| 11. |
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| 12. |
- Ludvigsson, Johnny, et al.
(författare)
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GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus
- 2012
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 366:5, s. 433-442
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes.METHODS: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels.RESULTS: The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences.CONCLUSIONS: Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period.
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| 13. |
- Rewers, Marian, et al.
(författare)
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The Environmental Determinants of Diabetes in the Young (TEDDY) Study
- 2008
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1150, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- The etiology of type 1 diabetes (T1D) remains unknown, but a growing body of evidence points to infectious agents and/or components of early childhood diet. The National Institutes of Health has established the TEDDY Study consortium of six clinical centers in the United States and Europe and a data coordinating center to identify environmental factors predisposing to, or protective against, islet autoimmunity and T1D. From 2004-2009, TEDDY will screen more than 360,000 newborns from both the general population and families already affected by T1D to identify an estimated 17,804 children with high-risk HLA-DR,DQ genotypes. Of those, 7,801 (788 first-degree relatives and 7,013 newborns with no family history of T1D) will be enrolled in prospective follow-up beginning before the age of 4.5 months. As of May 2008, TEDDY has screened more than 250,000 newborns and enrolled nearly 5,000 infants--approximately 70% of the final cohort. Participants are seen every 3 months up to 4 years of age, with subsequent visits every 6 months until the subject is 15 years of age. Blood samples are collected at each visit for detection of candidate infectious agents and nutritional biomarkers; monthly stool samples are collected for infectious agents. These samples are saved in a central repository. Primary endpoints include (1) appearance of one or more islet autoantibodies (to insulin, GAD65 or IA-2) confirmed at two consecutive visits; (2) development of T1D. By age 15, an estimated 800 children will develop islet autoimmunity and 400 will progress to T1D; 67 and 27 children have already reached these endpoints.
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| 14. |
- Smith, Laura B., et al.
(författare)
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Psychological manifestations of celiac disease autoimmunity in young children
- 2017
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 139:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Psychological symptoms can be associated with celiac disease; abstract however, this association has not been studied prospectively in a pediatric cohort. We examined mother report of psychological functioning in children persistently positive for tissue transglutaminase autoantibodies (tTGA), defined as celiac disease autoimmunity (CDA), compared with children without CDA in a screening population of genetically at-risk children. We also investigated differences in psychological symptoms based on mothers' awareness of their child's CDA status. METHODS: The Environmental Determinants of Diabetes in the Young study followed 8676 children to identify triggers of type 1 diabetes and celiac disease. Children were tested for tTGA beginning at 2 years of age. The Achenbach Child Behavior Checklist assessed child psychological functioning at 3.5 and 4.5 years of age. RESULTS: At 3.5 years, 66 mothers unaware their child had CDA reported more child anxiety and depression, aggressive behavior, and sleep problems than 3651 mothers of children without CDA (all Ps ≤ .03). Unaware-CDA mothers also reported more child anxiety and depression, withdrawn behavior, aggressive behavior, and sleep problems than 440 mothers aware of their child's CDA status (all Ps ≤.04). At 4.5 years, there were no differences. CONCLUSIONS: In 3.5-year-old children, CDA is associated with increased reports of child depression and anxiety, aggressive behavior, and sleep problems when mothers are unaware of their child's CDA status. Mothers' knowledge of their child's CDA status is associated with fewer reports of psychological symptoms, suggesting that awareness of the child's tTGA test results affects reporting of symptoms.
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| 15. |
- Starck, Göran, et al.
(författare)
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A 1H magnetic resonance spectroscopy study in adults with obsessive compulsive disorder: relationship between metabolite concentrations and symptom severity.
- 2008
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Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 115:7, s. 1051-62
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Tidskriftsartikel (refereegranskat)abstract
- 1H magnetic resonance spectroscopy (1H MRS) studies exploring brain metabolites, especially glutamine + glutamate (Glx), in obsessive compulsive disorder (OCD) are of vital interest for trying to understand more about the pathophysiology of OCD. Therefore, we conducted the present 1H MRS study with the aims of (1) comparing MRS metabolites in a group of adult patients with OCD and a group of healthy controls, and (2) examining the relationship between MRS metabolite concentrations and symptom severity in the patient group. Three brain regions were studied, the right caudate nucleus, the anterior gyrus cinguli and the occipital cortex bilaterally. Since multivariate analysis is a highly useful tool for extraction of 1H MRS data, we applied principal component analysis (PCA) and partial least square projection to latent structures (PLS) to the MRS data. PLS disclosed a strong relationship between several of the metabolites and OCD symptom severity, as measured with Yale-Brown obsessive-compulsive scale (YBOCS): the YBOCS score was found to be positively correlated to caudate creatine, Glx, glutamate, and choline compounds as well as occipital cortex myoinositol, and negatively correlated to occipital cortex Glx. The negative correlation between occipital cortex Glx and YBOCS was the most impressive. PCA did not reveal any tendency for a separation between the patients with OCD and controls with respect to MRS metabolites. The results are discussed in relation to corticostriatothalamocortical feedback and previous observations of poor visuospatial ability in OCD.
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| 16. |
- Törn, Carina, et al.
(författare)
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Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.
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| 17. |
- Browall, Maria, et al.
