Bacterial adherence in otitis media: determination of N-acetylgalactosamine (GalNAc) residues in the submucosal glands and surface epithelium of the normal and diseased Eustachian tube.

BACKGROUND: Acute otitis media (AOM) is the most common childhood infection caused by bacteria. The pathogenesis of AOM implicates initial adherence of a pathogen to the nasopharyngeal epithelium, which is followed by bacterial colonization of the middle ear cavity through the Eustachian tube. N-acetylgalactosamine (GalNAc) is an important constituent of mucins and GalNAc containing sugar residues seem to be essential for initial adherence of respiratory bacteria to the surface of epithelial cells. OBJECTIVE: To explore the localization of GalNAc residues, we incubated Eustachian tube sections from Streptococcus pneumoniae infected and normal control rats with seven biotinylated, GalNAc recognizing lectins: Bauhinia purpurea lectin (BPA), Psophocarpus tetragonolobus lectin (PTA), Helix aspersa lectin (HAA), Helix pomatia lectin (HPA), Phaseolus lunatus lectin (PLA), Sophora japonica lectin (SJA) and Vicia Villosa isolectin B4 (VVA-B4). RESULTS: The mucin producing epithelium and submucosal glands of the normal Eustachian tube contained GalNAc residues, as evidenced by binding of several of the lectins. Lectin binding specificity and intensity changed following acute middle ear infection. BPA was the only lectin that exclusively stained the surface epithelium and the serous acini of the submucosal glands in the infected animals, whereas no binding was detected in the normal controls. HPA, HAA, PTA and VVA-B4 binding to surface epithelial cells increased after infection, indicating an active secretion of GalNAc containing glycans. Quantitative analysis of submucosal gland staining intensity showed significantly more GalNAc residues in the normal Eustachian tube, compared to infected animals. CONCLUSION: We conclude that the mucous producing elements of the normal rat Eustachian tube contain GalNAc residues essential for respiratory pathogen adherence. In addition, the GalNAc residue specificity and reacting intensity change in relation to acute infection, which may be important in relation to subsequent development of secretory otitis media or formation of a bacterial biofilm in the middle ear. The results show that GalNAc residues increased in both the submucosal serous glands and in the surface epithelium of the Eustachian tube after middle ear infection with S. pneumoniae.

The occurrence and characteristics of auras in a large epilepsy cohort.

OBJECTIVES: Despite several studies, estimates of the frequency with which auras occur in conjunction with epilepsy continue to be imprecise. The aim of this study was to assess the occurrence and characteristics of auras in a large population-based epilepsy cohort. MATERIALS AND METHODS: Subjects with verified epilepsy were recruited from population-based twin registries in the USA, Denmark and Norway. Using a structured interview in which a list of auras was provided, subjects were asked about the warning symptoms preceding their epileptic attacks. RESULTS: 31% of the total sample (n = 1897) and 39% of those with active epilepsy (n = 765) had experienced an aura. Six percent reported more than one type. Non-specified auras were most frequently reported (35%), followed by somatosensory (11%) and vertiginous (11%). While the majority of those reporting auras (59%) had focal epilepsies, auras of a mostly non-specific nature were experienced by 13% of those with generalized epilepsies. CONCLUSION: Auras serve an important purpose in that they may prevent seizure-related injuries and could provide an indication as to where the seizures originate. The occurrence of auras often is underestimated, especially in children and those with learning disabilities.

Genetic screening of Scandinavian families with febrile seizures and epilepsy or GEFS+.

BACKGROUND: Mutations in the three genes SCN1A, SCN1B and GABRG2, all encoding subunits of ion channels, have been known to cause generalized epilepsy with febrile seizures plus (GEFS+) in families of different origin. OBJECTIVE: To study the occurrence of mutations in these genes in families with GEFS+ or a GEFS+ resembling phenotype of Scandinavian origin. MATERIAL AND METHODS: We performed linkage analysis in 19 Scandinavian families with a history of febrile seizures (FS) and epilepsy or GEFS+. Where linkage could not be excluded, the genes of interest were sequenced. RESULTS: We identified only one mutation in SCN1A, which seems to be a rare variant with no functional consequence. CONCLUSION: This suggests that mutations in these three genes are not a prevalent cause of familial cases of FS and epilepsy or GEFS+ in Scandinavia.

A European perspective on costs and cost effectiveness of ophthalmic combinations in the treatment of open-angle glaucoma.

