tbuckley/cabot-search huggingface dataset:
β- and α-Cell Dysfunctions in Africans With Ketosis-Prone Atypical Diabetes During Near-Normoglycemic Remission
Authors: Siméon-Pierre Choukem, Eugene Sobngwi, Philippe Boudou, Lila-Sabrina Fetita, Raphael Porcher, Fidaa Ibrahim, Bertrand Blondeau, Patrick Vexiau, Franck Mauvais-Jarvis, Fabien Calvo, Jean-François Gautier
Journal: Diabetes Care (2012)

Ketosis-prone atypical diabetes (KPD) is a subtype of diabetes in which the pathophysiology is yet to be unraveled. The aim of this study was to characterize β- and α-cell functions in Africans with KPD during remission.We characterized β- and α-cell functions in Africans with KPD during remission. The cohort comprised 15 sub-Saharan Africans who had been insulin-free for a median of 6 months. Patients in remission were in good glycemic control (near-normoglycemic) and compared with 15 nondiabetic control subjects matched for age, sex, ethnicity, and BMI. Plasma insulin, C-peptide, and glucagon concentrations were measured in response to oral and intravenous glucose and to combined intravenous arginine and glucose. Early insulin secretion was measured during a 75-g oral glucose tolerance test. Insulin secretion rate and glucagon were assessed in response to intravenous glucose ramping.Early insulin secretion and maximal insulin secretion rate were lower in patients compared with control participants. In response to combined arginine and glucose stimulation, maximal insulin response was reduced. Glucagon suppression was also decreased in response to oral and intravenous glucose but not in response to arginine and insulin.Patients with KPD in protracted near-normoglycemic remission have impaired insulin response to oral and intravenous glucose and to arginine, as well as impaired glucagon suppression. Our results suggest that β- and α-cell dysfunctions both contribute to the pathophysiology of KPD.
ROENTGEN IRRADIATION FOR THYROTOXICOSIS
Authors: L. H. Garland
Journal: JAMA (1949)

To  Editor:—  The article in your April 16 issue by Robert H. Williams on selection of therapy for individual patients with thyrotoxicosis fails to accord roentgen irradiation  place it has established in  treatment of this disease.  The author's point that initial treatment with thiouracil is applicable in many cases is well taken. His frank comments on  complications and bad effects of this drug are to be commended. His impression that irradiation is best given by radioiodine is hardly supported by his statement that the main drawback of this type of treatment is  difficulty involved in selecting  appropriate dosage, errors in which may either cause myxedema or permit  thyrotoxicity to persist.... Radioiodine is distinctly less available throughout  country than are  other forms of therapy and, in  light of present information, it should remain so. Extensive use of it would pose a
Milk-Curd Bowel Obstruction in the Newborn Infant
Authors: Leonard Graivier
Journal: JAMA (1977)

IN 1969, Cook and Rickham<sup>1</sup>first reported a syndrome of neonatal intestinal obstruction due to inspissated milk curds. This new entity had not been seen before in more than 600 cases of bowel obstruction in newborn infants admitted to the Liverpool Neonatal Surgical Center and had not been previously described in the literature. They found that the obstruction occurred primarily in premature infants in whom high-caloric feedings were begun shortly after birth. In all eight cases, the babies were well at birth, passed normal meconium stools, and began receiving feedings of either reconstituted powdered milk or diluted milk-concentrate. Altered stools and then milk stools were passed until low small-bowel obstruction suddenly developed at ages 5 to 14 days. Studies indicated that milk-curd obstruction resulted from a combination of early feeding of high-caloric milk and the decreased ability of the infant to absorb proteins and amino acids. Of interest was
Reserpine and Raynaud's Phenomenon
Authors: Ray W. Gifford
Journal: New England Journal of Medicine (1971)

By dividing total fingertip blood flow into its two component parts, arteriovenous-shunt flow and the nutritionally important capillary flow, Coffman and Cohen (see page 259) have made some interesting observations in patients with Raynaud's phenomenon. Some of the seemingly contradictory reports of total hand or finger blood flow in patients with Raynaud's phenomenon might have been less confusing if previous investigators had measured capillary as well as total flows. The relative contributions of capillary flow and arteriovenous-shunt flow to total flow vary so greatly under different circumstances that it would be hazardous if not impossible to estimate capillary flow from . . .
The Doctor, his Patient and the Illness
Authors: James Curran
Journal: BMJ (2007)

