tbuckley/cabot-search huggingface dataset:
Juxtapapillary Duodenal Diverticula
Authors: T Løtveit, V Skar, M Osnes
Journal: Endoscopy (1988)

This paper presents a review of the clinical significance of juxtapapillary duodenal diverticula in man. The incidence of such diverticula varies considerably in the literature, and possibly depends on the methods of investigation used. Studies show that the incidence of biliary calculi is significantly higher in patients with juxtapapillary diverticula as compared with patients without such diverticula. The assumed higher rate of diverticula in patients with pancreatitis is probably due to the presence of biliary calculi in these patients. Studies have shown that there is an insufficient choledochoduodenal sphincter in patients with diverticula, and also a higher rate of bacterial contamination of the duodenum and bile ducts in these patients. Fecal type flora has been found in most patients with juxtapapillary duodenal diverticula. Further, pigment gallstones have been found in most patients with diverticula, and analyses of these calculi showed that calcium bilirubinate was the main component. Further studies in our laboratory have shown that bacterial cultures produced beta-glucuronidase, a fact which may be connected with the increased frequency of pigment gallstones. Other studies have shown that there is a higher rate of diverticula in patients with recurrent biliary calculi who had undergone cholecystectomy. Recent data have also shown that there is a higher rate of common bile duct calculi in patients with diverticula, than in those without diverticula and without prior cholecystectomy--a fact supporting the theory on the pathogenesis of biliary calculi in patients with juxtapapillary diverticula. Other, and rare complications due to such diverticula are also mentioned.
Functional Substitution by TAT-Utrophin in Dystrophin-Deficient Mice
Authors: Kevin J. Sonnemann, Hanke Heun-Johnson, Amy J. Turner, Kristen A. Baltgalvis, Dawn A. Lowe, James M. Ervasti
Journal: PLoS Medicine (2009)

The loss of dystrophin compromises muscle cell membrane stability and causes Duchenne muscular dystrophy and/or various forms of cardiomyopathy. Increased expression of the dystrophin homolog utrophin by gene delivery or pharmacologic up-regulation has been demonstrated to restore membrane integrity and improve the phenotype in the dystrophin-deficient mdx mouse. However, the lack of a viable therapy in humans predicates the need to explore alternative methods to combat dystrophin deficiency. We investigated whether systemic administration of recombinant full-length utrophin (Utr) or DeltaR4-21 "micro" utrophin (muUtr) protein modified with the cell-penetrating TAT protein transduction domain could attenuate the phenotype of mdx mice.Recombinant TAT-Utr and TAT-muUtr proteins were expressed using the baculovirus system and purified using FLAG-affinity chromatography. Age-matched mdx mice received six twice-weekly intraperitoneal injections of either recombinant protein or PBS. Three days after the final injection, mice were analyzed for several phenotypic parameters of dystrophin deficiency. Injected TAT-muUtr transduced all tissues examined, integrated with members of the dystrophin complex, reduced serum levels of creatine kinase (11,290+/-920 U versus 5,950+/-1,120 U; PBS versus TAT), the prevalence of muscle degeneration/regeneration (54%+/-5% versus 37%+/-4% of centrally nucleated fibers; PBS versus TAT), the susceptibility to eccentric contraction-induced force drop (72%+/-5% versus 40%+/-8% drop; PBS versus TAT), and increased specific force production (9.7+/-1.1 N/cm(2) versus 12.8+/-0.9 N/cm(2); PBS versus TAT).These results are, to our knowledge, the first to establish the efficacy and feasibility of TAT-utrophin-based constructs as a novel direct protein-replacement therapy for the treatment of skeletal and cardiac muscle diseases caused by loss of dystrophin.
The Phosphodiesterase Inhibitor Cilostazol Induces Regression of Carotid Atherosclerosis in Subjects With Type 2 Diabetes Mellitus
Authors: Naoto Katakami, Young-Seol Kim, Ryuzo Kawamori, Yoshimitsu Yamasaki
Journal: Circulation (2010)