PURPOSE: Efficacy, safety, and cost implications are important considerations when choosing an ophthalmic treatment. Fixed-combination glaucoma medications containing brimonidine 0.2% and timolol 0.5%, or dorzolamide 2% and timolol 0.5%, were compared with brimonidine 0.2% and dorzolamide 2% that were used as adjunctive therapy to timolol 0.5%. METHODS: A literature review was conducted to determine the outcome parameters of intraocular pressure reduction and tolerability after 3 months of use of brimonidine or dorzolamide, each together with timolol as a fixed-combination or in concomitant therapy. Modelled cost-minimization and cost-effectiveness analyses were performed to investigate the economic consequences of ophthalmic therapy with brimonidine, dorzolamide, and timolol from a societal perspective. RESULTS: The literature review found that brimonidine and dorzolamide used as fixed combinations with timolol as well as in adjunctive therapy to timolol were equally effective and safe. Furthermore, in the European countries studied, the fixed combination of brimonidine/timolol represented a less costly option when compared to the fixed combination of dorzolamide/timolol evaluated over both a 3-month and a 12-month horizon. CONCLUSIONS: Brimonidine used as a fixed-combination therapy with timolol provided better cost value than dorzolamide/timolol in all the countries studied. For most countries, the fixed combination of brimonidine and timolol also provided better cost value than adjunctive therapy with brimonidine, which was more cost effective than adjunctive therapy with dorzolamide.

Publisher Correction: Shedding new light on the Crab with polarized X-rays.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Shedding new light on the Crab with polarized X-rays.

Strong magnetic fields, synchrotron emission, and Compton scattering are omnipresent in compact celestial X-ray sources. Emissions in the X-ray energy band are consequently expected to be linearly polarized. X-ray polarimetry provides a unique diagnostic to study the location and fundamental mechanisms behind emission processes. The polarization of emissions from a bright celestial X-ray source, the Crab, is reported here for the first time in the hard X-ray band (~20-160 keV). The Crab is a complex system consisting of a central pulsar, a diffuse pulsar wind nebula, as well as structures in the inner nebula including a jet and torus. Measurements are made by a purpose-built and calibrated polarimeter, PoGO+. The polarization vector is found to be aligned with the spin axis of the pulsar for a polarization fraction, PF = (20.9 ± 5.0)%. This is higher than that of the optical diffuse nebula, implying a more compact emission site, though not as compact as, e.g., the synchrotron knot. Contrary to measurements at higher energies, no significant temporal evolution of phase-integrated polarisation parameters is observed. The polarization parameters for the pulsar itself are measured for the first time in the X-ray energy band and are consistent with observations at optical wavelengths.

Congenital heart defects in live-born children of epileptic parents.

In a study of congenital heart defects (CHD) in 2,461 live-born children of an unselected group of 979 male and 1,093 female epileptics, 18 children with CHD were recorded; eight had epileptic fathers and 10 epileptic mothers. The prevalence of CHD does not differ significantly from that of the background population. Many different CHD types were recorded with no single defect being predominant. Likewise, no association with a specific type of anticonvulsant treatment was noted. The fact that the prevalence of CHD among children of male and female epileptics and of the background population was similar supports the view that antiepileptic treatment is no major factor in the etiology of CHD in the off-spring of epileptics.

Electromyographic distinction between paramyotonia congenita and myotonia congenita: effect of cold.

We studied three patients with paramyotonia congenita and three with myotonia congenita. At room temperature myotonic bursts in the EMG were similar in the two disorders. After repetitive maximal contractions, patients with paramyotonia showed decreasing recruitment pattern and increasing after-activity, while myotonia patients showed unchanged recruitment pattern, and after-activity tended to decrease, but these differences were not consistent. However, immersion of the hand in ice water for 10 minutes caused unambiguous differences: In paramyotonia, the myotonic discharges disappeared and the muscles went into stiff, electrically silent, contracture; in myotonia patients, the myotonic activity increased and muscle contraction patterns remained normal.

Facial clefts in sibs and children of epileptic patients.

The prevalence of facial clefts in sibs and children of 2,072 epileptics ascertained in a defined region was determined by record linkage with a national cleft register, which also provided expected figures. Observed/expected ratios were increased only for cleft lip with or without cleft palate if the mother had manifested epilepsy: it was 4.7 when anticonvulsants were given before and during pregnancy, 2.7 in cases with no treatment, and zero in children born prior to maternal epilepsy. Children of epileptic men and sibs of epileptics showed no increase. The prevalence of isolated cleft palate was not above expectation in any group.

Steady state kinetics of pyridostigmine in myasthenia gravis.