This book arose out of a series of seminars that the author, a psychotherapist, conducted with general practitioners at the Tavistock Clinic in London in the 1950s. At these seminars the GPs presented case reports to discuss aspects of the doctor-patient relationship. What became of interest was those patients who presented repeatedly to GPs with psychological or physical complaints but whose investigation findings were often normal and who were difficult to treat satisfactorily. About such patients Balint came to the conclusion that “some of the people, who for …
Right ventricular function in an operating room model of mechanical left ventricular assistance and its effects in patients with depressed left ventricular function.
Authors: D J Farrar, P G Compton, J J Hershon, J D Hill
Journal: Circulation (1985)

Approximately 20% of patients who receive left ventricular assist devices (LVADs) for refractory cardiac failure after open heart surgery have had complications of right ventricular failure. To evaluate this problem in the diseased heart we simulated an LVAD in the operating room by bypassing and unloading the left ventricle with the heart-lung machine before routine open heart surgery. Right ventricular function was assessed in 12 patients with preoperative left ventricular ejection fractions of less than 0.55 (poor left ventricular function) (mean +/- SEM 0.40 +/- 0.03) and 10 patients with ejection fractions greater than 0.55 (normal left ventricular function) (0.63 +/- 0.02). Measurements before and during left ventricular bypass in the normal left ventricular function group revealed no change in cardiac output (from 5.7 +/- 0.6 to 5.8 +/- 0.4 liters/min), with a decrease in right ventricular end-diastolic pressure (from 8 +/- 2 to 6 +/- 1 mm Hg). However, in the poor left ventricular function group, cardiac output was increased significantly during left ventricular bypass from 4.5 +/- 0.2 to 5.3 +/- 0.4 liters/min and right ventricular end-diastolic pressure was decreased significantly from 13 +/- 2 to 8 +/- 2 mm Hg. During bypass there were significant reductions in mean pulmonary arterial pressure from 17 +/- 3 to 10 +/- 2 mm Hg in the normal left ventricular function group and from 27 +/- 3 to 12 +/- 2 mm Hg in the poor left ventricular function group. These measurements reflect passive changes in pulmonary pressures due to reductions in left ventricular filling pressure during left ventricular bypass.(ABSTRACT TRUNCATED AT 250 WORDS)
Genetic and environmental effects on exhaled nitric oxide and airway responsiveness in a population-based sample of twins
Authors: M. B. Lund, J. Kongerud, W. Nystad, J. Boe, J. R. Harris
Journal: European Respiratory Journal (2006)

Elevated levels of exhaled nitric oxide (eNO) and airway hyperresponsiveness are intermediate phenotypes of asthma. Using population-based data collected from a sample of twins, the present authors estimated the relative contribution of genes, family environment and nonshared environmental influences to variations in eNO and airway responsiveness (AR). In addition, the genetic and environmental sources of covariation between these two asthma-related phenotypes were investigated. The study population comprised a random sample of 377 adult twins identified through the Norwegian Twin Registry. The main outcome variables were eNO and AR to methacholine. Genetic effects accounted for 60% of the variation in eNO. Family environment accounted for 30% of the variation in AR, while nonshared environmental influences explained the remaining variation for both measures. For both eNO and AR, there were significant regression effects for atopy and smoking. The small, but significant association between eNO and AR was primarily explained by genetic factors. Sub-analyses restricted to atopic and nonsmoking twins strengthened the observation. In conclusion, variations in exhaled nitric oxide and airway responsiveness appear to be explained by different genetic and environmental variance structures. Variation in exhaled nitric oxide is explained by genetic and nonshared environmental effects, whereas an environmental model best explains the variation in airway responsiveness. Common genetic effects explain the small but significant association between exhaled nitric oxide and airway responsiveness.
Co-operative Membrane Disruption Between Cell-penetrating Peptide and Cargo: Implications for the Therapeutic Use of the Bcl-2 Converter Peptide D-NuBCP-9-r8
Authors: Catherine L Watkins, Edward J Sayers, Chris Allender, David Barrow, Christopher Fegan, Paul Brennan, Arwyn T Jones
Journal: Molecular Therapy (2011)

