tbuckley/cabot-search huggingface dataset:
The Glucose Area Under the Profiles Obtained With Continuous Glucose Monitoring System Relationships With HbAlc in Pediatric Type 1 Diabetic Patients
Authors: Silvana Salardi, Stefano Zucchini, Roberta Santoni, Luca Ragni, Stefano Gualandi, Alessandro Cicognani, Emanuele Cacciari
Journal: Diabetes Care (2002)

The purpose of this study was to determine whether the continuous glucose monitoring system (CGMS) (MiniMed, Sylmar, CA) 1) is sufficiently representative of the overall metabolic control as assessed by HbA(1c), 2) could be used to identify a particular blood glucose threshold value affecting hemoglobin glycation; and 3) is able to show any relationship between particular glycemic profiles and HbA(1c) levels.Of 44 pediatric patients with type 1 diabetes who wore CGMS devices, 28 subjects were selected for the study. Criteria for inclusion were high levels of HbA(1c) (> or =8%) for more than 1 year or a history of frequent hypoglycemic episodes and a complete CGMS registration for 72 h. Age of the subjects ranged from 5.7 to 24.8 years, the mean duration of disease was 7.63 +/- 4.75 years, and the mean HbA(1c) value was 8.7 +/- 1.3%. CGMS data were downloaded and glucose profiles were analyzed. The area under each glucose profile was calculated by means of a professional digital planimeter.The glucose profiles showed a high frequency of prolonged hyperglycemic periods (80% of subjects) and a low frequency of postmeal glycemic peaks (29% of subjects). Postlunch values were significantly correlated with HbA(1c) levels, but the correlation disappeared when controlling for glucose area values. Glucose area values significantly correlated with HbA(1c) levels both when considered as a whole (40-400 mg/dl; r = 0.53, P = 0.002) and when considered fractioned (40-150, 40-200, 40-250, 40-300 mg/dl), apart from the 40-90 mg/dl partial area. HbA(1c) levels were significantly decreased 3 and 6 months after use of CGMS (P = 0.05 and 0.03, respectively, paired Student's t test).HbA(1c) levels may be decreased by using the information obtained with the CGMS. Three-day glucose profiles are representative of the overall glucose control, because glucose area values correlate with HbA(1c) levels. The only glucose threshold below which there seems to be no correlation with HbA(1c) is 90 mg/dl. Only glucose area, and not postprandial glucose values, are directly and independently correlated with HbA(1c). Therefore, to improve metabolic control, it is necessary to lower the whole mean 24-h glycemia and not just the postprandial glucose values.
Locally Activated Renin-Angiotensin System Associated with TGF-β1 as a Major Factor for Renal Injury Induced by Chronic Inhibition of Nitric Oxide Synthase in Rats
Authors: MINORU KASHIWAGI, MICHIYA SHINOZAKI, HIDEKI HIRAKATA, KIYOSHI TAMAKI, TADASHI HIRANO, MASANORI TOKUMOTO, HIROSHIGE GOTO, SEIYA OKUDA, MASATOSHI FUJISHIMA
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Chronic inhibition of nitric oxide synthase (NOS) is known to cause renal parenchymal injury with systemic hypertension. To elucidate the pathogenetic mechanism in renal damage induced by NOS inhibition, N ω -nitro-L-arginine methyl ester (L-NAME) was given orally for 12 wk in Wistar rats, and the roles of tissue renin-angiotensin system and transforming growth factor-β1 (TGF-β1) were investigated. BP and urinary protein excretion increased significantly in L-NAME rats compared with control rats, and glomerulosclerosis and interstitial fibrosis developed. In L-NAME rats, the cortical tissue levels of angiotensin-converting enzyme activity and angiotensin II were significantly higher than those in control rats. The cortical mRNA expressions of both TGF-β1 and fibronectin were significantly elevated in L-NAME rats. Immunohistochemically, increased expressions of both fibronectin and α-smooth muscle actin were also revealed in L-NAME rats. In L-NAME rats, these histologic injuries and the increased expression of TGF-β1 were equally emeliorated by either angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor antagonist, but not by hydralazine. In conclusion, the locally activated renin-angiotensin system in connection with the increased TGF-β1 expression is a major pathogenetic feature of renal injury in chronically NOS-inhibited rats.
Effects of Liver Fractions on Myocardial Contractility
Authors: JACK PETER GREEN, L. H. NAHUM
Journal: Circulation Research (1957)

