tbuckley/cabot-search huggingface dataset:
Skin Intrinsic Fluorescence Is Associated With Hemoglobin A1c and Hemoglobin Glycation Index but Not Mean Blood Glucose in Children With Type 1 Diabetes
Authors: Dania L. Felipe, James M. Hempe, Shuqian Liu, Nate Matter, John Maynard, Carmen Linares, Stuart A. Chalew
Journal: Diabetes Care (2011)

To evaluate the relationship between skin advanced glycation end products (sAGEs) with mean blood glucose (MBG), hemoglobin A(1c) (HbA(1c)), and MBG-independent, between-patient differences in HbA(1c) among children with type 1 diabetes.Children aged 5 to 20 years with type 1 diabetes of at least 1 year duration participated. At a clinic visit, sAGE was estimated noninvasively by measurement of skin intrinsic fluorescence (SIF). SIF data were adjusted to correct for variation in skin pigmentation. MBG-independent, between-patient differences in HbA(1c) were examined by statistically controlling HbA(1c) for MBG or alternatively by use of a hemoglobin glycation index (HGI). Results were similar whether HbA(1c), MBG, and HGI were analyzed as single values from the time of the SIF examination visit or as the mean values from all available visits of the patient.HbA(1c) was correlated with MBG (r = 0.5; P < 0.001; n = 110). HbA(1c) and HGI, but not MBG, were statistically associated with SIF after adjustment for age, duration of diabetes, race, sex, and BMI z-score. SIF increased with age and duration of diabetes and was higher in girls than boys.sAGE levels estimated by SIF increase with age, duration of diabetes, and female sex. sAGE is correlated with MBG-independent biological variation in HbA(1c), but not with MBG itself. These results suggest that factors besides MBG that influence HbA(1c) levels also contribute to accumulation of sAGE.
A Study of the Cardiac Stigmata in Prolonged Human Thiamine Deficiency
Authors: DAVID T. ROWLANDS, CARL F. VILTER
Journal: Circulation (1960)

Eight clinically proved cases of prolonged thiamine deficiency were evaluated by routine pathologic study. The microscopic features were evaluated by comparison with sections of myocardium obtained from normal individuals and individuals suffering from cardiac diseases of other varieties. No specific transitory or permanent alterations were demonstrable. It is concluded that beriberi heart disease is largely the result of a reversible biochemical abnormality and is not characterized by specific pathologic lesions.
Jumperphagia: a woolly diagnosis
Authors: G. Nash, R. Evans, R. Cohen
Journal: Journal of the Royal Society of Medicine (2003)

Last year in the JRSM, Woywodt and Kiss recorded the history of earth-eating,1 and Grewal and Fitzgerald2 described the case of a learning-disabled man who consumed metal objects and pieces of clothing. Some workers hypothesize that such habits (pica) are related to dietary deficiencies. Here we report some evidence in support.

A woman of 67 was being investigated for longstanding iron deficiency. Upper gastrointestinal endoscopy had been negative, but on colonoscopy the bowel contained several clumps of what appeared to be fabric. A dietary history, taken thereafter, revealed that she was in the habit of consuming whole woollen jumpers at a single sitting; also her iron intake was low. After iron supplementation and nutritional advice, both her urge to eat wool and the anaemia gradually resolved.

Pica has been linked with severe iron-deficiency anaemia in children3 and adults.4 The question of cause and effect has not been resolved. In the past the habit has been seen as a manifestation of other disorders rather than an entity.5,6 Here, cessation of pica after successful treatment of the anaemia indicates that iron deficiency might have contributed to the causation.
STUDIES ON THE TOTAL BILE
Authors: G. O. Broun, Philip D. McMaster, Peyton Rous
Journal: The Journal of Experimental Medicine (1923)

In dogs fed the green bile or the liver tissue of herbivora, the bile later secreted frequently becomes green, changing from the previous yellow-brown. When they are fed sheep bile that contains cholohematin, their bile comes to contain this pigment. When they are fed dog bile in quantity a well marked increase in the output of bilirubin by the liver frequently follows. Taken together, these facts indicate the existence of an enterohepatic circulation of bile pigment.
Increased allergen production in turnip (Brassica rapa) by treatments activating defense mechanisms☆☆☆★
Authors: Anna-Riitta Hänninen, Jari H. Mikkola, Nisse Kalkkinen, Kristiina Turjanmaa, Leea Ylitalo, Timo Reunala, Timo Palosuo
Journal: Journal of Allergy and Clinical Immunology (1999)
Recombination of hepatitis D virus RNA sequences and its implications
Authors: J. C. Wu, T. Y. Chiang, W. K. Shiue, S. Y. Wang, I. J. Sheen, Y. H. Huang, W. J. Syu
Journal: Molecular Biology and Evolution (1999)

