Phenotypic spectrum of Salla disease, a free sialic acid storage disorder

Salla disease (MIM 269920) represents the mildest phenotype among recessively inherited lysosomal-free sialic acid storage disorders. Although the vast majority of Salla disease patients in Finland share the same founder mutation, R39C in the SLC17A5 gene, there still is a wide clinical variation among mentally retarded, ataxic patients. We evaluated neurologic and neurocognitive findings of Salla disease in a cross-sectional study of 41 Finnish patients who were 11 months to 63 years of age (median = 19.5 years). The phenotype of Salla disease could be classified into two main categories. The majority of patients (90%) had so-called conventional phenotype, including a subgroup of seven patients with relatively mild symptoms. All but two patients with conventional phenotype were homozygous for the Finnish founder mutation. Four severely disabled, profoundly mentally retarded patients, 15-28 years of age, clearly could be clinically delineated as a separate group, likely reflecting the underlying compound heterozygous genotype. A typical developmental pattern could be outlined in the conventional type of the disease, emphasizing a strong motor handicap in Salla disease. The cognitive profile consisted of better verbal ability, especially speech comprehension, compared with nonverbal functioning in all patients. Our results indicate a partial genotype-phenotype correlation, although factors other than the molecular background are also involved in the phenotypic manifestation of Salla disease.     

Neurotransmitter control of thyrotropin secretion in the rat

In rats adapted to a +30°C temperature for one week, transfer to a temperature of +4°C increased immunoassayable serum TSH from 150–300 ng/ml 800–2000 ng/ml in 30 min. Since this response, as well as the level of serum TSH without stimulation, were decreased by reserpine, phentolamine, phenoxybenzamine, disulfiram and diethyldithiocarbamate, noradrenaline may be involved in the stimulation of TSH secretion. TRH-induced TSH increase was not blocked by reserpine.

1-Dopa, a noradrenaline precursor, decreased the TSH response to cold; -methyl-p-tyrosine increased the TSH level. Apomorphine decreased the level of serum TSH and inhibited the response to cold. The possibility of a dopaminergic inhibitory factor released from the hypothalamus is discussed. 5-HT has possibly a role in the acetylcholine is involved.     

MR findings in humeral epicondylitis. A systematic review

Purpose: To highlight the importance of meta-analysis in diagnostic imaging by presenting a systematic search of the literature on the accuracy of MR imaging in epicondylitis.Material and Methods: The literature was comprehensively reviewed to identify studies on MR findings in epicondylitis. Reviewers blind to the clinical diagnoses screened the data according to predetermined inclusion criteria. Data were collected and validity and relevance were assessed on structured forms.Results: Seven studies including 148 patients with epicondylitis were accepted for the analysis. Eleven asymptomatic contralateral elbows and 29 elbows of healthy volunteers served as controls. The volunteers were distinctly younger than the patients. The MR technique was divergent, and the observed pathological changes also varied. The most frequent alteration was a change in the common extensor tendon signal (90%, 95% confidence interval 84-94%); 14% of the healthy volunteers and 50% of the contralateral elbows displayed the similar alteration.Conclusion: Small sample size and methodological shortcomings in the original studies make the assessment of MR findings in epicondylitis questionable. There is a need for well-designed studies in which clinical features and occupational backgrounds as well as imaging parameters are carefully documented.     

Effects of the wood extractives dehydroabietic acid and betulinol on reproductive physiology of zebrafish (Danio rerio)-a two-generation study

Two wood extractives, dehydroabietic acid (DHAA) and betulinol (BET), present in wood industry effluents were evaluated for their potential effects on the reproductive physiology of zebrafish. Adult zebrafish (F0) were exposed in a continuous flow-through system to 50 microg/l DHAA, 5 microg/l BET and 0.27 microg/l (1 nM) 17beta-estradiol (E2) for 3 months. Eggs were collected from F0 fish and the following F1 generation was exposed for 6 months. Biomarkers analyzed in both F0 and F1 fish were plasma vitellogenin (Vtg), testosterone (T), E2 (only females) and gonadal histology. DHAA and BET affected growth in terms of increased condition factor, and spawning was stimulated in BET-exposed fish of the F0 generation. F0 males exposed to DHAA and F0 females exposed to BET showed lower plasma Vtg concentration, but F1 males exposed to BET showed an increase in Vtg. In fish exposed to E2, the positive control for estrogenic effects, a pronounced increase in Vtg concentration was observed. Plasma sex steroids were not significantly affected by the wood extractives. However, although not statistically significant, the T concentration tended to be lower in fish of all BET treatments. The histological study revealed alterations in spermatogenic stages of F0 males exposed to DHAA and BET, which were different from those caused by E2. In F1 females, the percentage of vitellogenic oocytes was decreased in DHAA, BET and E2 exposures. This study shows that DHAA and BET may contribute to growth alterations and reproductive disturbances reported in fish exposed to pulp and paper mill effluents. Further, these wood extractives may have different effects in F0 and F1 generation fish, which highlights the value of two-generation studies in investigations regarding endocrine disrupting compounds.     

Impairment of lung function in asbestos-exposed workers in relation to high-resolution computed tomography

OBJECTIVES: The aim of the study was to determine the causes of impairment of ventilatory function and diffusing capacity in smoking asbestos-exposed workers (N=590) showing radiological pleural thickenings or pulmonary fibrosis. METHODS: High-resolution computed tomography (HRCT) and spirometry were performed, and diffusing capacity was measured. The workers were divided into five groups based on the HRCT scoring: pleural disease (N=190), pulmonary fibrosis (N=68), emphysema (N=148), combined fibrosis and emphysema (N=74), and marked adhesions (N=110). The graded lung function impairment was compared between the groups. RESULTS: Moderate impairment of forced expiratory volume in 1 second [odds ratio (OR) 2.72, 95% confidence interval (95% CI) 1.31-5.57] and forced vital capacity (OR 2.81, 95% CI 1.05-6.89) was associated with the persons with combined fibrosis and emphysema. Marked impairment of diffusing capacity was associated with the combined fibrosis and emphysema (OR 4.94, 95% CI 2.48-9.77) but not with pleural disease (OR 0.21, 95% CI 0.09-0.45) or pulmonary fibrosis (OR 0.36, 95% CI 0.08-1.05). For the persons with combined fibrosis and emphysema, the mean fibrosis score did not differ between normal, slightly reduced, or markedly reduced diffusing capacity, but the emphysema score was significantly higher for the patients with marked impairment than for those with normal diffusing capacity (P < 0.01). CONCLUSIONS: Different profiles of asbestos- and smoking-induced pulmonary or pleural disease were found. The results indicate that the most important factor determining the degree of functional impairment in smoking asbestos-exposed workers is the presence of pulmonary emphysema.