tbuckley/cabot-search huggingface dataset:
Effect of insulin on the distribution and disposition of glucose in man.
Authors: E Ferrannini, J D Smith, C Cobelli, G Toffolo, A Pilo, R A DeFronzo
Journal: Journal of Clinical Investigation (1985)

Understanding the influence of insulin on glucose turnover is the key to interpreting a great number of metabolic situations. Little is known, however, about insulin's effect on the distribution and exchange of glucose in body pools. We developed a physiological compartmental model to describe the kinetics of plasma glucose in normal man in the basal state and under steady-state conditions of euglycemic hyperinsulinemia. A bolus of [3-3H]glucose was rapidly injected into a peripheral vein in six healthy volunteers, and the time-course of plasma radioactivity was monitored at very short time intervals for 150 min. A 1-mU/min kg insulin clamp was then started, thereby raising plasma insulin levels to a high physiological plateau (approximately 100 microU/ml). After 90 min of stable euglycemic hyperinsulinemia, a second bolus of [3-3H]glucose was given, and plasma radioactivity was again sampled frequently for 90 min more while the clamp was continued. Three exponential components were clearly identified in the plasma disappearance curves of tracer glucose of each subject studied, both before and after insulin. Based on stringent statistical criteria, the data in the basal state were fitted to a three-compartment model. The compartment of initial distribution was identical to the plasma pool (40 +/- 3 mg/kg); the other two compartments had similar size (91 +/- 12 and 96 +/- 9 mg/kg), but the former was in rapid exchange with plasma (at an average rate of 1.09 +/- 0.15 min-1), whereas the latter exchanged 10 times more slowly (0.12 +/- 0.01 min-1). The basal rate of glucose turnover averaged 2.15 +/- 0.12 mg/min kg, and the total distribution volume of glucose in the postabsorptive state was 26 +/- 1% of body weight. In view of current physiological information, it was assumed that the more rapidly exchanging pool represented the insulin-independent tissues of the body, while the slowly exchanging pool was assimilated to the insulin-dependent tissues. Insulin-independent glucose uptake was estimated (from published data) at 75% of basal glucose uptake, and was constrained not to change with euglycemic hyperinsulinemia. When the kinetic data obtained during insulin administration were fitted to this model, neither the size nor the exchange rates of the plasma or the rapid pool were appreciably changed. In contrast, the slow pool was markedly expanded (from 96 +/- 9 to 190 +/- 30 mg/kg, P less than 0.02) at the same time as total glucose disposal rose fourfold above basal (to 7.96 +/- 0.85 mg/min kg, P less than 0.001). Furthermore, a significant direct correlation was found to exist between the change in size of the slow pool and the insulin-stimulated rate of total glucose turnover (r=0.92, P<0.01). We conclude that hyperinsulinemia, independent of hyperglycemia, markedly increases the exchangeable mass of glucose in the body, presumably reflecting the accumulation of free, intracellular glucose in insulin-dependent tissues.
A multi-institution phase II study of poly-ICLC and radiotherapy with concurrent and adjuvant temozolomide in adults with newly diagnosed glioblastoma
Authors: M. R. Rosenfeld, M. C. Chamberlain, S. A. Grossman, D. M. Peereboom, G. J. Lesser, T. T. Batchelor, S. Desideri, A. M. Salazar, X. Ye
Journal: Neuro-Oncology (2010)

