J. Neurochem. (2010) 112, 1465-1476. l-DOPA-induced dyskinesia in Parkinson's disease is associated with large increases in brain dopamine (DA) levels following drug dosing, but the precise ...significance of this phenomenon is not understood. Here we compare DA efflux and metabolism in the striatum and the substantia nigra in dyskinetic and non-dyskinetic animals following a standard dose of l-DOPA. Rats with 6-hydroxydopamine lesions were treated chronically with l-DOPA, monitored on the abnormal involuntary movements scale, and then subjected to intracerebral microdialysis under freely-moving conditions. Following s.c. l-DOPA injection, peak extracellular DA levels in both striatum and substantia nigra were about twice as large in dyskinetic animals compared to non-dyskinetic rats. This effect was not attributable to differences in DOPA levels or DA metabolism. The larger DA efflux in dyskinetic animals was blunted by 5-HT1A/5-HT1B receptor agonists and tetrodotoxin infusion, reflecting release from serotonin neurons. Striatal levels of serotonin and its main metabolite, 5-hydroxyindolacetic acid were indeed elevated in dyskinetic animals compared to non-dyskinetic rats, indicating a larger serotonergic innervation density in the former group. High DA release was, however, not sufficient to explain dyskinesia. The 'abnormal involuntary movements output' per unit concentration of striatal extracellular DA was indeed much larger in dyskinetic animals compared to non-dyskinetic cases at most time points examined. The present results indicate that both a high DA release post- l-DOPA administration and an increased responsiveness to DA must coexist for a full expression of dyskinesia.
Linked ContentThis article is linked to Aksan et al papers. To view these articles visit https://doi.org/10.1111/apt.14269 and https://doi.org/10.1111/apt.14043.
Purpose
Iron deficiency anemia is common in people with inflammatory bowel disease (IBD), causing deterioration in quality of life, which can be reversed by treatment that increases iron stores and ...hemoglobin levels. The present
post hoc
analyses estimate health state utility values for patients with IBD after treatment with ferric derisomaltose or ferric carboxymaltose and evaluate the health domains driving the changes.
Methods
SF-36v2 responses were recorded at baseline and day 14, 35, 49, and 70 from 97 patients enrolled in the randomized, double-blind, PHOSPHARE-IBD trial (ClinicalTrials.gov ID: NCT03466983), in which patients with IBD across five European countries were randomly allocated to either ferric derisomaltose or ferric carboxymaltose. Changes in SF-36v2 scale scores and SF-6Dv2 health utility values were analyzed by mixed models.
Results
In both treatment arms, SF-6Dv2 utility values and all SF-36v2 scale scores, except Bodily Pain, improved significantly (
p
= < 0.0001). The improvement in SF-6Dv2 utility values showed no significant treatment group difference. The improvement in utility values was completely explained by improvement in Vitality scores. Vitality scores showed significantly larger improvement with ferric derisomaltose versus ferric carboxymaltose (
p
= 0.026). Patients with the smallest decrease in phosphate had significantly larger improvements in Vitality scores at each time point (
p
= < 0.05 for all comparisons) and overall (
p
= 0.0006).
Conclusions
Utility values improved significantly with intravenous iron treatment. Improvement in utility values was primarily driven by Vitality scores, which showed significantly greater improvement in the ferric derisomaltose arm. Smaller decreases in phosphate were associated with significantly higher Vitality scores, suggesting that quality of life improvement is attenuated by hypophosphatemia. The utility values can inform future cost-utility analysis.
Safe and reliable venous access is mandatory in modern health care, but central venous catheters (CVCs) are associated with significant morbidity and mortality, This paper describes current Swedish ...guidelines for clinical management of CVCs The guidelines supply updated recommendations that may be useful in other countries as well. Literature retrieval in the Cochrane and Pubmed databases, of papers written in English or Swedish and pertaining to CVC management, was done by members of a task force of the Swedish Society of Anaesthesiology and Intensive Care Medicine. Consensus meetings were held throughout the review process to allow all parts of the guidelines to be embraced by all contributors. All of the content was carefully scored according to criteria by the Oxford Centre for Evidence‐Based Medicine. We aimed at producing useful and reliable guidelines on bleeding diathesis, vascular approach, ultrasonic guidance, catheter tip positioning, prevention and management of associated trauma and infection, and specific training and follow‐up. A structured patient history focused on bleeding should be taken prior to insertion of a CVCs. The right internal jugular vein should primarily be chosen for insertion of a wide‐bore CVC. Catheter tip positioning in the right atrium or lower third of the superior caval vein should be verified for long‐term use. Ultrasonic guidance should be used for catheterisation by the internal jugular or femoral veins and may also be used for insertion via the subclavian veins or the veins of the upper limb. The operator inserting a CVC should wear cap, mask, and sterile gown and gloves. For long‐term intravenous access, tunnelled CVC or subcutaneous venous ports are preferred. Intravenous position of the catheter tip should be verified by clinical or radiological methods after insertion and before each use. Simulator‐assisted training of CVC insertion should precede bedside training in patients. Units inserting and managing CVC should have quality assertion programmes for implementation and follow‐up of routines, teaching, training and clinical outcome. Clinical guidelines on a wide range of relevant topics have been introduced, based on extensive literature retrieval, to facilitate effective and safe management of CVCs.
