tbuckley/cabot-search huggingface dataset:
Scientists Find Promising Therapies for Fragile X and Down Syndromes
Authors: Bridget M. Kuehn
Journal: JAMA (2011)

CLINICIANS HAVE LONG VIEWED the intellectual disabilities associated with developmental disorders, such as fragile X and Down syndromes, as irreversible or untreatable. However, emerging data suggest that a number of potential drug therapies targeting the molecular pathways involved in these disorders may one day help to improve cognition, memory, and behavior in patients with these genetic conditions. Advances in the understanding of the genetic and molecular basis of developmental disorders, as well as the creation of mouse models for these conditions, have led scientists studying them to some surprising insights. Even later in life, mice with Down syndrome or fragile X syndrome (FXS) that are given targeted treatment can experience improvements in cognitive function. Findings from such animal studies have paved the way to human trials to assess some of these potential therapies, with some experimental therapies for FXS already entering latestage clinical trials. These developments have led to a “sea change” in the way developmental disorders are viewed by scientists and clinicians, said Mark F. Bear, PhD, professor of neuroscience at the Massachusetts Institute of Technology in Cambridge and a Howard Hughes Medical Institute investigator. Bear explained that the genes linked to intellectual disorders cause such devastating and complex consequences for patients with these conditions that many concluded the damage was permanent. “The consequences can be so diverse, it is hard to imagine that small molecules could have an effect,” he said. “But that’s what we are finding.”
Automated Perimetry Detects Visual Field Loss before Manual Goldmann Perimetry
Authors: Joanne Katz, James M. Tielsch, Harry A. Quigley, Alfred Sommer
Journal: Ophthalmology (1995)

Purpose: To determine if automated perimetry detects visual field defects before manual Goldmann perimetry.Methods: Subjects with ocular hypertension without field loss on detailed manual perimetry were followed prospectively with annual automated and manual perimetry.Subjects with field loss on manual perimetry were age-matched post hoc to subjects who did not have field loss, The automated fields 1 year before the development of field loss on manual perimetry were compared between the two groups.Subjects were recruited from ophthalmologists' offices, eye clinics, and a population-based glaucoma survey in the Baltimore area.Abnormal results detected on the Humphrey Field Analyzer were defined using the glaucoma hemifield test, mean defect, and corrected-pattern standard deviation.Results: Forty subjects who had field loss during 8 years of follow-up were compared with 145 control subjects with ocular hypertension who did not have defects.Seventy-five percent of converters had abnormal results of the glaucoma hemifield test 1 year before field loss on manual perimetry, whereas 22% of controls had abnormal results of the glaucoma hemifield test (odds ratio, 13.4).The odds ratio of field loss developing on manual perimetry within 12 months was 3.3 for those with borderline results of the glaucoma hemifield test relative to the control subjects.The odds ratio was 6.0 for corrected-pattern standard deviation (P < 0.05) and 3.9 for mean deviation (P < 0.05). Conclusions:Those with field loss on manual perimetry were more likely to have had an abnormal automated field 1 year before conversion than those who did not convert.However, 22% of subjects in whom definitive field loss did not develop on manual perimetry during the study had abnormal automated fields at one visit and 15% had abnormal automated fields on two consecutive visits.
Laser resurfacing of the skin for the improvement of facial acne scarring: a systematic review of the evidence
Authors: R. Jordan, C. Cummins, A. Burls
Journal: British Journal of Dermatology (2000)

