Lack of association with the CD28/CTLA4/ICOS gene region among Norwegian multiple sclerosis patients

Chromosome region 2q33 encodes several regulators of the immune system, among these the CD28, CTLA4, and ICOS molecules. Involvement of these genes in multiple sclerosis (MS) is not yet clear. We investigated six microsatellites and three SNPs in a relatively large and clinically well characterised Norwegian MS cohort. No associations were observed for any of the markers analysed in 575 MS patients and 551 controls. Associations were neither found when stratifying the material for the HLA-DRB1*1501, DQB1*0602 haplotype, gender, age at onset, disease course nor familial aggregation. In conclusion, this study could not confirm association with the CD28/CTLA4/ICOS gene region.     

Systemic T-cell activation in acute clinically isolated optic neuritis

We examined untreated 60 patients with acute monosymptomatic optic neuritis (ON). Patients examined early after onset showed increased expression of HLA-DR and CD45R0 on CD4 and CD8 T cells. Expression of HLA-DR on CD4 T cells was higher in patients without IgG oligoclonal bands. Expression of HLA-DR on CD4 and CD8 T cells correlated negatively with measures of disease activity and positively with measures of good visual function, and expression of CD45R0 on CD4 T cells correlated negatively with measures of disease activity. We hypothesize that HLA-DR expression may characterize a protective T-cell subset in ON.     

Abnormalities on ECG and telemetry predict stroke outcome at 3 months

BACKGROUND: ECG is a useful tool in monitoring vital functions in patients with acute stroke; however, fairly little evidence is available concerning the prevalence and the prognostic impact of ECG findings in patients with acute cerebral infarction and acute intracerebral haemorrhage (ICH). METHODS: This analysis was based on data from 692 patients with acute cerebral infarction, 155 patients with intracerebral haemorrhage (ICH), and 223 patients with transient ischaemic attack (TIA), who were admitted to hospital within 6 h of symptom onset. A 12 lead ECG was obtained on admission, and the patient was on telemetry for the first 12-24 h of hospitalisation. RESULTS: ECG abnormalities were observed in 60% of patients with cerebral infarction, 50% of patients with ICH, and 44% of patients with TIA. In multivariate analyses 3-month mortality in patients with ischaemic stroke was predicted by atrial fibrillation OR 2.0 (95% CI 1.3-3.1), atrio-ventricular block OR 1.9 (95% CI 1.2-3.9), ST-elevation OR (2.8, 95% CI 1.3-6.3), ST-depression OR 2.5 (95% CI 1.5-4.3), and inverted T-waves OR 2.7 (95% CI 1.6-4.6). This was independent of stroke severity, pre-stroke disability and age. In patients with ICH, sinus tachycardia OR 4.8 (95% CI 1.7-14.0), ST-depression OR 5.2 (95% CI 1.1-24.9), and inverted T-wave 5.2 (95% CI 1.2-22.5) predicted poor outcome. None of the changes reached significance in patients with TIA. In patients with severe cerebral infarction or ICH, heart rate did not decrease within the first 12 h after admission, which was the case in patients with mild to moderate stroke. Rapid heart rate predicted 3-month mortality in multivariate testing OR 1.7 (95% CI 1.02-2.7). CONCLUSIONS: ECG abnormalities are frequent in acute stroke and may predict 3-month mortality.     

Pericardial effusion in a patient with lymphangioleiomyomatosis

A 60-y-old woman with known lymphangioleiomyomatosis presented with a pericardial effusion. Chylous fluid was drained by pericardiocentesis, and EBV was demonstrated in the pericardial effusion. Treatment with a systemic antiviral agent removed the virus from the effusion. The effusion itself was treated surgically.     

Effect of xenon anaesthesia on accuracy of cardiac output measurement using partial CO2 rebreathing

Cardiac output (CO) determination based on partial CO(2) rebreathing has recently been introduced into clinical practice. The determination of flow is crucial for exact CO readings and the physical properties of xenon, i.e. high density and viscosity, may influence flow readings. This study compared echocardiography-derived CO measurements with the partial rebreathing method during total intravenous (TIVA) vs. xenon-based anaesthesia. Thirty-nine patients ASA physical status III undergoing aortic reconstruction were randomly assigned to receive either xenon (Xe, n = 20) or TIVA (T, n = 19) based general anaesthetic. Paired measurements were taken before xenon administration, after xenon administration, before and after clamping of the abdominal aorta and after declamping and at corresponding time points in the TIVA group. Data were analysed with a Bland-Altmann plot. Bias and precision were acceptable and comparable before xenon administration (T 0.54 +/- 0.92 l.min(-1) vs. Xe 0.11 +/- 1.1 l.min(-1)), but after xenon administration CO was largely overestimated by partial CO(2) rebreathing (T 0.04 +/- 0.91 l.min(-1) vs. Xe -4.0 +/- 2.1 l.min(-1)). In the TIVA group, bias and precision after declamping increased significantly (P < 0.01) compared to all time points except baseline. In its current application, the NICO cardiac output monitor appears to be inappropriate for determination of CO during xenon based anaesthesia.     