Delivering apoptosis inducing peptides to cells is an emerging area in cancer and molecular therapeutics. Here, we have identified an alternative mechanism of action for the proapoptotic chimeric peptide D-NuBCP-9-r8. Integral to D-NuBCP-9-r8 is the Nur-77-derived D-isoform sequence fsrslhsll that targets Bcl-2, and the cell-penetrating peptide (CPP) octaarginine (r8) that is required for intracellular delivery. We find that the N-terminal phenylalanine of fsrslhsll acts in synergy with the cell-penetrating moiety to enhance peptide uptake at low nontoxic levels and cause rapid membrane blebbing and cell necrosis at higher (IC(50)) concentrations. These effects were not observed when a single phenylalanine-alanine mutation was introduced at the N-terminus of D-NuBCP-9-r8. Using primary samples from chronic lymphocytic leukemia (CLL) patients and cancer cell lines, we show that NuBCP-9-r8 induced toxicity, via membrane disruption, is independent of Bcl-2 expression. Overall, this study demonstrates a new mechanism of action for this peptide and cautions its use as a highly specific entity for targeting Bcl-2. For delivery of therapeutic peptides the work emphasizes that key amino acids in cargo, located several residues away from the cell-penetrating sequence, can significantly influence their cellular uptake and mode of action.
The αD-Globin Gene Originated via Duplication of an Embryonic α-Like Globin Gene in the Ancestor of Tetrapod Vertebrates
Authors: Federico G. Hoffmann, Jay F. Storz
Journal: Molecular Biology and Evolution (2007)

Gene duplication is thought to play an important role in the co-option of existing protein functions to new physiological pathways. The globin superfamily of genes provides an excellent example of the kind of physiological versatility that can be attained through the functional and regulatory divergence of duplicated genes that encode different subunit polypeptides of the tetrameric hemoglobin protein. In contrast to prevailing views about the evolutionary history of the α-globin gene family, here we present phylogenetic evidence that the αA- and αD-globin genes are not the product of a single, tandem duplication of an ancestral globin gene with adult function in the common ancestor of extant birds, reptiles, and mammals. Instead, our analysis reveals that the αD-globin gene of amniote vertebrates arose via duplication of an embryonic α-like globin gene that predated the radiation of tetrapods. The important evolutionary implication is that the distinct biochemical properties of αD-hemoglobin (HbD) are not exclusively derived characters that can be attributed to a post-duplication process of neofunctionalization. Rather, many of the distinct biochemical properties of HbD are retained ancestral characters that reflect the fact that the αD-globin gene arose via duplication of a gene that had a larval/embryonic function. These insights into the evolutionary origin of HbD illustrate how adaptive modifications of physiological pathways may result from the retention and opportunistic co-option of ancestral protein functions.
Models of the Physician-Patient Relationship
Authors: Tomas Jose Silber
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Regarding the four models of the physician-patient relationship by Emanuel and Emanuel,<sup>1</sup>I suggest that they need to be expanded and/or adapted to the special case of the physician-adolescent patient relationship.<sup>2-4</sup>This is an important stage in life when abstract thought develops, the capacity for reflection grows, and the need to establish an identity (to which the development of a value system is essential) becomes first and foremost.<sup>3</sup>What happens at the time of this "second period of individuation" will have a dramatic impact throughout adult life.<sup>4</sup>Hence the importance of the interaction with parents, teachers, and physicians. For many teenagers, the physician-adolescent encounter may be the first time they experience being taken seriously "as persons."<sup>5</sup>The deliberative model is a natural for adolescents. Moreover, the deliberative model especially needs to be used with teenagers at any physician encounter because they are
318. Tumor Growth Inhibition from Tumor Targeted Delivery of Diphtheria Toxin Gene
Authors: Puthupparampil V. Scaria, Qin Zhou, Raymond M. Schiffelers, Aslam Ansari, Martin C. Woodle
Journal: Molecular Therapy (2005)

