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  • 1995-1999  (362)
  • 1999  (362)
  • apoptosis  (112)
  • Life and Medical Sciences  (96)
  • Children  (81)
  • Amino acids  (73)
  • Nuclear reactions
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Years
  • 1995-1999  (362)
Year
Keywords
  • 1
    ISSN: 1436-2813
    Keywords: thyroid tumor ; apoptosis ; TUNEL ; MIB-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To clarify the growth mechanisms of thyroid tumors, we examined apoptotic cells in 61 thyroid tumors, consiting of 14 adenomas, 35 papillary carcinomas, 4 follicular carcinomas, and 8 undifferentiated carcinomas, using terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate digoxigenin-nick end labeling (TUNEL). The proliferative activity was also evaluated immunohistochemically using the monoclonal antibody to Ki-67 antigen (MIB-1) in the same tumors. The apoptotic index (AI) was expressed as a percentage of the TUNEL-positive cells in the tumor cells, and a proliferation index (PI), being the percentage of Ki-67 positive cells, was calculated for each tumor. The overall level of AI was very low in all histotypes of the thyroid tumors analyzed, the mean AI being 0.5±0.4 in adenoma, 0.4±0.3 in differentiated carcinoma, and 1.8±1.5 in undifferentiated carcinoma. The PI in the thyroid tumor subtypes was significantly lower in adenoma and differentiated carcinoma, at 0.5 ±0.7 and 1.1±0.7, respectively, than that in undifferentiated carcinoma at 14.5±3.7 (P〈0.05). There was no correlation between clinicopathological factors and AI or PI in differentiated thyroid carcinoma. Our findings suggest that apoptosis occurs infrequently in thyroid tumors, and that proliferative activity markedly differs according to the thyroid tumor subtypes. Moreover, the ratio between proliferating cells and apoptotic cells may reflect thyroid tumor progression.
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  • 2
    ISSN: 1436-2813
    Keywords: Key Words: thyroid tumor ; apoptosis ; TUNEL ; MIB-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: P 〈 0.05). There was no correlation between clinicopathological factors and AI or PI in differentiated thyroid carcinoma. Our findings suggest that apoptosis occurs infrequently in thyroid tumors, and that proliferative activity markedly differs according to the thyroid tumor subtypes. Moreover, the ratio between proliferating cells and apoptotic cells may reflect thyroid tumor progression.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1434-5196
    Keywords: Key words Methadone ; Dihydrocodeine ; Substitution ; Poisoning ; Children ; Schlüsselwörter Methadon ; Dihydrocodein ; Substitution ; Intoxikationen ; Kinder
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: Zusammenfassung Es wird über 3 überlebte und 4 tödlich verlaufene akzidentelle Intoxikationen, sechs mit Methadon, eine mit Dihydrocodein, berichtet. Die Intoxikationen betrafen nicht die Substituierten selbst, sondern deren Familienangehörige, Bekannte oder Mit-Patienten. In allen Fällen wurden die Substitutionsmittel weitgehend ungesichert und teilweise vermutlich auch unbeschriftet stehengelassen. Den Substituierten selbst war dabei die Gefahr, die von ihrem Substitutionsmittel ausging, offenbar nicht ausreichend bewußt. Diese Fälle zeigen deutlich, daß qualitätssichernde Maßnahmen bei der immer großzügigeren Substitutionspraxis, insbesondere in Hinblick auf „take-home“-Dosen, notwendig sind.
    Notes: Abstract A total of seven cases of accidental ingestion of methadone or dihydrocodeine by four children and three adults are reported of which four were fatal. In each case, someone in the environment was taking methadone or dihydrocodeine as a substitute drug for heroin addiction who obviously did not realize the dangers of methadone for non-addicts. Possible preventive measures are the usage of child-proof containers with adequate labels for take-home medications. Furthermore substituted addicts have to be thoroughly indoctrinated concerning the toxicity and hazards of methadone.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 106 (1999), S. 1-21 
    ISSN: 1435-1463
    Keywords: Keywords: Paraquat ; Parkinson's disease ; transcription factor ; AP-1 ; apoptosis ; cycloheximide ; genistein ; SOD ; catalase ; oxidative stress.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Drugs and certain environmental toxins may be responsible for the pathogenesis of Parkinson's disease. We have used paraquat as a model toxin for this study since paraquat has been shown to make its way to the nerve terminals and cause cell death of dopamine neurons by oxidative injury. We have shown by the electrophoretic mobility shift assay that paraquat, together with low concentrations of chelated iron (Fe++/DETAPAC), induced the activation of transcription factor AP-1 binding activity to DNA. Under similar conditions we also found by both a DNA laddering assay procedure and by terminal deoxynucleotidyl transferase assay (TUNEL assay) that paraquat also induces apoptotic cell death. Interestingly, both apoptotic cell death and AP-1/DNA binding activity induced by paraquat were blocked by cyclohexamide and genistein, indicating that both the AP-1/DNA binding activation and apoptosis induced by paraquat are closely related. Moreover, cells were also protected from paraquat toxicity in the presence of antioxidant defense enzymes SOD and catalase. The results support the hypothesis that oxidative stress may be contributing to the apoptotic cell death of dopaminergic neurons, leading to the manifestation of Parkinson's disease. Since paraquat was an important herbicide in the mid 20th Century, our results have the important implication that exposure to environmental toxins such as paraquat may induce Parkinson's disease.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1248-9204
    Keywords: Contralateral hernia ; Children ; Incidence ; Predisposing disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is impossible to determine whether or not a child will develop a contralateral hernia after inguinal hernia repair. There exists no risk score for the occurrence of a contralateral hernia. This well-known fact prompted us to perform the underlying study. In a retrospective trial, we reviewed the files of all children operated on for inguinal hernias in our department from January 1986 until December 1994. During this period, we performed 1721 hernia repairs on 1708 children aged 0–16 years. In 96 (5.6%) of these patients, the indication to operate was a contralateral hernia following previous unilateral repair. Comparison of the ages at the time of primary inguinal repair of those children who developed a contralateral hernia (n=96) and those who did not (n=1612) showed a significantly increased incidence of contralateral hernias if the primary operation was performed before the age of two months (p〈0.0001). Diseases predisposing to hernias were found in 38% of all children (prematurity, dystrophia, ventriculo-peritoneal shunt, ascites, asthma). The authors recommend a contralateral exploration for children under the age of two months if they have any predisposing disease.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Italian journal of neurological sciences 20 (1999), S. 119-128 
    ISSN: 1126-5442
    Keywords: Key words Learning ; Development ; Memory ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immediate and 15-min delayed recall of semantically related or unrelated word lists was investigated in 144 normally developing children ranging from 5 to 10 years of age. Immediate recall for the related and unrelated lists increased in a parallel fashion as a function of age. The ability to cluster semantically related items during immediate recall also improved with age. However, in no age class recall scores and clustering indexes were significantly associated. Forgetting rate passing from the last immediate to the delayed recall trial increased for the unrelated list but decreased for the related list of words as a function of age. Results of regression analyses revealed that a developmental increase in forgetting on the unrelated list was actually due to the higher number of words recalled in the last immediate trial by older children. As for the related list, instead, the larger reliance on the clustering strategy of recall by older children was responsible for the progressive reduction of forgetting.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Italian journal of neurological sciences 20 (1999), S. 303-307 
    ISSN: 1126-5442
    Keywords: Key words Lyme disease ; Chronic neuroborreliosis ; Children ; MRI ; Demyelinating disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Lyme disease is a polymorphic and multisystemic disease caused by Borrelia burgdorferi. Neurological manifestations are found in 10%–50% of cases. We present 2 cases followed for 5 and 6 years of chronic relapsing-remitting neuroborreliosis. Diagnosis of neuroborreliosis in these cases was based on serum and cerebrospinal fluid findings. We discuss clinical, neurophysiological, laboratory and instrumental aspects regarding the difficulties of reaching a correct diagnosis. Further studies, especially in the field of immunology, should help identify the mechanisms responsible for the disease becoming chronic. With this knowledge, it may be possible to design immunological therapies for relapses, and to prevent the evolution of the disease.
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  • 8
    ISSN: 1438-2199
    Keywords: Amino acids ; RT/PCR ; Protooncogene ; ets-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Protooncogenes (PO) play a crucial role for brain biology and pathology. Only the concerted action of protooncogenes enables normal brain development. The reliable and sensitive quantification of brain PO is still holding centre stage in neurobiological research. The aim of our study was therefore the determination of PO in minute amounts of brain areas. For this purpose we decided to apply the most sensitive detection principle of competitive reverse transcriptase polymerase chain reaction using capillary electrophoresis and laser-induced fluorescence detection. We selected the PO ets-2 for our studies as this transcription factor was shown to be involved in neurodegenerative disease. As little as 10ng of total RNA each were extracted from 5 different regions of human postmortem brain and used in the assay system. Our results revealed that the ets-2 gene transcript was detectable at the atto-gram level in the brain (54.5 ± 17.7 ag/ 10 ng RNA in the occipital lobe, 34.2 ± 7.5 in temporal lobe, 40.2 ± 15.6 in the frontal lobe, 31.4 ± 15.7 in the cerebellum, and undetectably low in the parietal lobe). This is the first report at this sensitivity level providing neurobiology with a powerful analytical tool.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1438-2199
    Keywords: Amino acids ; Taurine ; Marathon ; Endurance exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The sulphonated amino acid taurine increased significantly in the plasma of trained athletes after three endurance exercises of different duration and intensity, a 90 min run on a treadmill at 75% of an individual's VO2 peak, a Marathon, 42.2km and a 100km run, by 19%, 77% and 36%, respectively. Such results indicated that the speed at which the exercise is per formed, referred to as the intensity, rather than the duration of the exercise, correlated with the elevated taurine levels possibly indicating its release from muscle fibres. The plasma amino acid pool decreased significantly in relationship with the duration of the exercise, caused by their utilisation for glucogenesis. The possible sources of the increased plasma taurine are discussed.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Amino acids 17 (1999), S. 369-376 
    ISSN: 1438-2199
    Keywords: Amino acids ; Non-proteinogenic dipeptides ; Dehydrodipeptides ; Diastereoselectivity ; N-Boc-Dehydroamino acids ; Asymmetric hydrogenation ; Chiral rhodium catalysts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary N-Boc protected non-proteinogenic dipeptides with D,L-and L,L-configuration were prepared by catalytic asymmetric hydrogenation of the corresponding dehydrophenylalanyl-(L)-phenylalanine derivatives. The configuration of the new stereogenic centre depends first of all on the catalyst configuration and is less influenced by the substrate configuration. Diastereomeric excesses in the range of 80–96% de could be increased up to 99% by recrystallization. Analytical data of selected new compounds are given.
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  • 11
    ISSN: 1438-2199
    Keywords: Amino acids ; Polyclonal antibodies ; Phosalone ; Immunodetection ; Hapten synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hapten synthesis for the production of specific insecticide phosalone polyclonal antibodies was carried out starting from an intermediate of the phosalone synthesis, 6-chloro-2-benzoxazolone1. Two haptens containing different spacers have been prepared: N-5-carboxypentyl-6-chloro-2-benzoxazolone7 and N-(2-oxo-3-aza-5-carboxypentyl)-6-chloro-2-benzoxazolone12. Each of these two haptens conjugated to bovine serum albumine (BSA) was used to immunize four rabbits. Immunoassays of phosalone were performed with ELISA using solid-phase bound hapten thyroglobulin conjugate and horseradish peroxidase labelled goat antirabbit IgG. The more sensitive response was observed when the antiserum obtained from the rabbit immunized with the hapten-BSA conjugate containing the N-2-oxo-3-aza-5-carboxypentyl spacer was in competition with the same hapten coupled to thyroglobulin. An identical response was obtained under the same conditions when using benzoxazolone instead of phosalone as competitor, showing a good recognition of the specific aromatic part of the organophosphate insecticide phosalone. Reduction of coating conjugate concentration (from 2 to 0.05μg/well) and also the use of heterologous coating protein instead of homologous did improve the sensitivity, resulting in a concentration of phosalone required to inhibit binding by 50% of 2 mg/l and a detection limit of 0.02 mg/l.
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  • 12
    ISSN: 1438-2199
    Keywords: Amino acids ; Liver ; Hepatic damage ; Carbon tetrachloride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aims of the present study were to assess the changes of individual plasma amino acid levels in relation (1) to the severity of liver damage and (2) to the process of liver recovery. Acute liver injury was induced by an intragastric administration of CCl4 diluted in olive oil in doses of 2, 4 and /or 6 g of CCl4 per kg b.w. The control rats received olive oil only. Animals were sacrificed at 16, 24, 48 and 96 hours after treatment. The severity of liver injury was assessed by histological examination, by changes in ALT and AST in the blood plasma and by changes in liver weight. Statistical analysis was carried by ANOVA, p 〈 0.05 was considered significant. The Spearman rank correlation coefficient was used as a measure of the degree of linear relationship between variable and dose. In the period of the development of acute liver damage, i.e. at 16 and 24 hours after treatment, an increase in blood plasma amino acid levels and positive correlations with the dose of CCl4 were observed for most individual amino acids. The only exception was arginine which decreased in a dose dependent manner. At a phase of liver recovery, i.e. at 48 and 96 hours after CCl4 treatment, the concentrations of some individual amino acids decreased below the control values. The negative correlation with the dose of CCl4 occurred for taurine and isoleucine (at 48 hours) and taurine, threonine, valine, methionine, isoleucine and leucine (at 96 hours).
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  • 13
    ISSN: 1438-2199
    Keywords: Amino acids ; Alanine ; Fatty acids ; Glutamine and glutamate synthesis ; Glycerol and lactate metabolism ; Malate-aspartate shuttle ; Rabbit kidney-cortex tubules ; Renal gluconeogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In isolated rabbit renal cortical tubules, glucose synthesis from 1 mM alanine is negligible, while the amino acid is metabolized to glutamine and glutamate. The addition of 0.5 mM octanoate plus 2 mM glycerol induces incorporation of [U-14C]Alnine into glucose and decreases glutamine synthesis, whereas oleate and palmitate in the presence of glycerol are less potent than octanoate. Gluconeogenesis is also significantly accelerated when glycerol is substituted by lactate. In view of an increase in14CO2 fixation and elevation of both cytosolic and mitochondrial NADH/NAD+ ratios, the activation of glucose formation from alanine upon the addition of glycerol and octanoate is likely due to (i) stimulation of pyruvate carboxylation, (ii) increased availability of NADH for glyceraldehyde-3-phosphate dehydrogenase and (iii) elevation of mitochondrial redox state causing a diminished provision of ammonium for glutamine synthesis. The induction of gluconeogenesis in the presence of alanine, glycerol and octanoate is not related to cell volume changes. The results presented in this paper show the importance of free fatty acids and glycerol for regulation of renal gluconeogenesis from alanine. The possible physiological significance of the data is discussed.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Amino acids 16 (1999), S. 79-89 
    ISSN: 1438-2199
    Keywords: Amino acids ; Anti-neoplastic amino acids ; Purine and DNA synthesis inhibitors ; PRPP amido transferase and IMP dehydrogenase inhibitors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 4-Hydroxyproline di- and tri-peptides and N-cbz-hydroxypropylglycinamides were observed to be potent cytotoxic agents against the growth of suspended single cells, L-1210, Tmolt3, and HeLa-S3. The agents were not as potent against the growth of cultured solid tumor cells. Selected derivatives were investigated for their mode of action in Tmolt3 leukemia cells. The compounds selectively inhibited DNA synthesis at 50 and 100smM. The target site of action of the agents appeared to be the purinede novo pathway with marked inhibition of the activities of the two regulatory enzymes of the pathway, i.e. PRPP amido-transferase and IMP dehydrogenase. d[NTP] pools were reduced by the agents consistent with their overall reduction of DNA synthesis. Other marginally inhibited targets of the agents were r-RNA polymerase and TMP-kinase activities. The DNA molecule itself did not appear to be a target of these agents.
