tbuckley/cabot-search huggingface dataset:
Epidemiological impact of prolonged systematic use of topical SDD on bacterial colonization of the tracheobronchial tree and antibiotic resistance
Authors: G. Nardi, U. Valentinis, A. Proietti, A. De Monte, A. Di Silvestre, R. Muzzi, R. Peressutti, M. G. Troncon, F. Giordano
Journal: Intensive Care Medicine (1993)
Abnormal conduction and repolarization in late-activated myocardium of dyssynchronously contracting hearts
Authors: D SPRAGG, F AKAR, R HELM, R TUNIN, G TOMASELLI, D KASS
Journal: Cardiovascular Research (2005)

Cardiac dyssynchrony due to intraventricular conduction delay produces heterogeneous regional wall stress and worsens arrhythmia susceptibility in failing hearts. We examined whether chronic dyssynchrony per se induces regionally heterogeneous electrophysiological remodeling.Adult dogs (n=9) underwent left bundle branch radiofrequency ablation (QRS duration increased from 50+/-7 to 104+/-7 ms); 6 untreated dogs served as controls. A subset of ablated (n=3) and control (n=4) dogs underwent tagged MR imaging to confirm ablation-induced left ventricular (LV) dyssynchrony. Four weeks later, hearts were excised and early (anterior)- and late (lateral)-activated myocardial segments were isolated. Conduction velocity (CV), action potential duration (APD), and refractory period (RP) of paced, arterially perfused myocardial wedges were studied by extracellular and optical mapping, and arrhythmia susceptibility was assessed by programmed stimulation. Regional stress-response kinase, calcium cycling, and gap junction protein expression were assayed by Western blotting, and the subcellular distribution of connexin43 was analyzed by immunofluorescence microscopy. CV, APD, and RP were significantly reduced in the late-activated, lateral wall of dyssynchronous hearts compared to the anterior wall. Normal differences in CV (endocardial>epicardial) were reversed in the dyssynchronous lateral LV. While the total expression of connexin43 was unaltered in dyssynchronous models, its subcellular location was redistributed in late-activated myocardium from intercalated discs to lateral myocyte membranes. Arrhythmias were rare in tissue from normal and dyssynchronous models. Total expression of calcium-cycling proteins (sarcoplasmic reticulum Ca2+-ATPase and phospholamban) and the stress-response kinase phospho-ERK did not vary regionally in either model.Dyssynchrony even in the absence of LV dysfunction induces regionally specific changes in conduction and repolarization. These changes support a novel mechanism linking mechanical dyssynchrony to persistent electrophysiological remodeling and heterogeneity.
Creatine kinase kinetics studied by phosphorus-31 nuclear magnetic resonance in a canine model of chronic hypertension-induced cardiac hypertrophy
Authors: Mary Osbakken, Pamela S. Douglas, Tamas Ivanics, Danning Zhang, Tom Van Winkle
Journal: Journal of the American College of Cardiology (1992)

To determine whether cardiac hypertrophy secondary to chronic renovascular hypertension is associated with altered in vivo myocardial metabolism, phosphorus-31 nuclear magnetic resonance saturation transfer techniques were used to study creatine kinase (CK) kinetics in six chronically hypertensive dogs with moderate cardiac hypertrophy and eight control dogs. The forward rate constant of CK and the flux of phosphocreatine to adenosine triphosphate were determined in both groups of dogs before and during norepinephrine administration (1 μg/kg per min), used to increase heart rate × systolic blood pressure (rate-pressure product), cardiac output and oxygen consumption. Baseline and norepinephrine-induced changes in rate-pressure product, cardiac output and oxygen consumption were similar in both groups of dogs, as were baseline forward rate constant and flux of phosphocreatine to adenosine triphosphate. However, the norepinephrine-induced changes in forward rate constant and flux were significantly less in hypertensive than in control dogs (p < 0.05) even though changes in hemodynamic and functional variables were similar in both groups. These data demonstrate that moderate myocardial hypertrophy is associated with altered CK kinetics, which do not appear to affect the heart's ability for global mechanical recruitment at this stage in the hypertensive process. It is possible that the changes in myocardial enzyme kinetics may contribute to diastolic dysfunction previously reported in this model and may be a precursor for ultimate development of heart failure if hypertension is maintained for prolonged periods. The data also suggest that the heart of moderately hypertensive animals may work less per gram muscle and that it may have greater metabolic efficiency because it can maintain lower adenosine diphosphate levels (as indicated by lower forward rate constant of CK) than those of control hearts. However, it appears that either the CK system has a large safety factor such that the lower forward rate constant and flux found in hypertensive dogs is sufficient to support normal global mechanical function or that the phosphocreatine shuttle is not a critical factor in maintaining mechanical function in the moderately hypertrophied heart.
PREGNANCY ACCIDENTS IN DIABETES
Authors: Elliott P. Joslin
Journal: JAMA (1941)

