Abnormal blood-brain barrier permeability in normal appearing white matter in multiple sclerosis investigated by MRI.

OBJECTIVES: To investigate whether blood-brain barrier (BBB) permeability is disrupted in normal appearing white matter in MS patients, when compared to healthy controls and whether it is correlated with MS clinical characteristics. METHODS: Dynamic contrast-enhanced MRI was used to measure BBB permeability in 27 patients with MS and compared to 24 matched healthy controls. RESULTS: Permeability measured as K(trans) was significantly higher in periventricular normal appearing white matter (NAWM) and thalamic gray matter in MS patients when compared to healthy controls, with periventricular NAWM showing the most pronounced difference. Recent relapse coincided with significantly higher permeability in periventricular NAWM, thalamic gray matter, and MS lesions. Immunomodulatory treatment and recent relapse were significant predictors of permeability in MS lesions and periventricular NAWM. Our results suggest that after an MS relapse permeability gradually decreases, possibly an effect of immunomodulatory treatment. CONCLUSIONS: Our results emphasize the importance of BBB pathology in MS, which we find to be most prominent in the periventricular NAWM, an area prone to development of MS lesions. Both the facts that recent relapse appears to cause widespread BBB disruption and that immunomodulatory treatment seems to attenuate this effect indicate that BBB permeability is intricately linked to the presence of MS relapse activity. This may reveal further insights into the pathophysiology of MS.

Retinal atrophy correlates with fMRI response in patients with recovered optic neuritis.

OBJECTIVE: We wanted to investigate if retinal nerve fiber layer thickness (RNFLT) measured by optical coherence tomography (OCT) might be a good marker of acute and chronic changes in the afferent visual pathway following acute optic neuritis (ON). METHODS: We studied the relationship of optic nerve lesion length, optic nerve mean area, and RNFLT, quantified by OCT, with fMRI response to a visual paradigm in 40 patients with acute ON and 19 healthy controls in a prospective cohort study over a 6-month period. RESULTS: The main finding was a significant correlation of optic nerve lesion length and mean area with fMRI response in affected eyes in the acute phase and between RNFLT and fMRI response in affected eyes after recovery. CONCLUSION: RNFLT is a very good measure of damage to the afferent visual pathway in recovered patients with ON and should be included in future fMRI studies when looking for visual reorganization in recovered patients with ON.

Retinal nerve fiber layer thickness is associated with lesion length in acute optic neuritis.

BACKGROUND: Acute optic neuritis occurs with and without papillitis. The presence of papillitis has previously been thought to imply an anterior location of the neuritis, but imaging studies seeking to test this hypothesis have been inconclusive. METHODS: This prospective observational cohort study included 41 patients with unilateral optic neuritis and 19 healthy volunteers. All patients were evaluated and examined within 28 days of onset of symptoms. The peripapillary retinal nerve fiber layer thickness (RNFLT), an objective quantitative measure of optic nerve head edema, was measured by optical coherence tomography and the length and location of the inflammatory optic nerve lesion were evaluated using MRI. RESULTS: Ophthalmoscopically, 34% of the patients had papillitis. The retinal nerve fiber layer in affected eyes (mean 123.1 microm) was higher during the acute phase than that of fellow eyes (mean 98.1 microm, p < 0.0001) and higher than that in healthy control eyes (mean 97.1 microm, p < 0.0001). The RNFLT was related to the length of the optic nerve lesion (p = 0.0002), but not to the location of the optic nerve lesions (p = 0.72). CONCLUSIONS: In this study of the acute phase of optic neuritis, the degree of optic nerve head edema depended upon the extent of the optic nerve lesion, but not on its location. This suggests that factors other than inflammation, such as compromised venous drainage, vascular leakage, impaired axonal transport, and other mechanisms, are involved in the development of optic nerve head edema in optic neuritis.

A new microduplication syndrome encompassing the region of the Miller-Dieker (17p13 deletion) syndrome.

