The role of infection and vaccination in the genesis of optic neuritis and multiple sclerosis in children

This article describes the association between previous infection and/or vaccination and the development of optic neuritis (ON) in 18 children. Ten of these children subsequently developed clinically definite multiple sclerosis (MS), while in 8 patients a clinically definite etiology could not be confirmed. Vaccination preceded the first ON attack in 6 patients, all but one of whom subsequently developed MS. It also preceded subsequent demyelinating events in 6 patients. Ten of the patients had a bacterial or viral infection within the 2 weeks prior to the first symptoms of ON. Intrathecal antibody synthesis against 2 or more viruses could be shown in 5 out of 8 patients studied; 5 out of 6 patients had oligoclonal antibodies in CSF and 12 out of 16 patients a high IgG index. Neither intrathecal antibody synthesis against 2 or more viruses nor elevated IgG indexes could be found in the control patients. Measles and mumps occurred at a significantly later age in the children who subsequently developed MS than in the control children, and these patients had significantly more events that might have impaired the blood-brain barrier than the controls. These results indicate that immunological events leading to MS may be triggered during childhood. Vaccination and infection often precede ON in childhood. Intrathecal viral antibody production can occur already in childhood at the time of the first symptoms of MS.     

Lymphocyte subclasses and function in patients with optic neuritis in childhood with special reference to multiple sclerosis

Ten patients with childhood optic neuritis (5 with a single attack of ON and 5 with later MS) were studied at various stages of the disease. Lymphocyte count and function were analysed in the peripheral blood of all patients, 3 repeatedly, and in one they were also analysed in the CSF. T-lymphocytes counts were normal in all but 2 MS cases who had high counts. In acute stages the T4/T8 ratio were high in 1/3 determinations, in recovery low in 2/2 determinations, and in stable stages normal in 6/8 determinations. Lymphocyte function, measured by PHA, ConA and PWM stimulation, was normal in all but one. One patient showed significantly higher T-cell percentages and a high number of stimulated lymphocytes in CSF but a lower count of suppressor cells than in the blood. We found no abnormalities specific to MS nor to childhood MS or to disease activity stage. Rather than peripheral blood, it would seem more worthwhile to study CSF to clarify the pathogenesis of ON and MS.     

Serum steroids and success of corticotropin therapy in infantile spasms

Serum levels of 8 steroids and urinary cortisol excretion were determined in 10 infants before and during corticotropin therapy for infantile spasms. High serum dehydroepiandrosterone-androstenedione concentration ratio distinguished the 6 infants with good therapeutic response from the 4 with poor response (p = 0.001). No such distinction was obtained directly by any of the serum steroid levels, 24-hour urinary cortisol, or serum pregnenolone-progesterone concentration ratio. This suggests that the therapeutic effect of corticotropin may be mediated by steroid factors other than cortisol. Inhibition of the 3 beta-hydroxysteroid dehydrogenase system in zona reticularis might be beneficial during the corticotropin therapy.     

IgE-mediated allergy to fungal allergens in Finland with special reference to Alternaria alternata and Cladosporium herbarum.

BACKGROUND: Alternaria alternata and Cladosporium herbarum are common fungi in outdoor environments, but their clinical significance has not been elucidated in Finland. OBJECTIVE: To evaluate the prevalence of IgE-mediated allergy and clinical outcomes caused by sensitization to fungal allergens in patients with suspected allergy. METHODS: Skin prick tests (SPTs) were performed with C. herbarum in 6,376 patients and also with A. alternata in 1,504 of these patients. SPTs were repeated in 40 patients who showed a positive reaction to either allergen using commercial and in-house extracts. The association of SPT with allergen-specific IgE antibodies in serum was evaluated. Seven patients also underwent a conjunctival challenge test with these fungal allergens. RESULTS: The prevalence of positive SPT results to A. alternata and C. herbarum was low (2.8% and 2.7%, respectively). Among the 40 patients, atopic eczema/dermatitis syndrome was found in 58%, asthma in 44%, and rhinitis in 31%. Most of the patients displayed SPT reactions also to several other fungal allergens, and 75% to 80% showed a positive SPT reaction to allergens of pet animals or pollens. Four patients had a positive reaction to A. alternata and 6 to C. herbarum in the conjunctival challenge test. CONCLUSION: In the Finnish population with allergic symptoms, IgE-mediated sensitization to 2 common fungal allergens was rare and of minor clinical importance. SPT reactions to fungi are mostly observed in patients with multiple sensitivity to various allergens.     