Antiplatelet drugs are effective in preventing recurrence of atherosclerosis in type 2 diabetic patients. However, the efficacy and usefulness of 2 different antiplatelet drugs, aspirin and cilostazol, in the progression of carotid intima-media thickening are unknown.To compare prevention by cilostazol and aspirin of progression of atherosclerosis, we conducted a prospective, randomized, open, blinded end point study in 4 East Asian countries. A total of 329 type 2 diabetic patients suspected of peripheral artery disease were allocated to either an aspirin-treated (81 to 100 mg/d) group or a cilostazol-treated (100 to 200 mg/d) group. The changes in intima-media thickness of the common carotid artery during a 2-year observation period were examined as the primary end point. The regression in maximum left, maximum right, mean left, and mean right common carotid artery intima-media thickness was significantly greater with cilostazol compared with aspirin (-0.088 + or - 0.260 versus 0.059 + or - 0.275 mm, P<0.001; -0.042 + or - 0.274 versus 0.045 + or - 0.216 mm, P=0.003; -0.043 + or - 0.182 versus 0.028 + or - 0.202 mm, P=0.004; and -0.024 + or - 0.182 versus 0.048 + or - 0.169 mm, P<0.001). In a regression analysis adjusted for possible confounding factors such as lipid levels and hemoglobin A(1c), the improvements in common carotid artery intima-media thickness with cilostazol treatment over aspirin treatment remained significant.Compared with aspirin, cilostazol potently inhibited progression of carotid intima-media thickness, an established surrogate marker of cardiovascular events, in patients with type 2 diabetes mellitus. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: C000000215.
Abstract 4834: Energy-dependent AMPK association with the ULK1-mTORC1 complex regulates autophagy
Authors: Jong Woo Lee, Sungman Park, Takahashi Yoshinori, Hong Gang Wang
Journal: Cancer Research (2010)

Abstract Autophagy is an intracellular catabolic process through which bulky cytosolic components are sequestered for lysosomal degradation. Recent evidence suggests that mTOR suppresses autophagy through direct interaction with the ULK1-Atg13-FIP200 complex. However, the mechanism by which mTOR is controlled to activate ULK1 activity for autophagy induction is not yet well elucidated. Using tandem affinity purification (TAP) assay, we screened for ULK1 binding proteins and identified several additional ULK1 binding proteins that mediate the pro-autophagic activity of ULK1. Here we report AMP-activated protein kinase (AMPK), which is known to be a highly-conserved cellular energy sensor that is activated under conditions of low intracellular ATP, as a new ULK1 binding protein. We found that AMPK binds to the PS domain of ULK1 in an energy-dependent manner, whereas mTOR associates with ULK1 through raptor interaction with the kinase domain of ULK1 independently of nutrient availability. Mechanistically, AMPK inhibits the mTOR activity by recruiting 14-3-3 to the mTORC1 through phosphorylation of raptor in response to energy stress. Importantly, activation of AMPK by 5-amino-4-imidazolecarboxamide ribose (AICAR) is able to suppress the mTORC1 and induce autophagy in TSC2-deficient cells with wild-type raptor but not the mutant raptor (S722A/S792A) lacking AMPK phosphorylation sites. Our study indicates, therefore, that AMPK-mediated raptor phosphorylation plays an important role in the activation of ULK1 to induce autophagy under energy stress conditions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4834.
SIMPLE CLINICAL AID IN DIAGNOSIS OF HEMORRHAGIC PERICARDIAC EFFUSION
Authors: Clarence W. Mills
Journal: JAMA (1952)