BACKGROUND: The use of array comparative genome hybridisation (CGH) analyses for investigation of children with mental retardation has led to the identification of a growing number of new microdeletion and microduplication syndromes, some of which have become clinically well characterised and some that await further delineation. This report describes three children with de novo 17p13.1 duplications encompassing the PAFAH1B1 gene, who had similar phenotypic features, including mild to moderate developmental delay, hypotonia and facial dysmorphism, and compares them to the few previously reported cases with this duplication. METHODS: Multiplex ligation-dependent probe amplification (MLPA) or array-CGH was used to diagnose three developmentally delayed children with duplications of 17p13. The duplications were characterised further using Agilent array technology, revealing duplication sizes from 1.8 to 4.0 Mb, with a region of overlap corresponding to 1.8 Mb. Detailed clinical information was obtained from patient files and personal examinations. RESULTS: The developmental delay and similar clinical features in the three patients were most likely due to a common microduplication of 17p13. CONCLUSIONS: In contrast to patients with deletion of the region (Miller-Dieker syndrome) the patients reported here had mild to moderate retardation and displayed no lissencephaly or gross brain malformations. Further cases with similar duplications are expected to be diagnosed, and will contribute to the delineation of a potential new microduplication syndrome of 17p13.

Disruption of the copper efflux pump (CopA) of Serratia marcescens ATCC 274 pleiotropically affects copper sensitivity and production of the tripyrrole secondary metabolite, prodigiosin.

The prodigiosin biosynthetic gene cluster (pig cluster) of Serratia marcescens ATCC 274 (Sma 274) is flanked by cueR/copA homologues. Inactivation of the copA homologue resulted in an increased sensitivity to copper, confirming that CopA is involved in copper homeostasis in Sma 274. The effect of copper on the biosynthesis of prodigiosin in Sma 274 and the copA mutant strain was investigated. Increased levels of copper were found to reduce prodigiosin production in the wild type Sma 274, but increase production in the copA mutant strain. The physiological implications for CopA mediated prodigiosin production are discussed. We also demonstrate that the gene products of pigB-pigE of Sma 274 are sufficient for the biosynthesis of 2-methyl-3-n-amyl-pyrrole and condensation with 4-methoxy-2,2'-bipyrrole-5-carboxyaldehyde to form prodigiosin, as we have shown for Serratia sp. ATCC 39006.

Phase locking and supermode selection in multicore photonic crystal fiber lasers with a large doped area.

We report on the laser properties of multicore photonic crystal fiber lasers. A stable phase locking of six- and seven-core structures through evanescent coupling is observed. Effective supermode selection is obtained by using both diffraction losses and the Talbot effect. A pure in-phase supermode is obtained (1.1 times diffraction limited). The laser operating in this mode has a slope efficiency of 70% with up to 44 W of output power. The modal area of the in-phase supermode multicore fiber is 1150 microm2, which makes it, to our knowledge, the single-mode fiber laser with the largest mode field area. In-phase laser action is stable when the fiber is bent.

Influence of Dermanyssus gallinae and Ascaridia galli infections on behaviour and health of laying hens (Gallus gallus domesticus).

(1) The effect of infections with Dermanyssus gallinae (poultry red mite or chicken mite) and Ascaridia galli (roundworm) on the behaviour and health of laying hens was investigated. (2) Six groups of 15 pullets (Isa Brown) were kept in indoor pens from 18 weeks of age. Two groups were artificially infected with D. gallinae, two groups with A. galli and two groups were kept as uninfected controls. The hens were observed for behavioural reactions and physiological changes (weight gain and various blood variables) to the parasitic infections. (3) Infections with D. gallinae resulted in reduced weight gain, anaemia and even death of some of the hens. Behavioural changes were also observed, as the mite-infected hens showed higher self-grooming and head scratching both during the day and night. (4) A. galli resulted in a lower weight gain but no significant changes were seen in blood variables or behavioural activities.

Glyceryl trinitrate may trigger endogenous nitric oxide production in patients with chronic tension-type headache.