<h3>To the Editor:—</h3> May I add a summary of my experience with pregnant diabetic women? In 1913 I was placed in charge of a pregnant diabetic woman by Dr. B. while he went to Europe. The woman left me for a cultist and on Dr. B.'s return I was upbraided because he found her toxemic and she and her infant died and her husband committed suicide. Thereupon I reported all my cases up to that time of pregnant patients with diabetes (Boston M. &amp; S. J. 173:841, 1915). The first notable achievement was Mrs. G. She had had twelve dead babies in succession and at least half of them while she was diabetic. I saw her first in coma in the sixth month of pregnancy. Later her diabetes proved so mild that she was able to omit insulin. As a stunt I brought her into the hospital, put
Adenosine: Tipping the balance towards hepatic steatosis and fibrosis
Authors: Simon C. Robson, Detlef Schuppan
Journal: Journal of Hepatology (2010)

Fatty liver is commonly associated with alcohol ingestion and abuse. While the molecular pathogenesis of these fatty changes is well understood, the histochemical and pharmacological mechanisms by which ethanol stimulates these molecular changes remain unknown. During ethanol metabolism, adenosine is generated by the enzyme ecto-5'-nucleotidase, and adenosine production and adenosine receptor activation are known to play critical roles in the development of hepatic fibrosis. We therefore investigated whether adenosine and its receptors play a role in the development of alcohol-induced fatty liver. WT mice fed ethanol on the Lieber-DeCarli diet developed hepatic steatosis, including increased hepatic triglyceride content, while mice lacking ecto-5-nucleotidase or adenosine A1 or A2B receptors were protected from developing fatty liver. Similar protection was also seen in WT mice treated with either an adenosine A1 or A2B receptor antagonist. Steatotic livers demonstrated increased expression of genes involved in fatty acid synthesis, which was prevented by blockade of adenosine A1 receptors, and decreased expression of genes involved in fatty acid metabolism, which was prevented by blockade of adenosine A2B receptors. In vitro studies supported roles for adenosine A1 receptors in promoting fatty acid synthesis and for A2B receptors in decreasing fatty acid metabolism. These results indicate that adenosine generated by ethanol metabolism plays an important role in ethanol-induced hepatic steatosis via both A1 and A2B receptors and suggest that targeting adenosine receptors may be effective in the prevention of alcohol-induced fatty liver.
Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions
Authors: john H. Sampson, Raghu Raghavan, Martin L. Brady, james M. Provenzale, james E. Herndon, David Croteau, Allan H. Friedman, David A. Reardon, R. Edward Coleman, Terence Wong, Darell D. Bigner, Ira Pastan, María Inmaculada Rodríguez-Ponce, Philipp Tanner, Raj Puri, Christoph Pedain
Journal: Neuro-Oncology (2007)