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  • 15
    ISSN: 1438-2199
    Keywords: Amino acids ; Targeting ; Mitochondria ; Chloroplasts ; Cysteine synthase ; Transit peptide ; Transgenic plants ; Processing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cysteme synthase, the key enzyme for fixation of inorganic sulfide, catalyses the formation of cysteine from O-acetylserine and inorganic sulfide. Here we report the cloning of cDNAs encoding cysteine synthase isoforms fromArabidopsis thaliana. The isolated cDNA clones encode for a mitochondrial and a plastidic isoform of cysteine synthase (O-acetylserine (thiol)-lyase, EC 4.2.99.8), designated cysteine synthase C (AtCS-C, CSase C) and B (AtCS-B; CSase B), respectively.AtCS-C andAtCS-B, having lengths of 1569-bp and 1421-bp, respectively, encode polypeptides of 430 amino acids (∼45.8 kD) and of 392 amino acids (∼ 41.8 kD), respectively. The deduced amino acid sequences of the mitochondrial and plastidic isoforms exhibit high homology even with respect to the presequences. The predicted presequence of AtCS-C has a N-terminal extension of 33 amino acids when compared to the plastidic isoform. Northern blot analysis showed thatAtCS-C is higher expressed in roots than in leaves whereas the expression ofAtCS-B is stronger in leaves. Furthermore, gene expression of both genes was enhanced by sulfur limitation which in turn led to an increase in enzyme activity in crude extracts of plants. Expression of theAtCS-B gene is regulated by light. The mitochondrial, plastidic and cytosolic (Hesse and Altmann, 1995) isoforms of cysteine synthase ofArabidopsis are able to complement a cysteine synthasedeficient mutant ofEscherichia coli unable to grow on minimal medium without cysteine, indicating synthesis of functional plant proteins in the bacterium. Two lines of evidence proved thatAtCS-C encodes a mitochondrial form of cysteine synthase; first, import ofin vitro translation products derived from AtCS-C in isolated intact mitochondria and second, Western blot analysis of mitochondria isolated from transgenic tobacco plants expressing AtCS-C cDNA/c-myc DNA fusion protein.
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  • 16
    ISSN: 1438-2199
    Keywords: Amino acids ; Non-proteinogenic optically active amino acids ; Dehydroamino acids ; Chiral rhodium catalysts ; Asymmetric hydrogenation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary (Z)-α-[(Benzyloxy)- or (tert.-butyloxy)carbonylamino]-β (thienyl)-or (furyl)-acrylic acids and their esters were prepared by known methods and hydrogenated to the corresponding optically active alanine derivatives with optical yields in the range of 58–93% ee using the cationic rhodium complex of “PROPRAPHOS”.
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  • 17
    ISSN: 1438-2199
    Keywords: Amino acids ; L-Tryptophan ; Serum albumin ; Transport ; L-Tryptophan depletion ; α-Methyl-DL-tryptophan ; Analbuminemic rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The role of serum albumin in the transport of orally administered L-tryptophan (Trp) into rat tissues was examined using analbuminemic and Sprague-Dawley (SD) rats with and without a-methyl-DL-tryptophan (AMT)-induced Trp depletion. Trp was orally administered to rats 16h after AMT or 0.85% NaCl administration, when liver tryptophan 2,3-dioxygenase and protein synthetic activities in AMT-treated rats were similar to those of 0.85% NaCl-treated rats. After oral Trp administration, regardless of the presence or absence of Trp depletion, free serum Trp concentrations were similar in the analbuminemic and SD rats, while total serum Trp concentrations were lower in analbuminemic rats than in SD rats. Although liver, brain, and muscle Trp concentrations after oral Trp administration under Trp depletion were lower in analbuminemic rats than in SD rats, the ratio of the liver Trp concentration in analbuminemic rats to that in SD rats was smaller than that of the brain or muscle Trp concentration. These results suggest that variations in serum albumin levels could affect the transport of orally administered Trp into the liver of rats with Trp depletion.
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  • 18
    ISSN: 1438-2199
    Keywords: Amino acids ; Tissue protein synthesis ; Stable isotope amino acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The tracers L15N-proline and L(1-13C)-leucine were used to explore the synthesis of skin proteins in vivo in rabbits. They orally received a single dose containing an equimolecular mixture of L(1-13C)-leucine and L15N-proline. The changes in the amounts of these tracers in blood and skin were monitored for a total of 8 h. The data showed the appearance of the two tracers in blood within 15 min and their clearance in 8h. They were both rapidly (15 min) incorporated into skin proteins, but more proline was incorporated than leucine. We therefore consider L15N-proline to be a better tracer than L(1-13C)-leucine for studying protein metabolism in the skin.
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  • 19
    ISSN: 1438-2199
    Keywords: Amino acids ; Taurine ; Kainic acid ; Epilepsy ; Anticonvulsants ; Neuroprotection ; Excitatory amino acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Male Sprague-Dawley rats received TAU supplementation (1.5% in drinking water) or TAU deficient diets for 4 weeks to test for a possible neuroprotective role of TAU in KA-induced (10 mg/kg s.c.) seizures. TAU supplementation significantly increased serum and hippocampal TAU levels, but not TAU content in temporal cortex or striatum. TAU deficient diets did not attenuate serum or tissue TAU levels. Dietary TAU supplementation failed to decrease the number or latency of partial or clonic-tonic seizures or wet dog shakes, whereas a TAU deficient diet decreased the number of clonictonic and partial seizures. This study does not support previous observations of an anticonvulsant effect of TAU against KA-induced seizures. KAtreatment decreasedα 2-adrenergic receptor binding sites and TAU content in the temporal cortex across all dietary treatment groups, supporting previous evidence of severe KA-induced damage and neuronal loss in this brain region.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Amino acids 16 (1999), S. 191-213 
    ISSN: 1438-2199
    Keywords: Amino acids ; Enzymatic resolution ; Ester hydrolysis ; Proteases ; Lipases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present review outlines recent examples of enzyme-based resolution procedures for amino acids via the hydrolysis of their esters. The resolutions have been achieved by using proteases (α-chymotrypsin, subtilisin and other microbial proteases, and sulfhydryl proteases of plant origin) and lipases. Relevant work utilizing yeast and other microbial cells is also included.
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  • 21
    Electronic Resource
    Electronic Resource
    Springer
    Amino acids 16 (1999), S. 251-272 
    ISSN: 1438-2199
    Keywords: Amino acids ; Unusual amino acids ; Aspartic acidβ-semialdehyde ; Aspartaldehyde ; 2-Amino-4-oxobutyric acid ; Enantioselective synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Strategies for the synthesis of optically active aspartaldehyde derivatives are reviewed. Most of them are using the chiral pool: allylglycine or naturally occurring homoserine, aspartic acid or methionme and side chain modifications. This will be developed in the first part. Some other original routes are also displayed in the second part. Different aspects of each strategy are discussed: the nature and number of steps, the problem of protecting groups, the price and availability of starting materials. Some synthetic applications of such interesting chiral synthons are shown in the last part.
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  • 22
    ISSN: 1438-2199
    Keywords: Amino acids ; Dipeptide derivatives ; Non-proternogenic optically active dipeptide esters ; Dehydrodipeptides ; Chiral rhodium catalysts ; Asymmetric hydrogenation ; Diastereoselectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary N-[(Z)-N-Benzoyl- orN-Boc-(2-fluorophenyl)dehydroalanyl]-(R)-or (S)-phenylalanine esters were synthesized and hydrogenated to give the corresponding dipeptide derivatives with optical yields in the range of 53–87%de using the cationic rhodium complexes of PROPRAPHOS and BPPM. The efficiency of chiral diphosphine ligands as well the effect of the chiral center in the substrate on the catalytic asymmetric induction was studied.
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  • 23
    ISSN: 1438-2199
    Keywords: Amino acids ; Phytotoxin AS-I analogues ; FAB ; PD ; ESI mass spectrometry ; 1H,13C and 2D NMR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A series of six tetrapeptides, analogues of AS-I phytotoxin, pathogenic to sunflower, have been synthesized either in solution and/or by solid phase methods and have been tested for phytotoxic activity in various plants and cytotoxic activity in three cancer cell lines. These peptides were identified as model compounds by fast atom bombardment (FAB), plasma desorption (PD), electrospray ionization (ESI) mass spectrometry and by1H,1H-1H,13C and1H-13C NMR. The data presented show that in protected tetrapeptides the molecular ion was easily identified whereas some difficulties appeared with the fully deprotected peptides. NMR spectra are given.
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  • 24
    ISSN: 1438-2199
    Keywords: Amino acids ; Diclofenac ; Anti-phlogistics ; Non-proteinogenic amino acids ; Voltaren®. Thionation ; Cyclo-oxygenase inhibitors ; Ulcerogenic gastritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In search for more potent, particularly less ulcerogenic gastritis that hopefully replace the universal NSAID “Diclofenac”, (2-[(2,6-di-chlorophenyl)amino]-phenylacetic acid, C.A.S. 15307-86-5), twelve new non-proteinogenic amino acid conjugates of the drug, namely that of sarcosine,β-alanine, D-leucine and D-phenylalanine, were synthesized and biologically screened for their anti-inflammatory, analgesic and ulcerogenic activity in rats. “Diclofenac” amino acid esters (IIa-d), were synthesizedvia the corresponding HOSu or HOBt active esters. Alkaline hydrolysis (NaOH) followed by acidification (KHSO4) or thioamide formation (Lawsson's Reagent, C.A.S. 19172-47-5), afforded the corresponding free acids IIIa-d or the thioamides IVa-d respectively. Interestingly, in contrary to the parent “Diclofenac”, the synthesized candidates (except IIId), were entirly nonulcerogenic in rats. Further, they considerably retained a generelized anti-phlogistic activity. The major “Diclofenac” irritating gastric side effect was thus eliminated. Particularly, the sarcosine conjugate IIa and its thiomimic IVa exhibit promising therapeutic perspectives.
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  • 25
    Electronic Resource
    Electronic Resource
    Springer
    Amino acids 17 (1999), S. 139-148 
    ISSN: 1438-2199
    Keywords: Amino acids ; Polyamine oxidase ; Polyamines ; Gender ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Variations in level of polyamines and their related enzymes are frequently observed in response to some treatments which affect in a different way male and female. The possibility of a gender-related difference in the oxidation of polyamines was investigated in rats by measuring the activity of polyamine oxidase, a ubiquitous enzyme of vertebrate tissues, which transforms spermine into spermidine and spermidine into putrescine. The study was carried out on thymus, spleen, kidney and liver of young rats of both sexes, and female rats showed a lower polyamine oxidase activity than male rats in all the tissues. We also found higher values of spermidine acetylation in female than male rats in thymus and liver. Owing to these gender-related differences, a higher spermidine N-acetyltransferase/ polyamine oxidase ratio was found in female than in male rats. A second gender-related difference was a higher spermidine/spermine ratio in female than in male, the only exception being the thymus. These basal differences possibly account for the gender-related differences of polyamine metabolic enzyme activities in response to some treatments, including drugs or hormones.
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  • 26
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    Amino acids 17 (1999), S. 195-205 
    ISSN: 1438-2199
    Keywords: Amino acids ; Apis mellifera ; Drones ; Osmolarity ; Age dependency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the haemolymph of honeybee drones, concentrations of free amino acids were higher than in worker haemolymph, with different relative proportions of individual amino acids. The overall concentration of free amino acids reached its highest level at the 5th day after adult drone emergence, and after the 9th day only minor changes in the concentration and distribution of free amino acids were observed. This coincides with the age when drones reach sexual maturity and change their feeding behaviour. Levels of essential free amino acids were high during the first 3 days of life and thereafter decreased. Osmolarity was lowest at emergence (334 ± 41 mOsm), increased until the age of 3 days (423 ± 32mOsm) and then stayed generally constant until the 16th day of life. Only 25-day-old drones had significantly higher osmolarity (532 ± 38 mOsm). The overall change in osmolarity during a drone's lifetime was about 40%.
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  • 27
    ISSN: 1438-2199
    Keywords: Amino acids ; Conformational constraint ; Cyclic disulfides ; -Cys-Cys-peptides ; Dipeptide mimetics ; Dithiols ; Glutathione analogues
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The glutathione analogue γ-(H-Glu-OH)- -OH (5), containing the 8-membered disulfide ring- replacing the native -Cys-Gly fragment, has been synthesized and characterized together with its reduced dithiol form γ-(H-Glu-OH)-Cys-Cys-OH (6).
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  • 28
    ISSN: 1438-2199
    Keywords: Amino acids ; Polyamine catabolism ; Polyamine oxidase ; Diamine oxidase ; Testosterone ; Mouse kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study developmental patterns of renal polyamineoxidizing enzymes polyamine oxidase (PAO) and diamine oxidase (DAO) in male and female ICR mice were demonstrated. The effects of testosterone (10μg/100g body weight) on renal PAO and DAO activities were also studied. The differences between sexes in both PAO and DAO activities were most clearly expressed in the immature kidney. At the age of 20 days PAO and DAO activities were 1.52 fold (p 〈 0.01) and 1.75 (p 〈 0.02) respectively higher in male mouse kidney than in female. Maturational processes reflected in significant increases in polyamine- oxidizing enzyme activities mainly in female mouse kidney, comparable with the gain in the kidney wet weight. Our data show that testosterone is able to influence renal PAO and DAO activities in addition to the well-known stimulation of polyamine biosynthesis. The hormonal effects were sex and age dependent. The influence of testosterone on renal PAO activity was mainly age dependent. The slight stimulation of renal PAO activity observed in 20- and 50-day old mice, 24h after testosterone administration, change with a decrease in the enzyme activity at the age of 70 days. The effects of testosterone on renal DAO activity were mainly sex dependent. Testosterone caused stimulation of DAO activity with a very close magnitude (nearly twice) in female mouse kidney, independently of the age of mice. In contrast, in male mice the hormone treatment resulted in a statistically significant increase in renal DAO activity at the age of 70 days (.1.3 fold, p 〈 0.05) only. It could be suggested that our data indicate the different contribution of renal PAO and DAO in androgen regulation of polyamine levels, depending on sex and the stage of the postnatal development.
