tbuckley/cabot-search huggingface dataset:
OP0282 The Association of PTPN22 RS2476601 with Juvenile Idiopathic Arthritis is Specific to Females:
Authors: R. Chiaroni-Clarke, Y.R. Li, J. Munro, R. Chavez, K. Scurrah, A. Pezic, J. Akikusa, R. Allen, S. Piper, M. Becker, S. Thompson, B. Lie, B. Flato, O. Forre, M. Punaro, C. Wise, R. Saffery, T. Finkel, H. Hakonarson, A.-L. Ponsonby, J.A. Ellis
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> A preponderance of females develop autoimmune disease, including juvenile idiopathic arthritis (JIA), yet the reason for this female bias remains elusive. Evidence suggests that genetic risk of disease may be influenced by sex. The JIA genetic risk variant, <i>PTPN22</i> rs2476601, has been reported to show female-specific association in type 1 diabetes. <h3>Objectives</h3> We sought to determine whether <i>PTPN22</i> rs2476601 exhibits a female-specific association with JIA. <h3>Methods</h3> The discovery sample was drawn from the Australian CLARITY JIA biobank. rs2476601 was genotyped in 413 cases (67% female, mean age 9.1 years) and 690 healthy controls (42% female, mean age 7.1 years). We used logistic regression to assess the association of rs2476601 with JIA in the total sample (males and females). We then explored the role of sex in this association: we <i>adjusted</i> the regression analysis for sex, <i>stratified</i> by sex, and performed a genotype x sex <i>interaction</i> analysis. Sensitivity analyses were performed by restricting to individuals of European descent, subtypes of oligoarticular and polyarticular RF negative disease course, and exclusion of systemic JIA. We sought to replicate the sex-specific associations in an independent JIA case-control sample collected from the USA and Norway and held at the Children9s Hospital of Philadelphia. Analyses were performed using Stata or PLINK. <h3>Results</h3> The outcomes of analyses are shown in the Table. rs2476601 was associated with all JIA in both the discovery and replication samples, and the association remained when adjusted for sex. When stratified by sex, a strong association was observed for females, but not for males. There was evidence for genotype-by-sex interaction (p=0.0087). Similar patterns were observed in all sensitivity analyses. In the replication sample, we also observed association of rs2476601 with JIA in females, but not in males. <h3>Conclusions</h3> We have demonstrated, in both a discovery and replication sample, that the association between <i>PTPN22</i> rs2476601 and JIA appears restricted to females, helping to explain the greater number of females that develop this disease. <h3>Disclosure of Interest</h3> None declared
Small intestine grasped by over-the-scope-clip during attempt to close an iatrogenic colonic perforation
Authors: Gunnar Loske, Tobias Schorsch, Emmerich Daseking, Eckard Martens, Christian Müller
Journal: Endoscopy (2016)

The over-the-scope-clip (OTSC; Ovesco, Tübingen, Germany) has been developed for the closure of intestinal defects [1] [2]. We report on the case of a misplaced OTSC, which grasped the small intestine through an iatrogenic colonic perforation.
Renal Retention of Uric Acid Induced by Infusion of Beta-Hydroxybutyrate and Acetoacetate
Authors: Stephen Goldfinger, James R. Klinenberg, J. Edwin Seegmiller, John Miller, Katherine Bradley
Journal: New England Journal of Medicine (1965)

HYPERURICEMIA has been observed in conjunction with a variety of metabolic aberrations, including starvation,1 2 3 4 obesity4 5 6 7 and diabetic ketoacidosis.8 The possibility that ketosis facilitates an increase in serum urate concentration by promoting renal retention of uric acid has been suggested in a number of reports.4,9 10 11 12 13 14 15 The purpose of the present study was to compare the influence of intravenously administered beta-hydroxybutyrate, acetoacetate and acetone on the renal clearance of uric acid in normal human subjects.Methods and MaterialsSodium acetoacetate was prepared by hydrolysis of freshly redistilled ethyl acetoacetate¶ with a 5 per cent excess of 1 N sodium hydroxide under . . .
Hemodynamics in Symptomatic Atherosclerotic Vertebrobasilar Occlusive Disease
Authors: Brian P. Walcott, Omar Choudhri, Michael T. Lawton
Journal: JAMA Neurology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Engineering and commercialization of human-device interfaces, from bone to brain
Authors: Melissa L. Knothe Tate, Michael Detamore, Jeffrey R. Capadona, Andrew Woolley, Ulf Knothe
Journal: Biomaterials (2016)