Abstract This review presents and evaluates the evidence of the effectiveness of laser resurfacing for facial acne scars. Primary studies of all types of design in any language were identified from MEDLINE, EMBASE, the Cochrane database, Science Citation Index and various internet sites. Studies were accepted if they included patients treated by any laser for atrophic or ice-pick acne scars. The quality of the studies was assessed and data extracted by two independent researchers. There were no controlled trials but 14 case series were found which reported the effects of either the carbon dioxide or erbium:YAG laser. All of the studies were of poor quality. The types and severity of scarring were poorly described and there was no standard scale used to measure scar improvement. There was no reliable or validated measure of patient satisfaction; most improvement was based on visual clinical judgement, in many cases without blinded assessment. The inaccurate use of ordinal scales meant that any improvement was impossible to quantify with any validity, although the evidence suggested that laser treatment had some efficacy (a range in individual patients of 25–90% for both the carbon dioxide laser and the erbium:YAG laser). Changes in pigmentation as a side-effect were common (in up to 44% of patients), although lasting only a few weeks. Laser resurfacing technology is increasingly used in clinical practice to treat acne scars. Despite the poor quality evidence, it is plausible that there is some improvement of acne scarring; there is insufficient information, however, for patients to make informed decisions on whether to opt for treatment and there is not enough evidence to compare the two types of laser. There is a particular lack of information about the psychological effects of acne scar improvement. Good quality randomized controlled trials are needed with standardized scarring scales and validated patient outcome measures in order to assess the effectiveness of laser resurfacing in this group of patients.
P377 THE FXR AGONIST OBETICHOLIC ACID IMPROVES A TRANSPLANT-FREE SURVIVAL-PROVEN BIOCHEMICAL RESPONSE CRITERION IN PLACEBO CONTROLLED PRIMARY BILIARY CIRRHOSIS STUDIES
Authors: V. Luketic, S.G. Gordon, C. Vincent, R. Chapman, M. Mayo, K. Kowdley, G. Hirschfield, A. Mason, K. Lindor, L. Macconell, T. Marmon, R. Hooshmand-Rad, D. Shapiro
Journal: Journal of Hepatology (2014)
ERCC1 Isoform Expression and DNA Repair in Non–Small-Cell Lung Cancer
Authors: Luc Friboulet, Ken André Olaussen, Jean-Pierre Pignon, Frances A. Shepherd, Ming-Sound Tsao, Stephen Graziano, Robert Kratzke, Jean-Yves Douillard, Lesley Seymour, Robert Pirker, Martin Filipits, Fabrice André, Eric Solary, Florence Ponsonnailles, Angélique Robin, Annabelle Stoclin, Nicolas Dorvault, Frédéric Commo, Julien Adam, Elsa Vanhecke, Patrick Saulnier, Jürgen Thomale, Thierry Le Chevalier, Ariane Dunant, Vanessa Rousseau, Gwénaël Le Teuff, Elisabeth Brambilla, Jean-Charles Soria
Journal: New England Journal of Medicine (2013)

The excision repair cross-complementation group 1 (ERCC1) protein is a potential prognostic biomarker of the efficacy of cisplatin-based chemotherapy in non–small-cell lung cancer (NSCLC). Although several ongoing trials are evaluating the level of expression of ERCC1, no consensus has been reached regarding a method for evaluation.
Use of Nutritional Supplements by Family Practice Patients
Authors: Eugenia C. English
Journal: JAMA (1981)

Sixty patients and their physicians were interviewed to assess their attitudes and practices with respect to nutritional supplements. Forty patients (67%) used nutritional supplements on a regular daily basis or had used them to treat an illness. Thirty-two (80%) of the supplement users believed supplements were effective in increasing energy, vitality, and physical strength. The majority of supplementation was suggested by friends, family, and lay publications. Thirty-seven (62%) of the supplement users had never discussed nutritional supplements with their physicians. For the most part, physicians were unaware of supplement use in their patients and did not regard this as their responsibility. Implications of the independent and unmonitored action of the patient in this aspect of health maintenance is discussed.
Identification of a new component in the murine Ia molecular complex.
Authors: A J Sant, B D Schwartz, S E Cullen
Journal: The Journal of Experimental Medicine (1983)

In this report, we describe a previously unidentified component in the murine Ia antigen complex. SDS-PAGE analysis of anti-Ia immunoprecipitates prepared from spleen cells biosynthetically labeled with 35S-sulfate showed no detectable incorporation of 35SO4 into alpha, beta, or Ii chains but did not reveal the presence of a novel sulfate-bearing molecule of considerable molecular weight heterogeneity (46-69-kdaltons). The 46-69-kdalton molecule could be precipitated with monoclonal antibodies specific for I-A, I-E, and Ii glycoproteins but was not seen in control precipitates, nor in association with IgG or class I MHC molecules. Preliminary biochemical characterization indicated that the 46-69-kdalton product is extremely polydisperse, both in charge and apparent molecular weight, is sensitive to proteases, and bears the sulfate moiety on a large pronase-resistant structure. These results suggested this component might be a proteoglycan. Definitive identification of this component as a proteoglycan was accomplished by selective enzymatic degradation experiments which showed that the sulfate-bearing component of the 46-69-kdalton molecule is chondroitin 6-sulfate.
Do Pharmacogenetics Have a Role in the Dosing of Vitamin K Antagonists?
Authors: Bruce Furie
Journal: New England Journal of Medicine (2013)