Tyramine was crystallized and identified as one of the cardioactive materials in liver extract. Of many other compounds tested on the isolated papillary muscle of the cat, only methionine, ethionine, serotonin, heparin, testosterone, Menadione, and Dicoumarol showed activity.
Clinical and Immunologic Results of a Phase II Trial of Sequential Imiquimod and Photodynamic Therapy for Vulval Intraepithelial Neoplasia
Authors: Ursula Winters, Sai Daayana, John T. Lear, Anne E. Tomlinson, Eyad Elkord, Peter L. Stern, Henry C. Kitchener
Journal: Clinical Cancer Research (2008)

Abstract Purpose: High-risk human papillomavirus (HPV)-associated vulval intraepithelial neoplasia (VIN) is difficult to treat by excision or ablation because of high recurrence rates. Small studies of photodynamic therapy (PDT) and imiquimod treatments have shown some success and function at least in part through stimulation of local immune responses. Indeed, there is evidence that immunosuppressed individuals have higher rates of VIN, suggesting immune control is relevant. Experimental Design: In the study, 20 women with high-grade VIN were treated with topical imiquimod and the PDT sequentially. Vulval biopsy and blood were taken pretreatment and, after imiquimod and PDT, with follow up for 1 year. Clinical response was assessed by measuring lesion size. Biopsies were analyzed for HPV DNA and tumor-infiltrating lymphocytes including T regulatory cells. Results: The treatment was well-tolerated. There was an overall response rate of 55% by intention treat and 64% per protocol. The 52-week symptom response was 65% asymptomatic, compared with 5% at baseline. The nonresponders showed a significantly higher level of T regulatory cells in the lesions after imiquimod treatment. Conclusions: The response rates are clinically relevant, and the treatment regimen was feasible for the majority. Initial nonresponders to imiquimod seem to be relatively refractory, and this may derive from their unfavorable local immune environment, in particular, the increased proportions of T regulatory cells, possibly the limiting action and/or development of any HPV T-cell immunity. The potential benefit of this treatment is its ability to treat multifocal disease.
You deserve what you eat: lessons learned from the study of the melanin-concentrating hormone (MCH)-deficient mice
Authors: Yan Wang, Dimitrios C Ziogas, Sudha Biddinger, Efi Kokkotou
Journal: Gut (2010)

<h3>Objectives</h3> Diet plays a crucial role in the development of obesity and insulin resistance via multiple mechanisms. Saturated fatty acids can directly trigger tissue specific proinflammatory pathways via Toll-like receptor-4 (TLR4)-dependent mechanisms. Moreover, diet can change the gut microbiome and increase gut permeability. However, very few studies have addressed the obesity-independent role of diet. Dissecting the effects of diet from those of obesity per se will enhance our understanding of the underlying pathogenesis, and, at the translational level, advance our treatment approaches for obesity and its co-morbidities. <h3>Methods</h3> Melanin-concentrating hormone (MCH) is an important regulator of appetite and energy balance. MCH-deficient mice are resistant to diet-induced obesity, primarily due to increased locomotor activity. We took advantage of the unique phenotype of these mice to examine the metabolic and inflammatory consequences of a 15-week consumption of a diet high in saturated fat. <h3>Results</h3> MCH-deficient mice chronically exposed to a high-fat diet gain less weight compared to their wild-type littermates, despite similar food intake, and are protected from hepatosteatosis. They also lack obesity-associated upregulation of serum leptin and insulin levels and have improved total body insulin sensitivity. Nevertheless, we found indistinguishable liver-specific innate immune responses in both genotypes associated with high-fat feeding, which involved activation of TLR4 and its downstream effectors, MyD88, p38 MAP kinase and STAT-3. <h3>Conclusions</h3> Our findings indicate that high-fat feeding is deleterious to the liver, independently of the obesity status. They also suggest that MCH is not necessary for the TLR4-dependent immune response triggered by the high-fat diet.
Establishment of the mouse ventricular conduction system
Authors: L. Miquerol, S. Beyer, R. G. Kelly
Journal: Cardiovascular Research (2011)

