tbuckley/cabot-search huggingface dataset:
P84 Towards cell based therapy for 1-antitrypsin deficiency through targeted bi-allelic gene correction in human iPS cells
Authors: S. T. Rashid, K. Yusa, H. Strick-Marchand, F. J. Rouhani, S. J. Marciniak, E. Miranda, A. Ordonez, N. Hannan, G. Alexander, J. di-Santo, A. Bradley, D. A. Lomas, L. Vallier
Journal: Gut (2011)

<h3>Introduction</h3> Human induced pluripotent stem cells (hIPSCs) represent a unique opportunity for regenerative medicine since they offer the prospect of generating unlimited quantities of cells for autologous transplantation as a novel treatment for a broad range of disorders. We have previously developed disease specific human hepatocyte-like cells by reprogramming dermal fibroblasts taken from individuals with PiZ α1-antitrypsin deficiency. The resulting cells recapitulated the protein misfolding and intracellular polymer formation that characterise this disease (Rashid <i>et al</i>, <i>J Clin Invest</i> 2010;<b>120</b>:3127–36). However, use of iPS cells in treatment of individuals with PiZ α1-antitrypsin deficiency would also require correction of the underlying genetic abnormality in a manner fully compatible with clinical applications. The methods currently available, such as homologous recombination, lack the necessary efficiency and also leave residual sequences in the targeted genome. <h3>Aim</h3> (1). To correct the genetic mutation responsible for PiZ α1-antitrypsin deficiency in human IPS cells in a clinically relevant way. (2). To investigate the potential of using corrected hIPS derived liver cells for cell based therapy by studying their in vivo function. <h3>Method</h3> The genetic defect responsible for PiZ α1-antitrypsin deficiency (Glu342Lys) was targeted using a combination of engineered Zinc finger nucleases and a piggyBac vector in patient specific hiPSCs. Corrected cells were differentiated to hepatocytes using a previously optimised chemically defined in vitro platform. Assessment of phenotypic correction was then made in vitro as well as in vivo. <h3>Results</h3> We demonstrate here for the first time an efficient gene editing technique capable of restoring normal structure, function and secretion of α1-antitrypsin in subsequently derived liver cells without leaving residual exogenous sequences in the targeted hiPSC genome. Moreover injection of corrected hiPS derived liver cells into a mouse model of liver injury confirmed their potential for functional capacity in vivo. Importantly none of the transplanted mice showed evidence of tumour formation. <h3>Conclusion</h3> Our results provide proof of principle for the potential of combining hiPSCs with gene therapy to generate cells for autologous cell based treatment of α1-antitrypsin deficiency in humans.
Internal Fixation by the Ender Method-Reply
Authors: Richard D. Corzatt
Journal: JAMA (1979)

Concerning the letter by Dr Skilbred about our article, Internal Fixation by the Ender Method, I certainly agree with him that the Ender nail is not a panacea for all fractures involving the intertrochanteric region of the hip. It is a new system.  On our particular service, the Ender nail has become the treatment of choice for stable intertrochanteric fractures. Its role in unstable intertrochanteric fractures is presently being further analyzed.  In response to the specific points in his letter, the average age of his patients was 85 years. The average age of our patients was 76 years. This indicates that in his series, osteoporosis was probably more of a problem than in our series. The results of any fixation device are worse in osteoporotic bone than in relatively more normal bone.  As stated, in our first 25 cases, blood loss was not a problem. We presently are
ECLAMPSIA AT THE UNIVERSITY HOSPITAL
Authors: E. D. PLASS
Journal: JAMA (1942)

During the sixteen years between Jan. 1, 1926 and Dec. 31, 1941, 80 eclamptic patients were observed and treated at the University Hospital. Thirty-seven women were admitted in the convulsive stage, and 43 suffered the seizures after admission; all but 13 of the latter were admitted because of toxemia. Throughout the series, eclampsia was viewed as a medical condition and treatment followed a fairly consistent pattern. This communication deals with the results obtained and involves a discussion of the lessons learned by the experience.  TREATMENT EMPLOYED  The essence of therapy revolves around the clinical observation that eclamptics generally do not have convulsions when the respirations are less than 14 to 16 per minute and the deduction therefrom that there is some relationship between the respiratory exchange and the appearance of the convulsive episodes. Heavy sedation was therefore employed, and the dosage was regulated solely by the effect on the respiratory
Protease nexin 1 in the murine kidney: Glomerular localization and up-regulation in glomerulopathies
Authors: Solange Moll, Nicole Schaeren-Wiemers, Annelise Wohlwend, Yves Pastore, Thierry Fulpius, Denis Monard, André-Pascal Sappino, Jürg A. Schifferli, Jean-Dominique Vassalli, Shozo Izui
Journal: Kidney International (1996)
Peritoneal Shunts in the Management of Hydrocephalus
Authors: Frederick Murtagh
Journal: JAMA (1967)