Summary
Background
In Sweden, the most common causes of liver cirrhosis are alcohol overconsumption and hepatitis C. However, recent data on the clinical characteristics of Swedish patients with ...cirrhosis are scarce.
Aims
To determine the incidence, clinical presentation, aetiological spectrum and survival rates of liver cirrhosis in Southern Sweden from 2001 to 2011.
Methods
We used population‐based medical registries to conduct a cohort study of all patients with liver cirrhosis in the southernmost region of Sweden with a population of 1.17 million. Medical records and histopathology data were reviewed. Patients were classified according to aetiology, and clinical parameters were registered. Patients were followed until death or December 2014.
Results
A total of 1317 patients with cirrhosis were identified. The crude annual incidence of cirrhosis was estimated at 14.1/100 000. The most common aetiology was alcohol overconsumption with or without additional causes of cirrhosis (58%) followed by HCV alone (13%) and cryptogenic cirrhosis (12%). At diagnosis, ascites occurred in 43%, variceal bleeding in 6% and overt encephalopathy in 4%. The median follow‐up was 4.3 years. The total 1‐, 5‐ and 10‐year survival rates were 79%, 47% and 27% respectively. Survival rates were better for women than for men. A 10‐year cumulative incidence of transplantation was 7.3%. Mortality was worst for alcoholic cirrhosis with concomitant HCV when adjusted for age and gender.
Conclusions
Sweden continues to have a low incidence of cirrhosis compared with other European countries. Mortality varies with gender, aetiology and severity at diagnosis. Patients with alcoholic cirrhosis with concomitant HCV infection fare worst.
Abstract
Dopamine transmission has been implicated in motor and cognitive function. In Parkinson’s disease (PD), dopamine replacement using the precursor drug
l
-DOPA is the predominant treatment ...approach, but long-term exposure leads to the onset of dyskinesias (LIDs). Chronic
l
-DOPA exposure has been associated with changes in gene expression and altered cortico-striatal plasticity. The aim of this research was to assess the functional consequence of long-term
l
-DOPA exposure on cognitive and motor function using a rodent model of PD. Across two independent experiments, we assessed the impact of chronic
l
-DOPA exposure, or a control D
2
R agonist, on motor and cognitive function in intact and in hemi parkinsonian rats, in the absence of drug. Abnormal involuntary movements associated with LID were measured and brain tissues were subsequently harvested for immunohistochemical analysis. Exposure to chronic
l
-DOPA, but not the D
2
R agonist, impaired motor and cognitive function, when animals were tested in the absence of drug. A meta-analysis of the two experiments allowed further dissociation of
l
-DOPA -treated rats into those that developed LIDs (dyskinetic) and those that did not develop LIDs (non-dyskinetic). This analysis revealed impaired cognitive and motor performance were evident only in dyskinetic, but not in non-dyskinetic, rats. These data reveal a functional consequence of the altered plasticity associated with LID onset and have implications for understanding symptom progression in the clinic.
Background
Intensive care for comatose survivors of cardiac arrest includes targeted temperature management (TTM) to attenuate cerebral reperfusion injury. A recent multi‐center clinical trial did ...not show any difference in mortality or neurological outcome between TTM targeting 33°C or 36°C after out‐of‐hospital‐cardiac‐arrest (OHCA). In our institution, the TTM target was changed accordingly from 34 to 36°C. The aim of this retrospective study was to analyze if this change had affected patient outcome.
Methods
Intensive care registry and medical record data from 79 adult patients treated for OHCA with TTM during 2010 (n = 38; 34°C) and 2014 (n = 41; 36°C) were analyzed for mortality and neurological outcome were assessed as cerebral performance category. Student's t‐test was used for continuous data and Fischer's exact test for categorical data, and multivariable logistic regression was applied to detect influence from patient factors differing between the groups.
Results
Witnessed arrest was more common in 2010 (95%) vs. 2014 (76%) (P = 0.03) and coronary angiography was more common in 2014 (95%) vs. 2010 (76%) (P = 0.02). The number of patients awakening later than 72 h after the arrest did not differ. After adjusting for gender, hypertension, and witnessed arrest, neither 1‐year mortality (P = 0.77), nor 1‐year good neurological outcome (P = 0.85) differed between the groups.