Experimental studies in humans have shown that nitric oxide (NO) may play an important role in initiation of primary headaches. It has been proposed that activation of L-arginine-NO pathway and increased endogenous production of NO may be responsible for NO induced headache. NO is synthesized from L-arginine and that reaction also yields citrulline. In the present study we aimed to investigate plasma levels of citrulline and arginine as markers of NO production after infusion of the NO donor, glyceryl trinitrate (GTN). We recruited 16 patients with chronic tension-type headache and 16 healthy controls. The subjects were randomly allocated to receive 0.5 microg/kg/min GTN or placebo over 20 min. Patients were examined on headache free days. Blood samples were collected at baseline and 60 min after start of infusion. Both patients and controls developed stronger immediate headache on the GTN day than on the placebo day (P = 0.008). The headache was more pronounced in patients than in controls (P = 0.02). Plasma levels of citrulline increased significantly 60 min after start of GTN infusion compared to placebo infusion in patients (P = 0.01) but not in controls (P = 0.50). Plasma levels of arginine were unchanged in both patients (P = 0.12) and controls (P = 0.18). We suggest that GTN administration may trigger endogenous production of NO in patients with chronic tension-type headache resulting in activation of perivascular sensory afferents.

Polarization maintaining large mode area photonic crystal fiber.

We report on a polarization maintaining large mode area photonic crystal fiber. Unlike, previous work on polarization maintaining photonic crystal fibers, birefringence is introduced using stress applying parts. This has allowed us to realize fibers, which are both single mode at any wavelength and have a practically constant birefringence for any wavelength. The fibers presented in this work have mode field diameters from about 4 to 6.5 micron, and exhibit a typical birefringence of 1.510(-4).

Low-loss photonic crystal fibers for transmission systems and their dispersion properties.

We report on a single-mode photonic crystal fiber with attenuation and effective area at 1550 nm of 0.48 dB/km and 130 microm(2), respectively. This is, to our knowledge, the lowest loss reported for a PCF not made from VAD prepared silica and at the same time the largest effective area for a low-loss (< 1 dB/km) PCF. We briefly discuss the future applications of PCFs for data transmission and show for the first time, both numerically and experimentally, how the group velocity dispersion is related to the mode field diameter.

Gas sensing using air-guiding photonic bandgap fibers.

We demonstrate the high sensitivity of gas sensing using a novel air-guiding photonic bandgap fiber. The bandgap fiber is spliced to a standard single-mode fiber at the input end for easy coupling and filled with gas through the other end placed in a vacuum chamber. The technique is applied to characterize absorption lines of acetylene and hydrogen cyanide employing a tunable laser as light source. Measurements with a LED are also performed for comparison. Detection of weakly absorbing gases such as methane and ammonia is explored.

Improved large-mode-area endlessly single-mode photonic crystal fibers.

We numerically study the possibilities for improved large-mode-area endlessly single-mode photonic crystal fibers for use in high-power delivery applications. By carefully choosing the optimal hole diameter, we find that a triangular core formed by three missing neighboring air holes considerably improves the mode area and loss properties compared with the case with a core formed by one missing air hole. In a realized fiber we demonstrate an enhancement of the mode area by approximately 30% without a corresponding increase in the attenuation.

Comparison of Kistler 9861A force platform and Chattecx Balance System for measurement of postural sway: correlation and test-retest reliability.

Measurement of postural sway has several potential applications in sports medicine. Traditionally, however, rather complicated equipment has been applied. The purpose of the study was to compare two devices based on two different methods of measuring postural sway: (i) a sophisticated Kistler 9861A force platform (KIS)--which all but requires a laboratory setting--and (ii) Chattecx Balance System (CBS)--which is particularly suited for measurement of sway in the dynamic environment of sports. Measurement of sway was performed in 29 subjects twice at baseline and twice at follow-up 2-4 weeks later. One measurement consisted of four 25-second sequences (eyes open, parallel feet; eyes closed, parallel feet; eyes open, tandem Romberg; eyes closed, tandem Romberg). Factor analysis revealed influence of sight and stance on sway, marked interaction between these two factors and a decrease in sway on retest on the same day. Coefficients of variation were--KIS: 0.13-0.23; CBS: 0.11-0.25. Body height was a covariate for all parameters. Kistler 9861A force platform and CBS were correlated (baseline: r(s) = 0.47; follow-up: r(s) = 0.9). These findings suggest that, when the effects of acclimatization and covariance of body height were taken into account, CBS was as reliable and reproducible as KIS in our laboratory.

