receptor (TCR), and the second is provided by costimulatory molecule(s) present on the surface of the antigen-presenting cell (APC). Stimulation of T helper type 1 T cell clones through the TCR in the absence of the costimulatory activity results in a lack of interleukin 2 (IL-2) secretion and proliferation, and the induction of a long-lived state of nonresponsiveness, termed anergy. In this study, we have examined the transcription factors involved in IL-2 gene expression that are expressed after stimulation of normal T cell clones through the TCR with and without engagement of the necessary costimulatory molecule(s). Antigen-specific activation of the clones results in the induction of a similar pattern of transcription factors that have been previously shown to regulate IL-2 expression. In contrast, antigen presentation by chemically fixed APC, a condition that results in T cell anergy, induces neither NF-AT nor one of the two NF-kappa B binding factors. Thus, the failure to express IL-2 during the induction of T cell anergy may be attributed to the absence of these two transcription factors. When anergized T cells are restimulated with antigen and conventional APC, they induce the transcription factors associated with IL-2 expression, but they fail to synthesize measurable IL-2. Taken together, these data indicate that the control of IL-2 gene expression during anergy induction and during normal stimulation of anergized cells are distinct, and suggest the presence of additional regulatory elements in the IL-2 gene.
Intestinal permeability: the cellobiose/mannitol test
Authors: R M CRAIG
Journal: Gut (2001)

Editor,—I should like to bring to your attention a conceptual error in the paper by Daniele et al ((2001) Gut 48:28–33; [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]) regarding the cellobiose/mannitol test. The authors suggest that improvement in the cellobiose/mannitol ratio reflects improvement in permeability from the use of oral glutamine. However, only mannitol excretion improved significantly with glutamine; cellobiose excretion remained unchanged. As … [1]: {openurl}?query=rft.jtitle%253DGastroenterology%26rft.stitle%253DGastroenterology%26rft.aulast%253DBjarnason%26rft.auinit1%253DI%26rft.volume%253D108%26rft.issue%253D5%26rft.spage%253D1566%26rft.epage%253D1581%26rft.atitle%253DIntestinal%2Bpermeability%253A%2Ban%2Boverview%26rft_id%253Dinfo%253Adoi%252F10.1016%252F0016-5085%252895%252990708-4%26rft_id%253Dinfo%253Apmid%252F7729650%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/0016-5085(95)90708-4&link_type=DOI [3]: /lookup/external-ref?access_num=7729650&link_type=MED&atom=%2Fgutjnl%2F49%2F2%2F312.1.atom [4]: /lookup/external-ref?access_num=A1995QV54500030&link_type=ISI
Urinary Sulfur Metabolites Associate with a Favorable Cardiovascular Risk Profile and Survival Benefit in Renal Transplant Recipients
Authors: Else van den Berg, Andreas Pasch, Welmoet H. Westendorp, Gerjan Navis, Elizabeth J. Brink, Reinold O.B. Gans, Harry van Goor, Stephan J.L. Bakker
Journal: Journal of the American Society of Nephrology (2014)

In post-transplant conditions, sulfur may be protective by intermediate conversion to hydrogen sulfide and thiosulfate. However, sulfate, the end product of sulfur-containing amino acids (SAAs), contributes to metabolic acid load and may adversely influence acid-base homeostasis. We investigated the association of urinary sulfur metabolites with cardiometabolic parameters in renal transplant recipients (RTRs) and analyzed their predictive capacity for mortality. We studied urinary sulfate and thiosulfate excretion in 24-hour urine samples from 707 RTRs at a median 5.4 years (interquartile range, 1.9 to 12.2) after transplantation as well as from 110 controls. Diet was assessed for SAA content and various risk factors were measured. Urinary sulfate was similar, whereas thiosulfate was higher in RTRs versus controls. SAA intake was lower in RTRs compared with controls and correlated with sulfate but not thiosulfate excretion. Sulfate beneficially associated with eGFR, net acid excretion, systolic BP, high-sensitivity C-reactive protein, N-terminal probrain natriuretic peptide, and proteinuria (all P≤0.01). Thiosulfate beneficially associated with eGFR, serum acidity, high-sensitivity C-reactive protein, and N-terminal probrain natriuretic peptide (all P≤0.001). During a median 27 months (interquartile range, 22-36) of follow-up, 47 RTRs died. After adjustment for age, sex, and eGFR, hazard ratios for mortality were 0.87 (95% confidence interval, 0.82 to 0.92; P<0.001) for urinary sulfate and 0.60 (95% confidence interval, 0.41 to 0.59; P=0.01) for thiosulfate. Thus, despite the association of urinary sulfate with metabolic acid load, urinary sulfate and thiosulfate beneficially associated with survival in RTRs, possibly by influencing cardiovascular parameters. Intervention studies with exogenous sulfur are warranted to elucidate mechanisms underlying these promising associations in RTRs.
Altered visceral perceptual and neuroendocrine response in patients with irritable bowel syndrome during mental stress
Authors: I Posserud
Journal: Gut (2004)

