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In the search for its role in inflammatory joint diseases, soluble HLA-DR (sHLA-DR) was quantitated in 72 synovial fluids (SF) by a newly established immunoenzyme assay. Unlike other soluble receptors which accumulated only moderately (sCD25, sCD4) or negligibly (sHLA class I, sCD8) in the SF, SF sHLA-DR levels exceeded serum levels by up to 3 orders of magnitude and varied disease dependently from "control" values (traumatic synovitis and osteoarthritis: 9.9 +/- 6.1 ng/ml). Clear-cut different SF sHLA-DR values in HLA-DR-associated "rheumatoid-like" (136.5 +/- 130.0 ng/ml) vs HLA-B27-associated "spondylarthropathy-like" arthritic forms (28.4 +/- 29.1 ng/ml) were most significant comparing oligoarticular juvenile chronic arthritis type I (147.6 +/- 112.6 ng/ml) and type II (3.3 +/- 1.1 ng/ml), thus offering a new classification marker. Also ex vivo, large amounts of sHLA-DR were released spontaneously by SF mononuclear cells and found to be related to the T-cell activation state. SF sHLA-DR may be shed in large complexes or micelles, as it eluted mainly at >450 kDa on gel filtration. Western blotting revealed that the majority of SF sHLA-DR consisted of full-length alpha- and beta-chains. Minor fractions of smaller sized antigens seemed to be generated by proteolytic cleavage rather than by alternative splicing, since only minute amounts of HLA-DRB mRNA lacking the transmembrane exon could be amplified by RT-PCR. Distinct forms of high-dose sHLA-DR, able to provoke rather than to suppress T-cell responses, are discussed as contributing to some HLA-DR disease association., (Copyright 2000 Academic Press.)

Lyme borreliosis is the most frequent tickborne++ disease of man in the Northern hemisphere. A variety of systems may be involved. The most frequent manifestations in childhood include erythema migrans, meningitis, cranial nerve palsy and arthritis. Erythema migrans usually is easily recognised and determination of antibodies to Borrelia burgdorferi should not be performed. Childhood neuroborreliosis is characterised mostly by aseptic meningitis with or without cranial nerve palsy, in most cases facial palsy. Basic CSF findings often show a combined evidence of lymphocytic pleocytosis, IgM-class dominance in intrathecal humoral immune++ response, and blood-CSF barrier dysfunction. Calculation of the Borrelia burgdorferi specific antibody index (according to Reiber) proved to be the most sensitive method for detecting intrathecal synthesis of specific antibodies. Lyme arthritis presents initially as episodic oligoarthritis, mostly involving the knee joint, and may turn into chronic monoarthritis of the knee; usually high titers of IgG antibodies to Borrelia burgdorferi are found. The rarer manifestations encephalomyelitis, chronic arthritis, carditis and inflammatory eye disease may be difficult to diagnosis due to clinical ambiguity and problems in the interpretation of serological results. Antibodies to Borrelia burgdorferi found by sensitive Elisa must always be confirmed by immunoblot analysis, but sometimes immunoblot analysis is more sensitive than Elisa. Treatment is by antibiotics, amoxicillin or doxyciclin for erythema migrans, and i.v. third generation cephalosporins for all other manifestations. Even after successful antibiotic therapy, antibodies may persist for months and years and no further antibiotic treatment is necessary in the absence of attributable clinical manifestations. The differentiation between a persisting immune response and a persisting infection therefore has to be based upon the clinical symptoms, non-specific laboratory data and the development of the antibody titers.

Objective: The lactulose H2-breath test is the most widely used non-invasive approach for evaluation of orocoecal transit time (OCTT). In the present study, doubly-labelled lactose-[13C, 15N]ureide (DLLU) was synthesized to investigate the OCTT in comparison to the conventional lactulose H2-breath test. Additionally the bacterial breakdown rate (BBR) and rate of elimination and the metabolic pathways of the cleavage products of DLLU (13CO2, [15N]urea, and 15NH3) were investigated., Design and Subjects: In a first study, DLLU was administered as a single oral-pulse-labelling (dosage: one gram) either without and after pretreatment of five grams of unlabelled lactoseureide (LU) on the day prior to the study to twelve healthy adult volunteers after breakfast. Breath and urine were collected in one and two hour-intervals, respectively, over a one-day period. 13C-enrichment in breath as well as 15N-enrichment in urine fractions were measured by continuous flow-isotope ratio mass spectrometry (CF-IRMS). In a second study, lactulose was administered to the same subjects (dosage: ten grams). Breath was collected in quarter, half and one hour-intervals over a ten hour-period. Hydrogen concentration in breath was analysed using an electrochemical detector., Results: The comparison of the lactose-[13C]ureide 13CO2-breath test and the lactulose H2-breath test showed that the mean increase of the 13C-enrichment in CO2 occurred 1.18 h later than the mean increase of H2 in breath. The resulting OCTTs derived from the two methods were 3.02 +/- 1.4 and 1.84 +/- 0.5 h (P < 0.05) and the corresponding BRs were 9.63 +/- 3.4 and 6.07 +/- 1.7 h (P < 0.01), respectively. The 15N-enrichment of urinary urea and ammonia without and after pretreatment with LU started between two and three hours after DLLU-administration. The cumulative percentage urinary excretion of the 15N- and 13C-tracer was 29.9% and 13.6% respectively, and was slightly increased after LU-pretreatment to 32.1% and 14.6% of the dose administered. A total of 35.2% of the 13C was found to be exhaled and remained approximately constant after LU-pretreatment (36.2%)., Conclusions: The use of the lactulose H2-breath test for evaluation of the OCTT showed a statistically significant shortening of 1.18 h in comparison to the lactose-[13C]ureide 13CO2-breath test in healthy adults. The most important limitations of the lactulose H2-breath test are its low specificity and sensitivity due to dose-dependent accelerations of OCTT, interfering H2-rise from malabsorbed dietary fibre and H2-non-producers. In contrast, our lactose-[13C]ureide 13CO2-breath test was confirmed to avoid these disadvantages and to yield reliable results. This test is recommended especially if higher sensitivity and specificity is required, if IRMS-technique is available and if lactulose H2-tests lead to insufficient results.