Cutting edge developments in engineering of tissues, implants and devices allow for guidance and control of specific physiological structure-function relationships. Yet the engineering of functionally appropriate human-device interfaces represents an intractable challenge in the field. This leading opinion review outlines a set of current approaches as well as hurdles to design of interfaces that modulate transfer of information, i.a. forces, electrical potentials, chemical gradients and haptotactic paths, between endogenous and engineered body parts or tissues. The compendium is designed to bridge across currently separated disciplines by highlighting specific commonalities between seemingly disparate systems, e.g. musculoskeletal and nervous systems. We focus on specific examples from our own laboratories, demonstrating that the seemingly disparate musculoskeletal and nervous systems share common paradigms which can be harnessed to inspire innovative interface design solutions. Functional barrier interfaces that control molecular and biophysical traffic between tissue compartments of joints are addressed in an example of the knee. Furthermore, we describe the engineering of gradients for interfaces between endogenous and engineered tissues as well as between electrodes that physically and electrochemically couple the nervous and musculoskeletal systems. Finally, to promote translation of newly developed technologies into products, protocols, and treatments that benefit the patients who need them most, regulatory and technical challenges and opportunities are addressed on hand from an example of an implant cum delivery device that can be used to heal soft and hard tissues, from brain to bone.
DNMT3A Loss Drives Enhancer Hypomethylation in FLT3-ITD-Associated Leukemias
Authors: Liubin Yang, Benjamin Rodriguez, Allison Mayle, Hyun Jung Park, Xueqiu Lin, Min Luo, Mira Jeong, Choladda V. Curry, Sang-Bae Kim, David Ruau, Xiaotian Zhang, Ting Zhou, Michael Zhou, Vivienne I. Rebel, Grant A. Challen, Berthold Göttgens, Ju-Seog Lee, Rachel Rau, Wei Li, Margaret A. Goodell
Journal: Cancer Cell (2016)
Renal Insufficiency in Treated Essential Hypertension
Authors: Stephen G. Rostand, Grace Brown, Katharine A. Kirk, Edwin A. Rutsky, Harriet P. Dustan
Journal: New England Journal of Medicine (1989)

We analyzed the clinical courses of 94 patients with treated primary hypertension and initially normal serum creatinine concentrations (≤133 μmol per liter [≤1.5 mg per deciliter]) who were followed for a mean (±SD) of 58±34 months (range, 12 to 174) to determine the frequency with which renal function deteriorated and the factors associated with deterioration. Fourteen patients (15 percent) had an increase in serum creatinine concentrations (≥35 μmol per liter [≥0.4 mg per deciliter]); in 16 percent of the 61 patients with apparently good control of blood pressure, the serum creatinine concentration rose 59±33 μmol per liter (0.67±0.38 mg per deciliter). Despite good control of diastolic blood pressure (≤90 mm Hg), black patients were twice as likely as white patients to have elevations in serum creatinine (23 percent vs. 11 percent). Stepwise discriminant function analysis showed that a significant rise in the serum creatinine concentration was most likely to occur in association with older age, black race, a higher number of missed office visits, and employment as a laborer. We conclude that although renal function was preserved in 85 percent of patients with treated hypertension, it may deteriorate in some patients despite good blood-pressure control. Our observations may partly explain why hypertension, particularly among black persons, remains a leading cause of renal disease in the United States. (N Engl J Med 1989; 320:684–8.)
Major-Histocompatibility-Complex Extended Haplotypes in Membranoproliferative Glomerulonephritis
Authors: Thomas R. Welch, Linda Beischel, Kamala Balakrishnan, Monica Quinlan, Clark D. West
Journal: New England Journal of Medicine (1986)