The ventricular conduction system represents the electrical wiring responsible for the co-ordination of cardiac contraction. Defects in the circuit produce a delay or conduction block and induce cardiac arrhythmias. Understanding how this circuit forms and identification of the factors important for its development thus provide insights into the origin of cardiac arrhythmias. Recent advances, using genetically modified mouse models, have contributed to our understanding of how the ventricular conduction system is established during heart development. Transgenic mice carrying different reporter genes have highlighted the conservation of the anatomy and development of the ventricular conduction system between mice and humans. Lineage tracing and retrospective clonal analysis have established the myogenic origin of the ventricular conduction system and determined properties of conductive progenitor cells. Finally, gene knock-out models reproducing human cardiac defects have led to the identification of transcription factors important for the development of the ventricular conduction system. These transcription factors operate at the levels of both conduction system morphogenesis and differentiation by controlling the expression of genes responsible for the electrical activity of the heart. In summary, defects in the ventricular conduction system are a major cause of arrhythmias, and deciphering the molecular pathways responsible for conduction system morphogenesis and the differentiation of conductive myocytes furthers our understanding of the mechanisms underlying heart disease.
Pernicious Anaemia treated with Pyloro-duodenal Extract and Liver in Tablet Form
Authors: J. S. Lawrence
Journal: BMJ (1943)

Pernicious Anaemia treated with Pyloroduodenal Extract and Liver in Tablet Form Parenteral liver therapy is occasionally complicated by severe reactions.These may take the form of local pain or general effects such as headache, flushing, urticaria, dyspnoea, and even collapse.They are usually overcome by injecting minute doses of liver extract-1/250 c.cm., 1/25 c.cm., and 1/2 c.cm.-at intervals, together with adrenaline.A nervous patient, upset by the.reaction, may refuse further injections, and in such a case resort must be had to an oral preparation.An order made by the Minister of Health prohibits the oral use of liver extract as such, but in this preparation the liver is unextracted.It was tested on the following untreated case of pernicious anaemia.
Stages in the development of a research project: putting the idea together
Authors: Roger G Eston, Ann V Rowlands
Journal: British Journal of Sports Medicine (2000)

We have considered some of the most important factors involved in designing a viable study that will adequately address the research question. Although we do not profess to be experts in all aspects of the above, we have learned through experience that attention to many of the above points will help to avoid frustration during the experimental process and when the study is presented for external review and subsequent presentation and publication. Good luck in your research.
Clinical and pharmacokinetic phase II study of fotemustine in refractory and relapsing multiple myeloma patients
Authors: C. Dumontet, J. Jaubert, C. Sebban, F. Bouafia, C. Ardiet, B. Tranchand, E. Berger, C. Lucas, D. Guyotat, B. Coiffier
Journal: Annals of Oncology (2003)
A longitudinal cohort study of Finnish patients with primary Sjogren's syndrome: clinical, immunological, and epidemiological aspects
Authors: M Pertovaara
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To evaluate outcome in a cohort of Finnish patients with primary Sjögren9s syndrome (pSS). <h3>METHODS</h3> Clinical and laboratory data from the time of diagnosis and follow up were collected from 110 patients with pSS (107 women, three men) diagnosed in 1977–1992 in central Finland. The standardised incidence ratio for cancers was determined as the ratio of the observed number of cases to the expected number based on regional population rates. Eighty one of the 93 patients still alive were interviewed, and clinical and laboratory examinations performed in 1994–1997. <h3>RESULTS</h3> The mean (SD) erythrocyte sedimentation rate (33 (22) <i>v</i> 45 (28) mm/1st h), serum IgG (18.8 (7.4) <i>v</i> 22.5 (8.5) g/l), and serum IgM (1.6 (1.1) <i>v</i> 2.0 (1.2) g/l) at the control visit were significantly (p&lt;0.0001) lower than those at baseline. A similar change was observed in a subgroup of patients never treated with glucocorticosteroids or disease modifying antirheumatic drugs. Three non-Hodgkin9s lymphomas were diagnosed (standardised incidence ratio 13; 95% confidence interval 2.7 to 38). In a logistic regression model, the patients with pSS with subsequent lymphoma were found to have higher baseline levels of serum β<sub>2</sub> microglobulin than the others (odds ratio 1.9; 95% confidence interval 1.1 to 3.4). <h3>CONCLUSION</h3> The results suggest that mean concentrations of serum IgG and IgM in patients with pSS decline with time, possibly reflecting diminishing inflammatory activity. As in previous studies, the incidence of non-Hodgkin9s lymphomas in this cohort of patients with pSS was significantly higher than in the reference population.
Effects of a novel noninvasive open ventilation system during constant work rate exercise in COPD
Authors: Janos Porszasz, Robert Cao, Richard Morishige, Richard Casaburi
Journal: European Respiratory Journal (2012)

