Multiple sclerosis and occupational exposure to chemicals: a co-twin control study of a nationwide series of twins

From the Finnish Twin Cohort (n = 27,100 pairs with known zygosity) all cases of diagnosed multiple sclerosis (MS) were reviewed and those with clinically verified MS were invited for further examinations at the Institute of Occupational Health, Helsinki, with their co-twins. Twenty one cases (19 pairs, of which 17 were discordant) fulfilled the strict criteria of MS. Detailed occupational history showed exposure to a mixture of solvents in six subjects, to lead in one, and to trichloroethylene in one. Of these seven, two monozygotic twins had MS whereas the other five cases were healthy co-twins. These results do not support a causal association between occupational exposure to chemicals and the aetiopathogenesis of MS.     

Prevalence and Prognosis of Epilepsy in Patients with Multiple Sclerosis

An analysis of 599 clinically definite multiple sclerosis (MS) patients including all known cases of the southern province of Finland in January 1, 1979 revealed epileptic seizures in 21 (3.5%) patients. On that date, 12 patients needed treatment (2.0%). The age-adjusted prevalence of active epilepsy was significantly higher than that in the general population. The percentage of partial seizures (67%) was significantly increased in proportion to a series of 100 adult epilepsy patients, with a comparable age distribution. In 10 patients (including three patients with symptomatic epilepsy), the attacks appeared before the MS symptoms. The mean follow-up after the first seizures was 19.3 years. In 10 patients, the seizures disappeared totally during the surveillance until September 1985. Our results show an increased comorbidity between MS and epilepsy. In most cases, however, the prognosis of epilepsy was good and there seemed not to be any clear correlation between the severity of MS and epilepsy.     

Regional differences in the prevalence of pre-eclampsia in relation to the risk factors for coronary artery disease in women in Finland.

AIMS: The aim of this study was to examine the prevalence of pre-eclampsia in Southern, Eastern, and Northern Finland, and the relationship between history of pre-eclampsia and maternal coronary artery disease (CAD) risk factors. METHODS AND RESULTS: Women aged 25-64 years, who participated in a cross-sectional population survey and had been pregnant (n=3650), were studied. The proportion of women who had ever had pre-eclampsia was lower in Southern (7.9%) compared with Northern Finland (13.9%) (P=0.001), but did not differ from Eastern Finland (11.1%). In the logistic regression model, the age-adjusted prevalence of pre-eclampsia was 1.92-fold in Northern (95% CI: 1.46-2.53, P<0.001) and 1.47-fold in Eastern Finland (95% CI: 1.11-1.96, P=0.008) compared with Southern Finland. The odds ratios (ORs) were 1.70 (95% CI: 1.21-2.38, P=0.002) and 1.16 (95% CI: 0.82-1.64, P=0.40), respectively, when adjusted for age at first birth, current age, parity, body mass index (BMI), increased blood cholesterol, hypertension, diabetes/impaired glucose tolerance, CAD, and mother's myocardial infarction. History of pre-eclampsia was associated with increased blood cholesterol, higher current BMI and blood pressure, and higher current prevalence of hypertension, diabetes/impaired glucose tolerance. CONCLUSIONS: Pre-eclampsia is most prevalent in the Northern part of Finland and could only be partly explained by higher prevalence of CAD risk factors.     

Lateral release and proximal realignment for patellofemoral malalignment: A prospective study of 40 knees in 36 adolescents followed for 1-8 years

We performed lateral release and proximal realignment for painful patellofemoral malalignment in 36 adolescents (40 knees), with a mean age of 14 (9-16) years. The mean follow-up was 4 (1-8) years. The subjective outcome was excellent in 20 knees, good in 13, fair in 5, and poor in 2. The mean radiographic correction of the lateral patellar shift was 75%, and of the tilting angle of the patella 27%. There was a positive association between the realignment effect and the subjective outcome.     