Membranoproliferative glomerulonephritis is often associated with evidence of immune derangement, especially hypocomplementemia. We studied genetic markers for membranoproliferative glomerulonephritis within the major histocompatibility complex in 34 patients and their families and in 29 normal families. We examined the frequencies of extended haplotypes (combinations of alleles that tend to occur together) in patients and controls. The extended haplotype HLA-B8,DR3,SC01,GLO2(glyoxalase I 2) was observed in 9 of 68 disease-associated haplotypes (13 percent), but in only 3 of 205 controls (1 percent) (relative risk, 14.79; P<0.001). An extended haplotype similar except for a different glyoxalase allotype (B8,DR3,SC01,GLO1) did not occur with increased frequency, nor did any other extended haplotypes. Patients with the extended haplotype B8,DR3,SC01,GL02 had a higher incidence of renal insufficiency than those without it (P<0.01). The data support the hypothesis that a specific extended haplotype of the major histocompatibility complex is associated with susceptibility to membranoproliferative glomerulonephritis, and that patients with glomerulonephritis who have this extended haplotype have a poorer prognosis for kidney survival than those without the haplotype. (N Engl J Med 1986; 314:1476–81.)
Attempts to Reproduce Cirrhosis of the Liver in Rats After Total-Body X Irradiation&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: H W CARROLL, A P SPIVACK, R W BRAUER
Journal: JNCI Journal of the National Cancer Institute (1959)

Rats fed a low-protein (6% casein) diet in these experiments had fatty infiltration and varying degrees of fibrous proliferation of the liver regardless of whole-body X irradiation. Severity of the fibrotic lesions was reduced by choline supplementation. The degree of severity of fibrous proliferation also seemed to be dependent on the age of the rats when placed on the low-protein diet. Fibrosis was seen generally in the animals with the most severe degree of fat infiltration.
Progestational Agents in the Treatment of Carcinoma of the Endometrium
Authors: Rita M. Kelley, William H. Baker
Journal: New England Journal of Medicine (1961)

THE successful treatment of carcinoma of the uterus is usually accomplished by total hysterectomy, irradiation or a combination of both procedures.1 Data from 27 clinics, in 8366 cases, are surveyed in the Tenth Annual Report on the Results of Treatment in Carcinoma of the Uterus.2 The over-all five-year cure rate was 54.3 per cent. The five-year cure rate was 60 per cent when the tumor was confined to the uterus (Stage I, Group 1) but only 19.6 per cent for those in whom the growth had spread outside the uterus (Stage II). Such survival figures do not justify the . . .
M25 Oxygen: Too much of a good thing? Can simulation improve education?
Authors: JL Parkin, E Lloyd
Journal: Thorax (2015)

<h3></h3> A cohort of chronic obstructive pulmonary disease patients experience acute exacerbations (AECOPD) presenting with worsening sputum production, cough and breathlessness. The recommended treatment for AECOPD involves using a 28% Venturi mask to achieve an arterial oxygen saturation of 88–92%. These guidelines have been poorly adhered to with many health professionals still administering high flow oxygen. An AECOPD model, created on the human patient simulator, was administered with 28% or 100% oxygen. 28% oxygen relieved hypoxia (PaO<sub>2</sub> = 84.9 mmHg), caused mild hypercapnia (PaCO<sub>2</sub> = 49.6 mmHg) and the blood pH was normal (pH = 7.37). 100% oxygen enabled better arterial oxygenation (PaO<sub>2</sub> = 129.3 mmHg) but caused severe hypercapnia (PaCO<sub>2</sub> = 100.9 mmHg) and acidosis (pH = 6.98). Preclinical medical students were randomly allocated to simulation or lecture-based learning (the study has a crossover design) and were taught the correct use of oxygen administration. A greater proportion of students rated they had an excellent understanding of the key learning points after simulation (100%) compared to the lecture- based learning (33%) and it was sufficient to significantly improve test scores (p = 0.0135). Simulation could be used to educate future health professionals in using 28% oxygen to reduce the risk of hypercapnic respiratory acidosis in AECOPD.
Deaths from Paracervical Anesthesia Used for First-Trimester Abortion, 1972–1975
Authors: David A. Grimes, Willard Cates
Journal: New England Journal of Medicine (1976)