We measured the fluctuations in plasma pyridostigmine concentration from day to day on 3 consecutive days and hour to hour during 1 day in 11 myasthenic patients, by studying their usual dosage regime. Plasma pyridostigmine was measured by gas chromatography/mass spectrometry. The intraindividual day-to-day variation in plasma pyridostigmine levels was small. A highly significant relationship was found between the oral pyridostigmine dose and the area under the plasma concentration/time curve. The bioavailability of oral pyridostigmine was 3.6%, estimated by replacing one dose with an intravenous dose amounting to 1/30 of the oral dose. The relatively stable kinetic behavior of pyridostigmine is in contrast to the interpatient variability in dose requirement, indicating that monitoring of plasma pyridostigmine levels should be reserved for special cases.

Immunoglobulin deposits in peripheral nerve endings detected by skin biopsy in patients with IgM M proteins and neuropathy.

Immunofluorescence studies of sural nerve and skin biopsies from three patients with IgM M proteins and clinical neuropathy showed that IgM M protein was bound to the nerve myelin in two patients and by the peri- and endoneurium in one. It is suggested that immunohistochemical studies of skin biopsies provide a simple effective method of detecting immunoglobulin binding to peripheral nerves in patients suspected of having an autoimmune neuropathy. In contrast to sural nerve biopsy, skin biopsy does not cause sensory loss or pain in a denervated area and can easily be repeated.

Identification of mutations in the CACNL1A3 gene in 13 families of Scandinavian origin having hypokalemic periodic paralysis and evidence of a founder effect in Danish families.

Familial hypokalemic periodic paralysis (hypoPP) is an autosomal dominant disorder characterised by episodic attacks of paralysis of varying severity. Recently, linkage was found to markers in 1q31-32 and to the gene encoding the muscle DHP-sensitive calcium channel alpha 1-subunit (CACNL1A3). Subsequently, three mutations in this gene were identified in patients with hypoPP: Arg528His, Arg1239His and Arg1239Gly. In this study, two different mutations were found in the CACNL1A3 gene in 13 Scandinavian families, 10 of whom have the Arg528His mutation while 3 families have the Arg1239His. Furthermore, there is evidence of a founder effect in 8 of the 9 Danish hypoPP families investigated, consisting of haplotypes of microsatellite markers close to and within the CACNL1A3 gene and of the geographic origin of the families. For the first time, reduced penetrance in males with the Arg528His mutation was found in several cases.

Inter-observer variation in the evaluation of neurological signs: patient-related factors.

The influence of patient-related factors on inter-observer variability in the evaluation of neurological signs was investigated. Two hundred and two consecutive unselected inpatients were examined by two senior neurologists who were unaware of the neurological case history. Eight signs were evaluated: anisocoria, jerky eye movements, facial palsy, difference in elbow extension force, abnormal finger-nose test, Barré sign, difference in knee jerk, and extensor plantar reflex. Agreement rates were calculated in order to compare the inter-observer variability with reference to the patients' sex, age, mode of admission, and diagnosis at discharge. Observed agreement rates for the eight examined signs only sporadically showed statistically significant differences between the chosen patient-related factors. In general, inter-observer variation does not appear to be influenced by the sex, age, mode of admission or diagnosis at discharge of the patients.

Genetic and environmental factors in epilepsy: a population-based study of 11900 Danish twin pairs.

The contribution of genetic and environmental factors to the occurrence of epilepsy was examined in an unselected sample of twins recruited from the population-based Danish Twin Registry. Information on the occurrence of epilepsy in both members of a twin pair was obtained from 11900 pairs whose ages ranged from 12 to 41 years. Concordance rates, odds ratios and tetrachoric correlations were used to quantify the similarity of monozygotic (MZ) and dizygotic (DZ) twins. The sample was stratified by sex and separated into two age cohorts for analysis. Significantly higher probandwise concordance rates were found for MZ compared with DZ twins (0.37 and 0.08, P<0.01). Odds ratios and tetrachoric correlation showed similar pattern. An etiological model including additive genetic and individual specific environmental factors provided the best overall fit to the data, with 70 and 88% of the liability to develop epilepsy being accounted for by genetic factors in the younger and older cohorts, respectively. Individual specific environmental factors explained the remaining 30 and 12%, respectively. In conclusion, this study has confirmed the substantial impact, which genetic factors have in the etiology of epilepsy. The heritability of epilepsy is high and seems to increase with age.

Iodixanol in paediatric gastrointestinal imaging: safety and efficacy comparison with iohexol.