The problem of differentiating grossly bloody fluid in the pericardiac sac from intracardiac blood during a pericardicentesis may sometimes be difficult. Fortunately, this situation seldom occurs, but, when it does, it is usually in a patient who is acutely ill and can poorly tolerate loss of an appreciable quantity of blood as the result of unintentional aspiration of blood from the heart. In the following abridged case report, such a distinction was rendered difficult by the anatomic changes caused by the underlying disease and the effects of therapy. The use of the procedure described below as an aid in determining the source of the blood obtained at pericardicentesis was arrived at by fortuitous circumstances, and its simplicity was sufficiently appealing to warrant publication. <h3>REPORT OF A CASE</h3> A 17-year-old white boy had an extensive lymphoblastic lymphoma of the mediastinum and right pleura of three months' duration at the time of
Melanoma Susceptibility Gene
Authors: Joan Stephenson
Journal: JAMA (2002)

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Abscess of the Brain in an Infant
Authors: F. Warner
Journal: BMJ (1873)

the head; this, however, passed off under treatment in a few days.Lymph was soon effused in the wound, and shortly became organised; the wounds all healing in a very rapid and satisfactory manner.She complained, on getting better, of loss of sensation in her left ear.August 28th.The ligature round the small artery came away.September 2nd.On this (the nineteenth) day the lower of the two ligatures of the internal jugular came away.
Long-term cardiorespiratory effects of amelioration of renal anaemia by erythropoietin
Authors: I.C. Macdougall, G.A. Coles, J.D. Williams, M.E. Davies, R.D. Hutton, D.L. Cochlin, N.P. Lewis, K.A.A. Fox, M.J. Saunders
Journal: The Lancet (1990)
Conservatism in Surgical Treatment of Bronchial Carcinoma
Authors: G. Flavell
Journal: BMJ (1962)

receiving oral alpha-chymotrypsin.Recognizing that purulent sputum is less viscous than mucoid sputum, a record was made of the incidence of purulent specimens in each group.The number of purulent samples in group 2 differed only slightly from that in group 1: 57 mucopurulent specimens in group 1 (60%), and 70 in group 2 (67%).From this observation one may deduce that the reduced viscosity in group 2 patients is due to. the direct mucolytic effect of the enzyme.No side-effects were observed and most of the patients in both groups described improvement in their symptoms and felt the tablets assisted them in expectorating sputum.Summary A small-scale double-blind trial using oral alphachymotrypsin is described.The results indicate that oral alpha-chymotrypsin causes liquefaction of sputum as denoted by a reduction in its viscosity.The Armour Pharmaceutical Company Ltd. supplied the tablets of alpha-chymotrypsin (chymoral).
Atherosclerosis and Related Factors in Immigrants to Israel
Authors: M. TOOR, A. KATCHALSKY, J. AGMON, D. ALLALOUF
Journal: Circulation (1960)

Clinical experience in Israel, supported by statistical surveys, showed a low incidence of atherosclerosis among immigrants from eastern countries as compared to immigrants from western countries. In particular, the incidence of atherosclerosis among immigrants from Yemen was found to be strikingly low. An investigation of the socioeconomic condition, diet, and nutritional status of 2,200 immigrants from western and eastern countries belonging to different social groups was carried out. Determinations of serum total lipids, total cholesterol, alpha and beta cholesterol, phospholipids, lipoproteins, proteins, and protein fractions were performed. Significantly the lowest serum cholesterol and beta cholesterol values were found among the "recent" Yemenites (after 5 years in Israel), the poorest economically, and with an imbalanced caloric intake of the lowest fat content. Higher cholesterol and beta cholesterol values were found among "early" (after 20 years in Israel) Yemenites, Iraqi, and European manual workers with no significant differences among them, whereas in Europeans of higher economic level these values were even higher. Review of 5,000 hospitalized cases of myocardial infarction showed a very low incidence for Yemenites, higher for immigrants from other eastern countries, and considerably higher for European immigrants. A statistical survey of the entire population for the years 1953 to 1957 showed that the mortality rate from atherosclerosis was extremely low for "recent" Yemenites, considerably higher for "early" Yemenites, and still higher for European immigrants. These results suggest the influence of socioeconomic conditions, diet, and total caloric balance on serum cholesterol values and atherosclerosis morbidity and mortality. They support the assumption that atherosclerosis is a disease of lipid metabolism influenced by phenotypic factors and therefore can be prevented.
Vaccines are essential in campaigns against HIV and TB, say researchers
Authors: P. Moszynski
Journal: BMJ (2012)

Major breakthroughs in the development of vaccines against HIV and tuberculosis over the past decade have resulted in a number of promising candidates entering late stage clinical trials. Yet participants at a symposium held last week by the UK Consortium on AIDS and International Development warned that this progress could be jeopardised by the recent downturn in global health funding.

