Clinical course of congenital toxoplasmosis in children]

Hundred eleven children with the congenital toxoplasmosis were treated at the Department of Infectious and Parasitic Diseases in Childhood in 1979-1988. Multi-symptomatic toxoplasmosis has been diagnosed in 35 cases, ocular form in 65, oligosymptomatic in 6, and asymptomatic in 5 cases. Clinical symptoms suggesting congenital toxoplasmosis was seen in the majority of children (63 cases) in the first year of life and the disease was diagnosed in 50% of cases (33 children) at this age. Congenital toxoplasmosis in the group of 78 children has been diagnosed later. The majority of cases was ocular form. Diagnosis of the oligo- and asymptomatic congenital toxoplasmosis is possible in the first year of life, only. A titre of antibodies is exclusively an indicator of the immunologic response, not a severity of infection and does not contribute to the prognosis. Antitoxoplasma drugs were administered to 102 children including 33 under the first year of life. Pyrimethamine, sulphonamides, and spiramycin were used in the treatment. Dosage, duration of therapy, and way of administration have been established individually in dependence of patients age and clinical form of the congenital toxoplasmosis. Two out of 35 children with multi-symptomatic congenital toxoplasmosis died whereas 13 demonstrate psychomotor retardation of significant degree despite the fact that 11 of them were treated in the first year of life.     

Mutations in PMCA2 and hereditary deafness: a molecular analysis of the pump defect

The inner ear converts sound waves into hearing signals through the mechanoelectrical transduction (MET) process. Deflection of the stereocilia bundle of hair cells causes the opening of channels that allow the entry of endolymph K⁺ and Ca²⁺. Ca²⁺ that enters is crucial to the hearing process and is exported to the endolymph by the plasma membrane Ca²⁺ pump (isoform PMCA2w/a): disturbances of the balance between Ca²⁺ penetration and ejection, e.g. by pump mutations, generate deafness. Hearing loss caused by PMCA defects is frequently exacerbated by mutations in cadherin 23, a single pass stereociliar Ca²⁺ binding protein that forms the tip links which permit the deflection of the stereocilia bundle and thus the opening of the MET channels. The PMCA2w/a pump ejects Ca²⁺ to the endolymph even in the absence of the natural activator calmodulin. This satisfies the special Ca²⁺ homeostasis requirements of the stereocilia/endolymph system. Here we have analyzed a mice and a human previously described pump mutant. The human mutant only exacerbated the deafness produced by a cadherin 23 mutation. The murine mutant overexpressed in model cells displayed an evident defect both in the basal activity of the pump and in the long range ejection of Ca²⁺, the human mutant instead failed to impair the Ca²⁺ ejection by the pump.     

Clinical course and treatment regimes of Salmonella infection in children

Salmonella infection in children caused by polyresistant S. typhimurium strains is characterized by a highly severe course with possible complications. In the treatment of young children with salmonellosis the use of the locally manufactured biologically active additive Bektit-M, possessing adsorption capacity, is recommended. The use of this preparation in complex treatment has made it possible to establish its clinical effect and positive influence on the biochemical characteristics of the blood.     

Growth and biochemical alterations in coffee due to selenite toxicity

Two experiments were conducted to investigate selenite toxicity in coffee (Coffea arabica cv. Catuaí). In the first aqueous selenite solution (10 µM Na₂SeO₃) was used to infiltrate leaves of an adult coffee plant. The infiltrated leaves and fruits adjacent to them showed enhanced contents of caffeine and soluble sugars. Amino acid contents were not affected, whereas pigments (chlorophylls, carotenoids and xanthophylls) exhibited a significant decrease. In the second experiment, coffee seedlings were irrigated with aqueous selenite solutions (10,100 and 1000 µM Na₂SeO₃) and the first and third pairs of leaves were analyzed. Control plants did not receive selenium. The plants were not different in height, but at the highest selenium concentration showed lower dry matter accumulation in roots and leaves, lower leaf area and thicker leaves. Increases in caffeine and soluble sugars were observed in the first pair of leaves at the highest selenium concentration, although selenium content itself increased steadily with increasing solution concentration. Phenols increased in both leaf pairs and pigments decreased in the third pair. Nitrate reductase activity, measured in the second leaf pair, was much lower at all selenium levels. The profile of free amino acid was altered in leaves of plants treated with selenium.     