Vitamin K plays a single role in human biology — as a cofactor for the synthesis of γ-carboxyglutamic acid. This amino acid is a component of at least 14 proteins, including 4 blood-coagulation proteins (factor IX, factor VII, factor X, and prothrombin) and 2 regulatory proteins (protein C and protein S), and it is critical for the physiologic function of these proteins. Humans do not synthesize vitamin K. Rather, we ingest it in our diet. The vitamin K quinone is reduced to the semiquinone, and this reduced vitamin K is a cofactor that is required for the conversion of specific . . .
Calcium Phosphate and Oxalate Ion-products in Normal and Stone-forming Urines
Authors: B. E. C. Nordin, W. G. Robertson
Journal: BMJ (1966)

Infection after Splenectomy-Lowdon et al.BEDRITCISHJRNALin adults where the primary illness predisposes to infection.This is also indicated in patients in whom the spleen has been removed whenever the patient is receiving corticosteroids. SummaryDuring 1961 1,167 patients had splenectomy performed in England and Wales.A postal follow-up of these patients was carried out, informa- tion being sought from the family doctor or hospital consultant in whose care the patient had been.Altogether, details were achieved from 1,118 (96%).The reason for splenectomy, cause of death, and occurrence of infection in the subsequent two to three years is reported.It was confirmed that pneumococcal septicaemia and other fulminating infections sometimes follow splenectomy.Such infections are more common in childhood, in patients where the underlying disease predisposes to infection, and in patients on continued treatment with corticosteroids.Further study is needed before an authoritative estimate of the risk in relation to age and underlying condition can be achieved.In the meanwhile it is suggested that splenectomy be avoided whenever possible during the first four years of life, and that post-operative antibiotic cover for two years might well be provided in young children, in patients where the primary illness may predispose to infection, and in any patient while receiving corticosteroid therapy.This study has been made possible by the co-operation of hundreds of doctors throughout the country.We acknowledge with thanks the trouble that family doctors have taken to supply data about their patients, and to hospital staff for abstracting relevant data from hospital records.This could not have been carried out without the good will of senior administrative medical officers in all regions and the generosity of the many surgeons and physicians who have allowed access to their records.When patients had "disappeared" the surgeon has often gone to considerable effort to trace them and provide the information requested.Executive council staffs have played a large part in tracing patients who had changed their doctor.
Amiodarone as Compared with Lidocaine for Shock-Resistant Ventricular Fibrillation
Authors: Paul Dorian, Dan Cass, Brian Schwartz, Richard Cooper, Robert Gelaznikas, Aiala Barr
Journal: New England Journal of Medicine (2002)

Lidocaine has been the initial antiarrhythmic drug treatment recommended for patients with ventricular fibrillation that is resistant to conversion by defibrillator shocks. We performed a randomized trial comparing intravenous lidocaine with intravenous amiodarone as an adjunct to defibrillation in victims of out-of-hospital cardiac arrest.
Risk Factors For Acute Asthma In The City Of Esmeraldas, Ecuador
Authors: Cristina Ardura-Garcia, Gisela Oviedo, Maritza Vaca, Carlos Sandoval, Stefanie Menzies, Lisa J. Workman, Matthew S. Perzanowski, Maria Jose Rosa, Thomas A.E. Platts-Mills, Phil J. Cooper
Journal: Journal of Allergy and Clinical Immunology (2014)
Transaminase Levels in Acute Pancreatitis and After Secretin Stimulation
Authors: William M. Lukash
Journal: JAMA (1966)