Recent advances in the nucleic acid delivery technology have renewed interest in gene therapy. These advances can benefit not only gene therapy but also nucleic acid therapeutic approaches based on RNA interference, antisense etc. To realize the full potential of nucleic acid therapy, efficient vector systems that are tissue targeted and administered systemically need to be developed. Developing viral systems for systemic delivery is still challenging due to the immunogenecity and safety concerns. Non-viral delivery systems are more amenable to systemic delivery since they can be created from less toxic molecules. First generation non-viral systems were proven to be ineffective for systemic delivery due to their poor bio-availability and pharmacology. Some of the problems of the first generation systems can be overcome by providing the targeting capability and inhibiting non-specific interactions. There have been a number of efforts to achieve this by developing molecular conjugates where molecules capable of providing different functions required for nucleic acid delivery are linked together to form single molecules possessing multiple delivery functions. We have developed a molecular conjugate based on synthetic polymers that has some of the essential properties of a gene delivery molecule. This is based on a polyethyleneimine (PEI) polymer conjugate where a fraction of PEI amine is conjugated with polyethyleneglycol (PEG) and an integrin targeted peptide (RGD) ligand is attached to the end of PEG molecules. This polymer conjugate when combined with nucleic acid such as plasmid or short RNA, form nanoparticles with condensed nucleic acid core, a steric surface coat and a layer of ligands on the surface. This ligand surface is expected to target the nanoparticle to the endothelial cells in the neo-vasculature. In vivo experiments using reporter gene plasmid combined with this polymer conjugate in tumor bearing mice showed selective gene expression in tumor tissue with minimal expression in other tissues. Expression appears to be in the tumor blood vessels indicating neo-vascular targeting by the RGD peptide. We further examined if the level of expression obtained in tumor is sufficient to show tumor growth inhibition. Tumor bearing mice were treated with a plasmid encoding the A-chain of Diphtheria Toxin (DT-A) combined with the polymer conjugate by tail vein injection, once every three days. This resulted in significant tumor growth inhibition indicating that the tumor delivery achieved by this polymer conjugate may be sufficient for therapeutic efficacy.
Global Health Justice and Governance
Authors: Jennifer Prah Ruger
Journal: The American Journal of Bioethics (2012)

While there is a growing body of work on moral issues and global governance in the fields of global justice and international relations, little work has connected principles of global health justice with those of global health governance for a theory of global health. Such a theory would enable analysis and evaluation of the current global health system and would ethically and empirically ground proposals for reforming it to more closely align with moral values. Global health governance has been framed as an issue of national security, human security, human rights, and global public goods. The global health governance literature is essentially untethered to a theorized framework to illuminate or evaluate governance. This article ties global health justice and ethics to principles for governing the global health realm, developing a theoretical framework for global and domestic institutions and actors.
Prevalence and Mechanism of NSAID-Induced Clinical Relapse in Patients With Inflammatory Bowel Disease
Authors: K. Takeuchi, S. Smale, P. Premchand, L. Maiden, R. Sherwood, B. Thjodleifsson, E. Bjornsson, I. Bjarnason, Patrick S. Kamath
Journal: Clinical Gastroenterology and Hepatology (2006)
COMPARATIVE PATHOLOGY OF SOUTH AFRICAN JAGZIEKTE AND MONTANA PROGRESSIVE PNEUMONIA OF SHEEP
Authors: E. V. Cowdry, Hadleigh Marsh
Journal: The Journal of Experimental Medicine (1927)

As long as the exact etiology of jagziekte and of progressive pneumonia remains unknown, it cannot be said that they are identical, although on the basis of the observations detailed above, they certainly appear to be. It is extremely doubtful whether it is possible to distinguish between them. In the localities in which they occur, each is recognized as an infection quite distinct and apart from other better known pneumonias. Predisposing factors which lead to bacterial invasion are presumably of great importance in both. We have no precise information regarding the organisms concerned, but in both diseases, the initial changes are alike and occur in the interalveolar tissue and the subsequent proliferations of epithelium and the pneumonia are of the same character and apparently follow in exactly the same sequence. Finally, in both diseases, there is much fibrosis and the animals inevitably die through depletion of respiratory area and pneumonia. The view hitherto held, that jagziekte is a disease definitely restricted to the Union of South Africa, is thus rendered improbable. Nor does it appear likely that jagziekte is due to a single specific virus acting primarily upon the epithelial cells of the lungs, which is is likewise a conception widely accepted in South Africa.
Ranitidine nocte (Rhs) v ranitidine mane and nocte (Rbid)
Authors: J Plas, P. Van Wilder
Journal: Gut (1990)