Since January 1, 1972, five women in the United States are reported to have died from paracervical anesthesia used for first-trimester abortions. This report describes the three most recent deaths. Toxic doses of lidocaine, substantiated by post-mortem blood levels of 5 and 9 μg per milliliter, probably led to two deaths; an intolerance to or inadvertent intravenous administration of mepivacaine probably caused the third. Administration of an appropriate dose of local anesthetic appears to be the single most important factor in preventing catastrophic reactions. (N Engl J Med 295:1397–1399, 1976)
Acute Meprobamate Poisoning
Authors: Leon W. Powell, Geoffrey T. Mann, Sidney Kaye
Journal: New England Journal of Medicine (1958)

MEPROBAMATE, or 2-methyl-2-n-propyl-1,3-propanediol dicarbamate, is a tranquilizing drug that has become widely used in the short time since its synthesis in 1950.1 It has been proved to be of particular value in anxiety and tension states and numerous related conditions.2 It has also been used to good advantage in various types of skeletal-muscle spasm.3 The pharmacology of meprobamate has been worked out largely by Berger,4 , 5 according to whom it shows three properties of special interest: a muscle-relaxant action; an anticonvulsant action; and a taming effect on monkeys. The muscle-relaxant action affects only voluntary skeletal muscles. The diaphragm, however, is relatively . . .
Differentiation of Leukemia Cells to Polymorphonuclear Leukocytes in Patients with Acute Nonlymphocytic Leukemia
Authors: Eric R. Fearon, Philip J. Burke, Charles A. Schiffer, Barbara A. Zehnbauer, Bert Vogelstein
Journal: New England Journal of Medicine (1986)

We used recombinant-DNA techniques to determine the origin of polymorphonuclear leukocytes in patients with acute nonlymphocytic leukemia, at presentation, in remission, and in relapse. Studies using X chromosome-linked DNA polymorphisms strongly suggested that leukemic blast cells in this form of leukemia can differentiate in vivo to form mature granulocytes. Common chromosomal changes seen in blast cells, such as the addition of a chromosome 8 or the loss of a chromosome 7, were found to be present in the mature granulocytes of patients with leukemia. In addition, rearrangement of the immunoglobulin heavy-chain gene was detected in the polymorphonuclear leukocytes of one patient. Finally, we have observed the persistence of a single dominant hemopoietic clone in the granulocytes of 3 of 13 patients in complete remission. These findings demonstrate that recombinant-DNA probes can detect clonal populations of granulocytes in patients with acute nonlymphocytic leukemia, and provide further evidence that in some patients leukemic blast cells differentiate to form mature cells.
Abstract #3218: Characterization of a new hairless SCID murine model
Authors: Huiling Liang, Robb Kimberly, MacInnis David, Alice Itz, Charles Clifford
Journal: Cancer Research (2009)