Convection-enhanced delivery (CED) is a novel drug delivery technique that uses positive infusion pressure to deliver therapeutic agents directly into the interstitial spaces of the brain. Despite the promise of CED, clinical trials have demonstrated that target-tissue anatomy and patient-specific physiology play a major role in drug distribution using this technique. In this study, we retrospectively tested the ability of a software algorithm using MR diffusion tensor imaging to predict patient-specific drug distributions by CED. A tumor-targeted cytotoxin, cintredekin besudotox (interleukin 13-PE38QQR), was coinfused with iodine 123-labeled human serum albumin (123I-HSA), in patients with recurrent malignant gliomas. The spatial distribution of 123I-HSA was then compared to a drug distribution simulation provided by the software algorithm. The algorithm had a high sensitivity (71.4%) and specificity (100%) for identifying the high proportion (7 of 14) of catheter trajectories that failed to deliver drug into the desired anatomical region (p = 0.021). This usually occurred when catheter trajectories crossed deep sulci, resulting in leak of the infusate into the subarachnoid cerebrospinal fluid space. The mean concordance of the volume of distribution at the 50% isodose level between the actual 123I-HSA distribution and simulation was 65.75% (95% confidence interval [CI], 52.0%-79.5%), and the mean maximal inplane deviation was less than 8.5 mm (95% CI, 4.0-13.0 mm). The use of this simulation algorithm was considered clinically useful in 84.6% of catheters. Routine use of this algorithm, and its further developments, should improve prospective selection of catheter trajectories, and thereby improve the efficacy of drugs delivered by this promising technique.
Sleep disordered breathing in patients receiving therapy with buprenorphine/naloxone
Authors: Robert J. Farney, Amanda M. McDonald, Kathleen M. Boyle, Gregory L. Snow, R.T. Nuttall, Michael F. Coudreaut, Theodore J. Wander, James M. Walker
Journal: European Respiratory Journal (2012)

Patients using chronic opioids are at risk for exceptionally complex and potentially lethal disorders of breathing during sleep, including central and obstructive apnoeas, hypopnoeas, ataxic breathing and nonapnoeic hypoxaemia. Buprenorphine, a partial μ-opioid agonist with limited respiratory toxicity, is widely used for the treatment of opioid dependency and chronic nonmalignant pain. However, its potential for causing sleep disordered breathing has not been studied. 70 consecutive patients admitted for therapy with buprenorphine/naloxone were routinely evaluated with sleep medicine consultation and attended polysomnography. The majority of patients were young (mean±sd age 31.8±12.3 years), nonobese (mean±sd body mass index 24.9±5.9 kg·m(-2)) and female (60%). Based upon the apnoea/hypopnoea index (AHI), at least mild sleep disordered breathing (AHI ≥5 events·h(-1)) was present in 63% of the group. Moderate (AHI ≥15- <30 events·h(-1)) and severe (AHI ≥30 events·h(-1)) sleep apnoea was present in 16% and 17%, respectively. Hypoxaemia, defined as an arterial oxygen saturation measured by pulse oximetry, of <90% for ≥10% of sleep time, was present in 27 (38.6%) patients. Despite the putative protective ceiling effect regarding ventilatory suppression observed during wakefulness, buprenorphine may induce significant alterations of breathing during sleep at routine therapeutic doses.
Short-Term Preservation of the Cadaveric Kidney
Authors: Ami Barzilai
Journal: JAMA (1968)

A new method for performing cadaveric renal homoplastic grafts shortens ischemic time; reduces the possibility of tubular necrosis, genetic incompatibility, and trauma to the graft; and eliminates the necessity for emergency operation. These advantages are a result of temporarily connecting the proposed graft to an arteriovenous shunt before transplantation. Good results were obtained in six patients on 11 occasions.
Aid agencies ignored special needs of elderly people after tsunami
Authors: Ganapati Mudur
Journal: BMJ (2005)

Elderly people who survived the Asian tsunami on 26 December last year were unable to get health care, food aid, or cash support because relief packages were not specially designed for them, the non-profit agency HelpAge International has said. Despite attempts in the past to highlight the vulnerability of elderly people during emergencies, the tsunami relief effort did not take into account the special needs of this group in its initial phase, the agency said in a report released last week.
Death and Dignity
Authors: T E Quill
Journal: New England Journal of Medicine (1991)

Diane was feeling tired and had a rash. A common scenario, though there was something subliminally worrisome that prompted me to check her blood count. Her hematocrit was 22, and the white-cell count was 4.3 with some metamyelocytes and unusual white cells. I wanted it to be viral, trying to deny what was staring me in the face. Perhaps in a repeated count it would disappear. I called Diane and told her it might be more serious than I had initially thought — that the test needed to be repeated and that if she felt worse, we might have to . . .
Canonical notch pathway protects hepatocytes from ischemia/reperfusion injury in mice by repressing reactive oxygen species production through JAK2/STAT3 signaling
Authors: Heng-Chao Yu, Hong-Yan Qin, Fei He, Lin Wang, Wei Fu, Dong Liu, Feng-Cheng Guo, Liang Liang, Ke-Feng Dou, Hua Han
Journal: Hepatology (2011)