<b>Background and aims:</b> Stress often worsens the symptoms of irritable bowel syndrome (IBS). We hypothesised that this might be explained by altered neuroendocrine and visceral sensory responses to stress in IBS patients. <b>Subjects and methods:</b> Eighteen IBS patients and 22 control subjects were assessed using rectal balloon distensions before, during, and after mental stress. Ten controls and nine patients were studied in supplementary sessions. Rectal sensitivity (thresholds and intensity—visual analogue scale (VAS)) and perceived stress and arousal (VAS) were determined. Plasma levels of corticotropin releasing factor (CRF), adrenocorticotropic hormone (ACTH), cortisol, noradrenaline, and adrenaline were analysed at baseline, immediately after stress, and after the last distension. Heart rate was recorded continuously. <b>Results:</b> Thresholds were increased during stress in control subjects (p&lt;0.01) but not in IBS patients. Both groups showed lower thresholds after stress (p&lt;0.05). Repeated distensions without stress did not affect thresholds. Both groups showed increased heart rate (p&lt;0.001) and VAS ratings for stress and arousal (p&lt;0.05) during stress. Patients demonstrated higher ratings for stress but lower for arousal than controls. Basal CRF levels were lower in patients (p&lt;0.05) and increased significantly during stress in patients (p&lt;0.01) but not in controls. Patients also responded with higher levels of ACTH during stress (p&lt;0.05) and had higher basal levels of noradrenaline than controls (p&lt;0.01). Controls, but not patients, showed increased levels of adrenaline and noradrenaline in response to stress (p&lt;0.05). <b>Conclusions:</b> Stress induced exaggeration of the neuroendocrine response and visceral perceptual alterations during and after stress may explain some of the stress related gastrointestinal symptoms in IBS.
Heat-related Emergency Hospitalizations for Respiratory Diseases in the Medicare Population
Authors: G. Brooke Anderson, Francesca Dominici, Yun Wang, Meredith C. McCormack, Michelle L. Bell, Roger D. Peng
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

The heat-related risk of hospitalization for respiratory diseases among the elderly has not been quantified in the United States on a national scale. With climate change predictions of more frequent and more intense heat waves, it is of paramount importance to quantify the health risks related to heat, especially for the most vulnerable.To estimate the risk of hospitalization for respiratory diseases associated with outdoor heat in the U.S. elderly.An observational study of approximately 12.5 million Medicare beneficiaries in 213 United States counties, January 1, 1999 to December 31, 2008. We estimate a national average relative risk of hospitalization for each 10°F (5.6°C) increase in daily outdoor temperature using Bayesian hierarchical models.We obtained daily county-level rates of Medicare emergency respiratory hospitalizations (International Classification of Diseases, Ninth Revision, 464-466, 480-487, 490-492) in 213 U.S. counties from 1999 through 2008. Overall, each 10°F increase in daily temperature was associated with a 4.3% increase in same-day emergency hospitalizations for respiratory diseases (95% posterior interval, 3.8, 4.8%). Counties' relative risks were significantly higher in counties with cooler average summer temperatures.We found strong evidence of an association between outdoor heat and respiratory hospitalizations in the largest population of elderly studied to date. Given projections of increasing temperatures from climate change and the increasing global prevalence of chronic pulmonary disease, the relationship between heat and respiratory morbidity is a growing concern.
Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study
Authors: Zhong Jiang, Peigou G Chu, Bruce A Woda, Kenneth L Rock, Qin Liu, Chung-Cheng Hsieh, Cuizhen Li, Wengang Chen, Hai Ou Duan, Scott McDougal, Chin-Lee Wu
Journal: The Lancet Oncology (2006)
Effects of volatile organic compounds, damp, and other environmental exposures in the home on wheezing illness in children
Authors: A J Venn
Journal: Thorax (2003)