Conclusion
Our results, showing no difference between TTM at 34°C and TTM at 36°C as to mortality or neurological outcome after OHCA, are in line with the previous TTM‐trial results, supporting the use of either target temperature in our institution.
Dietary linoleic acid, an n-6 polyunsaturated fatty acid, is metabolised to arachidonic acid, a component of colonocyte membranes. Metabolites of arachidonic acid have pro-inflammatory properties and ...are increased in the mucosa of patients with ulcerative colitis. The aim of this investigation was to conduct the first prospective cohort study investigating if a high dietary intake of linoleic acid increases the risk of developing incident ulcerative colitis.
Dietary data from food frequency questionnaires were available for 203 193 men and women aged 30-74 years, resident in the UK, Sweden, Denmark, Germany or Italy and participating in a prospective cohort study, the European Prospective Investigation into Cancer and Nutrition (EPIC). These participants were followed up for the diagnosis of ulcerative colitis. Each case was matched with four controls and the risk of disease calculated by quartile of intake of linoleic acid adjusted for gender, age, smoking, total energy intake and centre.
A total of 126 participants developed ulcerative colitis (47% women) after a median follow-up of 4.0 years (range, 1.7-11.3 years). The highest quartile of intake of linoleic acid was associated with an increased risk of ulcerative colitis (odds ratio (OR) = 2.49, 95% confidence interval (CI) = 1.23 to 5.07, p = 0.01) with a significant trend across quartiles (OR = 1.32 per quartile increase, 95% CI = 1.04 to 1.66, p = 0.02 for trend).
The data support a role for dietary linoleic acid in the aetiology of ulcerative colitis. An estimated 30% of cases could be attributed to having dietary intakes higher than the lowest quartile of linoleic acid intake.
.
Objective. To determine the causes and outcome of all patients with acute liver failure (ALF) in Sweden 1994–2003 and study the diagnostic accuracy of King's College Hospital (KCH) criteria and ...the model for end‐stage liver disease (MELD) score with transplant‐free deaths as a positive outcome.
Research design and methods. Adult patients in Sweden with international normalized ratio (INR) of ≥1.5 due to severe liver injury with and without encephalopathy at admission between 1994–2003 were included.
Results. A total of 279 patients were identified. The most common cause of ALF were acetaminophen toxicity in 42% and other drugs in 15%. In 31 cases (11%) no definite etiology could be established. The KCH criteria had a positive‐predictive value (PPV) of 67%, negative‐predictive value (NPV) of 84% in the acetaminophen group. Positive‐predictive value and negative‐predictive value of KCH criteria in the nonacetaminophen group were 54% and 63% respectively. MELD score >30 had a positive‐predictive value of 21%, negative‐predictive value of 94% in the acetaminophen group. The corresponding figures for the nonacetaminophen group were 64% and 76% respectively.
Conclusions. Acetaminophen toxicity was the most common cause in unselected patients with ALF in Sweden. KCH criteria had a high NPV in the acetaminophen group, and in combination with MELD score <30 predicts a good prognosis in acetaminophen patients without transplantation.
Summary
Background
There are plausible mechanisms for how dietary docosahexaenoic acid (DHA), an n−3 polyunsaturated fatty acid, could prevent Crohn's disease (CD).
Aim
To conduct a prospective study ...to investigate the association between increased intake of DHA and risk of CD.
Methods
Overall, 229 702 participants were recruited from nine European centres between 1991 and 1998. At recruitment, dietary intakes of DHA and fatty acids were measured using validated food frequency questionnaires. The cohort was monitored through to June 2004 to identify participants who developed incident CD. In a nested case–control analysis, each case was matched with four controls; odds ratios (ORs) were calculated for quintiles of DHA intake, adjusted for total energy intake, smoking, other dietary fatty acids, dietary vitamin D and body mass index.
Results
Seventy‐three participants developed incident CD. All higher quintiles of DHA intake were inversely associated with development of CD; the highest quintile had the greatest effect size (OR = 0.07; 95% CI = 0.02–0.81). The OR trend across quintiles of DHA was 0.54 (95% CI = 0.30–0.99, Ptrend = 0.04). Including BMI in the multivariate analysis, due to its correlation with dietary fat showed similar associations. There were no associations with the other dietary fatty acids studied.
Conclusion
There were inverse associations, with a biological gradient between increasing dietary docosahexaenoic acid intakes and incident Crohn's disease. Further studies in other populations should measure docosahexaenoic acid to determine if the association is consistent and the hypothesis tested in randomised controlled trials of purely docosahexaenoic acid supplementation.
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