In a series of 133 patients with hydrocephalus for whom follow-up data is known, cerebrospinal fluid was shunted to the peritoneal cavity in 53. Forty-six of these were shunts from the lumbar subarachnoid space in patients with communicating hydrocephalus. In 40 patients, the procedure was felt to be of definite value either as the sole method of controlling the hydrocephalus for over ten years, or effective for a period of time sufficient to allow the patient to survive a crisis with intracranial hypertension. In 13 patients the method was a total failure.
Port Pirie Cohort Study: Environmental Exposure to Lead and Children's Abilities at the Age of Four Years
Authors: Anthony J. McMichael, Peter A. Baghurst, Neil R. Wigg, Graham V. Vimpani, Evelyn F. Robertson, Russell J. Roberts
Journal: New England Journal of Medicine (1988)

We studied the effect of environmental exposure to lead on children's abilities at the age of four years in a cohort of 537 children born during 1979 to 1982 to women living in a community situated near a lead smelter. Samples for measuring blood lead levels were obtained from the mothers antenatally, at delivery from the mothers and umbilical cords, and at the ages of 6, 15, and 24 months and then annually from the children. Concurrently, the mothers were interviewed about personal, family, medical, and environmental factors. Maternal intelligence, the home environment, and the children's mental development (as evaluated with use of the McCarthy Scales of Children's Abilities) were formally assessed. The mean blood lead concentration varied from 0.44 μmol per liter in midpregnancy to a peak of 1.03 μmol per liter at the age of two years. The blood lead concentration at each age, particularly at two and three years, and the integrated postnatal average concentration were inversely related to development at the age of four. Multivariate analysis incorporating many factors in the children's lives indicated that the subjects with an average postnatal blood lead concentration of 1.50 μmol per liter had a general cognitive score 7.2 points lower (95 percent confidence interval, 0.3 to 13.2; mean score, 107.1) than those with an average concentration of 0.50 μmol per liter. Similar deficits occurred in the perceptual-performance and memory scores. Within the range of exposure studied, no threshold dose for an effect of lead was evident. We conclude that postnatal blood lead concentration is inversely related to cognitive development in children, although one must be circumspect in making causal inferences from studies of this relation, because of the difficulties in defining and controlling confounding effects. (N Engl J Med 1988; 319:468–75.)
Points from Letters: Nasopharyngeal Involvement in Temporal Arteritis
Authors: P. Gibbs
Journal: BMJ (1974)

1) That this commnittee agrees to ap- point an appropriate number of members to serve on its two District Medical Committees."(2) That if the General Medical Services Committee so advises, these members will not participate in-the work of the District Medical Committees until the ques- tion of remuneration or reimbursement for loss of earnings is agreed with the Depart- ment of Health and Social Security."-Weare, etc.,
The Incidence of Fracture among Patients with Inflammatory Bowel Disease: A Population-Based Cohort Study
Authors: Charles N. Bernstein
Journal: Annals of Internal Medicine (2000)

The clinical significance of the high prevalence of osteopenia in inflammatory bowel disease is unclear.To determine whether persons with inflammatory bowel disease have increased incidence of fracture.Population-based matched cohort study.Manitoba, Canada.Patients with inflammatory bowel disease in the University of Manitoba IBD Database (n = 6027) were matched to 10 randomly selected persons in the general population without inflammatory bowel disease (n = 60 270) by year, age, sex, and postal area of residence.The incidence of hospitalization for hip fracture was determined on the basis of hospital discharge abstracts. Outpatient medical billing records and hospital discharge abstracts were used to calculate the incidence of spine, rib, and forearm fractures. Rates were calculated on the basis of person-years of follow-up for 1984 to 1997.Persons with inflammatory bowel disease had significantly increased incidence of fractures at the spine (incidence rate ratio [IRR], 1.74 [95% CI, 1.34 to 2.24]; P < 0.001), hip (IRR, 1.59 [CI, 1.27 to 2.00]; P < 0.001), wrist/forearm (IRR, 1.33 [CI, 1.11 to 1.58]; P = 0.001), and rib (IRR, 1.25 [CI, 1.02 to 1.52]; P = 0.03) and of any of these fractures (IRR, 1.41 [CI, 1.27 to 1.56]; P < 0.001).The incidence of fracture among persons with inflammatory bowel disease is 40% greater than that in the general population.
Evaluating information technology in health care: barriers and challenges
Authors: H. Heathfield, D. Pitty, R. Hanka
Journal: BMJ (1998)