Hepatic ischemia/reperfusion (I/R) injury is initiated by reactive oxygen species (ROS) accumulated during the early reperfusion phase after ischemia, but cellular mechanisms controlling ROS production and scavenging have not been fully understood. In this study, we show that blocking Notch signal by knockout of the transcription factor RBP-J or a pharmacological inhibitor led to aggravated hepatic I/R injury, as manifested by deteriorated liver function and increased apoptosis, necrosis, and inflammation, both in vitro and in vivo. Interruption of Notch signaling resulted in increased intracellular ROS in hepatocytes, and a ROS scavenger cured exacerbated hepatic I/R injury after Notch signaling blockade, suggesting that Notch signal deficiency aggravated I/R injury through increased ROS levels. Notch signal blockade resulted in down-regulation of Hes5, leading to reduced formation of the Hes5-STAT3 complex and hypophosphorylation of STAT3, which further attenuated manganese superoxide dismutase (MnSOD) expression and increased ROS and apoptosis. Indeed, overexpression of a constitutively active STAT3 rescued MnSOD expression and I/R injury-induced apoptosis in the absence of Notch signaling. Finally, forced Notch activation by ligand stimulation or Hes5 overexpression reduced intracellular ROS and protected hepatocytes from apoptosis after I/R injury through the activation of STAT3 and MnSOD expression.Notch signal protects hepatocytes from I/R injury by Hes5-dependent activation of STAT3, which activates the expression of MnSOD, leading to the scavenging of ROS.
Transplantation of the mouse heart--a useful research model
Authors: D. W. JIRSCH, N. KRAFT, E. DIENER
Journal: Cardiovascular Research (1974)

Journal Article Transplantation of the mouse heart—a useful research model Get access D. W. JIRSCH, D. W. JIRSCH 2 From the Medical Research Council of Canada Transplantation Unit, Surgical-Medical Research Institute and the Department of Surgery, The University of Alberta, Edmonton, Alberta, Canada 2Address for reprints: Dr D. W. Jirsch, Surgical-Medical Research Institute, The University of Alberta, Edmonton, Alberta, Canada. Search for other works by this author on: Oxford Academic PubMed Google Scholar N. KRAFT, N. KRAFT From the Medical Research Council of Canada Transplantation Unit, Surgical-Medical Research Institute and the Department of Surgery, The University of Alberta, Edmonton, Alberta, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar E. DIENER E. DIENER From the Medical Research Council of Canada Transplantation Unit, Surgical-Medical Research Institute and the Department of Surgery, The University of Alberta, Edmonton, Alberta, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 8, Issue 1, January 1974, Pages 145–148, https://doi.org/10.1093/cvr/8.1.145 Published: 01 January 1974
Proposed Meeting at the Royal College of Surgeons
Authors: E. Trimmer
Journal: BMJ (1889)

<h3>Abstract</h3> Visual perception fluctuates in-synch with ongoing neural oscillations in the delta, theta, and alpha frequency bands of the human EEG. Supporting the relationship between alpha and perceptual sampling, recent work has demonstrated that variations in individual alpha frequency (IAF) correlate with the ability to discriminate one from two stimuli presented briefly in the same location. Other studies have found that after being presented with a flickering stimulus at alpha frequencies, perception of near-threshold stimuli fluctuates for a short time at the same frequency. Motivated by previous work, we were interested in whether this alpha entrainment involves shifts in IAF. While recording EEG, we tested whether two-flash discrimination (a behavioral correlate of IAF) can be influenced by ∼1s of rhythmic visual stimulation at two different alpha frequencies (8.3hz and 12.5hz). Speaking against the bottom-up malleability of IAF, we found no change in IAF during stimulation and no change in two-flash discrimination immediately afterwards. We also found synchronous activity that persisted after 12.5hz stimulation, which suggests that a separate source of alpha was entrained. Importantly, we replicated the correlation between IAF and two-flash discrimination in a no-stimulation condition, demonstrating the sensitivity of our behavioral measure. We additionally found that IAF increased during the task compared to rest, which demonstrates that IAF is influenced by top-down factors but is not involved in entrainment. In the framework of existing findings, we suggest that visual entrainment may involve ongoing perceptually-relevant oscillations from the delta to alpha frequency bands, serving to maintain rhythmic temporal expectations.
How Pakistan's media spreads the message about reproductive and sexual health
Authors: S. H. Abidi, M. Raees, S. Ali
Journal: BMJ (2015)