Immunological studies on patients with optic neuritis without evidence of multiple sclerosis

We studied 6 patients with idiopathic optic neuritis (ON) after a mean follow-up period of 12 years. No evidence of multiple sclerosis (MS) was found on clinical grounds, nor by magnetic resonance imaging (MRI) or evoked responses. Levels of spontaneous proliferation, serum gamma-interferon (IFN-gamma) and lymphocyte MHC locus II antigen were similar in ON and in 6 patients with progressive MS, but different in healthy controls. This suggests that similar immunological conditions in vivo prevail after an idiopathic ON and in MS. A normal PHA-induced interleukin-2 receptor expression and lymphocyte proliferation but a low IFN-gamma secretion and MHC locus II antigen expression were observed. This suggests that an ON and MS defect is expressed after an interleukin-2 receptor ligand but before IFN-gamma secretion. Our findings also suggest that immunological factors do not explain the neuropathological confinement of the lesions in ON but the protective influence may rather be exerted by some as yet undefined genetic influence or may be explained by the different etiology of ON and MS.     

N‐Syndecan and HB‐GAM (Heparin‐Binding Growth‐Associated Molecule) associate with early axonal tracts in the rat brain

Heparin-Binding Growth-Associated Molecule (HB-GAM)/pleiotrophin is an 18 kDa extracellular matrix- and cell-surface-associated protein shown to enhance neurite outgrowth of perinatal forebrain neurones in vitro. The heparan sulphate proteoglycan N-syndecan ( 1 ) has been isolated as a receptor/coreceptor for the HB-GAM. We have investigated, whether HB-GAM and N-syndecan could have a similar role in neurite outgrowth and axon guidance in early axonal tracts of brain. In the present study N-syndecan was found to be spatiotemporally associated with the developing axonal tracts already on embryonic day 9 in rat, as revealed by coexpression with class III β-tubulin, which is one of the earliest neuronal markers ( 2 ; 3 ). Later, N-syndecan and HB-GAM were detected in the first afferent serotonergic projections arising from the pontine raphe nuclei. The expression pattern of HB-GAM peaked in the developing rhombencephalon at embryonic stage (E) 13–14. At the same time, N-syndecan was expressed in the developing raphe neurones growing neurites towards the diencephalon along HB-GAM immunoreactive pathways. When rhombencephalic neurones were cultured on decreasing concentrations of substrate-bound HB-GAM, E13 neurones showed a significantly better neurite outgrowth response than E11, E16 or E18 neurones. The neurite outgrowth of raphe neurones in vitro was inhibited by adding soluble heparin or N-syndecan into the culture medium, whereas addition of chondroitin sulphate had no effect. In a simple pathway assay, E13 raphe neurones selectively preferred attaching and growing neurites on pathways containing HB-GAM as compared with regions containing either laminin or fibronectin alone. Our results suggest that HB-GAM may function as a developmentally regulated cue for rhombencephalic neurones that possess N-syndecan on their cell membrane.     

Enantiomers of neuroactive steroids support a specific interaction with the GABA-C receptor as the mechanism of steroid action

Neuroactive steroids can either potentiate or inhibit a variety of membrane channels. Most studies have suggested that the effects are mediated by specific association of the steroid with the affected channel. However, a recent study of the rho1 (GABA-C) receptor (Mol Pharmacol 66:56-69, 2004) concluded that the actions were consistent with an action of the steroid in the lipid bilayer to alter the lateral pressure profile in the membrane. The enantiomers of an optically active compound are expected to have identical physical properties, including interactions with hydrophobic portions of the cell membrane. We have used two pairs of enantiomers (pregnanolone and ent-pregnanolone, allopregnanolone and ent-allopregnanolone) and show that the ability to potentiate (allopregnanolone) or inhibit (pregnanolone) the rho1 receptor is enantioselective. Therefore, these results strongly suggest that the actions of these neuroactive steroids are mediated by interactions with chiral regions of the target protein, rather than by a change in membrane properties (including lateral pressure).     

Arteriomegaly

The features of a patient with arteriomegaly of thoracic and abdominal aorta, common and external iliac, and femoral arteries are described.