Many studies of the growth and chemotherapeutic sensitivities of human cancer require an  in vivo  test system. The most common rodent models in oncology research are immunodeficient mice incapable of rejecting the tumor grafts, xenografts. However, the two most widely used models, athymic nude mice and severe combined immunodeficient (SCID) mice both have limitations. Athymic nude mice lack T lymphocytes, but retain functional NK cells and B lymphocytes, limiting the growth of some tumor lines but are still commonly used because the lack of a hair coat facilitates tumor assessment. SCID mice lack both B and T lymphocytes and support the growth of a broader range of tumor lines, but SCID mice have a normal hair coat which can hinder accurate tumor measurement and interfere with many imaging modalities. In order to attempt to combine the favorable attributes of both athymic nude and SCID mice, we produced a SCID hairless outbred mouse by crossing an outbred SCID mouse (Crl:HA- Prkdc scid  ) with an immunocompetent hairless mouse (Crl:SKH1- Hr hr  ). We have now characterized this new strain, named Crl:SHO- Prkdc scid Hr hr   (SHO). The  scid  mutation, i.e., presence of mutated protein kinase, DNA activated, catalytic polypeptide (Prkdc), in the SHO mouse was verified with PCR followed by enzyme restriction digestion. Grossly, the SHO mice lacked hair. Histopathologic evaluation of skin of the SHO mouse detected numerous dilated hair follicles in the dermis, but no evidence of hair production. Hematology of the SHO mouse found an absolute lymphopenia, similar to that of SCID mice; other leukocytic and erythrocytic parameters were within normal limits. Immunological phenotyping showed a marked cytopenia in the thymus, lymph node and spleen. Flow cytometric analysis demonstrated, like its parental SCID mouse, the SHO mouse lacked mature B and T cells. Further investigation suggested the differentiation of B cells was blocked in the transition from Pro-B to Pre-B; while the development of T cells was retarded at Pro-T and Pre-T stages. To assess the engraftment efficiency, we implanted mice subcutaneously with a human breast cancer cell line, MDA-MB-231, which poorly propagates in athymic nude mice. The SHO mouse had a higher tumor take rate (90%) than the nude mice, Crl:NU- Foxn1 nu   (40%). The tumor growth rate in the SHO mice was more than twice as fast as in the Crl:NU- Foxn1 nu   . (SHO vs. Crl:NU- Foxn1 nu  : 870 mm 3  vs. 415 mm 3  at  88 days post cell injection). Our data demonstrate that the Crl:SHO- Prkdc scid Hr hr   mouse combined the immune deficiency of the SCID mouse with the hairlessness of the SKH-1 mouse. The SHO mouse provides a higher efficiency murine xenograft model for cancer research than the nude mouse, while the hairlessness facilitates precise tumor measurement and imaging.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3218.
The Optimal Use of Radiotherapy in Small Cell Lung Cancer
Authors: David B. Shultz, John C. Grecula, James Hayman, Maximilian Diehn, Billy W. Loo
Journal: Journal of the National Comprehensive Cancer Network (2013)

Small cell lung cancer is an aggressive malignancy that is highly responsive to radiation therapy (RT), which has an important role in all stages of disease. For locally advanced, limited-stage disease, the standard of care is chemotherapy with concurrent radiation, which should be started early. The optimal radiation dose and field design remain to be determined. Randomized trials are currently being conducted to determine if dose intensification will improve outcomes, whereas consensus on elective nodal irradiation is evolving. Current studies are evaluating the potential benefit of consolidative thoracic RT in the management of patients with extensive-stage disease that has responded favorably to chemotherapy. Finally, prophylactic cranial irradiation improves survival in both limited- and extensive-stage disease that has responded to initial therapy.
Biochemical Abnormalities of the Sarcoplasmic Reticulum in Muscular Dystrophy
Authors: Frederick J. Samaha, John Gergely
Journal: New England Journal of Medicine (1969)

Calcium-uptake and ATPase studies carried out on fragmented sarcoplasmic reticulum from muscle of patients with Duchenne dystrophy showed low initial and total calcium uptake, low ATPase activity and normal efficiency, without any relation to the stage of the disease. In myotonic dystrophy, on the other hand, high initial and normal total calcium uptake and normal or higher than normal efficiencies were found. The data suggest early involvement of both fiber types in Duchenne dystrophy and primary involvement of red fibers in myotonic dystrophy. Actomyosin abnormalities found in three cases of Duchenne dystrophy indicate involvement of the contractile apparatus in the later stages of the disease. The only clinical-biochemical correlation observed in this study was the relation of the ATPase activity of the fragmented sarcoplasmic reticulum to the onset of Duchenne dystrophy.