Serum neurofilament light chain in patients with acute cerebrovascular events.

BACKGROUND AND PURPOSE: Serum neurofilaments are markers of axonal injury. We addressed their diagnostic and prognostic role in acute ischemic stroke (AIS) and transient ischemic attack (TIA). METHODS: Nested within a prospective cohort study, we compared levels of serum neurofilament light chain (sNfL) drawn within 24 h from symptom onset in patients with AIS or TIA. Patients without magnetic resonance imaging on admission were excluded. We assessed whether sNfL was associated with: (i) clinical severity on admission, (ii) diagnosis of AIS vs. TIA, (iii) infarct size on admission magnetic resonance diffusion-weighted imaging (MR-DWI) and (iv) functional outcome at 3 months. RESULTS: We analyzed 504 patients with AIS and 111 patients with TIA. On admission, higher National Institutes of Health Stroke Scale (NIHSS) scores were associated with higher sNfL: NIHSS score < 7, 13.1 pg/mL [interquartile range (IQR), 5.3-27.8]; NIHSS score 7-15, 16.7 pg/mL (IQR, 7.4-34.9); and NIHSS score > 15, 21.0 pg/mL (IQR, 9.3-40.4) (P = 0.01). Compared with AIS, patients with TIA had lower sNfL levels [9.0 pg/mL (95% confidence interval, 4.0-19.0) vs. 16.0 pg/mL (95% confidence interval, 7.3-34.4), P < 0.001], also after adjusting for age and NIHSS score (P = 0.006). Among patients with AIS, infarct size on admission MR-DWI was not associated with sNfL, either in univariate analysis (P = 0.15) or after adjusting for age and NIHSS score on admission (P = 0.56). Functional outcome 3 months after stroke was not associated with sNfL after adjusting for established predictors. CONCLUSIONS: In conclusion, among patients admitted within 24 h of AIS or TIA onset, admission sNfL levels were associated with clinical severity on admission and TIA diagnosis, but not with infarct size on MR-DWI acquired on admission or functional outcome at 3 months.

Impact of body mass index on outcome in stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: The impact of body mass index (BMI) on outcome in stroke patients treated with intravenous thrombolysis (IVT) was investigated. METHODS: In a multicentre IVT-register-based observational study, BMI with (i) poor 3-month outcome (i.e. modified Rankin Scale scores 3-6), (ii) death and (iii) symptomatic intracranial haemorrhage (sICH) based on criteria of the ECASS II trial was compared. BMI was used as a continuous and categorical variable distinguishing normal weight (reference group 18.5-24.9 kg/m2 ) from underweight (<18.5 kg/m2 ), overweight (25-29.9 kg/m2 ) and obese (≥30 kg/m2 ) patients. Univariable and multivariable regression analyses with adjustments for age and stroke severity were done and odds ratios with 95% confidence intervals [OR (95% CI)] were calculated. RESULTS: Of 1798 patients, 730 (40.6%) were normal weight, 55 (3.1%) were underweight, 717 (39.9%) overweight and 295 (16.4%) obese. Poor outcome occurred in 38.1% of normal weight patients and did not differ significantly from underweight (45.5%), overweight (36.1%) and obese (32.5%) patients. The same was true for death (9.5% vs. 14.5%, 9.6% and 7.5%) and sICH (3.9% vs. 5.5%, 4.3%, 2.7%). Neither in univariable nor in multivariable analyses did the risks of poor outcome, death or sICH differ significantly between BMI groups. BMI as a continuous variable was not associated with poor outcome, death or sICH in unadjusted [OR (95% CI) 0.99 (0.97-1.01), 0.98 (0.95-1.02), 0.98 (0.94-1.04)] or adjusted analyses [OR (95% CI) 1.01 (0.98-1.03), 0.99 (0.95-1.05), 1.01 (0.97-1.05)], respectively. CONCLUSION: In this largest study to date, investigating the impact of BMI in IVT-treated stroke patients, BMI had no prognostic meaning with regard to 3-month functional outcome, death or occurrence of sICH.

Zurich Fabry study - prevalence of Fabry disease in young patients with first cryptogenic ischaemic stroke or TIA.