There is strong push for clinical leadership in the development and procurement of information technology in health care.1 The lack of clinical input to date has been cited as a major factor in the failure of information technology in health services2 and has prompted many clinicians to become involved in such endeavours. Furthermore, there are various clinical decision support systems available, the merits of which clinicians are expected to judge (such as Prodigy3 and Capsule4).

It is essential that clinicians have a knowledge of evaluation issues in order that they can assess the strengths and weaknesses of evaluation studies and thus interpret their results meaningfully, and also contribute to the design and implementation of such studies to provide them with useful information.

#### Summary points

Clinicians are becoming increasingly involved in the development and procurement of information technology in health care, yet evaluation studies have provided little useful information to assist them

Evaluations by means of randomised controlled trials have not yet provided any major indication of improved patient outcomes or cost effectiveness, are difficult to generalise, and do not provide the scope or detail necessary to inform decision making

Clinical information systems are a different kind of intervention from drugs, and techniques used to evaluate drugs (particularly randomised controlled trials) are not always appropriate

The challenge for clinical informatics is to develop multi-perspective evaluations that integrate quantitative and qualitative methods

Evaluation is not just for accountability but to improve our understanding of the role of information technology in health care and our ability to deliver systems that offer a wide range of clinical and economic benefits

Decision makers may be …
Relationship between parental reports of environmental and food triggers of asthma symptoms and allergic sensitization—The Childhood Asthma Research and Education (CARE) network
Authors: I.M. Paul, T.W. Guilbert, D.T. Mauger, S.J. Boehmer, R.F. Lemanske, R.S. Zeiger, T.J. Craig, F.D. Martinez, S.J. Szefler, R.C. Strunk, L.M. Taussig, V.M. Chinchilli
Journal: Journal of Allergy and Clinical Immunology (2003)
Topical Application of Nitrates onto the Papilla of Vater: Manometric and Clinical Results
Authors: T. Wehrmann, T. Schmitt, N. Stergiou, W. Caspary, H. Seifert
Journal: Endoscopy (2001)

Background and Study Aims: Systemic administration of nitrates inhibits motility of the sphincter of Oddi (SO) but is hampered by a decrease of the arterial blood pressure. We evaluate whether topical application of glyceril trinitrate (GTN) onto the papilla can facilitate cannulation of the common bile duct during routine endoscopic retrograde cholangiopancreatography (ERCP) and compare the effect of topical GTN with that of isosorbide dinitrate (ISDN) on SO motility.
Hyperglycemia and Hyperosmolarity in an Eighteen-Month-Old Child
Authors: Robert M. Ehrlich, Harry W. Bain
Journal: New England Journal of Medicine (1967)

DURING a review of the records for juvenile diabetes mellitus at the Hospital for Sick Children, a case was discovered in which severe hyperglycemia was accompanied by an altered level of consciousness but not by ketosis. A recent review1 of the syndrome of hyperglycemic hyperosmolar coma in adults indicated that no case in a person under twenty-seven years of age had ever been reported. The child described below was seen in 1954, three years before the initial report of the syndrome in the literature.2 Case ReportAn 18-month-old boy was admitted to the emergency department acutely and seriously ill. He . . .
Key Topics in Accident and Emergency Medicine
Authors: P Driscoll
Journal: BMJ (1994)

Bios, pounds sterling 20, pp 332 ISBN 1-872748-67-8.