Liberalising influences in the past 20 years have led to a media policy that may have helped improve reproductive and sexual health in the country, say <b>Syed H Abidi</b>, <b>Muhammad Raees</b>, and <b>Syed Ali</b>
AN EXAMINATION OF THE STOOLS OF 100 HEALTHY INDIVIDUALS, WITH ESPECIAL REFERENCE TO THE PRESENCE OF ENTAMŒBÆ COLI.
Authors: EDWARD B. VEDDER
Journal: JAMA (1906)

Numerous investigators have found amebas in the stools of healthy persons, but, since they have mostly made no distinction between<i>Entamœba coli</i>and<i>Entamœba dysenteriœ</i>, their results can not be considered in this connection. Schaudinn,<sup>1</sup>however, examining the stools of healthy individuals, demonstrated the presence of the<i>Entamœba coli</i>in the stools of 50 per cent. of those examined in West Prussia, in 20 per cent. of those examined in Berlin, and in 66 per cent. of those dwelling on the shores of the Adriatic. Craig<sup>2</sup>demonstrated the presence of<i>Entamœba coli</i>in the stools of healthy individuals in 65 per cent. of the cases and in 50 per cent. of the 150 cases examined of patients suffering from other than intestinal disease. These results would seem conclusively to demonstrate the fact that the<i>Entamœba coli</i>is an extremely common intestinal parasite and the strong probability of its
A6.42 The role of micro-RNA-146a in inflammatory arthritis
Authors: V Saferding, A Puchner, E Goncalves Alves, E Sahin, M Hofmann, V Roth, S Hayer, MI Koenders, JS Smolen, K Redlich, S Blüml
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> MicroRNA (MiR-) 146a is a key regulator of the innate immune response and has also been shown to suppress cancer development in myeloid cells. Although in late stages of arthritis elevated expression of miR-146a in synovial tissue of rheumatoid arthritis patients was detected, it was also shown that the level of this miRNA is down regulated in early disease, but its role in the development of inflammatory arthritis is yet unknown. <h3>Methods</h3> We induced K/BxN serum transfer arthritis in wild type and miR-146a<sup>–/–</sup> mice. As a second inflammatory arthritis model we crossed miR-146a deficient into hTNFtg mice. Disease severity was assessed clinically and histologically. Blood of arthritis animals was analysed by flow cytometry. Serum cytokine levels were measured by Elisa. MiR-146a and cytokine expression levels in bone marrow, spleen and paws were analysed by real time PCR. <h3>Results</h3> Both arthritis disease models led to a significantly reduced expression of miR-146a in spleen and bone marrow cells of arthritic wild type mice compared to healthy mice. Absence of miR-146a leads to increased clinical signs of the induced serum transfer arthritis. In line, higher serum levels of the proinflammatory cytokines IL12 and TNF were measured in miR146a deficient mice compared to wt mice. When we crossed miR-146a<sup>-/-</sup> mice into hTNFtg mice, while detecting no clinical difference between hTNFtg and miR-146a<sup>-/-</sup>/hTNFtg mice, we found a significant increase in circulating CD11b<sup>+</sup> myeloid cells as well as CD11c<sup>+</sup> dendritic cells in blood of miR-146a<sup>-/-</sup>/hTNFtg mice compared to hTNFtg mice. Histological examination revealed a significant increase in synovial inflammation in miR-146a<sup>-/-</sup>/hTNFtg mice compared to hTNFtg mice. Even more striking, miR-146a<sup>-/-</sup>/hTNFtg mice displayed a more than twofold increase in local bone destruction which was due to increased generation of osteoclasts in the tarsal joints of the mice. Measuring cytokine levels in serum, we show that IL-1β levels are increased in mice lacking miR-146a. Moreover mRNA expression levels of IL6 and IL-1β in arthritic paws of these mice were significantly elevated in miR-146a<sup>-/-</sup>/hTNFtg mice compared to hTNFtg mice. <h3>Conclusions</h3> These data clearly demonstrate a negative regulatory role of miR-146a in inflammatory arthritis. During arthritis, miR-146a is centrally involved in the regulation of proinflammatory cytokines as well as local bone destruction. These results identify an important anti-inflammatory role of miR-146a, which might possibly be exploited for therapeutic purposes.