Upprepad administrering av trimetoprim/sulfadiazin till neonatala föl

Today most dosages used in horse medicine are based on studies in adult horses. Since there are differences between adult and neonatal horses with respect to different pharmacological parameters this can cause problems when administring drugs to neonatal foals. Neonatal sepsis is a common cause of morbidity and mortality in foals and aggressive antibiotic treatment is needed immediately when sepsis is suspected. In Sweden the combination of trimethoprim/sulphadiazine and bensylpenicillin is often used as the initial treatment. When administering drugs, interactions can occur between the drugs and endogenous substances. An example of such an interaction is called "displacement" and refers in this case to the competition for binding places on plasma proteins between drugs and highly protein-bound enogenous substances. Drugs that themselves are highly protein-bound are at a greater risk for displacement. Bilirubin is an example of an endogenous substance that to a great extent (>99 %) is bound to albumin. When displacement occur more free unconjugated bilirubin becomes available systemically and to a greater extent can pass the blood-brain barrier and cause cellular damage, so called kernicterus. Kernicterus has mostly been reported in neonatal children and is rarely seen in animals. Kernicterus in foals in association with trimethoprim/sulfadiazine treatment has not been reported but it is theoretically possible that also foals could be affected. The aims of the study were to evaluate the dosage used today and its safety with respect to displacement of bilirubin. Seven healthy foals were treated with trimethoprim/sulfadiazine, 15 mg/kg q 12 h for three days. Blood samples were taken daily at the same time points during four days and the concentrations of total protein, albumin and bilrubin (total, conjugated, unconjugated and free unconjugated) were analysed in plasma. Blood samples were taken at the same time points in a matched control group with seven healthy foals. No differences in levels between the different parameters were seen betweeen the foals treated with trimetoprim/sulfadiazin and the controls. The concentration of free unconjugated bilirubin was analysed with equilibrium dialysis and no differences were seen between the foals treated with trimetoprim/sulfadiazin and the control group. The protein binding was 23 % for trimethoprim and 14 % for sulfadiazine, which is a bit lower than the protein binding measured in adult horses at 35 % and 20% respectively. The results in this study, and the clinical experience without reported cases of kernicterus associated with treatment of trimethoprim/sulfadiazin, implies that the dosage used today does not seem to enhance the risk of kernicterus in neonatal foals. One should, however, consider that this study was performed on clinically healthy foals. Since it is known that many diseases affect the turnover of different endogenous and exogenous substances, further studies are warranted in which focus should be put on septicaemic foals, younger neonatal and prenatal foals.Idag bygger de flesta doseringsangivelser inom hästmedicinen på data från vuxna hästar. Detta kan skapa problem då läkemedelsomsättningen hos neonatala föl kan skilja sig från omsättningen hos vuxna hästar. Neonatal sepsis är en vanlig anledning till morbiditet och mortalitet hos föl och kräver snabbt insatt antibiotikabehandling. I Sverige används ofta kombinationen trimetoprim/sulfadiazin tillsammans med bensylpenicillin. Vid användning av läkemedel kan interaktioner mellan läkemedlen och endogena substanser inträffa. Ett exempel på detta är så kallad ”displacement” där det uppstår en konkurrenssituation mellan läkemedlet och endogena substanser om bindningplatser på plasmaproteiner. Detta gäller framför allt endogena substanser med hög proteinbindningsgrad och risken för displacement är större vid användning av ett läkemedel som själv har hög proteinbindningsgrad. Bilirubin är ett exempel på en endogen substans med hög proteinbindningsgrad, > 99 %. Vid displacement innebär detta att fritt okonjugerat bilirubin i större utsträckning riskerar att passera blodhjärnbarriären och orsaka skada, så kallad kernikterus. Kernikterus har framförallt rapporterats på neonatala barn och är väldigt sällsynt hos djur. Kernikterus på föl i samband med trimetoprimsulfabehandling finns inte rapporterat men teoretiskt är det fullt möjligt att föl skulle kunna drabbas. Denna studie syftar till att undersöka om den nuvarande doseringen för trimetoprim/sulfadiazin är säker att använda för neonatala föl med avseende på displacement av bilirubin. Sju kliniskt friska varmblodiga travarföl injicerades intravenöst med trimetoprim/sulfadiazin i doseringen 15 mg/kg q 12 h under tre dagar. Blodprov togs dagligen vid samma tidpunkt i fyra dagar och koncentrationen totalprotein, albumin och bilirubin (totalt, konjugerat, okonjugerat samt fritt okonjugerat) i plasma analyserades. Blodprov togs vid samma tidpunkter hos en matchad kontrollgrupp på sju friska föl. Inga skillnader i nivåer av de olika parametrarna kunde ses mellan fölen som behandlats med trimetoprim/sulfadiazin och kontrollgruppen. Koncentrationen fritt okonjugerat bilirubin analyserades med hjälp av jämviktsdialys och inte heller där sågs några skillnader mellan fölen som behandlats med trimetoprim/sulfadiazin och kontrollgruppen. Proteinbindningsgraden uppmättes till 23 % för trimetoprim och 14 % för sulfadiazine, vilket är lägre än proteinbindningsgraden för vuxna hästar på 35 % respektive 20 %. Resultaten i denna studie, samt den kliniska erfarenheten med avsaknad av rapporterade fall av kernikterus på föl i samband med trimetoprim/sulfadiazinbehandling, tyder på att den dosering av trimetoprim/sulfadiazin som idag används inte ökar risken för kernikterus hos neonatala föl. Denna studie har dock utförts på kliniskt friska föl. Eftersom man vet att diverse sjukdomstillstånd påverkar omsättningen av olika substanser bör vidare studier utföras där man fokuserar på föl sjuka i sepsis, och gärna även yngre neonatala samt prenatala föl