There has been a rapid development in the specialty of accident and emergency medicine over the past 30 years. Consultant numbers have increased, a faculty of accident and emergency medicine has been set up, and professorial positions have been created. Furthermore, the role of the accident and emergency specialist is becoming more standardised. Although there will always be slight variations due to local …
525Distinctive miRNA signature associated to inflammation in monocytes exposed to atherogenic low density lipoproteins: miR126
Authors: R Escate, T Padro, L Badimon
Journal: Cardiovascular Research (2014)

Purpose: Small non-coding microRNAs (miRNAs), that post-transcriptionally regulate gene expression, have emerged as key regulators of molecular pathways that may critically control monocyte differentiation and function in hypercholesterolemia, a major risk factor for atherosclerotic plaque evolution. The present study was aimed to investigate the differential miRNA signature profile in cultured human monocyte exposed to atherosclerotic concentrations of low density lipoproteins (LDL). Methods: Human monocytes from healthy donors were isolated and exposed to atherogenic concentrations (180 mg/dL) of LDL during 24 hours. miRNA pattern was determined using a Taqman array micro fluidic card. Gene and protein analysis of in silico selected targets was performed by RT-PCR and western-blot. Results: We consistently identified 73 miRNAs in human monocytes. Ten miRNAs were differentially upregulated and 1 downregulated, with >1.5fold difference, after exposition to atherogenic concentrations of LDL. Among the differential miRNA pattern, miR-126 showed the largest changes (>3 fold increase, p<0.05). In silico IPA core analysis revealed inflammation as the most representative process associated to the LDL-induced differential miRNA profile (p<0.0001). By combining MiRNA Target Filter prediction and minimum free energy (mfe) analysis using RNAhybrid, we identified the member of the tumor necrosis factor receptor superfamily TNFRSF10B, receptor for ligands involved in cell-apoptosis pathway, as the gene regulated by miR-126 with a highest score. Monocyte exposed to LDL did not show any significant change in TNFRSF10B mRNA expression. However, TNFRSF10B protein level in monocytes was >2 fold decreased (p<0.05) after 24 h exposure to LDL, indicating its post-transcriptional regulation. Conclusions: our data suggest that the increase of miR-126 expression in monocyte exposed to atherogenic LDL might identify a novel mechanism involving the monocyte-dependent inflammatory response in hypercholesterolemia and regulate TNFRSF10B protein levels in monocytes.
'Decade of Brain' Holds Promise for Answers to Schizophrenia
Authors: Phil Gunby
Journal: JAMA (1990)

THE "Decade of the Brain" decreed by Congress (<i>JAMA</i>. 1989;262:2201) lies ahead. Before the decade ushers in a new millennium, answers will be found to many of the questions surrounding schizophrenia. Or at least that is the hope of researchers, as expressed in Tulsa, Okla, at the inaugural symposium ("Schizophrenia: New Frontiers in Research and Treatment") of Laureate Psychiatric Clinic and Hospital (<i>JAMA</i>. 1990;263:2028). The site of the symposium is the nation's newest psychiatric and substance-abuse care facility for adults, adolescents, and children, which just began admitting patients this year. Dwight Holden, MD, is chief executive officer and medical director, and Laureate has the support of the William K. Warren Foundation, named for the late Tulsa oil executive. <h3>Many Answers Needed</h3> As far as schizophrenia is concerned, it remains to be seen, of course, whether research in the next few years will provide the "mosaic of many answers" that National
Grass Roots Participation in Health Care Reform
Authors: Ralph Crawshaw
Journal: Annals of Internal Medicine (1994)

Concerned citizens have responded to the health care crisis by developing the health decisions movement. American Health Decisions, a national consortium of 21 state organizations, leads a grass roots discussion network of community meetings committed to education and consensus on the ethical, technologic, legal, and economic issues (the tough issues) of health policy. The movement (with its stages of development, structure, process, and accomplishments) is described, and potential roles for physician cooperation and participation in forging functional, community-based health policy are delineated.
Antibiotics in Myasthenia Gravis
Authors: E. Hokkanen
Journal: BMJ (1964)

B 1111 irreconcilable division of views exists con- cerning a proposed College of Psychiatrists.Most aware of the need for change in the professional representation of psychiatry are those directly engaged in the mental hospital service, with its network of out-patient clinics, domiciliary services, child psychiatric clinics, rehabilitation units, and community care programmes-a developing service second tc none in the world.On the other hand arc the psychiatrists directly concerned with undergraduate teaching and with scientific research.They have made outstanding con- tributions to British psychiatry both by theit insistence, often against much opposition, on the adequate basic training of medical students, and by establishing a firm yet un- committed basis for scientific research in this
Visualization of the Liver, Gallbladder, and Intestine on Bone Scintigraphy
Authors: LARRY SHERKOW, U YUN RYO, DOUGLAS FABICH, GHANSHYAM C. PATEL, STEVEN M. PINSKY
Journal: Clinical Nuclear Medicine (1984)