Multi-mode photonic crystal fibers for VCSEL based data transmission.

Quasi error-free 10Gbit/s data transmission is demonstrated over a novel type of 50 microm core diameter photonic crystal fi ber with as much as 100m length. Combined with 850 nm VCSEL sources, this fi ber is an attractive alternative to graded-index multi-mode fi bers for datacom applications. A comparison to numerical simulations suggests that the high bit-rate may be partly explained by inter-modal diffusion.

Hypoglycaemia and elevated urine ethylmalonic acid in a child homozygous for the short-chain acyl-CoA dehydrogenase 625G > A gene variation.

UNLABELLED: The aim of this case report is to call attention to short-chain acyl-CoA dehydrogenase (SCAD) deficiency as a possible contributory factor to hypoglycaemia in childhood. We report on a previously healthy 14 mo-old Danish boy who presented with hypoglycaemia and metabolic acidosis after a few days of upper airway infection. After two days on a normal diet, he recovered clinically and biochemically. A thorough biochemical examination did not reveal the cause of the hypoglycaemia. However, the excretion of ethylmalonic acid in two morning urine samples was moderately increased, and hence the SCAD gene was screened for mutations. We found the child homozygous for the G > A SCAD gene variation at position 625. CONCLUSION: In this patient, reduced function of the SCAD protein is reflected in the excretion of ethylmalonic acid, a marker of intracellular accumulation of butyryl-CoA and the cytotoxic butyric acid. Furthermore, gluconeogenesis might be compromised owing to lack of reducing equivalents from the oxidation of short-chain fatty acids in the fasting or stressed state, thus contributing to the predisposition for fasting hypoglycaemia.

Tail biting in pigs.

One of the costly and welfare-reducing problems in modern pig production is tail biting. Tail biting is an abnormal behaviour, characterized by one pig's dental manipulation of another pig's tail. Tail biting can be classified into two groups: the pre-injury stage, before any wound on the tail is present, and the injury stage, where the tail is wounded and bleeding. Tail biting in the injury stage will reduce welfare of the bitten pig and the possible spread of infection is a health as well as welfare problem. The pigs that become tail biters may also suffer, because they are frustrated due to living in a stressful environment. This frustration may result in an excessive motivation for biting the tails of pen mates. This review aims to summarize recent research and theories in relation to tail biting.

Neurobehavioral deficits associated with PCB in 7-year-old children prenatally exposed to seafood neurotoxicants.

Prenatal exposure to polychlorinated biphenyls (PCBs) was examined by analysis of cord tissue from 435 children from a Faroese birth cohort. Analysis of 50 paired cord blood samples showed excellent correlation with the cord tissue concentration (r=.90). Among 17 neuropsychological outcomes determined at age 7 years, the cord PCB concentration was associated with deficits on the Boston Naming Test (without cues, two-tailed P=.09 not adjusted for mercury; with cues, P=.03), the Continuous Performance Test reaction time (P=.03), and, possibly, on long-term recall on the California Verbal Learning Test (P=.15). The association between cord PCB and cord-blood mercury (r=.42) suggested possible confounding. While no PCB effects were apparent in children with low mercury exposure, PCB-associated deficits within the highest tertile of mercury exposure indicated a possible interaction between the two neurotoxicants. PCB-associated increased thresholds were seen at two of eight frequencies on audiometry, but only on the left side, and no deficits occurred on evoked potentials or contrast sensitivity. The limited PCB-related neurotoxicity in this cohort appears to be affected by concomitant methylmercury exposure.