BACKGROUND AND PURPOSE: The etiology of stroke in young patients remains undetermined in up to half of the cases. Data on prevalence of Fabry disease (FD) in young people with cryptogenic ischaemic stroke are limited and controversial. We aimed to evaluate the frequency of unrecognized FD in a cohort of stroke patients at a tertiary stroke center. METHODS: Patients suffering from first cryptogenic ischaemic stroke or transient ischaemic attack (TIA) at the age of 18-55 years were screened for the presence of FD. We measured the serum activity of α-galactosidase (α-GAL) in all patients. In addition, sequencing of α-GAL gene was performed in men with low enzyme activity and in all women. RESULTS: Between January, 2006, and October, 2009, we recruited 150 patients (102 men, 48 women) with a mean age of 43 ± 9 years at symptom onset (135 ischaemic stroke, 15 TIA). The α-GAL activity was low in nine patients (6%; six men and three women). Genetic sequencing in six men with low enzyme activity and all 48 women detected no α-GAL gene mutation. CONCLUSION: Our study suggests that the yield of screening for FD in patients with first cryptogenic ischaemic stroke or TIA is very low. Further large-scale studies are needed to investigate the importance of FD amongst patients with recurrent cryptogenic strokes.

Outcome of intravenous thrombolysis in stroke patients weighing over 100 kg.

BACKGROUND: Intravenous thrombolysis with alteplase for ischemic stroke is fixed at a maximal dose of 90 mg for safety reasons. Little is known about the clinical outcomes of stroke patients weighing >100 kg, who may benefit less from thrombolysis due to this dose limitation. METHODS: Prospective data on 1,479 consecutive stroke patients treated with intravenous alteplase in six Swiss stroke units were analyzed. Presenting characteristics and the frequency of favorable outcomes, defined as a modified Rankin scale (mRS) score of 0 or 1, a good outcome (mRS score 0-2), mortality and symptomatic intracranial hemorrhage (SICH) were compared between patients weighing >100 kg and those weighing ≤100 kg. RESULTS: Compared to their counterparts (n = 1,384, mean body weight 73 kg), patients weighing >100 kg (n = 95, mean body weight 108 kg) were younger (61 vs. 67 years, p < 0.001), were more frequently males (83 vs. 60%, p < 0.001) and more frequently suffered from diabetes mellitus (30 vs. 13%, p < 0.001). As compared with patients weighing ≤100 kg, patients weighing >100 kg had similar rates of favorable outcomes (45 vs. 48%, p = 0.656), good outcomes (58 vs. 64%, p = 0.270) and mortality (17 vs. 12%, p = 0.196), and SICH risk (1 vs. 5%, p = 0.182). After multivariable adjustment, body weight >100 kg was strongly associated with mortality (p = 0.007) and poor outcome (p = 0.007). CONCLUSION: Our data do not suggest a reduced likehood of favorable outcomes in patients weighing >100 kg treated with the current dose regimen. The association of body weight >100 kg with mortality and poor outcome, however, demands further large-scale studies to replicate our findings and to explore the underlying mechanisms.

Intravenous thrombolysis in patients with stroke attributable to small artery occlusion.

BACKGROUND: Intravenous thrombolysis (IVT) for stroke seems to be beneficial independent of the underlying etiology. Recent observations raised concern that IVT might cause harm in patients with strokes attributable to small artery occlusion (SAO). OBJECTIVE: The safety of IVT in SAO-patients is addressed in this study. METHODS: We used the Swiss IVT databank to compare outcome and complications of IVT-treated SAO-patients with IVT-treated patients with other etiologies (non-SAO-patients). Main outcome and complication measures were independence (modified Rankin scale 0.8). Fatal ICH occurred in 3.3% of the non-SAO-patients but none amongst SAO-patients. Ischaemic stroke within 3 months after IVT reoccurred in 1.5% of SAO-patients and in 2.3% of non-SAO-patients (P = 0.68). CONCLUSION: IVT-treated SAO-patients died less often and reached independence more often than IVT-treated non-SAO-patients. However, the variable 'SAO' was a dependent rather than an independent outcome predictor. The absence of an excess in ICH indicates that IVT seems not to be harmful in SAO-patients.

Triple and quadruple spontaneous cervical artery dissection: presenting characteristics and long-term outcome.