The meeting heard that currently 71 HIV vaccine trials and 15 trials of tuberculosis vaccines are ongoing.

Robin Shattock, of Imperial College London, said that one HIV vaccine candidate, RV144, had recently completed stage III trials in Thailand, showing a protective efficacy of over 30%.1 Although this figure was not yet ideal …
Human Collagenase (Matrix Metalloproteinase-1) Expression in the Lungs of Patients with Emphysema
Authors: KAZUSHI IMAI, SEEMA S. DALAL, EDWARD S. CHEN, ROBERT DOWNEY, LARRY L. SCHULMAN, MARK GINSBURG, JEANINE D'ARMIENTO
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Pulmonary emphysema is believed to result from an imbalance between proteolytic enzymes and their inhibitors. Multiple studies have examined the presence of various proteases within the bronchoalveolar lavage fluid from patients with chronic obstructive pulmonary disease (COPD). However, to date extensive examination of the lung parenchyma for the expression of destructive enzymes has not yet been determined. The following study examines the lung parenchyma of 23 patients with emphysema and 8 normal control samples for the expression of matrix matalloproteinase-1 (MMP-1), MMP-12, and MMP-9. We report here that interstitial collagenase (MMP-1) RNA, protein, and activity are present in the lung parenchyma of patients with emphysema and not in the lung of normal control subjects. In contrast, metalloelastase (MMP-12) expression is absent in these samples. Immunohistochemistry studies localized MMP-1 to the Type II pneumocyte in patients with emphysema and not normal control subjects or smokers without emphysema. This observation demonstrates that the lung is altered in emphysema such that the Type II pneumocyte secretes MMP-1 and suggests that MMP-1 may be an important enzyme involved in the destruction of the lung in the human disease. In addition, the induction of a proteolytic enzyme within the Type II pneumocyte suggests that the cells within the lung itself are capable of producing degradative enzymes in this disease process.
Conceptual and Technical Challenges in Network Meta-analysis
Authors: Andrea Cipriani, Julian P.T. Higgins, John R. Geddes, Georgia Salanti
Journal: Annals of Internal Medicine (2013)

The increase in treatment options creates an urgent need for comparative effectiveness research. Randomized, controlled trials comparing several treatments are usually not feasible, so other methodological approaches are needed. Meta-analyses provide summary estimates of treatment effects by combining data from many studies. However, an important drawback is that standard meta-analyses can compare only 2 interventions at a time. A new meta-analytic technique, called network meta-analysis (or multiple treatments meta-analysis or mixed-treatment comparison), allows assessment of the relative effectiveness of several interventions, synthesizing evidence across a network of randomized trials. Despite the growing prevalence and influence of network meta-analysis in many fields of medicine, several issues need to be addressed when constructing one to avoid conclusions that are inaccurate, invalid, or not clearly justified. This article explores the scope and limitations of network meta-analysis and offers advice on dealing with heterogeneity, inconsistency, and potential sources of bias in the available evidence to increase awareness among physicians about some of the challenges in interpretation.
Busulphan versus combination chemotherapy for initial treatment of chronic granulocytic leukaemia
Authors: Peter Jacobs
Journal: American Journal of Hematology (1986)