The objectives of this study were to determine the safety and efficacy of polyinosinic-polycytidylic acid stabilized with poly-l-lysine and carboxymethylcellulose (poly-ICLC) when added to radiation and temozolomide (TMZ) in adults with newly diagnosed glioblastoma (GB). Patients received external beam radiation with concurrent TMZ (75 mg/m2/day) followed by adjuvant TMZ (150–200 mg/m2/day for 5 consecutive days once every 9 weeks) and intramuscular poly-ICLC (20 mg/kg/dose given 3× per week for weeks 2–8). An adjuvant cycle was operationally defined as 9 weeks and patients continued adjuvant therapy until toxicity or disease progression. Ninety-seven patients were enrolled (60 men) with a median age of 56 years (range 21–85) and Karnofsky performance status of 90% (range 60%–100%). Fourteen patients did not start adjuvant treatment. Common treatment-related Grade 3–4 toxicities included neutropenia (20.6%), leukopenia (16.5%), thrombocytopenia (9%), and rash (1%). The entire cohort had a median survival of 17.2 months (95% CI: 15.5–19.3 months) with survival at 12, 18, and 24 months of 73.2%, 47.4%, and 29.9%. For subjects 18–70 years old, median overall survival was 18.3 months (95% CI: 15.9–19.8 months), as compared with 14.6 (95% CI: 13.2–16.8) reported by the EORTC 26981/22981 trial. These results demonstrate that poly-ICLC can be added to standard radiation and TMZ in patients with newly diagnosed GB without additional significant toxicities. Survival data at 12 and 18 months suggest that this may improve the efficacy of chemoradiation and adjuvant TMZ in this patient population.
Short- and long-term efficacy of a community-based COPD management programme in less advanced COPD: a randomised controlled trial
Authors: C R van Wetering, M Hoogendoorn, S J M Mol, M P M H Rutten-van Molken, A M Schols
Journal: Thorax (2009)

<h3>Background:</h3> The effectiveness of pulmonary rehabilitation in advanced COPD is well established, but few data are available in less advanced disease. <h3>Methods:</h3> In a 2 year randomised controlled trial, 199 patients with an average moderate airflow obstruction but impaired exercise capacity (mean (SD) forced expiratory volume in 1 s (FEV<sub>1</sub>) 60 (16)%, peak work load (Wmax) &lt;70%) were randomised to the INTERdisciplinary COMmunity-based COPD management programme (INTERCOM) or usual care. Intervention consisted of 4 months multidisciplinary rehabilitation followed by a 20-month maintenance phase. Outcomes (4, 12, 24 months): health-related quality of life (St George’s Respiratory Questionnaire (SGRQ)), exacerbation frequency, MRC dyspnoea score, cycle endurance time (CET), 6-minute walking distance (6MWD), skeletal muscle strength and patients’ and caregivers’ perceived effectiveness. <h3>Results:</h3> Between-group comparison after 4 months revealed the following mean (SE) significant differences in favour of INTERCOM: SGRQ total score 4.06 (1.39), p = 0.004; activity and impact subscores, p&lt;0.01; MRC score 0.33 (0.13), p = 0.01; Wmax 6.0 (2.3) Watt, p = 0.02; CET 221 (104) s, p = 0.04; 6MWD 13 (6) m, p = 0.02; hand grip force 4.3 (1.5) lb, p&lt;0.01; and fat-free mass index 0.34 (0.13) kg/m<sup>2</sup>, p = 0.01. Between-group differences over 2 years were as follows: SGRQ 2.60 (1.3), p = 0.04; MRC score 0.21 (0.10), p = 0.048; CET 253 (104) s, p = 0.0156; 6MWD 18 (8) m, p = 0.0155. Exacerbation frequency was not different (RR 1.29 (95% CI 0.89 to 1.87)). Patients’ and caregivers’ perceived effectiveness significantly favoured the INTERCOM programme (p&lt;0.01). <h3>Conclusions:</h3> This study shows that a multidisciplinary community-based disease management programme is also effective in patients with COPD with exercise impairment but less advanced airflow obstruction. <h3>Trial registration number:</h3> NCT00840892
The Zuni Kidney Project
Authors: Christine A. Stidley, Vallabh O. Shah, Marina Scavini, Andrew S. Narva, David Kessler, Arlene Bobelu, Jean W. MacCluer, Thomas K. Welty, Philip G. Zager
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. There is an epidemic of renal disease among the Zuni Indians. In contrast to most other American-Indian communities, the epidemic of renal disease among the Zuni Indians reflects high rates of diabetic and nondiabetic renal disease. Almost every Zuni Indian has a relative with end-stage renal disease. This epidemic offers a unique opportunity to advance our understanding of the risk factors for the susceptibility and/or progression of renal disease. Thus, Zuni Tribal leaders formed a research partnership with the University of New Mexico Health Sciences Center, Indian Health Service, Southwest Foundation for Biomedical Research and Dialysis Clinic Inc., to establish the Zuni Kidney Project (ZKP). The ZKP conducted a population-based, cross-sectional survey of the Zuni Pueblo. Age and gender distributions among survey participants were similar to those of the eligible Zuni population. Among diabetics the prevalence (95% confidence interval) of incipient albuminuria (IA) was 32.3% (25.1, 39.5) in women and 36.1% (24.7, 47.5) in men. The prevalence of IA among nondiabetics was 9.3% (6.9, 11.7) in women and 12.2% (9.7, 14.7) in men. Among diabetics, the prevalence of overt albuminuria (OA) was 17.7% (11.9, 23.5) in women and 20.8% (11.4, 30.2) in men. Among nondiabetics, OA was present in 1.2% (0.3, 2.1) of women and 2.3% (1.1, 3.5) of men. Although IA and OA were each more common among diabetics, the majority of participants with albuminuria were nondiabetics. Hematuria was common among both diabetics and nondiabetics. Among diabetics, the crude prevalence of hematuria was similar among men and women. Among nondiabetics, however, hematuria was more common among women. Diabetes and obesity were more common among women than men. In contrast, hypertension and hypercholesterolemia were more common among men than women. The ZKP is incorporating these preliminary data into planning for the development and implementation of primary and secondary prevention programs. E-mail: [email protected]
INFANTILE AMAUROTIC FAMILY IDIOCY
Authors: A. T. Steegmann, Louis J. Karnosh
Journal: American Journal of Psychiatry (1936)