BACKGROUND: Spontaneous cervicocephalic artery dissection (sCAD) of more than two cervical arteries is rare. PATIENTS AND METHODS: Vascular and potential sCAD risk factors, triggering events, clinical and neuroimaging findings, and outcome of patients with multiple sCAD were studied. Patients were drawn from prospective hospital-based sCAD registries. RESULTS: Of 740 consecutive patients with sCAD, 11 (1.5%) had three, and one had four (0.1%) sCAD. Eight of these 12 patients were women. One patient had additional dissections of the celiac trunk and hepatic artery. Vascular risk factors included hypertension (n = 1), hypercholesterolaemia (n = 6), current smoking (n = 5) and migraine (n = 6). No patient had a family history of sCAD, fibromuscular dysplasia (FMD) or connective tissue disease. SCAD was preceded by a minor trauma in five and infection in four patients. Clinical manifestations included ischaemic stroke (n = 8), transient ischaemic attack (n = 3), headache (n = 9), neck pain (n = 4), Horner syndrome (n = 5), pulsatile tinnitus (n = 2) and dysgeusia (n = 1). Brain MRI revealed ischaemic infarcts that affected one vessel territory in seven and two territories in two patients. The 3-month outcome was favourable (modified Rankin scale score 0-1) in 10 patients (83%). No new recurrent stroke or sCAD occurred during a mean follow-up of 50 (SD 29) months. CONCLUSION: Multiple sCAD occurred preferentially in women and caused clinical symptoms and signs mainly in one vascular territory. In none of the patients was FMD or any other underlying arteriopathy apparent. The majority of multiple sCAD was preceded by a minor trauma or infection. Clinical outcome was favourable in most patients, and long-term prognosis benign. The data suggest that transient vasculopathy may be a major mechanism for multiple sCAD.

Importance of the sampled milk fraction for the prediction of total quarter somatic cell count.

This study investigated the changes in somatic cell counts (SCC) in different fractions of milk, with special emphasis on the foremilk and cisternal milk fractions. Therefore, in Experiment 1, quarter milk samples were defined as strict foremilk (F), cisternal milk (C), first 400 g of alveolar milk (A1), and the remaining alveolar milk (A2). Experiment 2 included 6 foremilk fractions (F1 to F6), consisting of one hand-stripped milk jet each, and the remaining cisternal milk plus the entire alveolar milk (RM). In Experiment 1, changes during milking indicated the importance of the sampled milk fraction for measuring SCC because the decrease in the first 3 fractions (F, C, and A1) was enormous in milk with high total quarter SCC. The decline in SCC from F to C was 50% and was 80% from C to A1. Total quarter SCC presented a value of approximately 20% of SCC in F or 35% of SCC in C. Changes in milk with low or very low SCC were marginal during milking. Fractions F and C showed significant differences in SCC among different total SCC concentrations. These differences disappeared with the alveolar fractions A1 and A2. In Experiment 2, a more detailed investigation of foremilk fractions supported the findings of Experiment 1. A significant decline in the foremilk fractions even of F1 to F6 was observed in high-SCC milk at concentrations >350 x 10(3) cells/mL. Although one of these foremilk fractions presented only 0.1 to 0.2% of the total milk, the SCC was 2- to 3-fold greater than the total quarter milk SCC. Because the trait of interest (SCC) was measured directly by using the DeLaval cell counter (DCC), the quality of measurement was tested. Statistically interesting factors (repeatability, recovery rate, and potential matrix effects of milk) proved that the DCC is a useful tool for identifying the SCC of milk samples, and thus of grading udder health status. Generally, the DCC provides reliable results, but one must consider that SCC even in strict foremilk can differ dramatically from SCC in the total cisternal fraction, and thus also from SCC in the alveolar fraction.

Leukocyte populations and mRNA expression of inflammatory factors in quarter milk fractions at different somatic cell score levels in dairy cows.