Exercise intolerance limits daily activities of COPD patients. Noninvasive ventilation improves exercise capacity in severe COPD, but previous systems are impractical for ambulatory use. This study evaluated a 0.45 kg noninvasive open ventilation (NIOV) system (Breathe Technologies), designed for nasal delivery of compressed O 2  with each inhalation.  This was a randomized single-blinded study of 10 men with severe-to-very severe COPD and exercise desaturation. Following a test day in which a cycle ergometer constant work rate (CWR) was established, subjects completed 3 additional days in which 2-3 CWR tests (separated by 1.5 hrs) were performed in random order. Tests were: unencumbered room air, NIOV+air, NIOV+O 2 , or O 2  via standard nasal cannula. Data collected included exercise time, SpO 2  and transcutaneous (Tc) PCO 2 .  Subjects ages were 67±9y, with FEV 1 /FVC=29±6% and FEV 1 =30±12% pred. Compared to unencumbered and NIOV+air arms, endurance was prolonged ∼75% by nasal cannula O 2  and ∼330% by NIOV+O 2  (Table). The greater endurance in the NIOV+O 2  tests was accompanied by higher SpO 2  but unaltered TcPCO 2 .  Exercise endurance was dramatically enhanced using the NIOV system+O 2 . These data suggest that this system is a practical means to improve tolerance of everyday activities in oxygen-dependent severe COPD.
Who bears the costs of occupational asthma?
Authors: P. S. Burge
Journal: Thorax (2010)

Most workers with occupational asthma who remain exposed to the causative agent have accelerated loss of FEV11 and recover less when eventually removed from exposure than those removed within the first year of occupational asthma symptoms.2 The reasons for this are not obvious, as most childhood onset asthmatics remain exposed to the causative allergens and infrequently develop severe airflow obstruction later in life. It is possible that the timing of exposure related to the maturity of the immune system is critical, and the development of a degree of tolerance is more common in childhood than later in life. Whatever the reasons, the recommendation for removal from exposure within a year of first occupational asthma symptoms is based on good evidence.2

There is an established societal view that those disabled by their work through no fault of theirs are entitled to some form of compensation. How this is achieved varies widely between countries. Most countries rely on an insurance-based system, sometimes with support from the government.3 In the UK there is a dual system with a no-fault compensation system without employer contribution funded by the central government and a common law system which requires the establishment of negligence on the part of the employer. Neither work well in the context of occupational asthma. Central to compensation is the assessment …
Use of Magnetic Resonance Imaging to Assess Blood-Brain/Blood-Glioma Barrier Opening During Conformal Radiotherapy
Authors: Yue Cao, Christina I. Tsien, Zhou Shen, Daniel S. Tatro, Randall Ten Haken, Marc L. Kessler, Thomas L. Chenevert, Theodore S. Lawrence
Journal: Journal of Clinical Oncology (2005)

For chemotherapy to act synergistically and safely with radiation against high-grade gliomas, drugs must pass the endothelial junctions of the blood-tumor barrier (BTB) to reach all tumor cells, and should not pass the blood-brain barrier (BBB) to cause toxicity to normal brain. The objective of this study was to assess BBB/BTB status using magnetic resonance imaging (MRI) during a course of radiotherapy of high-grade gliomas.Sixteen patients with grade 3 or 4 supratentorial malignant glioma receiving conformal radiotherapy (RT) underwent contrast-enhanced MRI before, during, and after completion of RT. A gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) uptake index was analyzed with respect to the tumor and RT dose received.In the nonenhanced tumor region, contrast uptake increased significantly after the receipt of approximately 10 Gy (P < .01), and reached a maximum after the receipt of approximately 30 Gy. In the initially contrast-enhanced tumor region, contrast uptake decreased over the course of RT and became significant after completion of RT in patients without progressive disease. The healthy brain showed only nonsignificant changes during and after irradiation.Contrast MRI reveals increases in Gd-DTPA uptake in the initially nonenhanced tumor region but not in the remaining brain during the course of RT, suggesting opening of the BTB. This finding suggests that the effect of conformal radiation is more selective on the BTB than the BBB, and there may be a window extending from 1 week after the initiation of radiotherapy to 1 month after the completion of treatment during which a pharmaceutical agent has maximum access to high-grade gliomas.
Differential Tumor Surveillance by Natural Killer (Nk) and Nkt Cells
Authors: Mark J. Smyth, Kevin Y. T. Thia, Shayna E.A. Street, Erika Cretney, Joseph A. Trapani, Masaru Taniguchi, Tetsu Kawano, Sonja B. Pelikan, Nadine Y. Crowe, Dale I. Godfrey
Journal: The Journal of Experimental Medicine (2000)