Images of the liver, gallbladder, and/or intestine were visualized on bone scans on several occasions. Radiopharmaceutical quality control data, including molybdenum-99 and aluminum ion content in the Tc-99m eluate, free unbound Tc-99m, and hydrolyzed reduced Tc-99m in the labeled MDP, were all satisfactory. A minor defect in the quality of the Tc-99m generator was considered to be the probable cause of the unusual localization of the bone imaging agent.
Universal Grammar and the critical age
Authors: Julia Herschensohn
Journal: Behavioral and Brain Sciences (1998)

Differences of opinion between Epstein, Flynn &amp; Martohardjono (1996) and some commentators can be traced to different interpretations of Universal Grammar (UG) form or strategy. Potential full access to the form of linguistic universals in second language acquisition may be distinguished from access to UG strategy, but Epstein et al.'s dismissal of the Critical Age Hypothesis clouds their central argument.
Similar levels of nitric oxide in exhaled air in non‐asthmatic rhinitis and asthma after bronchial allergen challenge
Authors: C. E. Lopuhaä, J. G. Koopmans, H. M. Jansen, J. S. Van Der Zee
Journal: Allergy (2003)

Background: Nitric oxide in exhaled air (eNO) is elevated in allergic asthma compared with healthy subjects and has been proposed as a marker of bronchial inflammation. However, eNO is elevated to a lesser extent in allergic non‐asthmatic rhinitis as well. Considering the distinctive clinical appearances of both allergic diseases, differences in eNO are expected to persist after allergen exposure. The aim of the study was to compare allergen‐induced changes in eNO in house dust mite sensitized patients with asthma and patients with perennial rhinitis without asthma symptoms. Methods: Bronchial allergen challenge was performed in 52 patients sensitized to house dust mite ( Dermatophagoides pteronyssinus ), of whom 26 had non‐asthmatic rhinitis and 26 had asthma. Levels of eNO were measured before and 1 h, 1 day and 1 week after challenge. Results: At baseline eNO was significantly lower in non‐asthmatic rhinitis compared with asthma (geometric mean eNO (SEM): 121 (1.1) in non‐asthmatic rhinitis vs 197 (1.1) nl/min in asthma, P &lt; 0.006). However, the increase in eNO after bronchial allergen challenge in non‐asthmatic rhinitis, in particular in those patients with a dual asthmatic response, significantly exceeded the increase in asthma resulting in similar levels of eNO after challenge (geometric mean eNO (SEM) at 24 h postchallenge 204 (1.1) in non‐asthmatic rhinitis vs 244 (1.1)nl/min in asthma, P = 0.3). Conclusion: The difference in eNO between non‐asthmatic rhinitis and asthma at baseline is abolished after allergen exposure due to a significantly greater increase in eNO in non‐asthmatic rhinitis.
Timothy Grass Allergy Immunotherapy Tablets Reduce Nasal and Ocular Symptoms Associated With Allergic Rhinoconjunctivitis During Grass Pollen Season in North American Children and Adults: 2 Randomized, Placebo-Controlled Trials
Authors: D. Skoner, H. Nolte, P. Creticos, M. Blaiss, J. Maloney, H. Nelson
Journal: Journal of Allergy and Clinical Immunology (2012)
ACUTE TRANSIENT EPIPHYSITIS OF THE HIP JOINT
Authors: O. L. MILLER
Journal: JAMA (1931)

There is a disease of the hip incident to childhood, which, in view of the frequency of its occurrence, is not given as much textbook emphasis or as much detailed description in collateral writings as it deserves. To distinguish it from acute septic epiphysitis, or septic hip, this condition should be termed acute transient epiphysitis. The clinical course of the latter differs so decidedly from that of the former that I believe it should be recognized as an entity with its own classification. Certainly, a different method of clinical management is indicated. Much emphasis has been given to destructive septic epiphysitis of the hip, no doubt owing to the fact that it is attended by profound illness and prone to be followed by permanent disability and deformity. Acute transient epiphysitis of the hip as described here causes a child to be sick, creates temporary or permanent deformity depending on the