Recombination between RNA sequences plays a role in the fast evolution of a few viruses. There has been no report on hepatitis D virus (HDV) recombination. In this study, we analyzed genetic recombination of HDV and its possible impact on evolution and clinical course. The aligned HDV sequences allowed us to construct a phylogenetic tree which supported the notion of distinct lineages of HDV. The tree was also used in the analysis of recombination using partial likelihoods assessed through optimization. Nine segments of the HDV genome with significant levels of genetic recombination were detected. Five segments were in the hypervariable region, and four were in the delta-antigen- coding region. None could be found in the well-conserved autocleavage region that is essential for replication. Recombination occurred both between and within types. The results of this study indicated that the remarkable variation in HDV genomic sequences, particularly in the hypervariable region, among different genotypes may at least partly result from multiple episodes of genetic recombination during evolution. Genetic recombination may play a significant role in increasing genetic diversity. Importantly, a genetic recombination (nt 1082-1093) occurred in one of the immunogenic domains of hepatitis delta virus antigen recognized by human and woodchuck antibodies (amino acids 174-195). Genetic recombination also occurred at another segment between nt 1517 and 1535, which was close to one of the predicted T-cell epitopes (amino acids 26-41). In longitudinal analysis of HDV genomes at different time points during chronic infection, novel dominant HDV strains with amino acid changes at these epitopes usually emerged after severe hepatitis attacks. In the comparison of HDV clones during or shortly after flare-up of liver disease, Ka/Ks ratios of > 1 were frequently found, suggesting Darwinian positive selection. Therefore, recombination in these two segments may play an important role for HDV in the evasion of immunity.
Calcineurin Inhibitor Attenuates the Development and Induces the Regression of Cardiac Hypertrophy in Rats With Salt-Sensitive Hypertension
Authors: Masaki Shimoyama, Doubun Hayashi, Yunzeng Zou, Eiki Takimoto, Miho Mizukami, Koshiro Monzen, Sumiyo Kudoh, Yukio Hiroi, Yoshio Yazaki, Ryozo Nagai, Issei Komuro
Journal: Circulation (2000)

Background —It remains unclear how hemodynamic overload induces cardiac hypertrophy. Recently, activation of calcium-dependent phosphatase, calcineurin, has been elucidated to induce cardiac hypertrophy. In the present study, we examined the role of calcineurin in load-induced cardiac hypertrophy by using Dahl salt-sensitive (DS) rats, which develop both pressure and volume overload when fed a high salt diet. Methods and Results —In the DS rat heart, the activity of calcineurin was increased and cardiac hypertrophy was induced by high salt diet. Treatment of DS rats with the calcineurin inhibitor FK506 (0.1 or 0.01 mg/kg twice daily) from the age of 6 weeks to 12 weeks inhibited the activation of calcineurin in the heart in a dose-dependent manner and attenuated the development of load-induced cardiac hypertrophy and fibrosis without change of hemodynamic parameters. Additionally, treatment with 0.1 mg/kg twice daily but not with 0.01 mg/kg twice daily of FK506 from the age of 12 weeks to 16 weeks induced regression of cardiac hypertrophy in DS rats. Load-induced reprogramming of gene expression was also suppressed by the FK506 treatment. Conclusions —These results suggest that calcineurin is involved in the development of cardiac hypertrophy in rats with salt-sensitive hypertension and that inhibition of calcineurin could induce regression of cardiac hypertrophy.
Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection
Authors: Manfred Brigl, Raju V.V. Tatituri, Gerald F.M. Watts, Veemal Bhowruth, Elizabeth A. Leadbetter, Nathaniel Barton, Nadia R. Cohen, Fong-Fu Hsu, Gurdyal S. Besra, Michael B. Brenner
Journal: The Journal of Experimental Medicine (2011)