SERUM transaminase levels have been reported to be elevated in pancreatitis, but the elevations are usually seen in icteric patients and probably reflect liver and biliary disease. The enzymes, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT), are found in various tissues. Wroblewski and LaDue<sup>1</sup>established the levels of transaminase activity in homogenates of different human tissues and observed a level of concentration in the pancreas equal to 20% of that found in the liver. Diseases involving tissue containing these enzymes are thought to cause elevation of serum levels. On this basis, Foulk and Fleisher<sup>2</sup>studied 32 patients during episodes of pancreatitis. Transaminase activity was increased in 22 of these patients. They concluded, however, that increased transaminase activity is not entirely dependent on pancreatic necrosis, but related to increased intrabiliary pressure and associated obstruction of the biliary tract. Weinstein et al<sup>3</sup>further emphasized the
R56865, an antiarrhythmic drug with class III effects that terminates ouabain induced ventricular tachycardia in an inverse rate dependent manner
Authors: M. A Vos, R. T A M van Deursen, A. P M Gorgels, J. D M Leunissen, H. J J Wellens
Journal: Cardiovascular Research (1993)

Objective: R56865 has been described as a substance that protects cells from intracellular Na+ and Ca2+ overload. The aim of this study was to investigate its mechanism of action, which is at present unknown. Methods: The haemodynamic and (rate dependent) electrophysiological effects of R56865 (0.48 mg·kg−1) were examined and compared with its antiarrhythmic effect on ouabain-induced ventricular tachycardia (n=10), and ventricular tachycardia occurring within 24 h of occlusion of the left anterior descending artery (n=8). The experiments were all performed in dogs. Results: In anaesthetised dogs R56865 increased (p < 0.05) the cycle length of the sinus rhythm, the corrected QT duration (+8%) and the effective refractory period (+16%) of the right ventricle. No rate dependency was found. R56865 had no effect on blood pressure, conduction, or refractoriness of the AV node, nor on conduction in the ventricle. In conscious dogs, R56865 did not change the cycle length of the sinus rhythm, but it did increase the QT duration (+5%, p < 0.05). The cycle length of the slower ouabain induced ventricular tachycardias which were terminated by R56865 increased to a greater extent (+55%) than that of the non-suppressible, faster ventricular tachycardias (+16%): 335(SD 30) ms, n=5 v 285(10) ms, n=5. The effect of R56865 on ventricular tachycardias 24 h after infarction was considered to be of minor antiarrhythmic importance. Conclusions: R56865 has (1) class III effects, (2) a partial effect in terminating ouabain induced ventricular tachycardias which is inverse rate dependent, and (3) a weak effect on ventricular tachycardias 24 h after infarction. Cardiovascular Research 1993;27:1491-1497
Probable Trichomonas vaginalis Epididymitis
Authors: Arjan D. Amar
Journal: JAMA (1967)

ONLY within the past decade has infection with<i>Trichomonas vaginalis</i>as the explanation for a significant proportion of cases of "nonspecific" urethritis been widely recognized. As far as I am aware, however, attention has not been drawn to<i>T vaginalis</i>as a cause of epididymitis. That trichomoniasis is transmitted venereally, at least in most instances, appears to be rather well established.<sup>1"</sup>The importance of adequate, and if repeated examination of the symptomatic or asymptomatic sexual partner of the woman with this disease, and of eradication of the infection in the male if treatment is to have permanent effect in the female, has been stressed by Perl<sup>3</sup>and others. It is equally true that, for the man with this disease, effectual management must include adequate investigation and treatment of the female partner. Trichomoniasis, long familiar to gynecologists, is thus also a problem for the urologist and the family physician.
The heritability of congenital heart disease.
Authors: J Insley
Journal: BMJ (1987)

encourage reattachment-for example, expanding gases such as sulphurhexafluoride, or longer acting materials such as silicone oil.'2Sometimes vitrectomy will be the primary treatment.Typical premonitory symptoms or a profound reduction in visual acuity should alert a general practitioner or an optician to the possibility of impending or actual retinal detachment.Neither, however, can be expected to make the diagnosis with certainty.Retinal breaks are usually in the periphery of the retina and hard to see, and even with good pupillary dilatation viewing the retina of the myopic fundus with a direct ophthalmoscope is extremely unreliable.A simple confrontation field test may, however, show a field defect, and if the macula is detached visual acuity will be profoundly depressed.The patient must be referred promptly to hospital (within 24 hours), and the hospital must respond quickly.The examination demands binocular indirect ophthalmoscopy, scleral depression, and three mirror gonioscopy.The unaffected eye must also be examined for lesions that may need prophylactic treatment.These examination skills will often be beyond the scope of the ophthalmologist in the early stages of training.Prompt diagnosis and treatment are essential in managing retinal detachment.
Rheumatoid Arthritis — A Collagenase Disease?
Authors: Edgar S. Cathgart
Journal: New England Journal of Medicine (1977)