1. A case of amaurotic family idiocy was studied clinically and pathologically. 2. Clinically interesting tonic and decerebrate phenomena were observed in addition to the retinal changes. 3. Pathologically, megalocephaly, cerebellar atrophy and the changes in the retina were described.
DNA flow cytometric evaluation of cell cycle distribution in ulcerative colitis: a proposed method for assessing severity of disease.
Authors: F Bortoluzzi, M Valentini, C Cernigoi, G Toffoli, M Boiocchi, M Poletti, M Sozzi, M Fornasarig, R Cannizzaro, E Bertolissi
Journal: Gut (1995)

The assessment of disease severity in ulcerative colitis depends mainly on subjective variables, and an objective method of assessing mucosal inflammation is needed. Determination of the synthetic phase of the cell cycle is an accurate expression of inflammatory activity in the colonic mucosa. The aim of the study was to find out if the proliferative index or the synthetic phase (S phase) of the colonic mucosa of patients with ulcerative colitis, as evaluated by DNA flow cytometry, is a reliable and reproducible marker of disease activity. Sixty consecutive patients with ulcerative colitis of different degrees of activity were entered into the study and submitted to colonoscopy plus multiple rectal biopsies. Disease severity was defined for each patient by means of a clinical, endoscopic, and histological score. Flow cytometry was used to calculate the proliferative index and the S phase of the cell cycle. A statistically significant correlation (p < 0.001) was found between all indices of severity. It is suggested that flow cytometric evaluation of the cell cycle in the rectal mucosa may be an efficient method of assessing severity of disease and efficacy of medical treatment in ulcerative colitis.
Respiratory resistive impedance in obstructive patients: linear regression analysis vs viscoelastic modelling
Authors: AM Lorino, F Zerah, C Mariette, A Harf, H Lorino
Journal: European Respiratory Journal (1997)