Invariant natural killer T cells (iNKT cells) are critical for host defense against a variety of microbial pathogens. However, the central question of how iNKT cells are activated by microbes has not been fully explained. The example of adaptive MHC-restricted T cells, studies using synthetic pharmacological α-galactosylceramides, and the recent discovery of microbial iNKT cell ligands have all suggested that recognition of foreign lipid antigens is the main driver for iNKT cell activation during infection. However, when we compared the role of microbial antigens versus innate cytokine-driven mechanisms, we found that iNKT cell interferon-γ production after in vitro stimulation or infection with diverse bacteria overwhelmingly depended on toll-like receptor–driven IL-12. Importantly, activation of iNKT cells in vivo during infection with Sphingomonas yanoikuyae or Streptococcus pneumoniae, pathogens which are known to express iNKT cell antigens and which require iNKT cells for effective protection, also predominantly depended on IL-12. Constitutive expression of high levels of IL-12 receptor by iNKT cells enabled instant IL-12–induced STAT4 activation, demonstrating that among T cells, iNKT cells are uniquely equipped for immediate, cytokine-driven activation. These findings reveal that innate and cytokine-driven signals, rather than cognate microbial antigen, dominate in iNKT cell activation during microbial infections.
Slow progression rate of fibrosis in hepatitis C virus patients with persistently normal alanine transaminase activity
Authors: Philippe Mathurin, Joseph Moussalli, Jean-François Cadranel, Vincent Thibault, Frédéric Charlotte, Patrice Dumouchel, Alain Cazier, Jean-Marie Huraux, Bruno Devergie, Michel Vidaud, Pierre Opolon, Thierry Poynard
Journal: Hepatology (1998)

In hepatitis C virus (HCV) patients with persistently normal alanine transaminase (ALT), the progression rate of fibrosis is unknown. The aims of this study were: 1) to compare HCV patients with normal ALT (group I) with HCV patients with elevated ALT (group II) matched on independent factors associated with fibrosis; and 2) to assess the progression rate of fibrosis. One hundred two HCV patients were included in each group. Histological lesions were staged using the METAVIR score. We defined fibrosis progression per year as the ratio of the fibrosis stage in METAVIR units to the duration of infection. In group I, ALT values were normal, and lower than in group II (25 vs. 127 IU/L; P &lt; .0001). HCV RNA was present less frequently in group I (66% vs. 97%; P &lt; .0001). There were no significant differences for viremia and genotypes. Histological activities were lower in group I (0.6 vs. 1.38; P &lt; .0001). The stage of fibrosis was lower in group I (0.95 vs. 1.8; P &lt; .001). The median progression rate of fibrosis was lower in group I (0.05 vs. 0.13; P &lt; .001). In group I, after exclusion of negative HCV-RNA patients, the median progression rate of positives remained lower (0.05 vs. 0.13; P &lt; .001). In group I, all cirrhotic patients (n = 3) were heavy drinkers. HCV patients with normal ALT showed weaker histological activity and lower fibrosis scores, and the progression rate of fibrosis was twice as slow as in HCV patients with elevated ALT. In these patients, severe fibrosis was associated with high alcohol consumption.
Toxic shock syndrome associated arthropathy. Staphylococcus aureus: a further triggering event in reactive arthritis?
Authors: D Foley-Nolan, R J Coughlan, D Sugrue
Journal: Annals of the Rheumatic Diseases (1989)

AbstractAn HLA-B27 positive 24 year old woman is described with a Staphylococcus aureus induced toxic shock syndrome precipitating a reactive arthritis.
Chitosan amphiphile coating of peptide nanofibres reduces liver uptake and delivers the peptide to the brain on intravenous administration
Authors: A. Lalatsa, A.G. Schätzlein, N.L. Garrett, J. Moger, Michael Briggs, Lisa Godfrey, Antonio Iannitelli, Jay Freeman, I.F. Uchegbu
Journal: Journal of Controlled Release (2014)

The clinical development of neuropeptides has been limited by a combination of the short plasma half-life of these drugs and their ultimate failure to permeate the blood brain barrier. Peptide nanofibres have been used to deliver peptides across the blood brain barrier and in this work we demonstrate that the polymer coating of peptide nanofibres further enhances peptide delivery to the brain via the intravenous route. Leucine(5)-enkephalin (LENK) nanofibres formed from the LENK ester prodrug - tyrosinyl(1)palmitate-leucine(5)-enkephalin (TPLENK) were coated with the polymer - N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) and injected intravenously. Peptide brain delivery was enhanced because the GCPQ coating on the peptide prodrug nanofibres, specifically enables the peptide prodrug to escape liver uptake, avoid enzymatic degradation to non-active sequences and thus enjoy a longer plasma half life. Plasma half-life is increased 520%, liver AUC0-4 decreased by 54% and brain AUC0-4 increased by 47% as a result of the GCPQ coating. The increased brain levels of the GCPQ coated peptide prodrug nanofibres result in the pharmacological activity of the parent drug (LENK) being significantly increased. LENK itself is inactive on intravenous injection.
Excess risk of hospital admission for cardiovascular disease within the first 7 years from onset of inflammatory polyarthritis
Authors: J. Franklin, T. M. Farragher, M. Lunt, E. M. Camacho, D. Bunn, T. Marshall, D. P. M. Symmons
Journal: Annals of the Rheumatic Diseases (2010)