Clinical and functional characterisation of the combined respiratory chain defect in two sisters due to autosomal recessive mutations in MTFMT

Exome sequencing identified compound heterozygous mutations in the recently discovered mitochondrial methionyl-tRNA formyltransferase (MTFMT) gene in two sisters with mild Leigh syndrome and combined respiratory chain deficiency. The mutations lead to undetectable levels of the MTFMT protein. Blue native polyacrylamide gel electrophoresis showed decreased complexes I and IV, and additional products stained with complex V antibodies, however the overall steady state level of mt-tRNA^Met was normal. Our data illustrate that exome sequencing is an excellent diagnostic tool, and its value in clinical medicine is enormous, however it can only be optimally exploited if combined with detailed phenotyping and functional studies.     

Clinical significance of serum bone Gla protein and urinary gamma-Gla as biochemical markers in primary hyperparathyroidism

The serum bone Gla-protein (BGP) and urinary gamma-carboxyglutamic acid (gamma-Gla) levels were determined in patients with primary hyperparathyroidism (PHP). The mean serum BGP and urinary gamma-Gla levels were 18.6 +/- 2.34 ng/ml and 65.5 +/- 4.62 nmoles/mgCr, respectively, for the 11 patients with the skeletal type of PHP, 5.13 +/- 0.85 ng/ml and 45.2 +/- 1.33 nmoles/mgCr for the 4 with the chemical type, and 7.91 +/- 2.43 ng/ml and 43.2 +/- 3.47 nmoles/mgCr for the 5 with the renal type. Thus, patients with skeletal-type PHP had significantly higher serum BGP and urinary gamma-Gla levels than those with the other type of PHP. Serum BGP levels had significant positive correlations with serum Ca (r = 0.64, P less than 0.005), serum A1-p (r = 0.77, P less than 0.001) and serum PTH (r = 0.45, P less than 0.005). Urinary gamma-Gla levels also had significant positive correlations with serum Ca (r = 0.50, P less than 0.05), serum A1-p (r = 0.67, P less than 0.005), serum 1,25(OH)2D (r = 0.62, P less than 0.02), and serum BGP (r = 0.72, P less than 0.001). Mineral content in the left radius had significant negative correlations with serum BGP levels (r = -0.73, P less than 0.001) and urinary gamma-Gla levels (r = -0.59, P less than 0.01). As these data show, serum BGP and urinary gamma-Gla levels clearly reflect the abnormal bone metabolism and can therefore be useful biochemical markers in PHP.     

Neuroinfections due to Enterococcus faecalis in children

Enterococcal meningitis is a rare complication of neurosurgical procedure or high technology treatment of children and occurs mainly imunocompromised neonates with very low birth weight, severe prematurity and complicates sometime ventriculoperitoneal shunt insertion or perinatal trauma. E. faecalis caused 10 nosocomial meningitis and all strains were susceptible to vancomycin and chloramphenicol, and in our database 90% also to gentamicin and ampicillin. Mortality in our group of 10 children was 20% what is insignificantly higher than overall mortality in the whole cohort of meningitis within last 15 years in our database (15.1%). Early empiric therapy should include also ampicillin or vancomycin, if enterococcal etiology is suspected.     

Elemental and biochemical markers of stigma receptivity in sunflower

Stigma development in sunflower is accompanied with an accumulation of calcium (33 %), potassium (37 %) and boron (62 %) in mature stigma as compared to stigma at bud stage, thereby demonstrating their essential roles in attaining receptivity. Membrane-bound calcium accumulation is enhanced on the pellicle and is also evident in the cytoplasm accompanying stigma maturation. Total soluble carbohydrate content increases in the staminate stage (55 %) as compared to bud stage. Glucose and fructose are the major monosaccharides and their contents are maximum in the staminate stage. Total lipid content also increases with the passage of stigma development. Erucic acid (22:1) is expressed specifically in the bud and staminate stages. A variation in the contents of triacylglycerides and free fatty acids, and expression of fatty acyl esterases in mature stigma have been correlated with biochemical events associated with signalling mechanisms. Lastly, enhanced expression of two hydrolytic enzymes, namely β-1,3 glucanase and fatty acyl ester hydrolase, has been observed to correlate with stigma maturation. Present findings, thus, provide new information on the structural and biochemical changes marking various signalling events associated with successful pollen–stigma interaction.     