Personality may influence reactivity to stress

BACKGROUND: Possible mechanisms behind psychophysiological hyperreactivity may be located at a cognitive-emotional level. Several personality traits have been associated with increased cardiovascular reactivity. Subjects with white coat hypertension, which may constitute a kind of hyperreactivity, are found to suppress their emotions and adapt to the surroundings to a larger extent than controls. We hypothesized in this study that a) stress reactivity is related to personality, and that b) responses to cold pressor test (CPT) and mental stress test (MST) are associated with different personality traits. METHODS: 87 men were selected from the 1(st), 50(th )and 99(th )percentile of a blood pressure screening. Cardiovascular and catecholamine responses to MST and CPT were recorded. Fifteen personality traits were assessed using the Karolinska Scale of Personality. Possible independent explanatory predictors for cardiovascular and catecholamine variables at baseline and during stress were analyzed in multiple linear regression analyses using a stepwise forward procedure. RESULTS: Multiple regression analyses showed that muscular tension (β = 0.298, p = 0.004), irritability (β = 0.282, p = 0.016), detachment (β = 0.272, p = 0.017), psychasthenia (β = 0.234, p = 0.031) and somatic anxiety (β = 0.225, p = 0.046) were significant explanatory variables of reactivity to CPT. During MST, verbal aggression (β = -0.252, 0.031) and detachment (β = 0.253, p = 0.044) were significant predictors of norepinephrine and diastolic blood pressure response, respectively. Based on KSP-trait quartiles, delta (Δ) systolic (p = 0.025) and Δ diastolic blood pressure (p = 0.003) during MST were related to detachment score, with the highest reactivity in the 4(th )quartile, while Δ norepinephrine was significantly related to muscular tension (p = 0.033). Δ systolic and Δ diastolic blood pressure responses to CPT were dependent on detachment (p = 0.049 and p = 0.011, respectively) and psychasthenia (p = 0.020 and p = 0.015), while high verbal aggression was associated with lower reactivity measured by Δ norepinephrine (p = 0.037). CONCLUSION: The present study indicates that stress reactivity is clearly related to different personality traits, without any single trait being dominant over others. Furthermore, personality seems to have as much, or even more, importance of predicting responses to CPT than responses to MST

Prevalence of abnormal glucose metabolism in atrial fibrillation: A case control study in 75-year old subjects

<p>Abstract</p> <p>Background</p> <p>The prevalence of atrial fibrillation (AF) is increasing world wide and amongst factors that aggravate the risk is diabetes mellitus (DM), also in epidemic development.</p> <p>However, although DM is a potentially modifiable risk factor for AF, few, if any, studies have explored the prevalence of undiagnosed dysglycaemia among subjects with AF or if duration of AF are related to parameters of glycaemia or dysglycaemia prevalence.</p> <p>Methods</p> <p>In this case control study, amongst 75-year old subjects with and without AF, the prevalence of dysglycaemia, i.e., impaired fasting glycaemia, impaired glucose tolerance or DM, according to World Health Organisation criteria was assessed by a 75-g oral glucose tolerance test (OGTT).</p> <p>Results</p> <p>Prevalence of undiagnosed DM among the 108 subjects (male/female 73/35, BMI 25.4 ± 3.2) without and the 46 (male/female 34/12, BMI 25.3 ± 3.7) with AF (median AF duration five years) where 3.7% and 13.0%, respectively (p = 0.031, Odds ratio (OR) 3.86 (95% Confidence interval [CI]: 1.01, 16.25)) whereas the overall prevalence of dysglycaemia (prediabetes and DM) where similar (respectively 43.5% and 39.1%, p = 0.46, OR 0.83 [95% CI: 0.41, 1.69]). Patients with AF duration ≥ 5 years had however a higher dysglycaemia prevalence (61.1% [DM 22.2%, prediabetes 38.9%]) as compared to AF duration < 5 years (25% [DM 7.1%, prediabetes 17.9%], p = 0.0014, OR 4.7 [95% CI: 1.30, 16.90]) or no AF (p = 0.17, OR 2.04 [95% CI: 0.73, 5.66]). There was also a significant correlation between the duration of AF and HbA1c (r = 0.408, p = 0.005) and fasting glucose levels (r = 0.353, p = 0.016).</p> <p>Conclusion</p> <p>AF is associated with chronic hyperglycaemia amongst 75-year old subjects. Prediabetes and DM should be pro-actively assessed if AF duration ≥ 5 years.</p