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  • 29
    ISSN: 1438-2199
    Keywords: Amino acids ; Allohydroxyproline ; Allothreonine ; Chiral separation ; Chirasil-Val ; Hydroxyproline ; Threonine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experimental conditions for the derivatization and resolution by GLC of all stereoisomers of threonine and 4-hydroxyproline are reported. Threonine was in two steps converted toN,O-bisisobutoxycarbonyl 2,2,2-trifluoroethyl ester derivatives, the second of which was performed under anhydrous conditions. As such the enantiomers could pairwise be separated by capillary gas chromatography on a Chirasil-Val column. SinceL- andD-threonine eluted much earlier than the corresponding allo forms, quantitative determination of the allothreonine content inD- orL-threonine down to the one percent level could be simply accomplished but also enantiomeric impurities could be determined. Unlike for threonine, the corresponding 4-hydroxyproline isomers could not all be resolved asN,O-bisisobutoxycarbonyl 2,2,2-trifluoroethyl esters on this column. Although diastereomers could still be separated, the allo pair cochromatographed and the resolution for theL- andD-isomers was low. Complete separation of the 4-hydroxyproline isomers could be accomplished asN,O-bisprotected isobutyl amides, the formation of which required three derivatization steps. These were used for the determination of allohydroxyproline.
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  • 30
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    Amino acids 17 (1999), S. 323-334 
    ISSN: 1438-2199
    Keywords: Amino acids ; Taurine release ; Cerebellar granule cells ; Celldamaging conditions ; Glutamate receptors ; Veratridine ; Potassium stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The release of taurine from cultured cerebellar granule neurons was studied in different cell-damaging conditions, including hypoxia, hypoglycemia, ischemia, oxidative stress and in the presence of free radicals. The effects of both ionotropic and metabotropic glutamate receptor agonists on the release were likewise investigated. The release of [3H]taurine from the glutamatergic granule cells was increased by K+ (50mM) and veratridine (0.1 mM), the effect of veratridine being the greater. Hypoxia and ischemia produced an initial increase in release compared to normoxia but resulted in a diminished response to K. Hypoglycemia, oxidative stress and free radicals enhanced taurine release, and subsequent K− treatment exhibited a correspondingly greater stimulation. A common feature of taurine release in all the bove conditions was a slow response to the stimulus evoked by K+ and particularly to that evoked by veratridine. All ionotropic glutamate receptor agonists potentiated taurine release, but only the action of kainate seemed to be receptor-mediated. Metabotropic receptor agonists of group I slightly stimulated the release. The prolonged taurine release seen in both normoxia and cell-damaging conditions may be of importance in maintaining homeostasis in the cerebellum and reducing excitability for a longer period than other neuroprotective mechanisms.
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  • 31
    ISSN: 1438-2199
    Keywords: Amino acids ; Taurine ; Osmoregulation ; Rat ; Osmolarity sensor protein ENVZ
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Although the involvement of taurine in osmoregulation is well-documented and widely accepted, no detailed mechanism for this function has been reported so far. We used subtractive hybridization to study mRNA steady state levels of genes up- or downregulated by taurine. Rats were fed taurine 100mg/kg body weight per day for a period of three days and hearts (total ventricular tissue) of experimental animals and controls were pooled and used for mRNA extraction. mRNAs from two groups were used for subtractive hybridization. Clones of the subtractive library were sequenced and the obtained sequences were identified by gen bank assignment. Two clones were found to contain sequences which could be assigned to the osmolarity sensor protein envZ, showing homologies of 61 and 65%. EnvZ is an inner membrane protein in bacteria, important for osmosensing and required for porine gene regulation. It undergoes autophosphorylation and subsequently phosphorylates OmpR, which in turn binds to the porin (outer membrane protein) promoters to regulate the expression of OmpF and OmpC, major outer membrane porines. This is the first report of an osmosensing mechanism in the mammalian system, which was described in bacteria only. Furthermore, we are assigning a tentative role for taurine in the osmoregulatory process by modifying the expression of the osmoregulatory sensor protein ENVZ.
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  • 32
    ISSN: 1438-2199
    Keywords: Amino acids ; Protein ; arginine methyltransferase ; Inhibitors ; Ginseng extract ; Arginine derivatives ; Basic amino acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Protein-arginine N-methyltransferase (protein methylase I) catalyzes methylation of arginyl residues on substrate protein posttranslationally utilizing S-adenosyl-L-methionine as the methyl donor and yields NG-methylarginine residues. Arginyl-fructose and arginyl-fructosyl-glucose from Korean red ginseng were found to inhibit protein methylase I activity in vitro. This inhibitory activity was shown to be due to arginyl moiety in the molecules, rather than that of carbohydrates. Several basic amino acids as well as polyamines were also found to inhibit protein methylase I activity. Interestingly, the intensity of the inhibitory activity was correlated with the number of amino-group in polyamines, thus, in the order of spermine 〉 spermidine 〉 putrescine 〉 agmatine-sulfate, with IC50 at approximately 15 mM, 25 mM, 35 mM, and 50 mM, respectively. On the other hand, neutral amino acids or NaCI did not inhibit the enzyme activity. Lineweaver-Burk plot analysis of the protein methylase I activity in the presence of arginine and spermidine indicated that the inhibition was competitive in nature in respect to protein substrate, with the Ki values of 24.8 mM and 11.5 mM, respectively.
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  • 33
    ISSN: 1438-2199
    Keywords: Amino acids ; Hexafluoroacetone ; α-N-Methylamino acids ; α-N-Phosphinoylmethylamino acids ; Pro-Glu-chimeras ; Pro-Tauchimeras
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A new method for the preparation of N-methylamino acids and some of their derivatives starting from hexafluoroacetone protected amino acids is described. The new concept results in saving of steps compared to conventional protection/activation techniques. Protection and deprotection proceed without racemization.
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  • 34
    ISSN: 1438-2199
    Keywords: Amino acids ; Perfluorinated compounds ; Surfactants ; Complexing properties ; Carnosine ; β ; Amino acids ; Blood substitutes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The reaction of amines or sodium azide with 3-perfluoroalkyl-3-fluoroprop-2-enoate, followed by hydrogenation, affords perfluoroalkylatedβ-alanine analogues in very good yields. These compounds can be linked via an amide bond to produce peptide analogues such as carnosine or carcinine derivatives, which could have surfactive and complexing properties.
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  • 35
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    Amino acids 16 (1999), S. 415-423 
    ISSN: 1438-2199
    Keywords: Amino acids ; SOD-like activity ; Cu (III)-Poly-L-lysine ; Cu(III)-Poly-L-glutamic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The SOD-like activity of Cu(III) -complexes with polypeptides poly-L-lysine and poly-L-glutamic acid respectively was investigated. The Cu(II)-polypeptide complexes were first oxidized by K2IrCl6 to give the corresponding Cu(III) -compounds. The oxidation of Cu(II) and the corresponding Cu(II)/Cu(III) potential was evaluated by cyclic voltammetry (c.v.), UV-Vis and EPR spectroscopic (r.t.) experiments. Spin trapping EPR spectra were also conducted to confirm the formation of the superoxide radical. The SOD-like activity of each Cu(III)-complex was proved using the nitro blue tetrazolium (NBT) method slightly modified.
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  • 36
    ISSN: 1438-2199
    Keywords: Amino acids ; Lysine ; Herbicides ; Azotobacter ; Xenobiotics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Production of lysine byAzotobacter chroococcum strain H23 was studied in chemically-defined media amended with different concentrations of alachlor, metolachlor, 2,4-D, 2,4,5-T and 2,3,6-TBA. The presence of 5, 10, and 50μg/ml of alachlor or 2,3,6-TBA significantly decreased quantitative production of lysine. However, the presence 2,4-D or 2,4,5-T at concentrations of 10 and 50μg/ml enhanced the production of lysine. Quantitative production of lysine was not affected as consequence of the addition of metolachlor to the culture medium, showing that the release lysine to the culture media byA. chroococcum was not affected by that herbicide.
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  • 37
    ISSN: 1438-2199
    Keywords: Amino acids ; Trypanothione ; Glutathione ; Benzyloxycarbonyl-reductase ; Hydrocinnamoyl
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Kinetic data for alternative substrates of recombinant trypanothione reductase fromTrypanosoma cruzi were measured for a series ofN-substituted-L-cysteinylglycyl-3-dimethylaminopropylamides, in which the cysteineN-substituent was either a variant of the benzyloxycarbonyl group or was L-phenylalanine or L-tryptophan. Replacing the benzylic ether oxygen atom by CH2. or NH had relatively minor effects on kcat, but raised the value of Km, 4.5- and 10-fold, respectively. Similarly, relative to the carbobenzoxy group, anN-L-phenylalanyl orN-L-tryptophanyl replacement on the cysteine hardly altered kcat, but increased Km, values by 16.6 and 7.4 fold, respectively. These observations were consistent with the Km, values referring primarily to binding for this series of nonspecific substrates.
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  • 38
    ISSN: 1438-2199
    Keywords: Amino acids ; Serotonin receptor ; Serotonin-3 receptor ; Ion channel ; Ion permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human 5-HT3 receptors expressed in HEK 293 cells were studied using patch-clamp techniques. The permeability ratios of cations to Na+ were Li+, 1.16; K+, 1.04; Rb+, 1.11; Cs+ 1.11; NMDG+, 0.04; Ca2+, 0.49, and Mg2+, 0.37. The permeability sequence of the alkali metal cations was Li+ 〉 Rb+ = Cs+ 〉 K+ 〉 Na+. Increased external concentrations of Ca2+ or Mg2+ decreased 5-HT-induced currents at all potentials tested in a voltage-independent manner. The single-channel conductance of human 5-HT3 receptors measured by fluctuation analysis of whole-cell currents was 790 ± 100fS. Differences in the basic properties of 5-HT3 receptors between species may explain interspecies differences in pharmacological properties.
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  • 39
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    Amino acids 17 (1999), S. 301-313 
    ISSN: 1438-2199
    Keywords: Amino acids ; Taurine ; Transporter ; Rat ; Brain ; Heart
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In pro- and eucaryotic life, cellular and subcellular compartments are separated by membranes and the regulated and selective passage of specific molecules across these membranes is a basic and highly conserved principle. We were interested whether taurine, a naturally occuring amino acid, would be able to induce or suppress expression of transporters with the Rationale that taurine was shown to detoxify a series of endogenous toxins and xenobiotics of various chemically non-related structures. For this purpose we used a gene hunting technique, subtractive hybridization, subtracting mRNAs of taurine-treated rat brain and heart from untreated controls. Subtracted mRNAs were then converted to cDNAs, amplified, sequenced and identified by gene bank data. We found five transporter transcripts, the phosphonate transport ATPase PHNC, multidrug transporter homolog MTH104, protein-exportmembrane protein SECD, oligopeptide transporters oppA and oppD, in the brain and two: ABC-transporter BRAF-2 and cation-transport ATPase PACS, in the heart. Homologies of the sequences found were in any case 〉50% thus permitting the identification of transporters with high probability. The biological meaning could be that a naturally occuring amino acid, taurine, modulates complex transport systems. The most prominent finding is the upregulation of a multidrug transporter transcript, explaining a mechanism for the nonselective detoxifying action of taurine.
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  • 40
    ISSN: 1438-2199
    Keywords: Amino acids ; Tyrosine ; Phenylalanine ; Aromatic compounds ; Rumen microorganisms[/klw]
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rumen contents from three fistulated Japanese native goats fed Lucerne hay cubes (Medicago sativa) and concentrate mixture were collected to prepare the suspensions of mixed rumen bacteria (B), mixed protozoa (P) and a combination of the two (BP). Microbial suspensions were anaerobically incubated at 39°C for 12h with or without 1 MM ofl-phenylalanine (Phe). Phe, tyrosine (Tyr) and other related compounds in both supernatant and microbial hydrolysates of the incubations were analyzed by HPLC. Tyr can be produced from Phe not only by rumen bacteria but also by rumen protozoa. The production of Tyr during 12h incubation in B (183.6 μmol/g MN) was 4.3 times higher than that in P. One of the intermediate products between Phe and Tyr seems to bep-hydroxyphenylacetic acid. The rate of the net degradation of Phe incubation in B (76.O μmol/g MN/h) was 2.4 times higher than in P. In the case of all rumen microorganisms, degraded Phe was mainly (〉53%) converted into phenylacetic acid. The production of benzoic acid was higher in P than in B suspensions. Small amount of phenylpyruvic acid was produced from Phe by both rumen bacteria and protozoa, but phenylpropionic acid and phenyllactic acid were produced only by rumen bacteria.
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  • 41
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    Amino acids 17 (1999), S. 357-368 
    ISSN: 1438-2199
    Keywords: Amino acids ; o-Carboranylalanine ; Histidine ; Bacteria ; Fungi ; Oomycota ; Plasmopara
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Functionalized polyhedral carboranes, including amino acid analogs, have unique physicochemical properties and are used as experimental anticancer agents. However, our current knowledge on their effect in nonmammalian biological systems is limited. We investigated the activity spectrumin vitro ofo-carboranylalanine (o-Cba), considered to be a highly lipophilic analog of phenylalanine, against representative plant pathogenic bacteria and fungi of various taxonomic position. The antibacterial effect ofo-Cba against some species was comparable to that of the widely used agricultural antibiotic, streptomycin. The sensitivity of individual bacterial species too-Cba within the same genus varied to a greater extent than the average sensitivity of various genera. In general, this carborane-containing amino acid was more toxic to Gram positive bacteria (Bacillus, Corynebacterium, Curtobacterium, Micrococcus, Rhodococcus, and Staphylococcus) than to Gram negative ones (Agrobacterium, Erwinia, Escherichia, Pseudomonas, Rhizobium, and Xanthomonas). Compared to the commercial fungicide, prochloraz,o-Cba was weakly toxic against various fungi (Zygo- and Ascomycota). It was also inferior to the commercial fungicide metalaxyl in inhibiting the vegetative growth of oomyceteous plant pathogens (Pythium irregulare, Phytophthora cryptogea and Plasmopara halstedii). Against the asexual spores of P. halstedii,o-Cba, however, was over a thousandfold more active than tridemorph, a selective zoospore inhibitor fungicide. For all taxonomic groups, the observed antimicrobial effect ofo-Cba could be diminished with histidine, but not with phenylalanine. In studies on healthy and mildew-infected sunflower and tobacco plantso-Cba showed neither fungicidal nor phytotoxic effects at 500ppm. This is the first report on the biological activity spectrum of a carborane-containing amino acid.