Natural tumor surveillance capabilities of the host were investigated in six different mouse tumor models where endogenous interleukin (IL)-12 does or does not dictate the efficiency of the innate immune response. Gene-targeted and lymphocyte subset-depleted mice were used to establish the relative importance of natural killer (NK) and NK1.1(+) T (NKT) cells in protection from tumor initiation and metastasis. In the models examined, CD3(-) NK cells were responsible for tumor rejection and protection from metastasis in models where control of major histocompatibility complex class I-deficient tumors was independent of IL-12. A protective role for NKT cells was only observed when tumor rejection required endogenous IL-12 activity. In particular, T cell receptor Jalpha281 gene-targeted mice confirmed a critical function for NKT cells in protection from spontaneous tumors initiated by the chemical carcinogen, methylcholanthrene. This is the first description of an antitumor function for NKT cells in the absence of exogenously administered potent stimulators such as IL-12 or alpha-galactosylceramide.
Racial Differences in Survival After In-Hospital Cardiac Arrest
Authors: Paul S Chan, Graham Nichol, Harlan M Krumholz, John A Spertus, Philip G Jones, Eric D Peterson, Saif S Rathore, Brahmajee K Nallamothu
Journal: JAMA (2009)

<h3>Context</h3>Racial differences in survival have not been previously studied after in-hospital cardiac arrest, an event for which access to care is not likely to influence treatment.<h3>Objectives</h3>To estimate racial differences in survival for patients with in-hospital cardiac arrests and examine the association of sociodemographic and clinical factors and the admitting hospital with racial differences in survival.<h3>Design, Setting, and Patients</h3>Cohort study of 10 011 patients with cardiac arrests due to ventricular fibrillation or pulseless ventricular tachycardia enrolled between January 1, 2000, and February 29, 2008, at 274 hospitals within the National Registry of Cardiopulmonary Resuscitation.<h3>Main Outcome Measures</h3>Survival to hospital discharge; successful resuscitation from initial arrest and postresuscitation survival (secondary outcome measures).<h3>Results</h3>Included were 1883 black patients (18.8%) and 8128 white patients (81.2%). Rates of survival to discharge were lower for black patients (25.2%) than for white patients (37.4%) (unadjusted relative rate [RR], 0.73; 95% confidence interval [CI], 0.67-0.79). Unadjusted racial differences narrowed after adjusting for patient characteristics (adjusted RR, 0.81 [95% CI, 0.75-0.88]; P &lt; .001) and diminished further after additional adjustment for hospital site (adjusted RR, 0.89 [95% CI, 0.82-0.96]; P = .002). Lower rates of survival to discharge for blacks reflected lower rates of both successful resuscitation (55.8% vs 67.4% for whites; unadjusted RR, 0.84 [95% CI, 0.81-0.88]) and postresuscitation survival (45.2% vs 55.5% for whites; unadjusted RR, 0.85 [95% CI, 0.79-0.91]). Adjustment for the hospital site at which patients received care explained a substantial portion of the racial differences in successful resuscitation (adjusted RR, 0.92 [95% CI, 0.88-0.96]; P &lt; .001) and eliminated the racial differences in postresuscitation survival (adjusted RR, 0.99 [95% CI, 0.92-1.06]; P = .68).<h3>Conclusions</h3>Black patients with in-hospital cardiac arrest were significantly less likely to survive to discharge than white patients, with lower rates of survival during both the immediate resuscitation and postresuscitation periods. Much of the racial difference was associated with the hospital center in which black patients received care.