(författare)
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Information needs of women with recently diagnosed ovarian cancer - A longitudinal study
- 2004
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Ingår i: European Journal of Oncology Nursing. - : Elsevier. - 1462-3889 .- 1532-2122. ; 8:3, s. 200-207
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the information needs among patients with ovarian cancer and whether these information needs change over time. The information needs were evaluated three times, through structured interviews, and were based on the paired comparison approach developed by Degner and colleagues. A consecutive sample of patients (n=82) with recently diagnosed ovarian cancer was asked to participate.Sixty-four patients (78%) chose to participate. The three different measurements of participants' information needs revealed only small changes in these needs. The three most important information needs, in all measurements, were information about the likelihood of cure, information about the stage and spreading of the disease, and information about different treatment options. Information regarding sexual attractiveness was the lowest ranked item in all measurements. Regarding subgroups (age, education) the only significant difference throughout all measurements was that younger patients rated issues of sexual attractiveness higher than older patients (p=0.005).In this longitudinal study patients with ovarian cancer ranked information about the disease and its treatment (i.e. likelihood of cure, stage of disease, and treatment options) highest, and information about psychosocial aspects and self-care lowest. These findings are in accordance with the results from studies of women diagnosed with other types of cancer, which used the same methodology. © 2004 Elsevier Ltd. All rights reserved.
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| 18. |
- Burstein, ES, et al.
(författare)
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II. In vitro evidence that (-)-OSU6162 and (+)-OSU6162 produce their behavioral effects through 5-HT2A serotonin and D2 dopamine receptors
- 2011
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Ingår i: JOURNAL OF NEURAL TRANSMISSION. - 0300-9564. ; 118:11, s. 1523-1533
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: (-)-OSU6162 has promise for treating Parkinson's disease, Huntington's disease and schizophrenia. Behavioral tests evaluating the locomotor effects of (-) and (+)-OSU6162 on 'low activity' animals (reserpinized mice and habituated rats) and 'high activity' animals (drug naive mice and non-habituated rats) revealed that both enantiomers of OSU6162 had dual effects on behavior, stimulating locomotor activity in 'low activity' animals and inhibiting locomotor activity in 'high activity' animals. To elucidate a plausible mechanism of action for their behavioral effects, we evaluated the intrinsic actions of (-)- and (+)-OSU6162, and a collection of other antipsychotic and antiparkinsonian agents at 5-HT2A and D2 receptors in functional assays with various degrees of receptor reserve, including cellular proliferation, phosphatidyl inositol hydrolysis, GTP gamma S and beta-arrestin recruitment assays. We also tested for possible allosteric actions of (-)-OSU6162 at D2 receptors. Both enantiomers of OSU6162 were medium intrinsic activity partial agonists at 5-HT2A receptors and low intrinsic activity partial agonists at D2 receptors. (+)-OSU6162 had higher efficacy at 5-HT2A receptors, which correlated with its greater stimulatory activity in vivo, but (-)-OSU6162 had higher potency at D2 receptors, which correlated with its greater inhibitory activity in vivo. (-)-OSU6162 did not display any convincing allosteric properties. Both (+)- and (-)-OSU6162 were significantly less active at 27 other monoaminergic receptors and reuptake transporters tested suggesting that D2 and 5-HT2A receptors play crucial roles in mediating their behavioral effects. Compounds with balanced effects on these two receptor systems may offer promise for treating neuropsychiatric diseases.
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| 19. |
- Carlsson, Arvid, 1923, et al.
(författare)
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A dopaminergic deficit hypothesis of schizophrenia: the path to discovery.
- 2006
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Ingår i: Dialogues in clinical neuroscience. - 1294-8322. ; 8:1, s. 137-42
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Tidskriftsartikel (refereegranskat)abstract
- In contrast to the conventional view of dopamine involvement in schizophrenia, which posits hyperactive dopaminergic transmission, we propose that for unknown developmental and/or biochemical reasons, a primary defect occurs in efficient, tight dopaminergic synaptic transmission, triggering feedback activation and receptor upregulation, and resulting in the well-characterized increase in dopaminergic tone. This hypothesis is driven by suggestive evidence for subpopulations of dopamine D2 receptors delivering contrasting forms of dopaminergic transmission: synaptic receptors, responsible for basic dopaminergic function and subject to effective feedback control, and poorly controlled extrasynaptic receptors partly responsible for the positive symptoms of psychosis. Since the primary defect is dopamine deficiency, we term this theory the dopaminergic deficit hypothesis of schizophrenia. It is currently informing clinical studies with novel partial dopamine antagonists (dopamine stabilizers) such as ACR16, which preferentially target extrasynaptic receptors while leaving synaptic transmission and basic dopamine function intact.
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| 20. |
- Carlsson, Arvid, 1923, et al.
(författare)
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Adaptive properties and heterogeneity of dopamine D(2) receptors - pharmacological implications.
- 2008
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Ingår i: Brain research reviews. - : Elsevier BV. - 0165-0173. ; 58:2, s. 374-8
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Tidskriftsartikel (refereegranskat)abstract
- In this review, we focus on the marked adaptability of dopamine D(2) receptors to varying agonist levels and we discuss the extent to which this phenomenon can account for the heterogeneity of these receptors in regard to function and pharmacological responsiveness. We emphasize the significance of a distinction between synaptic and extrasynaptic receptors in this context. For example, the application of this dichotomy appears to shed new light on the various subgroups of antipsychotic drugs and the mechanisms underlying their different profiles.
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