An initial activation signal via the TCR in a restricted cytokine environment is critical for the onset of Th cell development. Cytokines regulate the expression of key transcriptional factors, T-bet and GATA-3, which instruct the direction of Th1 and Th2 differentiation, through changes in chromatin conformation. In this study, we investigated the kinetics of IL-4-mediated signaling in a transgenic mouse, expressing human IL-4R on a mouse IL-4αR-deficient background. These experiments, allowing induction with human IL-4 at defined times, demonstrated that an IL-4 signal was required at the early stage of TCR-mediated T cell activation for lineage commitment to Th2, along with structural changes in chromatin, which take place in the conserved noncoding sequence-1 and -2 within the IL-4 locus. At later times, however, IL-4 failed to promote efficient Th2 differentiation and decondensation of chromatin, even though GATA-3 was clearly induced in the nuclei by IL-4 stimulation. Moreover, IL-4-mediated Th2 instruction was independent from cell division mediated by initial TCR stimulation. The role of IL-4 signaling may have a time restriction during Th2 differentiation. In late stages of initial T cell activation, the chromatin structure of the IL-4 locus retains condensation state. These results demonstrate that IL-4-induced GATA-3 expression is time-restriction switch for Th2 differentiation.
Importance of the great vessels in the genesis of the electrocardiogram.
Authors: D Kilpatrick, S J Walker, A J Bell
Journal: Circulation Research (1990)

The electrocardiogram is the graphic representation against time of the difference in potential between points of the body caused by the current field of the heart. To examine the origin of this current field, a method of transforming body surface electrocardiographic data to the epicardial surface has been developed. The computed epicardial current density distributions in 219 patients with acute inferior myocardial infarction showed that, in 89% of patients, the current flow out of the heart during the ST segment came from two regions, not only from the infarction region but also from a region over the great vessels. This findings suggests that current flows from the ischemic region, through the low-resistance pathway provided by the intracavity blood, out the great vessels, and back to the epicardium. A similar pathway has been hypothesized when ischemia caused endocardial ST elevation, such as during a stress test or with unstable angina. To test this hypothesis, a group of patients with ST depression on the 12-lead electrocardiogram, not associated with ST elevation, was examined with body surface mapping. Ninety-four percent of patients had epicardial current density distributions that showed a region of current flow out of the heart and over the great vessels that was consistent with this hypothesis. This could explain the poor localization of coronary artery disease by electrocardiographic techniques when there is ST depression on the body surface.
Areca nuts can have deleterious effects
Authors: C. Trivedy, S. Warnakulasuriya, T. J Peters
Journal: BMJ (1999)

EDITOR—The United States nurses' study1 and the editorial that accompanies it report some health benefits of eating several helpings of nuts a week. These benefits cannot be generalised to all nuts commonly consumed, and it is important to specify which nuts confer them.

The areca nut (erroneously referred to as the betel nut) is chewed by over 200 million people worldwide—a tenth of the world's population. It is chewed …
Mechanism of acute pancreatitis after peroral double-balloon enteroscopy
Authors: M. Matsushita, M. Shimatani, K. Uchida, K. Okazaki
Journal: Endoscopy (2007)

We read with interest the article by Honda et al. [1] on hyperamylasemia and acute pancreatitis after peroral double-balloon enteroscopy (DBE). They performed peroral DBE in 13 patients, and hyperamylasemia occurred in 6 of the 13 (46.2 %). Among the 6 patients with hyperamylasemia, acute pancreatitis subsequently occurred in one patient. In the last 3 months, we performed a total of 32 DBE procedures (15 peroral and 17 peranal approaches). Whereas hyperamylasemia did not occur in the 17 patients after peranal DBE, we too saw hyperamylasemia in 7 of 15 patients treated perorally (46.7 %), and one of these suffered acute pancreatitis after the procedure. Although Honda et al. [1] suspect that the pancreatitis is mainly caused by duodenal intraluminal hypertension, we believe that another plausible mechanism should receive more attention based on the site of the pancreatitis.