The effect of somatic cell count (SCC) and milk fraction on milk composition, distribution of cell populations, and mRNA expression of various inflammatory parameters was studied. Therefore, quarter milk samples were defined as cisternal (C), first 400 g of alveolar (A1), and remaining alveolar milk (A2) during the course of milking. Quarters were assigned to 4 groups according to their total SCC: 1) <12 x 10(3)/mL, 2) 12 to 100 x 10(3)/mL, 3) 100 to 350 x 10(3)/mL, and 4) >350 x 10(3)/mL. Milk constituents of interest were SCC, fat, protein, lactose sodium, and chloride ions as well as electrical conductivity. Cell populations were classified into lymphocytes, macrophages, and neutrophils (PMN). The mRNA expression of the inflammatory factors tumor necrosis factor-alpha, interleukin-1beta, cyclooxygenase-2, lactoferrin, and lysozyme was measured via real-time, quantitative reverse transcription PCR. Somatic cell count decreased from highest levels in C to lowest levels in A1 and increased thereafter to A2 in all groups. Fat content increased from C to A2 and with increasing SCC level. Lactose decreased with increasing SCC level but remained unchanged during milking. Concentrations of sodium and chloride, and electrical conductivity increased with increasing SCC but were higher in C than in A1 and A2. Protein was not affected by milk fraction or SCC level. The distribution of leukocytes was dramatically influenced by milk fraction and SCC. Lymphocytes were the dominating cell population in group 1, but the proportion of lymphocytes was low in groups 2, 3, and 4. Macrophage proportion was highest in group 2 and decreased in groups 3 and 4, whereas that of PMN increased from group 2 to 4. The content of macrophages decreased during milking in all SCC groups whereas that of PMN increased. The proportion of lymphocytes was not affected by milk fraction. The mRNA expression of all inflammatory factors showed an increase with increasing SCC but minor changes occurred during milking. In conclusion, milk fraction and SCC level have a crucial influence on the distribution of leukocyte populations and several milk constituents. The surprisingly high content of lymphocytes and concomitantly low mRNA expression of inflammatory factors in quarters with SCC <12 x 10(3)/mL indicates a different and possibly reduced readiness of the immune system to respond to invading pathogens.

Effect of some operational parameters on the decolorization of textile effluents and dye solutions by ozonation.

Treatment of three wastewaters and two acid dye solutions by ozonation with varying ozone dose, initial pH, and initial dye concentration were examined. Ozonation of all the wastewaters were shown to be pseudo-first-order reaction with respect to color, chemical oxygen demand (COD) and dissolved organic carbon (DOC). Increasing ozone dose increased the removal of color, COD, and DOC, as well as decreased ozone consumption ratio, and increased apparent rate constants. Ozonation was more successful at decolorization than the removal of COD and DOC or augmentation of biodegradability. Increasing initial dye concentration increased the ozone consumption and decreased the rate constant. Color removal efficiencies for different ozone dose application were in the range of 60-91% for sample A (dye bath effluent), and 70-96% for sample B (plant effluent). For sample A, COD and DOC removal efficiencies at several ozone dose applications were between 13-22 % and 8-13%, respectively. For sample B, they were between 11-33% and 6-15% respectively. Increasing pH could expand the efficiency of ozone slightly. Ozone consumption per unit color, COD and DOC removal at any time was found to bealmost the same whereas the applied ozone dose was different at a constant pH. Ozonation increased the biochemical oxygen demand (BOD,) of sample A and B 1.22 and 1.37 times by consuming 300 and 225 mg ozone, respectively. Ozonation of acid dyes was a pseudo-first order reaction with respect to dye. Increases in dye concentration raised specific ozone consumption. Specific ozone consumption for Acid Red 183 (AR-183) dye solution with 50 mg l(-1) of concentration rose from 0.32 to 0.72 mg-O3 per mg dye decomposed as the dye concentration was increased to 500 mg l(-1).

Adenocarcinoma of prostate in a twenty-seven-year-old man.

A case of adenocarcinoma of the prostate in a twenty-seven-year-old man is reported. He responded initially to cobalt radiation to the prostate, but metastases developed subequently and he died thriteen months after the histologic diagnosis was made. Three of the 4 previously documented cases in men below age thirty who also presented with symptoms of obstruction of the lower urinary tract or bone pain died four, five, and twelve months later. The other patient was asymptomatic and alive thirty-one months after detection on a routine physical examination. Although based on a small number of cases, men below age thirty with prostatic adenocarcinoma have a poor prognosis, which appears to be related to the presence of symptoms at the time of diagnosis.