Factors related to postmenopausal muscle performance: a cross-sectional population-based study

The aim of the present study was to investigate cross-sectionally the association of postmenopausal muscle strength with simple performance tests. A random sample of 1,166 naturally postmenopausal women (born 1932–1941) was selected from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study cohort. Grip and quadriceps strength were measured with strain gauge dynamometers and reported in both absolute values (KPa and kg) and per kilogram of body mass (N cm^–2 kg^–1 and N kg^–1). In addition, two performance tests, ability to stand on one foot and ability to squat down to touch the floor were carried out. A five-category self-assessment of overall health (very good, good, moderate, bad, and very bad) was obtained by postal questionnaire. The women that were able to stand on one foot and able to squat down to touch the floor had greater grip and quadriceps strength than their counterparts (P<0.001 and P<0.03 in ANOVA, respectively). In addition, self-assessed health had a strong positive association with muscle strength in the grip and leg extensor muscles in ANOVA (P<0.001 between very good and moderate or poorer state of health) and regression model (P<0.001). Adjustment for age, duration of menopause, body mass, height, physical activity level, use of HRT, and number of diseases and medications did not change any of the main effects. Also, there were no differences in results between absolute measurement values and values reported per kilogram of body mass. According to the present study, a simple performance test may be useful in the prediction of postmenopausal muscle strength. Furthermore, self-assessed state of health is strongly associated with muscle strength in postmenopausal women.     

Parent Support Programmes for Families Who are Immigrants: A Scoping Review

Journal of Immigrant and Minority Health - Parental support is of paramount importance in the promotion of positive parenting, strengthening parenthood and protecting children from disadvantages...     

Low insulin-like growth factor (IGF-1) in the cerebrospinal fluid of children with progressive encephalopathy, hypsarrhythmia, and optic atrophy (PEHO) syndrome and cerebellar degeneration

PURPOSE: In patients with progressive encephalopathy, hypsarrhythmia, and optic atrophy (PEHO) syndrome, the pathophysiology underlying early progressive cerebellar and brainstem degeneration and severe epilepsy is unknown. Because insulin-like growth factor (IGF)-1 has been shown significantly to promote survival of cerebellar neurons, we wanted to see if the IGF system played a role in the pathogenesis of cerebellar atrophy. METHODS: We used a sensitive enzyme immunoassay kit for measuring cerebrospinal fluid (CSF) IGF-1 and insulin-like growth-binding protein (IGFBP)-3 in four groups of patients: PEHO syndrome patients (eight), PEHO-like patients (seven), age-matched controls (31), and patients with other types of cerebellar atrophy (11). RESULTS: Patients with PEHO syndrome and those with other progressive, degenerative cerebellar diseases had lower levels of CSF IGF-1 than the controls with other neurologic diseases. The CSF IGF-1 also allowed us to differentiate the "true" PEHO patients from the "PEHO-like" patients (those with similar clinical symptoms but without the typical neuroophthalmologic or neuroradiologic findings). The concentrations of IGFBP-3 did not significantly differ in any of the patient or control groups studied. CONCLUSIONS: CSF IGF-1 levels might be used as a marker of the degeneration of neurons in specific areas.     

Different behaviour of radioiodinated human recombinant interleukin-1 and its receptor antagonist in an animal model of infection

Recently, we demonstrated that radiolabelled interleukin-l (IL-1) specifically accumulates in focal infection in mice through interaction with its receptor. Unfortunately, systemic side-effects of IL-1 limit its clinical application. We investigated whether this problem could be circumvented by using the interleukin-1 receptor antagonist (IL-Ira), an equally sized protein that binds to the same receptors as IL-1 without induction of biological effects. Biodistribution of¹²⁵I-IL-1 and¹²⁵I-IL-Ira was determined in Swiss mice withStaphylococcus aureus-induced abscesses in the left calf muscle at 4, 12, 24 and 48 h after injection of either 0.4 MBq¹²⁵I-IL1 or 0.4 MBq¹²⁵I-IL-Ira. In vitro, the proteins displayed similar binding characteristics. High-performance liquid chromatographic analysis revealed a tendency for IL-Ira to associate with serum proteins. Both proteins rapidly cleared from most organs. However, the abscess uptake of¹²⁵I-IL-Ira was significantly lower than that of¹²⁵I-IL-1 at all time points (48 h p.i.: 0.06±0.01%ID/g vs 0.60±0.04%ID/g;P<0.02). The abscess-to-contralateral muscle ratios did not exceed 15.5±2.9 for¹²⁵I-IL-lra, while the ratios for¹²⁵I-IL-1 reached 46.9±5.7 at 48 h p.i. Despite similar in vitro receptor binding, the abscess uptake of IL-Ira was much lower than that of IL-1. The interaction of IL-Ira with serum proteins in vivo may reduce its availability for receptor binding in the infection. Although on theoretical grounds IL-Ira is very interesting, these characteristics will prevent its development as a clinically useful radiopharmaceutical to image infection.