The aim of this study was to test the ability of a simple two segment model to describe the frequency dependence of resistive impedance in obstructive patients, and to investigate the significance of parameters derived from this model. The study was performed in 38 patients, in the basal state and after inhalation of 200 micrograms salbutamol. Impedance data measured over 4-32 Hz were fitted by a general four parameter viscoelastic model describing gas redistribution, and completed by an inertial component. This model yielded Newtonian resistance (Rmin) and maximal resistance (Rmax = Rmin plus delayed resistance due to gas redistribution). Resistive impedance data were also submitted to linear regression analysis over the 4-16 and 17-32 Hz frequency ranges, which respectively, yielded resistive impedance extrapolated at 0 Hz (R0) and resistive impedance estimated at 32 Hz (R32). R0 and R32 were compared to Rmax and Rmin, respectively. The airway response to salbutamol inhalation was assessed by the percentage changes in these parameters (R0%, R32%, Rmax%, and Rmin%, respectively). Significant linear correlations (p &lt; 0.0001) were found between R0 and Rmax, R32 and Rmin, and R0% and Rmax%. Furthermore, the linear regression lines of R0 vs Rmax, and R0% vs Rmax%, were not significantly different from the identity line. These results demonstrate that resistive impedance extrapolated at zero frequency is equivalent to maximal resistive impedance, and can be proposed as an index, not only of the level of airway obstruction, but also of its reversibility.
In vitro granulocyte adherence and in vivo margination: two associated complement-dependent functions
Authors: J Fehr, HS Jacob
Journal: The Journal of Experimental Medicine (1977)

To study mechanisms and mediators regulating the distribution of intravascular granulocytes between circulating and marginated pools, a human model with extreme transient margination, the neutropenia of continuous flow filtration leukophoresis, was analyzed. Studies in animals demonstrated the existence of a complement (C)-derived granulocytopenia-inducing factor. Thus, autologous plasma, exposed to nylon fibers (NF) of the filtration system, produced an acute selective decrement of circulating granulocytes and monocytes. This phenomenon was blocked by decomplementing plasma, by pretreatment of plasma with EDTA or hydrazine, and by preheating at 56 degrees C, but did occur after recombination of heat-inactivated and hydrazine-treated plasma before NF exposure. Preheating plasma at 50 degrees C did not inhibit the neutropenic response, suggesting involvement of the classical pathway of C activation. Ultrafiltration studies indicated that the NF-provoked neutropenia-inducing factor has a mol wt in the range of 10,000-30,000, and is heat stable (56 degrees C). To analyze the hypothesis that C- induced neutrophil margination might be consequent to increased cell adhesiveness to endothelial surfaces, the role of C in promoting granulocyte adherence was evaluated in vitro. Measured with a plastic Petridish assay, granulocyte adherence was significantly reduced in heat- inactivated (56 degrees C) and hydrazine-treated plasma, but adherence promoting capacity was restored by mixing the two plasmas, or by adding purified C3 to hydrazine-treated plasma. After exposure to activated C, neutrophils showed significantly increased adhesiveness which was maintained when cells were resuspended in heat-inactivated plasma, but progressively lost when resuspended in fresh plasma. On the basis of these results we conclude that granulocyte adhesiveness in vitro and margination in vivo are closely associated, C-dependent phenomena.
A genome-wide association analysis of serum iron concentrations
Authors: Toshiko Tanaka, Cindy N. Roy, Wenliang Yao, Amy Matteini, Richard D. Semba, Dan Arking, Jeremy D. Walston, Linda P. Fried, Andrew Singleton, Jack Guralnik, Gonçalo R. Abecasis, Stefania Bandinelli, Dan L. Longo, Luigi Ferrucci
Journal: Blood (2009)
Phase II Study of Carboplatin in Children With Progressive Low-Grade Gliomas
Authors: Sridharan Gururangan, Christina M. Cavazos, David Ashley, James E. Herndon, Carol S. Bruggers, Albert Moghrabi, Deborah L. Scarcella, Melody Watral, Sandra Tourt-Uhlig, David Reardon, Henry S. Friedman
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To assess the rate of tumor response and activity of carboplatin in stabilizing the growth of progressive low-grade gliomas. PATIENTS AND METHODS: Eligible patients received carboplatin 560 mg/m 2 intravenously every 4 weeks for 1 year after maximum tumor response or until disease progression or unacceptable toxicity. RESULTS: Between October 1993 and October 2000, 81 children (median age, 79 months; range, 6 to 204) were enrolled onto this study. Patients received a median of 11 cycles of carboplatin (range, one to 29). Median follow-up from the time of enrollment was 55 months (range, 10 to 93). The overall objective response (complete response [CR] + partial response [PR] + minor response [MR]) and disease stabilization (CR + PR + stable disease + MR) rates to carboplatin treatment were 28% (95% confidence interval [CI], 18% to 38%) and 85% (95% CI, 74% to 93%), respectively. Eleven and 14 patients suffered progressive disease on study and after stopping therapy, respectively. Toxicity was predominantly myelosuppression and included grade 3/4 neutropenia in 56 patients and grade 3/4 thrombocytopenia in 40 patients. The 3-year failure-free survival (FFS) and overall survival (OS) for all patients were 64% (95% CI, 54% to 76%) and 84% (95% CI, 76% to 93%), respectively. Patients with diencephalic tumors had inferior FFS and OS compared with those with tumor at other sites (38% v 74% for FFS, P = .011; 54% v 91% for OS, P = .004). Neurofibromatosis type 1 patients with progressive low-grade glioma had a significantly better OS (95% v 80%; P = .052). CONCLUSION: Carboplatin, in the schedule used in this study, produced disease stabilization or improvement in a majority of children with progressive low-grade glioma, with manageable toxicity. Improved treatment strategies are particularly required for patients with diencephalic tumors.
Knee Effusion in Young Adults as an Early Sign of Degenerative Arthritis
Authors: R. W. Parnell
Journal: Annals of the Rheumatic Diseases (1951)