with rheumatoid factor positive inflammatory polyarthritis (IP) are known to have increased mortality from cardiovascular disease (CVD). A study was undertaken to examine the risk and baseline predictors of admission with CVD in patients with recent-onset IP.Subjects are recruited by the Norfolk Arthritis Register if they present to primary or secondary care with > or =2 swollen joints lasting > or =4 weeks. This analysis includes subjects recruited between 1995 and 1999. Baseline data on lifestyle, demographic characteristics, disease and treatment characteristics were collected. CVD admissions were identified through record linkage with the only acute care hospital in the study region. First-episode hospitalisation rates were compared with those of the general population. Poisson regression was used to calculate the relative risk (RR) of admission for patients with IP (overall and for each risk factor). Death certificates were obtained from the national death register.800 patients with recent-onset IP were followed for a median of 7.0 years. 64 CVD-related hospitalisations were observed (11.7 per 1000 person-years). Patients with IP were twice as likely (RR=2.0; 95% CI 1.5 to 2.5) to be hospitalised for CVD as the general population. Difficulty walking at baseline was a significant predictor of CVD admission and baseline non-steroidal anti-inflammatory drug use was associated with a reduced risk of CVD admission.Patients with IP are at increased risk of CVD-related hospitalisation, within 7 years of symptom onset. Informing patients about lifestyle modification may reduce the risk of CVD.
Bone and joint changes in lower limb amputees.
Authors: M J Burke, V Roman, V Wright
Journal: Annals of the Rheumatic Diseases (1978)

A clinical and radiological survey of bone and joint changes in 42 lower limb amputees is reported. There was a significant increase in osteoarthrosis in the knee of the unamputated legs compared with the amputated side. The amputated side characteristically showed osteoporosis. Comparing the prevalence of osteoarthrosis in this study with figures in the population, it is more likely that the osteoporosis of the amputated limb had a protective effect on that side than that mechanical factors produced more osteoarthrosis on the contralateral side. Backache occurred in about half the patients, and was severe in 19%. It did not appear to be related to disc degeneration, but scoliosis was observed in 64% of patients.
Left ventricular function during sudden strenuous exercise.
Authors: C Foster, J D Anholm, C K Hellman, J Carpenter, M L Pollock, D H Schmidt
Journal: Circulation (1981)

Strenuous exercise without warm-up has been shown to produce ischemia-like electrocardiographic (ECG) abnormalities in 60-70% of healthy subjects. These abnormalities appeared to be related to the development of an unfavorable myocardial supply/demand balance and, in chronically instrumented dogs, to transient decreases in coronary blood flow. A mechanism involving subendocardial ischemia has been proposed to explain the response to sudden strenuous exercise (SSE). To determine whether the response to SSE included the development of changes in myocardial pump performance typical of ischemia, left ventricular (LV) function at rest, during graded exercise and during SSE was evaluated in nine young (26.6 +/- 3.4 years), well-trained male volunteers using first-pass radionuclide angiography. During graded exercise, the LV ejection fraction increased from 66.9 +/- 9.4% at rest to 73.0 +/- 7.1% during peak exercise, and the LV ejection rate increased from 3.36 +/- 0.67 sec-1 at rest to 6.58 +/- 1.10 sec-1 during peak exercise. Segmental wall motion was normal in all studies. During SSE, the LV ejection fraction decreased in very subject, from an average 72.2 +/- 8.6% at rst to 57.3 +/- 8.1% during exercise. The LV ejection rate remained relatively constant (3.98 +/- 0.92 sec-1 at rest vs 4.33 +/- 0.74 sec-1 during SSE). No segmental wall motion abnormalities were observed during SSE; however, LV wall motion appeared to be diffusely hypokinetic during SSE. In contrast to previous reports, few ECG abnormalities were observed during SSE. These results support the hypothesis that subendocardial ischemia is an important mechanism in the response to SSE. However, the lack of ECG changes and segmental wall motion abnormalities and the relatively high absolute value of the LV ejection fraction suggest that if subendocardial ischemia occurs during SSE, it is attributable to physiologic rather than pathologic mechanisms.
Umbilical cord stem cell therapy for bronchopulmonary dysplasia: ready for prime time?
Authors: Christopher D Baker, Steven H Abman
Journal: Thorax (2013)

Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), emphysema, idiopathic pulmonary fibrosis, cystic fibrosis, pulmonary arterial hypertension and others contribute significantly to morbidity and mortality worldwide, yet successful interventions are often limited. Over the past decade, there has been an explosion of excitement regarding potential roles for stem cell therapies to prevent, repair or regenerate lung tissue to improve outcomes of these severe, progressive and often fatal disorders.1 ,2 Based on strong preclinical data, early clinical studies are currently underway to explore safety and potential efficacy in adults with chronic pulmonary diseases, including COPD, idiopathic pulmonary arterial hypertension and others.

In children, bronchopulmonary dysplasia (BPD) remains one of the more common yet challenging respiratory disorders for which current strategies are extremely limited. BPD is the chronic lung disease that develops in premature newborns who require respiratory support and oxygen therapy after birth.3–7 BPD has changed remarkably since its original description over 45 years ago, and remains a ‘moving target:’ a disease modulated and at least partly defined by the impact of therapeutic interventions themselves. Routine use of prenatal steroids, surfactant therapy, improved ventilator strategies and other treatments have improved survival and the clinical course of infants with BPD. Importantly, infants with BPD now have very different clinical courses, outcomes and pathology than had been traditionally observed in preterm infants during the presurfactant era. The classic progressive stages leading to marked disruption of lung architecture with prominent fibroproliferative disease and cyst-like lesions that characterised BPD in the past are now often absent, and the disease is now predominantly defined as a disruption of distal lung airspace and vascular growth.6–8 Lung histology of infants with the ‘new BPD’ often demonstrates far milder fibrosis and fewer signs of lung injury, but impaired alveolar and vascular growth remains prominent. …
Mega-Randomized Clinical Trials for Blockbuster Drugs—Reply
Authors: John P. A. Ioannidis
Journal: JAMA (2013)

Mega-trials for blockbusters are readily feasible. There would be no cost for the government or health care system. Drug production cost to industry (as opposed to sales cost) is negligible. The proposed mandate could easily stipulate that blockbuster manufacturers donate drugs and placebos for such trials. Total cost to the industry would be approximately 1% of their cumulative sales for the product.
Promotion of Faster Weight Gain in Infants Born Small for Gestational Age
Authors: Atul Singhal, Tim J. Cole, Mary Fewtrell, Kathy Kennedy, Terence Stephenson, Alun Elias-Jones, Alan Lucas
Journal: Circulation (2006)

Background— Being born small for gestational age is associated with later risk factors for cardiovascular disease, such as high blood pressure. Promotion of postnatal growth has been proposed to ameliorate these effects. There is evidence in animals and infants born prematurely, however, that promotion of growth by increased postnatal nutrition increases rather than decreases later cardiovascular risk. We report the long-term impact of growth promotion in term infants born small for gestational age (birth weight &lt;10th percentile). Methods and Results— Blood pressure was measured at 6 to 8 years in 153 of 299 (51%) of a cohort of children born small for gestational age and randomly assigned at birth to receive either a standard or a nutrient-enriched formula. The enriched formula contained 28% more protein than standard formula and promoted weight gain. Diastolic and mean (but not systolic) blood pressure was significantly lower in children assigned to standard compared with nutrient-enriched formula (unadjusted mean difference for diastolic blood pressure, −3.2 mm Hg; 95% CI, −5.8 to −0.5; P =0.02) independent of potential confounding factors (adjusted difference, −3.5 mm Hg; P =0.01). In observational analyses, faster weight gain in infancy was associated with higher later blood pressure. Conclusions— In the present randomized study targeted to investigate the effect of early nutrition on long-term cardiovascular health, we found that a nutrient-enriched diet increased later blood pressure. These findings support an adverse effect of relative “overnutrition” in infancy on long-term cardiovascular disease risk, have implications for the early origins of cardiovascular disease hypothesis, and do not support the promotion of faster weight gain in infants born small for gestational age.