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  • 42
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    Amino acids 17 (1999), S. 401-413 
    ISSN: 1438-2199
    Keywords: Amino acids ; Indolylacrylic acid ; Tryptophan ; Indolylacryloylglycine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In addition to the main catabolic routes of tryptophan (Trp), there exist minor and less thoroughly investigated pathways; one of these leads to indolylacrylic acid (IAcrA). IAcrA is a plant growth hormone, whereas its biological role in animals is still obscure, as is the way and site where it is formed in the organism. A two-stage production is likely: Intestinal microorganisms catabolize Trp to indole derivatives which are then absorbed and converted to IAcrA and its glycine conjugate, indolylacryloylglyeine (IAcrGly). Our finding of IAcrGly in the urine of proven germ-free piglets points to the possibility that Trp can be converted to IAcrA without the intervention of intestinal microorganisms. Seasonal and age variations, influence of light and connection with photodermatoses have been reported. Besides other pathological conditions the differences in IAcrGly excretion relative to normal controls were especially pronounced in some myopathies, namely in boys with Duchenne muscular dystrophy.
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  • 43
    ISSN: 1572-8773
    Keywords: cadmium ; apoptosis ; RT-PCR ; p53 gene expression ; testes ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Reverse transcription (RT) PCR technique was used to investigate the mechanism of apoptosis induced by Cd and the change of its related genes in testes and prostate of rats. Adult male rats were given a single (s.c.) injection of CdC l2 0, 2.5, 5.0, 10 μmol/kg. 48 h and 72 h after administration of Cd, animals were sacrificed. The results indicated that Cd can induce apoptosis in testes via p53-independent pathway. No apoptosis occurred in prostate in any of the Cd-exposed groups. There was a clearly negative relationship in testes between p53 gene expression and Cd exposure and this dose-response relationship was observed both at 48 h and 72 h. There was a very small increase of this gene expression in the dorsolateral lobe of the prostate in Cd exposed groups. The other apoptosis related gene, bcl-x, was not detectable in either control or Cd-exposed group in testes and dorsal prostate. Although the MT-I gene was expressed in testes or dorsal prostate both in control and exposed groups, no overexpression of MT-I gene was found after administration of Cd . The expression of MT-I in the ventral prostate was not detected in the control group, but a weak expression was found after Cd exposure. Since p53 is a tumo r suppressor gene which can inhibit tumorigenesis, the consequence of a Cd-induced decrease of p53 in testes may have a relation to the known risk of Cd tumorigenesis in this tissue.
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  • 44
    ISSN: 1569-8041
    Keywords: AML ; apoptosis ; etoposide ; γ-GCS ; glutathione ; oxidative stress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Etoposide mediates its cytotoxicity by inducing apoptosis. Thus, mechanisms which regulate apoptosis should also affect drug resistance. Oxidants and antioxidants have been shown to participate in the regulation of apoptosis. We were interested in studying whether responsiveness of acute myeloblastic leukemia (AML) cells to etoposide is mediated by oxidative stress and glutathione levels. Patients and methods: Two subclones of the OCI/AML-2 cell line which are etoposide-sensitive (ES), and etoposide-resistant (ER), were established by the authors at the University of Oulu, and used as models. Assays for apoptosis included externalization of phosphatidylserine (as evidenced by annexin V binding), and caspase activation as indicated by cleavage of poly(ADP-ribose)polymerase (Western blotting). Peroxide formation was analyzed by flow cytometry. Glutathione and gamma-glutamylcysteine synthetase (γ-GCS) levels were determined spectrophotometrically and by Western blotting, respectively. Results: Etoposide-induced apoptosis was evident 12 hours after treatment in the ES subclone, but was apparent in the ER subclone only after 24 hours. The basal glutathione and γ-GCS levels were higher in the ER than the ES subclone. Etoposide increased peroxide formation in both subclones after 12-hour exposure. Significant depletion of glutathione was observed in the ES subclone during etoposide exposure, while glutathione levels were maintained in the ER subclone. In neither of the subclones was induction of γ-GCS observed during 24-hour exposure to etoposide. Furthermore, the catalytic subunit of γ-GCS was cleaved during apoptosis, concurrent with depletion of intracellular glutathione. When glutathione was depleted by treatment with buthionine sulfoximine, a direct inhibitor of γ-GCS, the sensitivity to etoposide was increased, particularly in the ER subclone. Conclusions: The results underline the significance of glutathione biosynthesis in the responsiveness of AML cells to etoposide. The molecular mechanisms mediating glutathione depletion during etoposide exposure might include the cleavage of the catalytic subunit of γ-GCS.
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  • 45
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    Annals of oncology 10 (1999), S. 495-503 
    ISSN: 1569-8041
    Keywords: antisense ; apoptosis ; bcl-2 ; lymphoma ; leukaemia ; phase I
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 46
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    Annals of oncology 10 (1999), S. 1011-1021 
    ISSN: 1569-8041
    Keywords: apoptosis ; chemosensitivity ; cytotoxicity ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Although hematologic malignancies and some solid tumors such as germ cell tumors and pediatric malignancies can be cured by cytotoxic treatment, the most prevalent solid tumors are relatively resistant to these interventions. Apoptosis is involved in the cell kill of anticancer drugs and p53 is believed to be of principal importance in this process. However p53 also plays a role in cell cycle arrest and DNA repair, cellular processes that can decrease the sensitivity to chemotherapy. Therefore, p53 may play a dual role after exposure to cytotoxic treatment, activating either mechanisms that lead to apoptosis or launching processes directing to DNA repair and survival of the cell. Design: In this article, we review in details the p53functions involved in the mediation of chemosensitivity. The preclinical and clinical data published in the recent years about the relation between p53 and chemosensitivity are discussed and the potential pitfalls associated to most of these studies, and that may account for the contradictory results produced so far are also mentioned.
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  • 47
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    Annals of oncology 10 (1999), S. 31-38 
    ISSN: 1569-8041
    Keywords: apoptosis ; lanreotide treatment ; neuroendocrine gastrointestinal tumors ; octreotide ; somatostatin analogs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neuroendocrine gastrointestinal tumors express somatostatin receptors (ssts) in 80%–90% of cases and somatostatin analogs have become increasingly important in the management of these patients. Most of the presently available somatostatin analogs (octreotide, RC-160, and lanreotide) bind to the sst2 and sst5, and in higher doses to sst3 of the ssts 1–5 described. Clinical improvement during somatostatin analog therapy is mainly mediated via a direct inhibitory effect on hormone production from the tumors, seen in 30%–70% of the patients. Also indirect non-tumor mediated effects on peripheral target organs contribute to the subjective improvement, achieved in 30%–70% of patients. Recently, significant improvement of quality of life has been demonstrated with long-acting depot formulations. There is little or no effect on tumor growth during octreotide therapy; tumor shrinkage has been reported in 10%–20% of patients, but stabilization of tumor growth can be achieved in about half of the patients with a duration of 8–16 months. Recently, induction of apoptosis has been described with high doses of lanreotide (12 mg/d). Eventually, however, all patients escape from somatostatin analog therapy with regard both to hormonal production and tumor growth, and the mechanism behind the tachyphylaxis is not yet known. Studies of optimal dosage and modes of administration, development of new slow release formulations, the potential value of high-dose somatostatin analog therapy and novel somatostatin receptor subtype specific analogs are important directions for the use of somatostatin analogs in the future. In addition, assessment of somatostatin receptor status for each patient and studies of tumor biology, e.g., inhibition of exocytosis, antiproliferative effects and induction of apoptosis during treatment will help to optimize treatment and provide new insights into mechanisms of action of somatostatin analogs.
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  • 48
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    Biology and fertility of soils 29 (1999), S. 257-261 
    ISSN: 1432-0789
    Keywords: Key words Alpine nitrogen cycle ; Amino acids ; Kobresia myosuroides ; Organic nitrogen ; Plant-microbe competition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract  Microbes are assumed to possess strong competitive advantages over plants for uptake of nutrients from the soil. The finding that non-mycorrhizal plants can obtain a significant fraction of their N requirement from soil amino acids contradicts this assumption. The amino acid glycine (Gly) has been used as a model amino acid in many recent studies. Our preliminary studies showed that Gly was a poor substrate for microbial growth compared to other amino acids. We tested the hypothesis that the alpine sedge Kobresia myosuroides competes better for Gly than for other amino acids because of decreased microbial demand for this compound. Soil microbial populations that could grow using Gly as a sole carbon source were about 5 times lower than those that could grow on glutamate (Glu). Gly supported a significantly lower population than any of the ten other amino acids tested except serine. In contrast, K. myosuroides took up Gly from hydroponic solution at faster rates than Glu. In plant-soil microcosms, plants competed with soil microbes 3.25 times better for Gly than for Glu. We conclude that the low microbial demand and the rapid plant uptake of Gly relative to other amino acids allow Gly to be an especially important nitrogen source for K. myosuroides.
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  • 49
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    Der Nervenarzt 70 (1999), S. 1-10 
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Tic-Störung ; Zwangsstörung ; Kinder ; Jugendliche ; Neurobiologie ; Psycho- pharmakologie ; Verhaltenstherapie ; Key words Tic-disorder ; Obsessive-compulsive disorder ; Children ; Adolescents ; Neurobiology ; Psychopharmacology ; Behavior therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In children and adolescents motor/vocal tics and obsessive-compulsive behavior are known to be closely related. Thereby, a continuum of symptoms ranging from single tics to a mixed picture of tics/rituals/obsessive-compulsive traits to clinically relevant obsessions and compulsions could be described. As neurobiological substrates dysfunctions in corresponding cortico-striato-thalamo-cortical circuits (sensorimotor circuit in tic symptomatology, orbitofrontal circuit in obsessive-compulsive behavior) were postulated. For both disturbances behavioral therapy can be used to improve control mechanisms to counterregulate tics and obsessive-compulsive behavior, respectively, and psychopharmacological agents can be administerd to compensate dysbalances in neurotransmitter systems. In case of a mixed symptomatologic picture it is necessary to include interventions for both pols of the symptom-continuum in the therapeutic programme to achieve extensive improvement as a basis for a further positive development of the patient.
    Notes: Zusammenfassung Motorische/vokale Tics und zwanghafte Verhaltensweisen kommen bei Kindern und Jugendlichen häufig gemeinsam vor; dabei kann ein Symptomkontinuum von solitär auftretenden Tics über ein Mischbild von Tics und Ritualen/zwanghaften Gedanken und/oder Handlungen bis hin zu eindeutigen Zwangsphänomenen beschrieben werden. Neurobiologisch können diesem Symptomkontinuum unterschiedlich ausgebreitete Dysfunktionen entsprechender kortiko-striato-pallido-thalamo-kortikaler Regulationssysteme zugrunde liegen. Therapeutisch lassen sich bei beiden Verhaltensauffälligkeiten mittels verhaltenstherapeutischer Techniken Steuerungs- und Kontrollmöglichkeiten zur Gegenregulation der Auffälligkeiten verbessern sowie durch Einsatz von Psychopharmaka Dysbalancen von Neurotransmittersystemen ausgleichen. Bei einem Mischbild von Tics und Zwängen sind therapeutische Interventionen für beide Zielbereiche erforderlich. Nur so können umfassende Verbesserungen erreicht und günstige Entwicklungsbedingungen für die betroffenen Kinder und Jugendlichen eröffnet werden.
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  • 50
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    Monatsschrift Kinderheilkunde 147 (1999), S. 328-332 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Asthma bronchiale ; Schulkinder ; Türkische Kinder ; Key words Asthma ; Children ; Turkish children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Objectives: In Germany 4.2% (in Munich 8.6%) of all children under 15 years of age are of Turkish origin, representing the largest ethnic minority in this age group. However, very little is known about the prevalence, severity and management of asthma and other atopic diseases in Turkish children living in Germany. Methods: In a cross-sectional survery the prevalence, severity and treatment of asthma and other atopic diseases was assessed in 7,445 schoolchildren aged 9 to 11 years, living in Munich, southern Germany. Questionnaires were distributed to the parents for self-completion and children underwent skin-prick tests and cold-air hyperventilation challenge. Results: Of those returning the questionnaires (n = 6490/87%), 5,030 (77.5%) were of German and 451 (7%) of Turkish origin. Turkish children showed a significantly lower prevalence of asthma (5.3% versus 9.4%, P 〈 0.05) than their German peers. Furthermore, Turkish children with asthma were less frequently free of symptoms (10.5% versus 34.6%, P 〈 0.05), reported more severe symptoms (41.2% versus 10.9%, P 〈 0.05) and more hospital admissions (55.6% versus 21.6%, P 〈 0.05) due to asthma than German children. Conclusions: The results of this study indicate that despite the lower prevalence of asthma and allergy in the Turkish population living in Germany, asthma is a major health problem for Turkish children. Furthermore, these findings suggest inadequate management of asthma in Turkish children.
    Notes: Zusammenfassung Fragestellung: Türkische Kinder stellen in der Bundesrepublik Deutschland mit 4,2% und in München mit 8,6% den größten Anteil nicht-deutscher Kinder in der Altersgruppe bis 15 Jahren. Wenig ist jedoch bisher über Häufigkeit, Symptome und Behandlung von Asthma bronchiale und anderer atopischer Erkrankungen der türkischen Minderheit in Deutschland bekannt. Methodik: In einer Querschnittstudie wurde bei 7445 Schulkindern im Alter von 9 bis 11 Jahren im Großraum München die Häufigkeit, der Schweregrad und die Behandlung des Asthma bronchiale und anderer atopischer Erkrankungen untersucht. Fragebögen wurden von den Eltern ausgefüllt, Lungenfunktionsuntersuchungen und Hautpricktests wurden bei den Kindern durchgeführt. Ergebnisse: Von denen, die die zugeschickten Fragebögen ausfüllten (n = 6490/87%), waren 5030 (77,5%) deutscher und 451 (7%) türkischer Nationalität. Die türkischen Kinder zeigten eine niedrigere Prävalenz von Asthma bronchiale (5,3% versus 9,4%, p 〈 0,05) und Neurodermitis (1,6% versus 12,9%, p 〈 0,001) im Vergleich zu den deutschen Kindern. Signifikante Unterschiede bestanden zwischen türkischen und deutschen Kindern in Art der Symptome und der Krankheitswahrnehmung. Türkische Kinder mit Asthma bronchiale waren seltener beschwerdefrei (10,5% versus 34,6%, p 〈 0,05) berichteten von schwereren Symptomen (41,2% versus 10,9%, p 〈 0,05) und von einer größeren Anzahl von Krankenhausaufenthalten (55,6% versus 21,6%, p 〈 0,05) aufgrund von Asthma bronchiale. Schlußfolgerung: Die Ergebnisse der Studie legen den Schluß nahe, daß Asthma bronchiale trotz der niedrigeren Prävalenz in der türkischen Bevölkerungsgruppe ein erhebliches Gesundheitsproblem bei türkischen Schulkindern darstellt. Die höhere Anzahl von Fehltagen in der Schule und die deutlich höhere Anzahl von Klinikaufenthalten aufgrund von Asthma bronchiale sprechen für eine mangelhafte präventive Behandlung dieser Erkrankung bei türkischen Kindern.