Neonatal screening for galactosemia by quantitative analysis of hexose monophosphates using tandem mass spectrometry: a retrospective study.

BACKGROUND: Classic galactosemia (OMIM 230400) is an inherited disorder in the metabolism of galactose caused by deficiency of the enzyme galactose 1-phosphate uridyl transferase (EC 2.7.7.12). Galactosemia leads to accumulation of galactose and galactose 1-phosphate (gal-1-P) in blood and tissues and, if untreated, produces neonatal death or severe mental retardation, cirrhosis of the liver, and cataracts. Hence, the disorder is included in many neonatal screening programs. METHODS: We retrospectively analyzed filter-paper blood samples obtained 4-8 days postpartum for routine neonatal screening from 12 galactosemia patients and 2055 random controls. Total hexose monophosphates (HMPs) were used as a marker of gal-1-P and were assayed by negative-ion mode electrospray tandem mass spectrometry (tandem MS) with settings biased toward gal-1-P detection. The predominant precursor/product ion pair m/z 259/79 was used to quantify total HMPs by external standardization. RESULTS: Linear calibration curves were obtained in the range 0-8 mmol/L gal-1-P. The detection limit was 0.1 mmol/L HMP, and total CVs ranged from 13% at the detection limit to <8% at >1 mmol/L HMP. The method was in agreement with an alkaline phosphatase-galactose dehydrogenase method. All samples from galactosemia patients contained increased HMP concentrations (range for patients, 2.6-5.2 mmol/L; range for reference group, <0.10-0.94 mmol/L). The diagnostic sensitivity and specificity were 100% at a cutoff of 1.2 mmol/L HMP. A Duarte/classic galactosemia compound heterozygous sample could be discriminated clearly from both patient and reference samples. CONCLUSION: Quantitative analysis of HMPs by tandem MS can be used in laboratory investigations of galactosemia.

Molecular genetic basis and prevalence of glycogen storage disease type IIIA in the Faroe Islands.

Glycogen storage disease type IIIA (GSD IIIA) is caused by mutations of the amyloglucosidase gene (AGL). For most populations, none of the AGL mutations described to date is particularly frequent. In this paper, we report that six children with GSD IIIA from the Faroe Islands were found to be homozygous for the novel nonsense mutation c.1222C>T (R408X) of the AGL gene. This mutation is easily detected by restriction enzyme digest with NsiI after mismatch PCR. Investigating five intragenic polymorphisms, we could show that this mutation was always associated with the same haplotype. The c.1222C>T mutation could be detected on two chromosomes of another 50 unselected GSD IIIA patients of other European or North American origin which means that this mutation plays a minor role worldwide. From the fact that we are currently aware of a total of 14 GSD IIIA cases in the Faroese population of 45 000, the observed prevalence is 1 : 3100. While the novel AGL mutation c.1222C>T was not detectable among 198 German newborns, nine out of 272 children from the Faroese neonatal screening program were found to be heterozygous for this mutation. Thus, the calculated prevalence is 1 : 3600 (95% CI 1:700-1:6400). We conclude that due to a founder effect, the Faroe Islands have the highest prevalence of GSD IIIA world-wide. The detection of the molecular defect has facilitated the diagnosis and has offered the opportunity for prenatal diagnosis in this patient group.

In vitro screening of Indian medicinal plants for antiplasmodial activity.

Plants traditionally used in India to treat fever or malaria were examined in vitro for antiplasmodial properties against Plasmodium falciparum. Of 80 analysed ethanol extracts, from 47 species, significant effects were found for 31 of the extracts. These represent 23 different species from 20 families. Of the active species 20 were tested against P. falciparum for the first time. The following five species seems to be of special interest for further antimalarial studies, Casearia elliptica, Holarrhena pubescens, Pongamia pinnata, Soymida febrifuga, and Plumbago zeylanica.