Abstract In a pilot study, 21 consecutive and previously untreated adults with chronic granulocytic leukaemia received either busulphan (group 1: n = 11) or a combination of the epipodophyllotoxin VP16‐213 with cytosine arabinoside and doxorubicin (group 2: n = 10). Using a standardised protocol, objective response, defined as a granulocyte count consistently less than 10 × 10 9 /1 with no clinical evidence of the disease, was achieved in 45 and 40% of the patients, respectively, and median survivals were 89 and 107 weeks (p &gt; 0.05). Although there was no difference in morbidity, the study was discontinued because the combination chemotherapy was more complex to administer, was associated with greater patient inconvenience, and offered no advantage over single‐agent therapy in managing the stable phase of chronic granulocytic leukaemia.
Measurement of Intracellular pH of Skeletal Muscle with pH-sensitive Glass Microelectrodes*
Authors: Norman W. Carter, Floyd C. Rector, David S. Campion, Donald W. Seldin
Journal: Journal of Clinical Investigation (1967)

We used three methods to examine the relationship among intracellular pH, transmembrane potential, and extracellular pH. Single-barreled electrodes permitted the determination of resting potential and intracellular pH with a minimum of cellular injury. Double-barreled electrodes, which incorporated a reference as well as a pH-sensitive electrode in a single tip, facilitated the direct measurement of intracellular pH without the interposition of the transmembrane potential. Triple-barreled electrodes permitted measurement of intracellular pH during the controlled hyperpolarization or depolarization of the cell membrane. The results of all three methods were in close agreement and disclosed that the H(+) activity of intracellular and extracellular fluid is in electrochemical equilibrium at any given transmembrane potential. This implies that the determinants of intracellular pH are the transmembrane potential and the blood pH. The actual pH of the normal resting muscle cell is 5.99, as estimated from the normal transmembrane potential and blood pH, or as determined by direct measurements of intracellular pH.
Inexplicable pulmonary oedema.
Authors: H. Marcovitch
Journal: BMJ (1989)

specialised team provides a special seating service for patients referred from a wider area.Our experience has resulted in an acute awareness of many shortfalls of standard issue wheelchairs and, together with the experience of other centres in Scotland, has enabled the Wheelchair Advisory Service, through the auspices of the Central Services Agency who are now responsible for purchasing chairs in Scotland, to address the problems thus identified with a view to improving the overall quality of care.
Coronary blood flow during cardiopulmonary resuscitation in swine.
Authors: R F Bellamy, L R DeGuzman, D C Pedersen
Journal: Circulation (1984)

Recent papers have raised doubt as to the magnitude of coronary blood flow during closed-chest cardiopulmonary resuscitation. We will describe experiments that concern the methods of coronary flow measurement during cardiopulmonary resuscitation. Nine anesthetized swine were instrumented to allow simultaneous measurements of coronary blood flow by both electromagnetic cuff flow probes and by the radiomicrosphere technique. Cardiac arrest was caused by electrical fibrillation and closed-chest massage was performed by a Thumper (Dixie Medical Inc., Houston). The chest was compressed transversely at a rate of 66 strokes/min. Compression occupied one-half of the massage cycle. Three different Thumper piston strokes were studied: 1.5, 2, and 2.5 inches. Mean aortic pressure and total systemic blood flow measured by the radiomicrosphere technique increased as Thumper piston stroke was lengthened (mean +/- SD): 1.5 inch stroke, 23 +/- 4 mm Hg, 525 +/- 195 ml/min; 2 inch stroke, 33 +/- 5 mm Hg, 692 +/- 202 ml/min; 2.5 inch stroke, 40 +/- 6 mm Hg, 817 +/- 321 ml/min. Both methods of coronary flow measurement (electromagnetic [EMF] and radiomicrosphere [RMS]) gave similar results in technically successful preparations (data expressed as percent prearrest flow mean +/- 1 SD): 1.5 inch stroke, EMF 12 +/- 5%, RMS 16 +/- 5%; 2 inch stroke, EMF 30 +/- 6%, RMS 26 +/- 11%; 2.5 inch stroke, EMF 50 +/- 12%, RMS 40 +/- 20%. The phasic coronary flow signal during closed-chest compression indicated that all perfusion occurred during the relaxation phase of the massage cycle. We concluded that coronary blood flow is demonstrable during closed-chest massage, but that the magnitude is unlikely to be more than a fraction of normal.