Therapy with benzoic acid in a case of classic neonatal non-ketotic hyperglycinaemia (NKH) was successful in stopping seizures but not in promoting mental development. Serum glycine levels were normalizable even by administering low doses of 53 mg sodium benzoate/kg body mass (BM) per day. Despite giving a higher dosage (240 mg/kg BM per day) normalization of glycine concentration in cerebrospinal fluid (CSF) was not achieved. However, seizures ceased. Restriction of protein intake (< or = 2 g/kg BM per day) seemed to be profitable. CSF glycine concentrations below 100 mumol/L may be sufficient to prevent seizures in older infants who have adapted to neuronal glycine exposure. No toxicity of sodium benzoate treatment was detected when administering doses of up to 470 mg/kg BM per day but side effects such as itching and hyperactivity were obvious.

Representatives of the working group of "Neuropaediatrics" and "Infectology" like to present recommendations on diagnostics and treatment of infectious diseases on the CNS. Individual opinions can not be considered in recommendations always. Therefore we have to understand these recommendations in this way that individual decisions will not be restricted in special situations.

Of 44 subjects identified by the screening procedure, 31 were enrolled in the study. Using the modified Vienna Rett score, we divided the patients into three groups: typical the Rett syndrome (RS) (n = 10), incomplete forms of RS (n = 5) and non-RS (n = 16). Genetic investigations were performed in some cases and abnormalities were found in two. EEG and cranial computerized tomography findings are discussed.

The testing of Convulsofin carried out in 220 patients at 14 clinics over a period of six months confirms the international experience gained with valproic acid and sodium valproinate. The main field of application of Convulsofin according to the experience gained will again be the treatment of fits in generalised primary epilepsy for which it permits to carry out a monotherapy to a remarkable extent. The favourable effect of the preparation in photosensitivity could be confirmed. Also in generalised secondary epilepsy and in fits of partial epilepsy. Convulsofin is partly effective, so that it can recommended as a co-medication in the treatment of therapy-resistant forms of these epilepsies which are difficult to treat. Decrease in thrombocytes, transient increase in serum transaminases, gastrointestinal disorders, loss of hair and undesired increases in body-weight were the more frequently occurring side-effects.

Clonazepam (Antelepsin) was tested on 179 patients in 8 institutions during a period of 180 days. 169 patients had been unsuccessfully treated with the usual standard medication and were additionally given Antelepsin. Typical absences and attacks of the West and Lennox syndromes yielded best to treatment with the drug, with favorable effects also being produced in cases of partial or focal epilepsy. The most important side-effect was tiredness, other collateral effects being balance disorders, sensations of dizziness, and musuclar weakness. The frequency of side-effects decreased in the course of therapy. In the electroencephalogram there was observed a significant increase in beta waves and a significant decrease in 3 Hz spike and wave complexes.

Follow-up examination of 95 former patients who had been suffering from encephalitis in infancy were performed. The coincidence of disturbance of consciousness, pathological-EEG and neurological irritation- and deficiency symptoms proved to be an unfavourable prognosis. These patients are especially handicapped in their concentration and motorial performances. Only 50% of the group with a severe course of the disease achieved a complete vocational training.

The cell and protein content of the cerebrospinal fluid (CSF) and the CSF/serum ratio of glucose, sodium, potassium, calcium, phosphate and chloride were investigated in 71 children without cerebromeningeal illness and aged 0-4 weeks, 5-8 weeks, 3-6 months, 7-12 months, 1-6 years and 7-14 years. The protein content of the CSF was 730 +/- 146 (530-950) mg/l for the age group 0-4 weeks, and 530 +/- 221 (270-950) mg/l for the age group 5-8 weeks. It was significantly higher than for all subsequent age groups. The CSF glucose accounted for 68-82% of the blood glucose. The serum/CSF ratio for sodium ranged from 101 to 104%, for potassium from 55 to 64%, for calcium from 48 to 70%, for phosphate from 24-29%, and for chloride from 106 to 114%. The decrease in serum and CSF potassium and phosphate concentrations from infancy to school age was significant. The greatest difference was evident in the serum/CSF calcium ratio which was significantly higher in the age groups up to 8 weeks than in the subsequent age groups. The electrolyte concentration of CSF with elevated protein and cell values did not differ significantly from CSF of children without cerebromeningeal disorders.