The effects of indoor exposure to volatile organic compounds (VOCs), including formaldehyde, on respiratory health are not clearly understood. The aim of this study was to determine the independent effects of VOCs and other common environmental exposures in the home on the risk and severity of persistent wheezing illness in children.Total volatile organic compounds, formaldehyde, nitrogen dioxide, damp (on a four category scale of % wood moisture equivalent), and environmental tobacco smoke (from salivary cotinine) were measured objectively in the homes of 193 children with persistent wheezing illness and 223 controls aged 9-11 years in Nottingham, UK.The risk of wheezing illness was significantly increased only in relation to damp (odds ratio (OR) per increasing category=1.32 (95% confidence interval (CI), 1.00 to 1.75)), and was unrelated to the other exposures measured. Among cases, formaldehyde and damp were associated with more frequent nocturnal symptoms (OR per increasing quartile and category, respectively, 1.45 (1.06 to 1.98) and 1.97 (1.10 to 3.53)), significantly more so in atopic cases, but there was no effect of total volatile organic compounds, nitrogen dioxide, or cotinine.Domestic volatile organic compounds are not a major determinant of risk or severity of childhood wheezing illness, though formaldehyde may increase symptom severity. Indoor damp increases both the risk and severity of childhood wheezing illness.
Markers of nitric oxide metabolism in sputum and exhaled air are not increased in chronic obstructive pulmonary disease
Authors: S R Rutgers, T. W van der Mark, W Coers, H Moshage, W Timens, H F Kauffman, G H Koeter, D S Postma
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Nitric oxide (NO) is involved in inflammation and host defence of the lung. It has been found in increased concentrations in the airways in asthmatic subjects but its levels in patients with chronic obstructive pulmonary disease (COPD) have not been investigated. A study was undertaken to determine whether markers of NO metabolism (NO in exhaled air, iNOS expression in sputum cells, and nitrite + nitrate (NO<sub>2</sub><sup>–</sup>/NO<sub>3</sub><sup>–</sup>) in sputum supernatant) are increased in subjects with COPD, and whether they correlate with inflammatory indices in induced sputum. The associations of these markers with smoking were also assessed. <h3>METHODS</h3> Sixteen subjects with COPD (median age 66 years, median forced expiratory volume in one second (FEV<sub>1</sub>) 63% predicted, eight current smokers) and 16 healthy subjects (median age 63 years, median FEV<sub>1</sub> 113% predicted, eight current smokers) participated in the study. NO was measured during tidal breathing and sputum was induced by inhalation of hypertonic saline. <h3>RESULTS</h3> No differences were observed between subjects with COPD and healthy controls in exhaled NO excretion rate (median 5.15 and 6.25 nmol/min), sputum macrophage iNOS expression (14% and 12%), and sputum supernatant NO<sub>2</sub><sup>–</sup>/NO<sub>3</sub><sup>–</sup> (46 and 73 μM). NO in exhaled air correlated with the percentage of sputum eosinophils in patients with COPD (rho = 0.65, p = 0.009) but not in healthy individuals. Exhaled NO and supernatant NO<sub>2</sub><sup>–</sup>/NO<sub>3</sub><sup>–</sup> levels were lower in healthy smokers than in healthy non/ex-smokers. <h3>CONCLUSIONS</h3> Our findings indicate that NO metabolism is not increased in patients with stable COPD. The close association between exhaled NO levels and sputum eosinophils suggests a role for NO in airway inflammation in COPD. Studies performed during exacerbations may clarify this role.
Weekly <i>nab</i>-Paclitaxel in Combination With Carboplatin Versus Solvent-Based Paclitaxel Plus Carboplatin as First-Line Therapy in Patients With Advanced Non–Small-Cell Lung Cancer: Final Results of a Phase III Trial
Authors: Mark A. Socinski, Igor Bondarenko, Nina A. Karaseva, Anatoly M. Makhson, Igor Vynnychenko, Isamu Okamoto, Jeremy K. Hon, Vera Hirsh, Paul Bhar, Hui Zhang, Jose L. Iglesias, Markus F. Renschler
Journal: Journal of Clinical Oncology (2012)

This phase III trial compared the efficacy and safety of albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin with solvent-based paclitaxel (sb-paclitaxel) plus carboplatin in advanced non-small-cell lung cancer (NSCLC).In all, 1,052 untreated patients with stage IIIB to IV NSCLC were randomly assigned 1:1 to receive 100 mg/m(2) nab-paclitaxel weekly and carboplatin at area under the concentration-time curve (AUC) 6 once every 3 weeks (nab-PC) or 200 mg/m(2) sb-paclitaxel plus carboplatin AUC 6 once every 3 weeks (sb-PC). The primary end point was objective overall response rate (ORR).On the basis of independent assessment, nab-PC demonstrated a significantly higher ORR than sb-PC (33% v 25%; response rate ratio, 1.313; 95% CI, 1.082 to 1.593; P = .005) and in patients with squamous histology (41% v 24%; response rate ratio, 1.680; 95% CI, 1.271 to 2.221; P < .001). nab-PC was as effective as sb-PC in patients with nonsquamous histology (ORR, 26% v 25%; P = .808). There was an approximately 10% improvement in progression-free survival (median, 6.3 v 5.8 months; hazard ratio [HR], 0.902; 95% CI, 0.767 to 1.060; P = .214) and overall survival (OS; median, 12.1 v 11.2 months; HR, 0.922; 95% CI, 0.797 to 1.066; P = .271) in the nab-PC arm versus the sb-PC arm, respectively. Patients ≥ 70 years old and those enrolled in North America showed a significantly increased OS with nab-PC versus sb-PC. Significantly less grade ≥ 3 neuropathy, neutropenia, arthralgia, and myalgia occurred in the nab-PC arm, and less thrombocytopenia and anemia occurred in the sb-PC arm.The administration of nab-PC as first-line therapy in patients with advanced NSCLC was efficacious and resulted in a significantly improved ORR versus sb-PC, achieving the primary end point. nab-PC produced less neuropathy than sb-PC.