Iodixanol (Visipaque) is a dimeric, non-ionic iodinated contrast medium that is isotonic with blood at all clinically relevant concentrations. Iodixanol was compared in a randomized, double blind, parallel group, phase III multicentre trial with a monomeric, non-ionic contrast medium, iohexol (Omnipaque), at two concentrations assessing safety, tolerability and radiographic efficacy during contrast enhanced gastrointestinal radiography examinations of children. 154 children entered the trial; 152 formed the safety population and 147 the efficacy population. All examinations were performed following standard departmental practice. Children were assigned into either a high or low concentration group (iodixanol, 150 mgI ml(-1) and 320 mgI ml(-1) vs iohexol, 140 mgI ml(-1) and 300 mgI ml(-1)). The primary outcome measure for efficacy was the overall quality of visualization, which was assessed using a 100 mm visual analogue scale (VAS). The secondary efficacy variables assessed were quality of contrast opacification, mucosal coating and overall quality of diagnostic information. Safety evaluation involved patient follow-up for at least 48 h. Taste acceptance was also assessed. There was no statistically significant difference between the two contrast media with regard to the primary and secondary efficacy variables assessed, although higher ratings were observed for iodixanol. The 100 mm VAS score overall was 86 mm for iodixanol and 82 mm for iohexol (95% confidence interval -2.56, 10.42). The frequency of adverse events was lower for patients receiving iodixanol. Adverse events, mainly diarrhoea, occurred in 12 patients (16.2%) in the iodixanol group and 28 patients (35.9%) in the iohexol group. This reached statistical significance (p=0.006). Overall, iodixanol is well suited for examinations of the gastrointestinal tract, giving good efficacy results and fewer adverse events than iohexol.

Madelung deformity treated with Ilizarov technique: a report of two cases.

Two children with painful and progressive Madelung deformities were treated by osteotomy of the radius and subsequent angular correction and bone lengthening using the Ilizarov technique. Both children were radiologically improved and free of pain at follow-up.

[Metabolic encephalopathy: oxcarbazepine (Trileptal)-induced hyponatremia]. / Metabolisk encefalopati: oxkarbazepin-(Trileptal)-induceret hyponatriaemi.

A patient is described with metabolic encephalopathy which developed as a result of hyponatraemia induced by oxcarbazepine (OXC). The literature reveals that up to 80% of the patients in OXC therapy develop hyponatraemia. Elderly patients and patients receiving high doses of OXC are at particular risk in this respect. The majority of patients are asymptomatic and the hyponatraemic condition does not demand changes in treatment. Control of serum natrium levels prior to and during treatment with OXC is recommended, particularly when side-effects occur.

[Mortality in epilepsy. A review]. / Dødelighed ved epilepsi. En oversigt.

The overall risk of premature death in patients with epilepsy is two to three times that of the general population. The mortality risk is highest in patients with symptomatic epilepsy, but the mortality rate is also increased in patients with idiopathic epilepsy, indicating that epilepsy itself carries an increased risk of premature death. Cerebrovascular disease and primary brain tumours are common causes of death in patients with symptomatic epilepsy, while sudden unexplained death (SUDEP), accidents, suicide and status epilepticus are important causes of epilepsy related deaths. Prevention of accidents and suicide in patients with epilepsy and further knowledge on SUDEP is essential in order to reduce the mortality rate of epilepsy.

[Retroperitoneal location of a chordoma]. / Retroperitonealt lejret kordom.

A case of a retroperitoneal chordoma is presented. The observed localization without relation to the axial skeleton has not been reported previously.

[Neuropathy in adult metachromatic leukodystrophy]. / Neuropati ved adult metakromatisk leukodystrofi.

Metachromatic leukodystrophy is a rare autosomal recessive disorder with deficient arylsulphatase A activity. Different forms occur according to the age at onset of symptoms. Adult forms generally present with presenile dementia and/or psychiatric symptoms. We report a case of a 45-year-old woman, without a family history of neuropsychiatric disorders, presenting with complaints of numbness and weakness of the lower limbs. No intellectual or behavioral disturbances were clinically detectable. Electrophysiological investigation was compatible with severe demyelinating neuropathy in upper and lower limbs. MRI of the brain showed multiple white matter lesions. Adult metachromatic leukodystrophy was diagnosed on the basis of low leucocyte arylsulfatase-A-activity and accumulation of metachromatic material in the sural nerve. Pseudo-deficiency was excluded by DNA analysis. This case indicates that adult metachromatic leukodystrophy should be considered in patients with symptoms and signs resembling multiple sclerosis with peripheral neuropathy and in patients with neuropathy of unknown etiology.