Clinical, biochemical and molecular genetic data in five children with Gitelman's syndrome.

Gitelman's variant of Bartter's syndrome, inherited hypokalemic alkalosis, is caused by mutation in the thiazide-sensitive NaCl co-transporter (NCCT). The main clinical symptoms are: muscular weakness, carpopedal spasm, constipation and short stature. The diagnosis was suspected in five children according to clinical criteria. All patients exhibited carpopedal spasm during febrile illness, three patients had short stature. Biochemical features were: metabolic alkalosis, hypokalemia, hypomagnesemia, low IGF-I levels, hyperkaliuria, hypernatriuria, hypocalciuria and normoprostaglandinuria. Three patients had elevated plasma renin activity and hyperaldosteronism. Mutational analysis of the NCCT gene confirmed the diagnosis in all five patients. Different forms of therapy, potassium and magnesium substitution, spironolactone and indomethacin failed to fully correct hypokalemia and hypomagnesemia, but markedly improved growth velocity and normalized IGF-I levels in the three patients with short stature. During therapy, clinical symptoms disappeared. We conclude that Gitelman's syndrome is a disorder with a variable symptom profile, but can be suspected on clinical signs already in early childhood. The early diagnosis is essential in preventing complications.     

Vitamin K in combination with other biochemical markers to diagnose osteoporosis.

The significance of a multiparametric classification approach of vitamin K is analysed to differentiate premenopausal (CTRL), postmenopausal non-osteoporotic (nOSP) and osteoporotic (OSP) women. Data records of women between 28 and 74 years of age were used for evaluation. Bone mineral density was determined by quantitative computed tomography of the lumbar spine using the T-score to diagnose osteoporosis. Vitamin K and biochemical markers of bone formation and resorption--alkaline phosphatase (AP), bone alkaline phosphatase (bAP), osteocalcin (OC), undercarboxylated osteocalcin (ucOC), procollagen type I carboxyterminal propeptide (PICP), pyridinoline (PYD), deoxypyridinoline (DPD), N-terminal cross-linked telopeptide of type I collagen (NTx) and bone sialo protein (BSP)--were analysed in all women on days 1 and 42. Vitamin K was significantly lower in the OSP group versus nOSP and CTRL. The odds ratio results revealed the following: vitamin K, 16.7; PYD, 7.5; NTx, 6.0; DPD, 2.7; and ucOC, 2.7. Vitamin K represented a sensitivity rate of 64% and a specificity rate of 82%. In the receiver operating curve analysis, vitamin K reached the highest area under curve (AUC) score. The combination of vitamin K and AP, bAP and PYD resulted in increased AUC scores (>0.9). The parameter combination of vitamin K/PYD and vitamin K/bAP demonstrated a sensitivity rate of 75-88%, with a specificity rate of more than 82%. The data suggests that a combination of vitamin K with other biochemical bone indices might be a useful tool for assessing bone metabolism, especially in metabolic bone diseases such as osteoporosis.     

Application of biochemical intake markers to passive smoking measurement and risk estimation

Measurement of the dose received from passive smoking complements epidemiological approaches and may provide an alternative method of estimating risk. Non-smokers absorb measurable amounts of nicotine from breathing other people's smoke, and dose-response relationships are apparent. On the basis of the limited data so far available, the dose of nicotine received by the average British non-smoker may represent about 0.5% of that of the heavy cigarette smoker, ranging up to 2% in more heavily exposed individuals. The dose of carbon monoxide appears relatively greater, as does that of tobacco-specific nitrosamines. The situation with respect to tar is unclear, but nicotine may provide a better guide than does CO.