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  • 51
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    HNO 47 (1999), S. 535-540 
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Hörschäden ; Knalltrauma ; Kinder ; Tinnitus ; Erweiterte Hochtonaudiometrie ; Key words Hearing loss ; Acoustic trauma ; Children ; Tinnitus ; High-frequency audiometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The study presents an analysis of 20 cases of acute acoustic trauma caused by toy pistols. The problem generally involves boys within the age range from 6 to 11 years. Half of the incidents involved attacks with toy pistols used as weapons. Auditory damage appeared in two types, each of which had a notch in the audiogram at the frequency range between 10 and 14 kHz. In children, a shot close to one ear can damage both ears. Great differences in the severity of tinnitus were apparent. The most severe cases of tinnitus were observed in the children with no or minor premanent auditory damage. Children experiencing long periods of uninterrupted tinnitus suffer significantly. This is not only detrimental to family-life but also to the performance of the children at school. The total expenses of treatment for these 20 cases were estimated to be approximately 80,000 DM (40.000 Euro).
    Notes: Zusammenfassung Im Rahmen einer Studie wurden 20 Fälle von Knalltraumata durch Kinderpistolen erfaßt und ausgewertet. Die Problematik betrifft fast nur männliche Personen und schwerpunktmäßig den Altersbereich von 6–11 Jahren. Die Hälfte der Vorfälle waren Angriffe, bei denen die Kinderpistole als Waffe eingesetzt wurde, 2 Typen von Hörschäden sind festzustellen, die jedoch beide durch eine Senke im Bereich von 10–14 kHz charakterisiert sind. Bei Kindern kann der Schuß in eines der Ohren auch das andere Ohr schädigen. Sehr große Unterschiede bestehen im Auftreten von Tinnitus. Die Fälle mit starkem Tinnitus haben keine oder nur geringe bleibende Hörschäden. Die von Knalltraumata betroffenen Kinder leiden oft sehr stark unter langanhaltendem Tinnitus. Dabei wird nicht nur das Leben der Familien beeinträchtigt, sondern auch die schulischen Leistungen der Kinder leiden teilweise sehr stark darunter. Für die Therapie dieser 20 Fälle entstanden Gesamtkosten von ca. 80.000,- DM
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  • 52
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Laryngotracheale Stenose ; Cricotracheale Resektion ; Kinder ; Tracheotomie ; Key words Laryngotracheal stenosis ; Cricotracheal resection ; Tracheostomy ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Approximately 90% of infants and children with severe acquired laryngotracheal stenoses are tracheotomy dependent and therefore impaired in their physical and speech developments. In addition, tracheotomized infants can be endangered by the cannula due to the possible crusting of secretions or its dislocation. Thus, early repair of a stenosis is mandatory. Within the last 10 years, we successfully operated on 18 children with severe laryngotracheal stenoses. Ten children were treated with a modified Cotton technique. This paper reports our results of cricotracheal resection performed in 8 children since 1994 (age distribution: 7 months through age 15 years). Four children had Cotton grade II stenoses, three had grade III stenoses and one grade IV stenoses. In 3 patients a tracheotomy had been performed at another institution. Since their tracheostomas were too far caudal, they could not be included in the primary resection. All 8 children have been successfully decannulated. Five children without tracheotomies could be extubated uneventfully on the 5th postoperative day. All three primarily tracheotomized children needed further endotracheal stenting with T-tubes because of stomal and suprastomal collapse. Two of these latter children additionally required a tracheoplasty with rib cartilage grafts in order to stabilize the suprastomal trachea prior to decannulation. No patient experienced injuries to the recurrent laryngeal nerves or insufficiencies of the anastomosis. All children’s voices were not impaired. This is the third report in literature of cricotracheal resections in infants and children, indicating that this effective, one-stage procedure is superior to laryngotracheal reconstruction with rib cartilage.
    Notes: Zusammenfassung Kinder mit schweren, erworbenen subglottischen laryngotrachealen Stenosen sind zu 90% tracheotomiert und daher in ihrer körperlichen und sprachlichen Entwicklung beeinträchtigt. Zusätzlich sind mit einer Trachealkanüle versorgte Kinder, insbesondere Kleinkinder, gefährdet, so daß die chirurgische Beseitigung der Stenose dringend geboten ist. Wir haben innerhalb der vergangenen 10 Jahre 18 Kinder mit einer schweren subglottischen laryngotrachealen Stenose operiert; 10 Kinder, über die kürzlich berichtet wurde, konnten mit der modifizierten Cotton-Technik erfolgreich dekanüliert werden. Über 8 Kinder (Alter 7 Monate bis 15 Jahre, 4mal Stenose II. Grades, 3mal Stenose III. Grades, einmal Stenose IV. Grades), die wir mit cricotrachealer Resektion (CTR) und thyrotrachealer Anastomose operierten, wird in der vorliegenden Arbeit berichtet. 3 Kinder waren anderenorts bereits tracheotomiert. Da die Stomata zu weit kaudal lagen, konnten sie nicht in die Resektion einbezogen werden. Alle 8 Kinder konnten inzwischen dekanüliert werden und sind beschwerdefrei: Die 5 nicht tracheotomierten Kinder konnten problemlos am 5. postoperativen Tag extubiert werden. Die zuvor tracheotomierten Kinder konnten erst nach endotrachealer Schienung (2mal nach zusätzlicher Trachealplastik mit Rippenknorpel bei suprastomaler Tracheomalazie) dekanüliert werden. Bei keinem der Kinder trat eine Recurrensparese auf. Die Stimme bei allen Kindern ist unbeeinträchtigt. Die CTR, über die bei kindlichen laryngotrachealen Stenosen mit dieser Arbeit in der Literatur zum 3. Mal berichtet wird, ist eine sehr effektive, einzeitige, komplikationsarme Operationsmethode, deren Resultate für Atmung und Stimme günstiger sind, als mit der Erweiterungsplastik nach Cotton.
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  • 53
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    Monatsschrift Kinderheilkunde 147 (1999), S. 122-127 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Körperliche Beschwerden ; CBCL/4 ; 18 ; Kultur-vergleichend ; Kinder ; Jugendliche ; Key words Somatic complaints ; CBCL/4 ; 18 ; Cross-cultural ; Children ; Adolescents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Question: What is the frequency of parent-reported somatic complaints of children in Germany and the Netherlands dependent on their age, sex and the education of their parents. Methods: 4876 CBCL (Child Behaviour Checklist) of children aged 4 through 17 years from the general population were analysed. Results: Dutch children were scored higher by their parents than German children. Moreover somatic complaints increased with age and girls were scored higher. The frequencies of somatic complaints varied from 2% for ’problems with eyes’ to 15% for ’headaches’. The presence of one somatic complaint increased the likelihood of concomitant somatic complaints. Conclusion: Somatic complaints of children without any known cause are often seen. Some symptoms are often reported together. More, especially causal studies on the somatic symptoms of children are recommended.
    Notes: Zusammenfassung Fragestellung: Wie verhält sich die Häufigkeit körperlicher Beschwerden bei Kindern in Deutschland und den Niederlanden nach Laieneinschätzung, gibt es Unterschiede abhängig vom Alter und Geschlecht der Kinder und des Ausbildungsniveaus der Eltern? Methode: 2757 deutsche und 2119 niederländische CBCL (child behavior checklist) über Kinder und Jugendliche im Alter zwischen 4 und 17 Jahren aus repräsentativen Studien wurden mit Hilfe von Varianzanalysen ausgewertet. Ergebnisse: Niederländische Eltern beschrieben mehr körperliche Beschwerden als deutsche. Die Ausprägung auf der Symptomskala stieg mit zunehmendem Alter und zeigte höhere Werte für Mädchen. Die Häufigkeit der Beschwerden variiert von 2% für „Augenbeschwerden” bis zu 15% für „Kopfschmerzen”. Bei Anwesenheit eines körperlichen Symptoms stieg die Frequenz zusätzlicher Beschwerden. Schlußfolgerung: Körperliche Beschwerden bei Kindern treten häufig ohne bekannte Ursache auf, bestimmte Beschwerden werden häufig gleichzeitig beschrieben, wobei die Koinzidenz nicht umkehrbar ist. Weitere, besonders ursächliche Studien auf dem Gebiet der körperlichen Beschwerden bei Kindern sind auch hinsichtlich steigender Kosten im Gesundheitswesen empfehlenswert.
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  • 54
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    Monatsschrift Kinderheilkunde 147 (1999), S. 351-355 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Latexallergie ; Neuogene Blasenentleerungsstörung ; Kinder ; Key words Latex allergy ; Neurogenic bladder dysfunction ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Objectives: The risk to suffer from natural latex allergy is increased in children with congenital neurogenic bladder dysfunction. We, therefore, evaluated whether or not a serologic screening for detection of sensitization to latex is reasonable in these children. Patients and Methods: 40 children aged from 6 months to 17 years were examined by specific questionnaire-based patient histories, and by determination of total serum immunoglobuline E (total IgE) and natural latex-specific serum immunoglobulin E (latex-IgE) by solid-phase immunoassays. Results: 5 children had a history of allergic reaction to rubber containing materials. In 10 children, latex-IgE was elevated 〉 0.35 kU/l, 6 out of these 10 children without a history of allergic reactions to rubber containing materials. There was a positive correlation of elevated latex-IgE values and the number of former surgical procedures (p 〈 0.006), while no correlation was found between elevated latex-IgE values and clean intermittent catheterization (p = 0.408). Conclusion: Compared to questionnaire-based patient histories, serologic screening examination including determination of latex-IgE values may better identify children at risk to suffer from sensitization to natural latex.
    Notes: Zusammenfassung Fragestellung: Naturlatexallergien kommen bei Kindern mit angeborener neurogener Blasenentleerungsstörung gehäuft vor. Es wurde deshalb untersucht, ob bei dieser Patientengruppe ein serologisches Screening zur Erfassung einer Sensibilisierung gegenüber Naturlatex sinnvoll ist. Patienten und Methode: Untersucht wurden 40 Kinder im Alter von 6 Monaten bis 17 Jahren. Die Untersuchung umfaßte eine gezielte Anamneseerhebung durch Fragebogen sowie die Bestimmung des Gesamtimmunglobulin E (Gesamt-IgE) und des naturlatexspezifischen Immunglobulin E (Latex-IgE) im Serum durch Festphasenimmunoassays. Ergebnisse: 5 Kinder hatten anamnestisch Zeichen einer allergischen Reaktion nach Gummikontakt. 10 Kinder wiesen im Serum erhöhte Werte des Latex-IgE auf, wobei 6 dieser Kinder bisher noch keine Zeichen einer Latexallergie hatten. Pathologische Werte für das Latex-IgE korrelierten statistisch signifikant mit der Anzahl operativer Eingriffe (p 〈 0,0006), nicht aber mit einem durchgeführten sauber intermittierenden Einmalkatheterismus (p = 0,408). Schlußfolgerung: Im Vergleich zur alleinigen fragebogengestützen Anamneseerhebung können durch ein serologisches Screening mit Bestimmung des Latex-IgE mehr Kinder entdeckt werden, die durch eine Sensibilisierung gegenüber Naturlatex gefährdet sind.
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  • 55
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    Pediatric surgery international 15 (1999), S. 32-35 
    ISSN: 1437-9813
    Keywords: Key words Appendicitis ; Ultrasonography ; Children ; Graded compression ultrasonography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The diagnosis of acute appendicitis in childhood is frequently difficult. In some situations the need to operate is clear, but in others the decisions may be much “tougher” because the clinical findings are equivocal. This is a retrospective study of a consecutive series of 253 children presenting with “acute abdominal pain? appendicitis” who had graded compression ultrasonography (GCUS) because the clinical scenario did not warrant immediate laparotomy. This represents 30% of all cases seen in the study period. The aim of the study was to examine the role of GCUS and a clinical scoring system (the Alvarado score) in patients in whom the diagnosis is uncertain.
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  • 56
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    Pediatric surgery international 15 (1999), S. 50-55 
    ISSN: 1437-9813
    Keywords: Key words Burns ; Inhalation injury ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Survival from serious burns in children has improved substantially in recent years. Mortality is predominantly determined by the total body surface area burned and the often unrecognised inhalation injury. A retrospective review of 4,451 consecutive children with thermal injuries over a 10-year period was undertaken to determine the incidence, clinical presentation, and pathology of inhalation injury and its contribution to morbidity and mortality. Inhalation burns were diagnosed clinically and confirmed endoscopically and post-mortem in 97 (2.2%) children; 77 sustained fire burns (mean age 4 years) and 20 hot-water burns (mean age 18 months). The Moylan classification stratified them into upper-airway burns in 59 children, major–airway burns in 29, and parenchymal burns in 44. Major-airway burns were always seen in conjunction with either upper-airway or parenchymal injury. Stridor and acute progressive respiratory distress were the two main symptoms, the onset of which was occasionally delayed for up to 72 h. Endoscopy was most helpful in confirming the diagnosis and determining airway management. Endotracheal intubation was needed in more than 50% of children, usually for less than 5 days, and was converted to tracheostomy in only 6. Persistent laryngeal and tracheal damage was identified in 4. Secondary pneumonia occurred in 41.5% of children with fire burns and 55% with hot-water burns. Extensive surface burns, parenchymal injury, and secondary pneumonia all contributed to the significant mortality. Post-mortem findings corroborated clinical and endoscopic evidence. This study suggests that inhalation burns were often not recognised, could present late, and usually had significant consequences. Early clinical diagnosis, supported by endoscopic findings and appropriate management, is essential if the high morbidity and mortality amongst these children is to be improved.
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    Pediatric surgery international 15 (1999), S. 63-65 
    ISSN: 1437-9813
    Keywords: Key words Actinomycosis ; Antibiotic treatment ; Appendicitis ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Abdominal actinomycosis (AMC) is a rare infection in children. The appendix is the most common intra-abdominal organ involved. It presents as an undifferentiated mass, forming abscesses and fistulas in the right lower quadrant. The case of a 15-year-old girl with a AMC of the appendix detected by the pathologist after routine appendectomy is discussed. Long-term antibiotic treatment and follow-up by ultrasound and laboratory controls are necessary.
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  • 58
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    Pediatric surgery international 15 (1999), S. 121-122 
    ISSN: 1437-9813
    Keywords: Key words Ingrowing nails ; Conservative treatment ; Children ; Adolescents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ingrowing nails are not uncommon in children, and even so receive little attention in the pediatric surgery literature. The purpose of the present study was to demonstrate our modification of the conservative treatment of ingrowing nails. Our technique of local treatment combined with patient education for better foot and toe care was successfully used and well tolerated by 19 out of 20 young patients with ingrown toenails.
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  • 59
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    Pediatric surgery international 15 (1999), S. 353-357 
    ISSN: 1437-9813
    Keywords: Key words Testis torsion ; Scrotum ; Appendage ; Cremasteric reflex ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A total of 543 boys suffering from acute scrotal pain underwent emergency surgery between 1986 and 1996. Of these, 91 had a testicular torsion (TT) (16.8%) and 250 had an appendage torsion (AT) (46%). The cause varied with patient age, with most TTs in newborns and boys of 15 years and most ATs in 10–11-year-olds; 21.5% were operated upon within 6 h of the onset of pain and 69.2% within 24 h. Most stayed in hospital for less than 24 h. Pre-surgical examination identified no criterion for excluding TT. We therefore believe that all children complaining of acute scrotal pain should undergo surgery. As release of an inflamed AT reduces pain, three-fourths of the children benefited directly from surgery.