Sammenheng mellom teknologiske og organisatorisk utvikling innenfor oljeboring.

Master in Business Administration (MBA) - Nord universitet 201

Non-invasive evaluation of the effect of metoprolol on the atrioventricular node during permanent atrial fibrillation.

During atrial fibrillation (AF), conventional electrophysiological techniques for assessment of refractory period or conduction velocity of the atrioventricular (AV) node cannot be used. We aimed at evaluating changes in AV nodal properties during administration of metoprolol from electrocardiogram data, and to support our findings with simulated data based on results from an electrophysiological study

Loss-of-Function Variants in Cytoskeletal Genes Are Associated with Early-Onset Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and it is associated with an increased risk of heart failure, stroke, dementia, and death. Recently, titin-truncating variants (TTNtv), which are predominantly associated with dilated cardiomyopathy (DCM), were associated with early-onset AF. Furthermore, genome-wide association studies (GWAS) associated AF with other structural genes. In this study, we investigated whether early-onset AF was associated with loss-of-function variants in DCM-associated genes encoding cytoskeletal proteins. Using targeted sequencing, we examined a cohort of 527 Scandinavian individuals with early-onset AF and a control group of individuals free of AF (n = 383). The patients had onset of AF before 50 years of age, normal echocardiogram, and no other cardiovascular disease at onset of AF. We identified six individuals with rare loss-of-function variants in three different genes (dystrophin (DMD), actin-associated LIM protein (PDLIM3), and fukutin (FKTN)), of which two variants were novel. Loss-of-function variants in cytoskeletal genes were significantly associated with early-onset AF when patients were compared with controls (p = 0.044). Using publicly available GWAS data, we performed genetic correlation analyses between AF and 13 other traits, e.g., showing genetic correlation between AF and non-ischemic cardiomyopathy (p = 0.0003). Our data suggest that rare loss-of-function variants in cytoskeletal genes previously associated with DCM may have a role in early-onset AF, perhaps through the development of an atrial cardiomyopathy

Prevalence and incidence rates of atrial fibrillation in Norway 2004-2014

Objective: To study time trends in incidence of atrial fibrillation (AF) in the entire Norwegian population from 2004 to 2014, by age and sex, and to estimate the prevalence of AF at the end of the study period. Methods: A national cohort of patients with AF (≥18 years) was identified from inpatient admissions with AF and deaths with AF as underlying cause (1994–2014), and AF outpatient visits (2008–2014) in the Cardiovascular Disease in Norway (CVDNOR) project. AF admissions or out-of-hospital death from AF, with no AF admission the previous 10 years defined incident AF. Age-standardised incidence rates (IR) and incidence rate ratios (IRR) were calculated. All AF cases identified through inpatient admissions and outpatient visits and alive as of 31 December 2014 defined AF prevalence. Results: We identified 175 979 incident AF cases (30% primary diagnosis, 69% secondary diagnosis, 0.6% out-of-hospital deaths). AF IRs (95% confidence intervals) per 100 000 person years were stable from 2004 (433 (426–440)) to 2014 (440 (433–447)). IRs were stable or declining across strata of sex and age with the exception of an average yearly increase of 2.4% in 18–44 year-olds: IRR 1.024 (1.014–1.034). In 2014, the prevalence of AF in the adult population was 3.4%. Conclusions: We found overall stable IRs of AF for the adult Norwegian population from 2004 to 2014. The prevalence of AF was 3.4% at the end of 2014, which is higher than reported in previous studies. Signs of an increasing incidence of early-onset AF (<45 years) are worrying and need further investigation.publishedVersio