Three successive undergraduates attending for routine health examination showed signs of a small effusion in the knee joint.This led to the question:Was such an amount of fluid normal, or was it, as is commonly taught, pathological when sufficient to be demonstrated clinically ? in the absence of symptoms there was no indication to draw attention to a condition the cause of which was so uncertain.
Adenine nucleotide translocator, a mitochondrial carrier protein, and fate of cardiomyocytes after ischaemia/reperfusion
Authors: M. Tanno, T. Miura
Journal: Cardiovascular Research (2008)

Mitochondria have multiple roles in the development of ischaemia/reperfusion injury. Consumption of ATP by mitochondrial ATPase during ischaemia and generation of reactive oxygen species (ROS) from complex III during ischaemia/reperfusion are detrimental to cardiomyocytes, whereas uptake of cytosolic Ca2+ into mitochondria attenuates cytosolic Ca2+ overload and thus activation of Ca2+-activated proteases such as calpain. However, the most important event in the mitochondria of cardiomyocytes subjected to ischaemia/reperfusion is opening of the mitochondrial permeability transition pore (mPTP).1 Although its molecular structure is still controversial, mPTP apparently consists of an adenine nucleotide translocator (ANT) in the inner membrane, a carrier exchanging matrix ATP with ADP in the intermembrane space,2 and a voltage-dependent anion channel (VDAC) in the outer membrane of the mitochondria.3 The mPTP is closed under physiological conditions but opens in response to cellular stresses, leading to ATP depletion, increase in inorganic phosphate levels, ROS generation, and mitochondrial Ca2+ overload. Opening of mPTP upon reperfusion following ischaemia abolishes mitochondrial membrane potential and compromises ATP generation, which is crucial for restoration of ionic homeostasis and maintenance of cell viability.4