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  • 60
    ISSN: 1437-9813
    Keywords: Key words Ovarian tumor ; Children ; Hypercalcemia ; Small-Cell carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tumors of the ovary in girls represent about 80% of pediatric genital tumors; approximately 30% of these tumors are malignant. The risk of malignancy increases with decreasing age. The most frequent finding is a teratoma; other tumors are rare. Small-cell carcinoma (SCCO) of the ovary is extremely rare, occurring mostly in young women. We present an 8-year-old girl with a SCCO of the hypercalcemic type. The findings and treatment are discussed with emphasis on the poor prognosis in these patients, even in stage 1 disease. The current literature is reviewed.
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  • 61
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    Pediatric surgery international 15 (1999), S. 579-581 
    ISSN: 1437-9813
    Keywords: Key words Hydatid disease ; Pancreas ; Children ; Echinococcosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Primary hydatid disease of the pancreas is rare. The authors report a 3-year-old girl who had a cystic mass in the head of the pancreas with no other viscera involved. At laparatomy the entire endocyst was totally extracted from the surrounding pancreatic parenchyma. The postoperative course was uneventful. She is currently disease-free with a follow-up of 5 years. Only four other pediatric cases have been reported in the English literature.
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  • 62
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    Pediatric surgery international 15 (1999), S. 525-526 
    ISSN: 1437-9813
    Keywords: Key words Central venous catheters ; Children ; Complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The insertion of central venous catheters has become an established practice in the management of children with different types of malignancies for the administration of chemotherapeutic agents, antibiotics, blood and blood products, as well as drawing blood for various investigations. A commonly encountered problem is that despite the catheter being patent it may be impossible to draw blood from it. We believe this is related to the cut of the catheter tip. To overcome this problem, a technique for cutting the tip of the catheter is described.
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  • 63
    ISSN: 1436-2813
    Keywords: Key Words: nitric oxide ; DNA damage ; apoptosis ; tumor necrosis factor-α ; mitochondrial respiration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: S -nitroso-N-acetylpenicillamine protected cul-tured L929 cells from apoptosis induced by tumor necrosis factor-α (TNF-α) plus actinomycin D, as determined by the detection of DNA fragmentation and morphological changes. NO also prevented an enhancement of the production of reactive oxygen intermediates by TNF-α plus actinomycin D, as assessed by the oxidation of dihydrorhodamine 123 and hydroethidine. Because the inhibition of mitochondrial respiration by rotenone or antimycin A suppressed the increased oxidation of both dihydrorhodamine 123 and hydroethidine, it was suggested that TNF-α accelerated the leakage of reactive oxygen intermediates from the mitochondrial electron transport system. Polarography showed that NO reversibly inhibited mitochondrial respiration at either complexes I–III, II–III, or IV, thus suggesting the inhibition of cytochrome oxidase. Taken together, these findings indicate that the decreased mitochondrial formation of reactive oxygen intermediates in the presence of NO might have a protective effect against TNF-α plus actinomycin D-induced apoptosis.
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  • 64
    ISSN: 1436-2813
    Keywords: angiogenesis ; p53 ; apoptosis ; lung adenocarcinoma ; hematogenous metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to clarify which factors are important as predictors not only of patient survival but also of hematogenic metastasis in 15 patients with stage I lung adenocarcinoma who underwent curative operation. The relationship between tumor angiogenesis, apoptosis, and p53 oncogene was also studied. A total of 15 patients were divided into two groups: surviving group (n=7) and nonsurviving (metastasis) group (n=8). We studied the medical charts, operative records, pathologic reports, and tumor specimens taken at surgical resection. We measured the apoptotic index using the ApopTag kit and the intratumoral microvessel count using an anti-CD34 monoclonal antibody. In addition, immunohistochemical staining for the expression of p53 was conducted simultaneously. The clinicopathological characteristics, including age, sex, tumor size (pT), and histological differentiation, were not significantly different between the surviving and the nonsurviving group. The microvessel count was significantly higher in nonsurviving group than in the surviving group. The apoptotic index and the expression of p53 was not significantly different between the two groups. An inverse correlation between the apoptotic index and microvessel count, and a positive correlation between the expression of p53 and microvessel count, were observed. Angiogenesis may be an important prognostic factor in patients with stage I lung adenocarcinoma.
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  • 65
    ISSN: 1436-2813
    Keywords: Key Words: angiogenesis ; p53 ; apoptosis ; lung adenocarcinoma ; hematogenous metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: n = 7) and nonsurviving (metastasis) group (n = 8). We studied the medical charts, operative records, pathologic reports, and tumor specimens taken at surgical resection. We measured the apoptotic index using the ApopTag kit and the intratumoral microvessel count using an anti-CD34 monoclonal antibody. In addition, immunohistochemical staining for the expression of p53 was conducted simultaneously. The clinicopathological characteristics, including age, sex, tumor size (pT), and histological differentiation, were not significantly different between the surviving and the nonsurviving group. The microvessel count was significantly higher in nonsurviving group than in the surviving group. The apoptotic index and the expression of p53 was not significantly different between the two groups. An inverse correlation between the apoptotic index and microvessel count, and a positive correlation between the expression of p53 and microvessel count, were observed. Angiogenesis may be an important prognostic factor in patients with stage I lung adenocarcinoma.
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  • 66
    ISSN: 1432-0584
    Keywords: Key words Hypergammaglobulinemia ; Polyclonal ; Acute myeloid leukemia ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Polyclonal hypergammaglobulinemia (PHG) associated with hematological malignancies is a rare occurrence. We reviewed our series of 47 children with AML in order to define the prevalence of PHG and its prognostic value in achieving complete remission (CR) after induction treatment. Patients were stratified by immunoglobulin levels into two groups: with PHG and without PHG. CR reached after induction chemotherapy was considered a positive response. Conditional exact tests were used for the statistical analysis; conditional maximum likelihood estimates of the odds ratio (OR) were obtained. Significance levels (p) were determined from two-tailed tests. Twenty-two of 38 (57.9%) evaluable children showed PHG. Children with PHG and AML were more likely to be in CR after first induction treatment (OR=6.25, p=0.021), independent of sex, age at diagnosis, white blood cell count, percentage of blasts in the bone marrow, FAB phenotype, and treatment protocol. Infections seemed to positively influence early treatment response (p=0.038). PHG and infections were not statistically associated (p=0.16). PHG may result from the uncontrolled stimulation of B lymphocytes by cytokines. Infections or transfusions may act as triggers for the immune system, leading to the antileukemic effect seen in patients with AML and PHG going into spontaneous remission. It could be that this activation caused the larger number of CRs observed in our series. Clarification of why PHG exerts a positive influence on children with AML could help us to understand the ways by which the organism is able to control a malignant disease.
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  • 67
    ISSN: 1432-0584
    Keywords: Key words Thrombopoietin ; Interleukin-11 ; Interleukin-6 ; Thrombocytopenia ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We measured serum levels of thrombopoietin (TPO), interleukin (IL)-11, and IL-6 in 90 different samples from 67 pediatric patients with thrombocytopenia (TP). The cytokine levels were determined by enzyme-linked immunosorbent assays (ELISA), and the biological activity of TPO was measured using a cell line transfected with human c-mpl. In patients with impaired megakaryocytopoiesis, as found in diseases such as aplastic anemia, amegakaryocytic TP, or TP with absent radii, we found TPO levels which were highly elevated compared with normal values (mean=261 AU/ml, n=52, vs. 22 AU/ml in healthy controls). In contrast, patients suffering from idiopathic thrombocytopenic purpura (mean=16 AU/ml, n=31) or platelet function defects (mean=23 AU/ml, n=7) demonstrated normal TPO levels. The biological activity tested in the bioassay correlated well with the ELISA data. However, sera of some patients with amegakaryocytic TP demonstrated a remarkably higher biological activity of TPO than expected from the ELISA data. Within the different groups there was no correlation between platelet counts and TPO levels. Only 27% of all samples had elevated levels of IL-11 (mean=450 pg/ml, n=20). Elevated IL-6 serum levels were detected in only 13% of all samples analyzed (mean=42 pg/ml, n=12). We conclude that megakaryocytopoiesis is regulated mainly by TPO, that it is dependent on the platelet and the megakaryocytic mass, and that IL-11 plays an additional role in supporting the platelet production. IL-6 does not appear to be up-regulated in children with thrombocytopenia.
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  • 68
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    Diabetologia 42 (1999), S. 711-718 
    ISSN: 1432-0428
    Keywords: Keywords Malnutrition ; ageing ; beta-cell mass ; apoptosis ; glucose tolerance.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. In a recently developed rat model, maternal food restriction from day 15 of pregnancy until weaning induced low birth weight and a 70 % reduction of beta-cell mass in the offspring at day 21 after birth. Subsequent renutrition from weaning was insufficient to fully restore beta-cell mass in young adult rats. The aim of this study is to investigate the long-term consequences of early malnutrition on beta-cell mass and function. Methods. Oral glucose tolerance tests were done in 3- and 12-month-old animals and beta-cell mass and apoptosis were determined by morphometrical measurements on pancreatic sections. The specific impact of postnatal malnutrition was studied by comparing control animals (C group) with animals malnourished during their fetal life only (R/C group), and animals malnourished during fetal life and until weaning (R group). Results. In 3-month-old R/C animals beta-cell mass reached 8.0 ± 1.5 mg with no further increase until 12 months (8.1 ± 1.5 mg), compared with 9.3 ± 1.9 mg in control rats. Twelve-month-old R/C animals showed normal plasma insulin responses and borderline glucose tolerance. In R animals, apoptosis reached 1.9 ± 0.4 % of the beta cells at 3 months, compared with 0.7 ± 0.5 % in control rats, and beta-cell mass did not increase between 3 and 12 months (4.7 ± 0.8 mg at 12 months). In aged control and R animals, apoptosis affected 8 % of the beta cells. At 12 months only, R animals showed profound insulinopenia and marked glucose intolerance. Conclusion/interpretation. In conclusion, perinatal malnutrition profoundly impairs the programming of beta-cell development. In animals with decreased beta-cell mass the additional demand placed by ageing on the beta cells entails glucose intolerance since beta-cell mass does not expand and apoptosis is increased. [Diabetologia (1999) 42: 711–718]
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  • 69
    ISSN: 1432-0428
    Keywords: Keywords Type I diabetes ; interferon-γ ; transgenic mice ; apoptosis ; insulin secretion ; tumour necrosis factor.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. To examine whether interferon-γ destroys islet beta cells directly or indirectly through lymphocyte activation, or whether direct action of interferon-γ on beta cells by itself induces diabetes without insulitis. Methods. To avoid possible nonspecific breakdown of beta cells by transgenic overexpression of interferon-γ by the insulin promoter, we generated transgenic mice expressing interferon-γ under the control of rat glucagon promoter (RGP-IFN-γ-Tg mice). Results. The absence of insulitis in RGP-IFN-γ-Tg mice enabled us to investigate the direct effects of paracrine interferon-γ. In RGP-IFN-γ-Tg mice, serum concentrations of interferon-γ and tumour necrosis factor-α (TNF-α) were 50 and 6 times higher than those in their littermates, respectively, and glucose-responsive insulin secretion decreased to one-half the level of that in the littermates. Transgenic interferon-γ induced remodelling of beta cells where apoptosis of many beta cells was compensated by their vigorous regeneration and diabetes did not occur in most of the RGP-IFN-γ-Tg mice. Conclusion/interpretation. Interferon-γ alone is insufficient for the complete destruction of beta cells in vivo, and factors other than interferon-γ including activated lymphocytes or other cytokines, are necessary in addition to interferon-γ for the development of Type I (insulin-dependent) diabetes mellitus. [Diabetologia (1999) 42: 566–573]
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  • 70
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    Zeitschrift für Lebensmittel-Untersuchung und -Forschung 208 (1999), S. 50-56 
    ISSN: 1431-4630
    Keywords: Key words Flavor enhancer ; Savory flavoring ; Taste ; Amino acids ; Partial least squares regression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Enzymatically hydrolyzed vegetable protein was produced from soy protein using hydrolysis times of 0–20 h. The development of sensory properties and the pattern of protein degradation was followed. Around two-thirds of the final amount of free amino acids and degree of hydrolysis (DH) were achieved during the first 4 h of hydrolysis. Between 6 h and 10 h of hydrolysis the bouillon-like tastes increased significantly (P〈0.001). In this time interval the amount of free amino acids exceeded 40% of the total amino acids and the DH exceeded 50% of the theoretically possible (100%). Using partial least squares regression with standardisation of free amino acid data according to their taste threshold values showed that free glutamic acid, aspartic acid and lysine correlated with the bouillon-like tastes. By standardisation of free amino acid data with respect to their SD the specificity of the enzymes for amino acid side-chains could be seen.
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  • 71
    ISSN: 1432-0428
    Keywords: Keywords Nicotinamide ; cytokine ; islet ; insulin ; apoptosis ; diabetes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Nicotinamide intervention trials are presently undertaken to prevent Type I (insulin-dependent) diabetes in high risk subjects. They are based on studies in rodents reporting nicotinamide protection against beta-cell injury in vitro and in vivo. This study examines whether nicotinamide can protect human beta cells in vitro. At concentrations (2 and 5 mmol/l) to protect rat beta cells against necrosis by streptozotocin or hydrogen peroxide, nicotinamide prevents hydrogen peroxide-induced necrosis of human beta cells. As with rat beta cells, nicotinamide fails to protect human beta cells against apoptosis induced by a combination of the cytokines interleukin-1β , interferon-γ and tumour necrosis factor-α. In rat beta cells, nicotinamide (2 to 20 mmol/l) was also found to induce apoptosis, in particular during the days following its protection against necrosis; this cytotoxic effect was not observed with human beta cells. These data demonstrate that nicotinamide can protect human beta cells against radical-induced necrosis, but not against cytokine-induced apoptosis. This effect is not associated with a delayed apoptosis as in rat beta cells. [Diabetologia (1999) 42: 55–59]
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  • 72
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    Zeitschrift für Lebensmittel-Untersuchung und -Forschung 208 (1999), S. 355-361 
    ISSN: 1431-4630
    Keywords: Key words Flavor enhancer ; Taste ; Amino acids ; Carbohydrates ; Maillard reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Hydrolyzed vegetable protein produced using hydrochloric acid (HVP) or proteolytic enzymes (EVP) was given a maturation period of up to 6 weeks at 30  °C. The maturation resulted in a darker color for both hydrolysates, but the sensory profiles were not altered to any great extent. For both hydrolysates a decrease in the amount of free amino acids or an increase in the amount of bound amino acids was seen, and for EVP, a decrease in the amount of free monosaccharides was likewise observed. In HVP the mono- and polysaccharides were destroyed during hydrolysis. The changes in amino acids could be due to, for example, a reversible binding to either a monosaccharide in EVP or a degradation product of carbohydrates in HVP, leading to the first stage of the Maillard reaction. These early reactions did not proceed to any flavor-giving Maillard reaction compounds. Maturation can therefore not be used to enhance the flavor of protein hydrolysates under the applied production conditions.
