68 research outputs found

    Antibiotic use in India

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    Master thesis, Programme in Medicine. TITLE: Antibiotic use in India -With aspects from a gender perspective. AUTHOR: Annika Wilbe. Background. Antibiotic resistance is one of the major upcoming health concerns in modern medicine. Bacteria are becoming resistant to antimicrobial therapies at an alarming rate. It is important to understand reasons and trends for prescribing these drugs, and also to see how the tools we have, such as microbial investigations, are being used. Objective. The aim of this study is to document how antibiotics are used in Kannur, India. To see who receives these drugs and why, and how microbial investigations are being used in the clinical work. The aim is also to see if there is any gender difference in these regards. Method. This study was conducted at Kannur Medical College in Kerala, southern India, during 8 weeks, February to April 2014. Information regarding antibiotic treatment and microbial investigations for patients admitted to the department for neurology and medicine with hospital stay >1 night was collected from case-sheets at discharge. Patients were also asked by the nurses if they were taking any antibiotics at admission. Results. 55% of the females and 70% of the males received antibiotic therapy during their hospitalization. 51% of all patients received a Cephalosporin, and 21% a Fluoroquinolone. 29% of the antibiotics were given by oral administration. 33% of the patients on antibiotics had a microbial culture investigated. 75% of these cultures were urine cultures. In 25% of the cultures a pathogen was found. No patients were at admission taking antibiotics without doctor’s prescription, and 7% were taking with prescription. Conclusions. Males tend to receive antibiotic treatment more frequently than females. Cephalosporins are widely used. Most antibiotics are administered IV. Microbial investigations are occasionally used. Patients did not use antibiotics without prescription, making doctor’s prescription the most important factor in the antibiotic use of the patient

    Discovery of a novel pathway for an SLE-related disease complex in the canine breed Nova Scotia duck tolling retriever

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    The dog is an excellent model to study inherited complex diseases, due to its unique population history and haplotype structure. In this thesis, dogs from the breed Nova Scotia duck tolling retriever (NSDTR) have been used as a model for defining the genetic factors controlling a systemic lupus erythematosus (SLE)-related disorder called immune-mediated rheumatic disease (IMRD) and a steroid responsive meningitis-arteritis (SRMA). IMRD is characterized by stiffness, mainly after resting, and pain from several joints of extremities and/or muscle pain. The majority of the affected dogs show anti-nuclear antibody (ANA)-positivity that can be divided either into a speckled (ANAS) or homogenous (ANAH) staining pattern. Dogs affected by SRMA display severe neck pain, fever and stiffness and an increased infiltration of immune cells in cerebrospinal fluid in the acute phase of disease. SRMA dogs show a negative ANA result. We performed a candidate gene study to investigate if dog leukocyte antigen (DLA) class II is associated with the canine SLE-related disease. An increased risk for ANAS dogs was observed for a homozygous risk haplotype and a general homozygosity at DLA class II gives ANAH dogs an increased risk for developing disease. Genome-wide association mapping identified additional susceptibility loci for the SLE-related disease on canine chromosomes (CFA) 3, 8, 11, 24 and 32. Further analysis revealed that most ANAS dogs homozygous for the DLA risk haplotype also have the genetic risk factors at CFA 11 and 32. Re-sequencing of the five associated regions was performed to identify specific genes and genetic variants involved in the disease. Expression studies of the candidate genes for ANAS dogs revealed that the PTPN3 (CFA 11) gene is downregulated and that DDIT4L and BANK1 (CFA 32) is upregulated in dogs with the risk haplotype. The identified genes may be important in T-cells, B-cells and possibly macrophages. This thesis describes the first successful mapping of a complex trait in the dog and shows that MHC class II together with two other identified genetic risk factors contribute to development of systemic autoimmune disease

    Genetic association of Canine Lymphocytic Thyroiditis (CLT) with DLA class II in Giant Schnauzer and Hovawart dogs