Cardiovascular effects of xenon and nitrous oxide in patients during fentanyl-midazolam anaesthesia

Xenon anaesthesia appears to have minimal haemodynamic effects. The purpose of this randomised prospective study was to compare the cardiovascular effects of xenon and nitrous oxide in patients with known ischaemic heart disease. In 20 patients who were due to undergo coronary artery bypass graft surgery, 30 min following induction of anaesthesia with fentanyl 30 microg x kg(-1) and midazolam 0.1 mg x kg(-1) but prior to the start of surgery, xenon or nitrous oxide 60% was administered for 15 min. The results showed that xenon caused a minimal decrease in the mean arterial pressure (from 81 (7) to 75 (8) mmHg, mean (SD)), but did not affect the systolic function of the left ventricle, as demonstrated by unchanged left ventricular stroke work index (LVSWI) and the fractional area change of the left ventricle (FAC) derived from transoesophageal echocardiography (TOE). However, in contrast, nitrous oxide was found to decrease the mean arterial pressure (from 81 (8) to 69 (7) mmHg), the LVSWI, and the FAC. The cardiac index, central venous and pulmonary artery occlusion pressures, systemic and pulmonary vascular resistances, and the TOE-derived E/A ratio through the mitral valve were unchanged by xenon or nitrous oxide. We conclude that xenon provides improved haemodynamic stability compared with nitrous oxide, conserving the left ventricular systolic function.     

A comparison of the effects of cheese and butter on serum lipids, haemostatic variables and homocysteine

Milk fat contains considerable amounts of saturated fatty acids, known to increase serum cholesterol. Little is known, however, about the relative effect of different milk products on risk factors for CHD. The aim of the present study was to compare the effects of Jarlsberg cheese (a Norwegian variety of Swiss cheese) with butter on serum lipoproteins, haemostatic variables and homocysteine. A controlled dietary study was performed with twenty-two test individuals (nine men and thirteen women) aged 23-54 years. The subjects consumed three isoenergetic test diets, with equal amounts of fat and protein, and containing either cheese (CH diet), butter + calcium caseinate (BC diet) or butter + egg-white protein (BE diet). The study was a randomised cross-over study and the subjects consumed each diet for 3 weeks, with 1 week when they consumed their habitual diet in between. Fasting blood samples were drawn at baseline and at the end of each period. Serum was analysed for lipids and plasma for haemostatic variables and homocysteine. Total cholesterol was significantly lower after the CH diet than after the BC diet (-0.27 mmol/l; P=0.03), while the difference in LDL-cholesterol was found to be below significance level (-0.22 mmol/l; P=0.06). There were no significant differences in HDL-cholesterol, triacylglycerols, apo A-I, apo B or lipoprotein (a), haemostatic variables and homocysteine between the diets. The results indicate that, at equal fat content, cheese may be less cholesterol increasing than butter.     

Surveillance for retinopathy of prematurity in a Copenhagen high-risk sample 1999-2001. Has progress reached a plateau?

PURPOSE: As part of a current quality control to evaluate ophthalmic findings in two combined central Copenhagen neonatology centers for birth years 1999-2001, and to compare the selected sample with data of the national register for childhood visual impairment. METHODS: In a prospective design to report on 372 infants mainly under regular surveillance for retinopathy of prematurity (ROP) in the stratified functional unit made up by the neonatal wards of Righospitalet (RH) and Hvidovre Hospital (HH). The median neonate under ophthalmic surveillance in the two wards (screening limits usually 32 weeks/1750 g) was given by gestational age (GA) and birthweight (BW) values of 27.3 weeks/907 g and 30.3 weeks/1420 g. respectively. Feedback regarding outcome was secured for those transferred to regional centres. RESULTS: The overall frequency of ROP was 38.5% in the RH (n=252) and 10.8% in the HH sample (n=120). From a peak share above 60% in those <26 weeks/750 g at delivery, the incidence of ROP showed a regular decrease with decreasing immaturity. The centralized retinal ablation therapy for advanced ROP was given to a total of 29, with birth year 2001 unexpectedly showing a peak of 17 cases. Seven of the 29 children treated are now in the register for visually impaired, mainly due to low vision. Fourteen of the 29 had been very small for gestational age. CONCLUSIONS: Supported also by recent regional Danish data, the apparent progress in the fight against ROP over many years seems to have come to a halt. Except for the continued increased survival of extremely preterm babies we have no obvious neonatological indication to explain the suggested 'adverse' trends.     

Labdanes and isopimaranes from Platycladus orientalis and their effects on erythrocyte membrane and on Plasmodium falciparum growth in the erythrocyte host cells

Six labdanes (1-6) and four isopimaranes (7-10), including three new natural products (7, 9, and 10), were isolated from Platycladus orientalis, and their structures determined using 1D and 2D NMR methods, ion-cyclotron resonance HRMS, and optical rotation data. Relative configurations of all chiral centers in the isopimaranes were determined using NOESY experiments at 600 and 800 MHz. Specific optical rotation data were used to correlate absolute configurations. Compounds 1-9 and aframodial (11) were tested for their in vitro antiplasmodial activity and for their ability to induce changes of erythrocyte shape in order to obtain data about possible correlation between the two effects. All compounds tested exhibited weak (IC(50) > 25 microM) in vitro antiplasmodial effects against Plasmodium falciparum strain 3D7. At the same time, the compounds caused echinocytic or stomatocytic changes of the erythrocyte membrane curvature, indicative of their incorporation into the lipid bilayer, in the concentration region where the antiplasmodial activity was observed. The antiplasmodial effect of these compounds thus appears to be an indirect effect on the erythrocyte host cell. Weak or moderate antiplasmodial activity observed with many other apolar natural products, in particular those with amphiphilic structures, is also likely to be an indirect effect.