Ever since Klemperer and his colleagues introduced the term "diffuse collagen diseases" in 1942, rheumatologists have been struggling with the concept that there may indeed be something wrong with collagen in conditions such as rheumatoid arthritis and acute rheumatic fever. With the realization that collagen is but one of many components of the connective tissues, other descriptions rapidly gained favor, including mesenchymal diseases, collagen-vascular diseases, connective-tissue disorders and, lately, autoimmune reactions. They have all been used to classify a group of illnesses in which the target organ may be the synovial membrane and in which connective tissue serves as the . . .
[408] IMMUNODOMINANCE ANALYSIS OF HBV-SPECIFIC CELLULAR IMMUNE RESPONSE IN TWO HLA IDENTICAL, VERTICALLY INFECTED SIBLINGS
Authors: E. Loggi, F.K. Bihl, L. Testa, J.V. Chisholm, E. Grandini, M. Bernardi, C. Brander, P. Andreone
Journal: Journal of Hepatology (2007)
THE SPLINTING OF COMPOUND FRACTURES
Authors: FRANK J. COX
Journal: JAMA (1941)

War and the treatment of the casualties of war have invariably stimulated the study of proper methods of caring for compound fractures. The present world conflict is no exception, and a considerable amount of controversial opinion has been voiced recently as to the best methods of external fixation of compound fractures. This difference of opinion can be accounted for largely by the fact that there exist two schools of primary therapy; one depends on frequent irrigations of the open wound, which necessitate the use of an open splint 1 ; the other relies on packing the wound open, applying a closed form of splint and changing the dressing at infrequent intervals. 2 No attempt to evaluate the relative merits of these methods will be made at this time. Forms of external fixation acceptable to each school are here described and various modifications to improve the efficiency of the fixation discussed.  With
Chemogene treatment consisting of recombinant adenoviral transfection of p16cDNA (SVN-22/3), and docetaxel eradicates chemoresistant aneuploid pancreatic adenosquamous ca characterised by overexpression of k-ras and hypermethylation of CPG islands of P16
Authors: J. Giannios
Journal: Gut (2011)

<h3>Introduction</h3> Adenosquamous Ca is an aggressive and highly metastatic variant of adenocarcinoma with both glandular and squamous differentiation. Usually, it occurs in chemoradiated patients. <h3>Methods</h3> Tumour cells were obtained from a resected pancreatic adenosquamous Ca which already had metastasised to regional lymph nodes. Methylation-specific PCR (MSP) detected methylated DNA template of p16. The methylated CpG islands in a promoter of p16 inhibited transcription by preventing RNA polymerase and the RNA transcription machinery from producing messenger RNA leading to gene inactivation. SSCP analysis has detected mutated K-Ras. We constructed an adenovirus p16 expression vector and we inserted p16cDNA into a cassette cosmid containing an adenovirus type 5 genome. Subsequently, we produced a recombinant adenovirus termed as SVN-22/3 by cotransfection of expression cosmid and adenovirus DNA-terminal protein complex into cells by calcium phosphate precipitation. <h3>Results</h3> After 1 h treatment with SVN-22/3, pancreatic Ca cells expressed high levels of p16 gene mRNA according to NB hybridisation analysis. The adenoviral mediated gene transfer of wt p16-INK4A formed a heterodimer with cyclin-dept kinase 4 and 6 preventing their interaction with cyclin D. PCR analysis has showed downregulation of cyclin D1 and K-Ras. Subsequent treatment with docetaxel has exerted a synergistic antimitotic effect exhibited by BrdU and Ki-67. Flow-cytometry has reported diploid DNA. A biochemical assay showed activation of caspase-3/CPP32 pathway which led to electron cytological signs of D2 apoptotic stage forming apoptotic bodies which were phagocytosed by adjacent tumour cells leading to a bystander killing effect. <h3>Conclusion</h3> Concluding, by restoring wild-type p16 protein in chemoresistant adenosquamous carcinoma cells, we have achieved to block cyclin D1 which led to inactivation of K-Ras allowing induction of apoptosis after the antimitotic action of docetaxel.