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    Canine Lymphocytic Thyroiditis (CLT) resembles naturally occurring lymphocytic thyroiditis in White Leghorn chickens and Hashimoto's thyroiditis in man. It is a common autoimmune endocrine disease in dogs which is a result of destruction of the thyroid glands. Many autoimmune diseases show associations with the major histocompability complex (MHC) class II alleles. Within the canine Major Histocompatibility Complex (DLA) some of the class II genes are highly polymorphic. In this study an evaluation of the association between DLA class II haplotype and the risk for developing CLT has been performed by sequencing the polymorphic exon 2 form the genes DLA-DRB1, DLA-DQA1 and DQB1. Two high-risk breeds for developing CLT, Giant Schnauzer and Hovawart, have been analysed from a total of 198 dogs. Included in the study were 35 healthy controls, 3 borderline cases and 87 CLT-positive dogs. Results show that Giant Schnauzers carrying the haplotype DRB1*01201DQA1*00101DQB1*0020 have an increased risk to develop CLT, cases 22.5% versus controls 4.5%. This with an odds ratio = 6.0667 and with a p value = 0.015401 which shows that the increased risk to develop CLT is statistically significant. In Hovawart dogs the risk haplotype 01201*00401*013017 was present in 45 % (cases 43% versus controls 50%) of the total dogs analyzed. In this breed there was no evidence for an increased risk to develop CLT for dogs with this haplotype

    Discovery of a novel pathway for an SLE-related disease complex in the canine breed Nova Scotia duck tolling retriever [Elektronisk resurs]

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    The dog is an excellent model to study inherited complex diseases, due to its unique population history and haplotype structure. In this thesis, dogs from the breed Nova Scotia duck tolling retriever (NSDTR) have been used as a model for defining the genetic factors controlling a systemic lupus erythematosus (SLE)-related disorder called immune-mediated rheumatic disease (IMRD) and a steroid responsive meningitis-arteritis (SRMA). IMRD is characterized by stiffness, mainly after resting, and pain from several joints of extremities and/or muscle pain. The majority of the affected dogs show anti-nuclear antibody (ANA)-positivity that can be divided either into a speckled (ANAS) or homogenous (ANAH) staining pattern. Dogs affected by SRMA display severe neck pain, fever and stiffness and an increased infiltration of immune cells in cerebrospinal fluid in the acute phase of disease. SRMA dogs show a negative ANA result. We performed a candidate gene study to investigate if dog leukocyte antigen (DLA) class II is associated with the canine SLE-related disease. An increased risk for ANAS dogs was observed for a homozygous risk haplotype and a general homozygosity at DLA class II gives ANAH dogs an increased risk for developing disease. Genome-wide association mapping identified additional susceptibility loci for the SLE-related disease on canine chromosomes (CFA) 3, 8, 11, 24 and 32. Further analysis revealed that most ANAS dogs homozygous for the DLA risk haplotype also have the genetic risk factors at CFA 11 and 32. Re-sequencing of the five associated regions was performed to identify specific genes and genetic variants involved in the disease. Expression studies of the candidate genes for ANAS dogs revealed that the PTPN3 (CFA 11) gene is downregulated and that DDIT4L and BANK1 (CFA 32) is upregulated in dogs with the risk haplotype. The identified genes may be important in T-cells, B-cells and possibly macrophages. This thesis describes the first successful mapping of a complex trait in the dog and shows that MHC class II together with two other identified genetic risk factors contribute to development of systemic autoimmune disease

    A rare regulatory variant in the MEF2D gene affects gene regulation and splicing and is associated with a SLE sub-phenotype in Swedish cohorts

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    Systemic lupus erythematosus (SLE) is an autoimmune disorder with heterogeneous clinical presentation and complex etiology involving the interplay between genetic, epigenetic, environmental and hormonal factors. Many common SNPs identified by genome wide-association studies (GWAS) explain only a small part of the disease heritability suggesting the contribution from rare genetic variants, undetectable in GWAS, and complex epistatic interactions. Using targeted resequencing of coding and conserved regulatory regions within and around 215 candidate genes selected on the basis of their known role in autoimmunity and genes associated with canine immune-mediated diseases, we identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0 .014 , CI = 1.1-10). Fisher's exact test revealed an association between the genetic variant and a triad of disease manifestations including Raynaud, anti-Ul-ribonucleoprotein (anti-RNP), and anti-Smith (anti-Sm) antibodies (p = 0.00037) among the patients. The DNA-binding activity of the allele was further studied by EMSA, reporter assays, and minigenes. The region has properties of an active cell-specific enhancer, differentially affected by the alleles of rs200395694:G > T. In addition, the risk allele exerts an inhibitory effect on the splicing of the alternative tissue-specific isoform, and thus may modify the target gene set regulated by this isoform. These findings emphasize the potential of dissecting traits of complex diseases and correlating them with rare risk alleles with strong biological effects
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