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  • 73
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    Cancer chemotherapy and pharmacology 44 (1999), S. 203-209 
    ISSN: 1432-0843
    Keywords: Key words Vincristine ; Pharmacokinetics ; Repetitive dosing ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: We studied vincristine disposition after 169 weekly i.v. bolus injections in 32 children with acute lymphoblastic leukemia, non-Hodgkin lymphoma, or Wilms' tumor. The aim of the study was to determine intrapatient and interpatient variability in vincristine disposition and demographic, clinical, and biochemical characteristics influencing this variability. Methods: Vincristine plasma concentrations were measured by a high-performance liquid chromatography assay with electrochemical detection. A limited sampling strategy was used based on a bayesian parameter estimation algorithm that is part of the ADAPT II software package. A two-compartment, first-order model was fitted to the data, and pharmacokinetic parameters were calculated from the model using the ADAPT II software. For statistical analysis, analysis of variance (ANOVA), t test, simple and multiple regression analysis, and non-parametric or robust equivalents were used. Results: Results showed a large intrapatient and interpatient variability in distribution half-life, elimination half-life, total body clearance, apparent volume of distribution at steady state, and area under the concentration–time curve. Intrapatient variability was significantly smaller than interpatient variability for all these parameters except distribution half-life. The diagnosis or treatment protocol turned out to be the most predictive characteristic; leukemia and non-Hodgkin lymphoma patients had a significantly higher total body clearance than Wilms' tumor patients. Conclusions: We conclude that both intrapatient and interpatient variability in vincristine pharmacokinetics is large in pediatric cancer patients and that variability, although significantly influenced by diagnosis, largely remains unpredictable.
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  • 74
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    European journal of pediatrics 158 (1999), S. 519-522 
    ISSN: 1432-1076
    Keywords: Key words Pulmonary function test ; Adjustment ; Children ; Prediction equations ; Population specific
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fitting adequate prediction equations for pulmonary function test (PFT) parameters is crucial in the analysis of lung function tests and their interpretation. Our work aimed at studying the necessity of building population specific prediction equations, rather than using prediction equations built-in in commercial equipment. We used as an example results of studies carried out among Israeli schoolchildren. Second to sixth grade children (7–13 years old), 1064 boys and 1211 girls, were studied in Tel-Aviv. PFT (forced vital capacity, forced expiratory volume in 1st second, peak expiratory flow, forced expiratory flow in 50% volume, forced expiratory flow in 75% volume) performed by these children were adjusted for height, weight and age, for each sex separately, by a multiple regression procedure. Predicted PFT parameters of 300 boys and 301 girls aged 7–13 years, living along the southern shore of Israel, were calculated using the equations built for the same aged Tel-Aviv children as well as the prediction equations built-in in the spirometer used. The ratios between the observed PFT parameters in the southern children and their expected values, using the Israeli population specific equations, were around 1.00. Using the built-in equations resulted in ratios around 0.90. Conclusion The development of population specific prediction equations for PFT parameters is necessary. Such equations should be used both in clinical assessment to minimize misclassification (healthy/sick child) and in epidemiological studies.
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  • 75
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    European journal of pediatrics 158 (1999), S. 550-552 
    ISSN: 1432-1076
    Keywords: Key wordsShigella ; Toxic encephalopathy ; Children ; Brain oedema ; Shiga toxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 6-year-old girl is described who died following rapid neurological deterioration, ending in lethal cerebral oedema. Despite the absence of severe intestinal and metabolic derangement, Shigella was cultured from the stool. Toxic encephalopathy is responsible for death following this rare complication of childhood shigellosis in developed countries. The pathophysiology is unknown. Conclusion Lethal toxic encephalopathy can be caused by Shigella despite the absence of severe intestinal and metabolic derangement. If shigelllosis is suspected, headache may be a first significant sign for the development of toxic encephalopathy. Early recognition and rapid measures to prevent brain oedema may improve outcome.
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  • 76
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    Experimental brain research 126 (1999), S. 200-204 
    ISSN: 1432-1106
    Keywords: Key words Motor development ; Anticipatory postural adjustments ; Bimanual coordination ; Children ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Anticipatory postural adjustments (APA) are needed to perform a movement without perturbing posture. We investigated the development of APA in 3- to 4-year-old children during a bimanual load-lifting task. The task required maintaining a stable elbow position despite imposed or voluntary unloading of the forearm. Although children can compensate the consequences of unloading by using APA, their performance did not reach an adults’ level. In addition, children showed high intra-individual variability in the voluntary situation, revealed by the coexistence of both adult-like and immature patterns in kinematic and electromyographic data. In conclusion, the present study reports that APA, associated with a bimanual load-lifting task, are still being set up in 3- to 4-year-old-children. The intra-individual variability should decrease with age and be associated with a progressive mastering of the timing parameters characterizing APA.
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  • 77
    ISSN: 1432-1106
    Keywords: Key words Gabaculine ; NMR spectroscopy ; Microdialysis ; Amino acids ; Compartmentation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The aim of this work was to study the neurochemical effects in the brain of GABA-transaminase inhibition by systemic administration of gabaculine (100 mg/kg, i.a.) in the rat. In order to investigate neurotransmitter and related amino-acid compartmentation and metabolism, we have developed an original tool: the coupling, in vivo, on the same animal, of 2D COSY 1H-NMR spectroscopy with intracerebral microdialysis. The main result is a continuous increase in GABA levels, both in the intracellular compartment (up to 3000±450%; P〈0.001) and extracellular compartment (up to 808±82%; P〈0.01) at the sixth hour. The intracellular increase in GABA level became significant at the first hour following gabaculine administration, whereas the extracellular level increased as of the second hour, probably indicating that accumulation of GABA in nerve endings precedes its release in synaptic clefts. Moreover, the levels of the excitatory amino acids, glutamate and aspartate, were decreased both in the intra- and extracellular compartments, thus enhancing sedative effects of the drug. We also observed a decrease in the global energetic creatine-phosphocreatine pool, which also could be related to the sedative properties of gabaculine, measurable by the diminution of cortical electrical activity and mean arterial blood pressure. Finally, the coupling between 2D 1H-NMR spectroscopy and intracerebral microdialysis appears to be an original tool for investigating the cerebral metabolic effects induced by pharmacological agents, in situ, in living animals.
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  • 78
    ISSN: 1432-1076
    Keywords: Key words HIV-1 ; T-cells ; CD69 ; Activation ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the use of a whole-blood assay that measures spontaneous and activation-induced CD69 expression on peripheral blood T-cells in vitro for assessment of T-cell function in HIV-1-infected paediatric patients. Heparinized venous blood from 28 HIV-1 positive children and adolescents and 23 healthy controls was incubated for 4 h with or without 5 μg/ml phytohaemagglutinin (PHA). Thereafter, analysis of CD69 expression on CD4+ and CD8+ T-cells was done by flow cytometry; simultaneously we determined CD4+ T-cell counts and plasma HIV-1 viral load. Neither spontaneous nor PHA-induced CD69 expression differed significantly between HIV-1 positive patients and healthy controls. However, T-cells from HIV-1 positive patients with plasma HIV-1 viral load levels above 70 × 103 copies/ml showed a higher spontaneous CD69 expression than T-cells from patients with lower plasma viral load levels in different stages of the disease. Antiretroviral treatment in four patients reduced spontaneous CD69 expression in CD4+ T-cells and PHA-induced CD69 expression in CD4+ and CD8+ T-cells significantly after 8 weeks of therapy. Conclusion Spontaneous and activation-induced expression of the early (activation) antigen CD69 on peripheral blood T-cells does not distinguish HIV-1 positive patients from HIV-1 negative healthy controls and is not correlated with peripheral blood CD4+ T-cell counts. This test may not be a reliable marker for functional T-cell deficiency during early stages of HIV disease. Increased spontaneous as well as PHA-induced CD69 expression on T-cells from HIV-1-infected children and adolescents in vitro may rather reflect HIV-induced pre-activation of T-cells in vivo.
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  • 79
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    European journal of pediatrics 158 (1999), S. 662-667 
    ISSN: 1432-1076
    Keywords: Key words Somatosensory evoked potentials ; Far-field potentials ; Achondroplasia ; Foramen magnum stenosis ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Children with achondroplasia may have high cervical myelopathy due to stenosis of the cranio-cervical junction resulting in neurological disability and an increased rate of sudden death. To detect myelopathy we recorded somatosensory evoked potentials (SEPs) after median nerve stimulation in 30 patients with achondroplasia aged 13 months to 18 years (mean 6 years). In addition to the conventional technique of recording the cortical N20 and the central conduction time (CCT), we employed a noncephalic reference electrode recording the subcortical waveforms N13b and P13, generated near the cranio-cervical junction. The findings were related to the clinical status and MRI results. Eighteen patients had MRI evidence of spinal cord compression with indentation or narrowing of the upper cervical cord, and 13 showed signs of myelomalacia. Seven patients had neurological abnormalities. The sensitivities of the SEPs were 0.89 for cervical cord compression, 0.92 for myelomalacia and 1.0 for the clinically symptomatic patients. There were no false-positive results. The subcortical SEPs were more sensitive than the conventional recordings. However, the conventional SEPs were highly specific in the most severely affected patients; here the specificity was 1.0 for patients with myelomalacia and 0.96 for symptomatic patients. Postoperative SEPs improved after occipital decompression in two children. Conclusion The analysis of somatosensory evoked potentials, in particular of subcortical tracings, is useful in the detection of early cervical myelopathy in children with achondroplasia. Early neurosurgical decompression may prevent irreversible damage.
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  • 80
    ISSN: 1432-1076
    Keywords: Key words Antithrombin concentrate ; Children ; Septicaemia ; Acquired antithrombin deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Consumption coagulopathy is a serious problem in childhood. In addition to treatment of the underlying disease, consumption coagulopathy was previously treated with heparin. Nowadays it is treated by substitution of coagulation factors, especially antithrombin (AT) concentrate, alone or in combination with heparin. In this pilot study we administered AT concentrate (dosage 80 U/kgbw/d), without additional heparin treatment, to 29 children beyond infancy with acquired AT deficiency. Antithrombin, platelet count, fibrinogen, PT, and APTT were assayed before and during the course of AT substitution. These coagulation parameters returned to normal 48 hours after normalisation of the plasma AT level. AT levels normalised within 24 h of initial substitution in all children. Lethal outcome due to the underlying disease was observed in only two children. Conclusion Data of this pilot study suggest that, concomitantly with the treatment of the underlying disease, consumption coagulopathy in childhood can be managed successfully with early substitution of AT concentrate.
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  • 81
    ISSN: 1432-1076
    Keywords: Key words Coagulation ; Fibrinolysis ; Head injury ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study was designed to evaluate the post-trauma haemostatic changes in 27 children with severe cranio-cerebral trauma defined by a modified Glasgow Coma Score (GCS) 〈10. Blood samples for coagulation studies (fibrinogen, von Willebrand factor (vWf), factor VIII:C, antithrombin, protein C, plasminogen, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI), D-dimer) were obtained within two hours of admission, 24 h later, and on days 3–5, 7–9, 21 and 35. Data of this study indicate that alterations of coagulation in paediatric patients are similar to those in adults: On hospitalisation, activated haemostasis was found with decreased fibrinogen, antithrombin and protein C along with enhanced t-PA and PAI. Twenty-four hours later, hypercoagulability with significantly increased vWF and fibrinogen started, with a peak level within the second week. Within 24 h of admission, 17 children developed disseminated intravascular coagulation (DIC) with a clear-cut decrease of antithrombin and fibrinogen together with platelet consumption and enhanced D-dimer. The outcome of children with DIC was significantly poorer than in those without DIC. Complete recovery was seen in five patients; sequelae no handicap and moderate disability were each found in six patients. Severe disability was diagnosed in two children, and fulminant DIC with lethal outcome occurred in eight patients. The GCS (P 〈 0.01) and the occurrence of DIC (P 〈 0.005) showed the strongest association with the patients' clinical outcome. Conclusion Our data underline the significance of post-trauma disturbances of the haemostatic system for the clinical course and outcome in children with severe cranio-cerebral injuries.
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  • 82
    ISSN: 1432-1084
    Keywords: Key words: Lung disease ; Pneumoconiosis ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. We report two cases of children with malignancies and subpleural nodules found on computed tomography (CT) scan. In both cases the diagnosis was anthracosis. This pathologic condition has never been reported in children. Causes of anthracosis include a smoking environment, living in urban areas and air pollution.
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  • 83
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    Neuroradiology 41 (1999), S. 512-516 
    ISSN: 1432-1920
    Keywords: Key words Meninges ; Tumours ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Childhood meningeal tumours are uncommon and mostly meningiomas. We reviewed the histological and radiological findings in meningeal tumours in six children aged 12 years or less (four benign meningiomas, one malignant meningioma and one haemangiopericytoma). Compared to the adult counterpart, childhood meningiomas showed atypical features: cysts, haemorrhage, aggressiveness and unusual location. MRI features varied according to the site of the tumour, histology, haemorrhage, and presence of intra- or peritumoral cysts. Diagnosis of the extra-axial tumour was relatively easy in two patients with meningiomas, one malignant meningioma and one haemangiopericytoma. MRI findings strongly suggested an intra-axial tumour in two patients with benign meningiomas, because of severe adjacent edema. Awareness of the variable findings of childhood meningiomas and similar tumours may help in differentiation from brain tumours.
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    Neuroradiology 41 (1999), S. 929-934 
    ISSN: 1432-1920
    Keywords: Key words Magnetic resonance imaging ; diffusion weighted ; Myelination ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the changes in brain water diffusion in childhood as seen on diffusion-weighted MRI in 30 children from 1 day of life to 17 years to provide a data base and to investigate the correlation of diffusion changes with known patterns of white matter maturation. The apparent diffusion coefficient (ADC) and apparent anisotropy (AA) were calculated in numerous regions of the brain to include major white matter tracts and gray matter. ADC and AA values were directly related to the structural maturity and compactness of the white matter tracts and changed with aging in a way that predated early myelination markers such as signal change on T1- or T2-weighted images. Diffusion of water is sensitive to structural changes in the brain such as white matter maturation and may be useful in investigating white matter disorders.