The threshold for opening of mPTP has been shown to be elevated by ischaemic pre- … 

*Corresponding author. Tel: +81 11 611 2111; fax: +81 11 644 7958. E-mail address : tannom{at}sapmed.ac.jp
The Paradox of Tobacco Control
Authors: David Satcher
Journal: JAMA (1994)

Under the best of circumstances, knowledge brings about changes in behavior and public policy. When thinking about what we know and what we have accomplished in the realm of smoking and health, we perceive a paradox. Decades of careful medical research have documented the hazards of smoking. Social scientists continue to investigate and define the factors that impede efforts to prevent the use of tobacco. We know that nicotine is an addictive substance and that our children are very vulnerable to this addiction. We know that smoking is the single greatest cause of death in the United States.<sup>1</sup>Yet, we are still plagued by an entirely preventable problem, and this is the paradox of tobacco control. To better understand this paradox and perhaps be better able to reconcile what we know and what we do, we have developed a framework that provides an organized approach to categorizing tobacco control
P244 Accuracy of Admission Diagnosis of Pneumonia
Authors: Lc Price, Ms Anwar, K Srikanthan, A Bercusson, E Williams, E Prior, A Owusu-Ageyi, H Umpleby, M Berry
Journal: Thorax (2013)

<h3>Background</h3> The inclusion of ‘new infiltrates’ on the admission chest radiograph (CXR) is part of the BTS audit tool (1), but it has been reported that up to 37% of inpatients coded (using the ICD-10 coding system) as pneumonia did not have CXR consolidation (2). We assessed our local audit population for potential reasons for this pneumonia miscoding. <h3>Methods</h3> Patients selected by coding for the 2012/13 BTS Pneumonia Audit at hospitals within Imperial Healthcare Trust (Charing Cross (CX), Hammersmith (HH) and St Mary’s (SMH) Hospitals) underwent a notes review. <h3>Results</h3> Of all patients clinically coded as community-acquired pneumonia (CAP), 88/176 (50%) had a diagnosis of CAP compatible with the audit criteria, with infiltrates on the admission CXR–in 15 (39%), 25 (61%) and 48 (50%) of cases at CX, HH and SMH respectively. Of the patients found not to have CAP by the current BTS audit criteria (n = 88), 47/88 (53%) had an abnormal admission CXR <i>not</i> showing CAP. The main abnormalities in these admission CXRs were pulmonary oedema (in 30%), COPD/bronchiectasis (27%), malignancy (13%), interstitial lung disease (ILD) (7%) and pleural effusions (7%). In the 88 ‘non-audit criteria CAP’ patients, in combination with symptoms, inflammatory markers (WCC 10.4 (1.7–33) x10<sup>9</sup> and CRP 84.8 (3.6–381) mg/L), and the CXR series, the likely diagnosis was felt to be LRTI (35%), CAP (17%), HAP (13%), COPD (10%), pulmonary oedema (9%), malignancy (4.5%), UTI (3%), and ILD, asthma and effusions (all 2%), in the ‘non-audited CAP’ patients. Of those remaining 41 patients with a normal admission CXR excluded from the audit, 24 patients (59%) had a repeat CXR within 72h, of which 5 (21%) then showed CAP. An additional 12 patients with normal admission CXRs had CT scans performed within 72h, 6 of which (50%) detected consolidation. Thus, of all the patients with a normal admission CXR, 11 (27%) had CAP that was missed by solely looking at the admission CXR. <h3>Conclusion</h3> We confirm earlier findings that coding diagnoses are insufficiently accurate to judge quality of care, but also show that current audit criteria exclude a significant proportion of cases. <h3>References</h3> WS Lim, <i>et al. Thorax</i> 2011;66:548–549 Ruickbie SV, <i>et al. Thorax</i> 2012;67(Suppl 2):A69