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  • 85
    ISSN: 1432-1939
    Keywords: Key words Estuarine food web ; Stable isotopes ; Amino acids ; Growth experiment ; Crustacean metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The stable isotope compositions (C and N) of plants and animals of a marsh dominated by Spartina alterniflora in the Delaware Estuary were determined. The study focused on the juvenile stage of the Atlantic blue crab, Callinectes sapidus, and the importance of marsh-derived diets in supporting growth during this stage. Laboratory growth experiments and field data indicated that early juvenile blue crabs living in the Delaware Bay habitat fed primarily on zooplankton, while marsh-dwelling crabs, which were enriched in 13C relative to bay juveniles, utilized marsh-derived carbon for growth. In laboratory experiments, the degree to which juvenile blue crabs isotopically fractionated dietary nitrogen, as well as the growth rate, depended on the protein quality of the diet. The range of δ13C of amino acids in laboratory-reared crabs and their diets was almost 20‰, similar to the isotopic range of amino acids of other organisms. In laboratory studies, the δ13C of nonessential and essential amino acids in the diet were compared to those in juvenile crabs. Isotopic fractionation at the molecular level depended on diet quality and the crabs' physiological requirements. Comparison of whole-animal isotope data with individual amino acid C isotope measurements of wild juvenile blue crabs from the bay and marsh suggested a different source of total dietary carbon, yet a shared protein component, such as zooplankton.
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  • 86
    ISSN: 1432-2099
    Keywords: Key words Case-control study ; Children ; CNS tumour ; Environmental exposure ; Indoor radon ; Leukaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract  A population-based case-control study on risk factors for childhood malignancies was used to investigate a previously reported association between elevated indoor radon concentrations and childhood cancer, with special regard to leukaemia. The patients were all children suffering from leukaemia and common solid tumours (nephroblastoma, neuroblastoma, rhabdomyosarcoma, central nervous system (CNS) tumours) diagnosed between July 1988 and June 1993 in Lower Saxony (Germany) and aged less than 15 years. Two population-based control groups were matched by age and gender to the leukaemia patients. Long-term (1 year) radon measurements were performed in those homes where the children had been living for at least 1 year, with particular attention being paid to those rooms where they had stayed most of the time. Due to the sequential study design, radon measurements in these rooms could only be done for 36% (82 leukaemias, 82 solid tumours and 209 controls) of the 1038 families initially contacted. Overall mean indoor radon concentrations (27 Bq m–3) were low compared with the measured levels in other studies. Using a prespecified cutpoint of 70 Bq m–3, no association with indoor radon concentrations was seen for the leukaemias (odds ratio (OR): 1.30; 95% confidence interval (95% CI): 0.32–5.33); however, the risk estimates were elevated for the solid tumours (OR: 2.61; 95% CI: 0.96–7.13), mainly based on 6 CNS tumours. We did not find any evidence for an association between indoor radon and childhood leukaemia, which is in line with a recently published American case-control study. There is little support for an association with CNS tumours in the literature.
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  • 87
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    Der Radiologe 39 (1999), S. 472-477 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Fremdkörper ; Ingestion ; Kinder ; Diagnostik ; Key words Foreign body ; Ingestion ; Children ; Diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Foreign body ingestion is not infrequent in infants and children. The diagnosis of radiopaque foreign body ingestion does not pose a major problem. It is crucial to take an X-ray from the pharynx to the level of the pylorus. If a foreign body that might get stuck at the ileocoecal valve is ingested, it is necessary to perform a radiograph of the whole abdomen. Foreign bodies that do not pass the cardia must be extracted endoscopically. In the case of foreign bodies with a smooth contour that have passed the pylorus, parents are advised to check the child’s stool or collect it and bring it for X-raying. If after a week there is no definite evidence that the foreign body has been excreted a follow-up radiograph is carried out. If the foreign body is still in the stomach or duodenum, endoscopy is necessary. The detection of nonopaque foreign bodies can be facilitated by giving oral contrast medium, making the depiction of the foreign body as a filling defect possible. As a complication, perforation can occur, the diagnosis of which may entail the use of sonography, conventional radiography and, to a lesser extent, CT.
    Notes: Zusammenfassung Fremdkörperingestion ist im späten Säuglings- und frühen Kleinkindalter kein seltenes Ereignis. Die Diagnose röntgendichter Fremdkörper bereitet keine Schwierigkeiten. Hierbei ist jedoch zu beachten, daß die Region vom Pharynx bis zum Pylorus abgebildet sein sollte. Wurden Fremdkörper verschluckt, bei denen die Gefahr der Einklemmung in der Bauhin’schen Klappe besteht, sollte das komplette Abdomen bis zum Anus dargestellt werden. Fremdkörper, welche die Kardia nicht passieren, müssen endoskopisch extrahiert werden. Haben glatt begrenzte Fremdkörper den Pylorus passiert, werden die Eltern aufgefordert, den Stuhl zu untersuchen oder zu sammeln und ihn zur röntgenologischen Untersuchung mitzubringen. Sollte der Fremdkörper innerhalb einer Woche nicht auffindbar sein, wird eine Kontrolluntersuchung durchgeführt. Ist der Fremdkörper dann noch im Magen oder im Duodenum, sollte er ebenfalls extrahiert werden. Der Nachweis nicht röntgendichter Fremdkörper kann mittels Gabe von positivem Kontrastmittel als Aussparungsfigur gelingen. Als Komplikation kann eine Perforation auftreten. Hierbei dienen Sonographie, konventionelles Röntgen und gegebenenfalls CT zur Diagnosefindung.
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  • 88
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    European journal of pediatrics 158 (1999), S. S154 
    ISSN: 1432-1076
    Keywords: Key words Veno-occlusive disease ; Antithrombin ; Children ; Chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hepatic veno-occlusive disease (VOD) is a well-known complication of chemotherapy in Wilms tumor patients, particularly young children. Although this complication resolves uneventfully in most patients, fatal cases have been reported. Severe VOD after transplantation has a high mortality rate ranging from 45% to 98%. New hemostatic therapeutic strategies have significantly improved the prognosis of VOD. Chemotherapy-related VOD in Wilms tumor usually has a good prognosis. We describe two patients with Wilms tumor and one with acute lymphoblastic leukemia, who developed severe veno-occlusive disease of the liver according to the Baltimore criteria while undergoing chemotherapy; the symptoms were hepatomegaly, ascites, hyperbilirubinemia, weight gain and, in one patient, short-term lethargy. Elevated LDH levels of 872 to 12,000 U/l were observed in our patients. All patients had thrombocytopenia between 29,000 and 40,000/μl and decreased antithrombin (AT) and protein C levels; two patients had gastrointestinal bleeding. All patients developed a coagulopathy because of severe hepatic dysfunction. Two patients received low-dose heparin at the onset of VOD. The thrombolytic therapy was rapidly changed to AT supplementation (20–80 IU/kg bw 2× per day) without heparin when thrombocytes were very low or gastrointestinal bleeding occurred. Resolution of VOD was observed in all patients receiving AT alone. The chemotherapy was discontinued in a patient with accidental actinomycin D overdosage in view of the severity of symptoms. The remaining two patients received chemotherapy according to the therapy protocol after restitution. All patients survived without sequelae with a median follow-up of 28 months (range 8–48 months). Conclusion Hepatic veno-occlusive disease is a rare but increasingly recognized complication in pediatric cancer patients receiving conventional chemotherapy. AT supplementation constitutes a good alternative treatment of severe VOD in comparison with other thrombolytic therapies, particularly in patients at high risk of bleeding.
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  • 89
    ISSN: 1432-1076
    Keywords: Keywords Liver ; Steatosis ; HIV ; AIDS ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thirty HIV-infected children were cross-sectionally examined for morphologic hepatic abnormalities, using ultrasonography or histology. Abdominal ultrasonography was performed in 27 children. The liver structure was normal in four patients, one of whom had moderate symptoms of the HIV infection and three of them severe symptoms. Abnormal liver structure, compatible with hepatic steatosis, was found in 23 (85%) patients. Five of them were in an early stage of the HIV infection (category N or A), three patients were ranked in category B and 15 patients in category C. Histological examination of the liver was performed in 11 children and steatosis was documented in ten (91%). In seven (70%) of these ten children steatosis had been suspected by ultrasonography. In conclusion, steatosis is common in HIV-infected children. It is non-specific and has no impact on disease, diagnostic evaluation or management. Conclusion Ultrasonography is a sensitive, accurate, non-invasive screening tool. It is more reliable than liver function tests.
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  • 90
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    European journal of pediatrics 158 (1999), S. 12-17 
    ISSN: 1432-1076
    Keywords: Key words Alternative medicine ; Complementary therapies ; Critical care ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The interest in alternative medicine (AM) is growing. In the USA and Canada, studies showed that 34% of adults and 11% of children use AM. In a prospective cohort study, we investigated the interest in AM among parents of critically ill children in the paediatric Intensive Care Unit (ICU) of a university hospital. From January 1996 to April 1997, we distributed questionnaires to the parents of critically ill children. These strictly anonymous questionnaires were completed at home and returned by mail. Exclusion criteria were short (〈1 day) or repeated hospitalizations, and insufficient proficiency of the German language. The inclusion criteria were fulfilled by 591 patients; 561 received the questionnaire (95%) and 289 (52%) were returned. Of the respondents, 70% would appreciate AM as a complementary therapy on the ICU, 23% found AM equally or more important than conventional medicine whereas only 7% regarded AM as unimportant. On the ICU, 18% used AM; surprisingly 41% of them did not discuss it with physicians or nurses. An additional 21% would have liked to use AM, but did not do so. Typically, AM-users administered AM also at home to their children and themselves. Their children were however, older. Conclusions A substantial proportion of parents used measures of alternative medicine in the intensive care unit, or would have like to do so. However, few had the confidence to discuss this wish with the medical personal. This suggests that alternative medicine is of great interest, even on an intensive care unit. Nevertheless, discussion about alternative medicine seems to be taboo in doctor-patient relations.
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  • 91
    ISSN: 1432-1076
    Keywords: Key words Mild head injury ; Fractured bone ; Late sequelae ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two years after an accident resulting in either a mild head injury or a fractured bone, two groups of 22 children each, aged 4–14 years, were examined for the existence of any neurobehavioural symptoms by means of a standardized questionnaire filled out by their caretakers. Selection of the children was based on reports of the Accident and Emergency Department in 1 year. Significantly more symptoms were reported after mild head injury. The main symptoms reported were headache, dizziness, fatigue and memory problems. The total number of symptoms in the children with mild head injury exceeded four times this in the group of children with a fractured bone. Conclusion Even 2 years after a mild head injury there are still residual symptoms in daily life.
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  • 92
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    European journal of pediatrics 158 (1999), S. S117 
    ISSN: 1432-1076
    Keywords: Key words Stroke ; Coagulation ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Many studies have shown a high percentage of venous thromboses in children to be associated with haematological disorders. However, studies assessing the influence of haemostaseological disorders on paediatric stroke are rare. We compared 26 children with cerebral infarction (median age 2 months, range 0–16.2 years) and 17 with venous thrombosis (median age 4.5 years, range 0–17 years) with regard to prothrombotic risk factors. Prothrombotic disorders were found in 8 out of 26 patients with cerebral infarction (FV Leiden mutation: n = 4; protein C deficiency: n = 1; FV Leiden mutation + protein C deficiency: n = 2; prothrombin mutation G20210A: n = 1) and in 13 out of 17 with venous thrombosis (FV Leiden mutation n = 3; protein C deficiency n = 5; elevated HRGP + PAI: n = 1; combined deficiency of AT, protein C and plasminogen: n = 1; F XII deficiency: n = 1; lupus anticoagulans n = 1; FV Leiden + F XII deficiency + lupus anticoagulans + PAI: n = 1). Comparison of these prevalences with those of 150 healthy paediatric controls showed in children with FV Leiden mutation and/or protein C deficiency an increased risk of cerebral infarction (patients vs. controls: 26.9% vs. 6%; OR 5.77; 95%-CI 1.92–17.3; P = 0.0031) as well as of venous thrombosis (53% vs. 5.3% 19.9; 95%-CI 6–65.6; P 〈 0.0001). This result is in contrast with reports on thrombophilia in cerebral infarction in adult patients. Conclusion Our results indicate that FV Leiden mutation and protein C deficiency may contribute to the multifactorial aetiology of stroke in early childhood.
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  • 93
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    European journal of pediatrics 158 (1999), S. 362-366 
    ISSN: 1432-1076
    Keywords: Key words Type 1 diabetes ; Children ; Risk factors ; Case control ; Environmental
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to investigate environmental risk factors in the development of type 1 diabetes mellitus in a population-based case-control study. Parents of all patients with manifestation of type 1 diabetes between 1989 and 1994 in Vienna were asked to complete a questionnaire (n = 114). Control children (n = 495), matched for age and sex, were randomly recruited from all schools in Vienna. Fathers of diabetic children were significantly older at the time their children were born than fathers of control children (P = 0.015). Children with diabetes were more likely to be second- or third-born children (P 〈 0.05) and fewer went to kindergarten than the control group children (P = 0.007). No significant difference in duration of gestation, percentage of delivery by caesarean section, birth weight or length was found. Neonatal jaundice was more often observed in the patient group (P = 0.038). Breast feeding was reported by 82.7% of mothers of diabetic children and by 81% of mothers of control children, and the duration of breast feeding was longer in patients than in controls (n.s.). Conclusion In our study, the development of type 1 diabetes mellitus was associated with higher paternal age and neonatal jaundice. No correlation could be found with dietary intake of cow's milk products in early infancy, vaccination and other environmental factors.
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  • 94
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    European journal of pediatrics 158 (1999), S. 24-28 
    ISSN: 1432-1076
    Keywords: Key words Hashimoto thyroiditis ; Graves disease ; Children ; TSH function-blocking antibody ; Cytotoxic antibody
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a cross-sectional study, 29 children aged between 1 month and 15.3 years (average age 6.8 years) born to mothers with Graves disease or Hashimoto thyroiditis were examined clinically, biochemically, and by sonography of the thyroid gland. At the time of examination all children were clinically euthyroid. Tests of thyroid peroxidase antibody, thyroglobulin antibody, TSH receptor antibody and free thyroxine (fT4) gave normal results. In 3 children subclinical hypothyroidism with elevated TSH and normal fT4 concentrations were found; one of these children had a minor decrease of total thyroxine. Three children with otherwise normal test results had marginally elevated tri-iodothyronine concentrations. Increased antibody titres were present in 8 out of 29 children. TSH function-blocking antibodies were elevated in 8 cases. In addition, cytotoxic antibodies were found in one of the children. The distribution pattern of antibodies was different in each child and unrelated to the type of maternal thyroid disease. Conclusion Children of mothers with auto-immune thyroid disease often have thyroid antibodies without signs of thyroid disease. Whether antibody-positive children have an increased risk of developing thyroid disorders later in life must be examined in a longitudinal study.
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  • 95
    ISSN: 1432-1076
    Keywords: Key words Gastro-intestinal bleeding ; Children ; Jejunal leiomyoma ; Neurofibromatosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gastro-intestinal bleeding is an uncommon presentation in children with neurofibromatosis. Gastro-intestinal involvement caused by jejunal leiomyoma has only been described in adults. To the best of our knowledge, this is the first paediatric case of jejunal leiomyoma associated with neurofibromatosis. We present a 10-year-old girl with a 9-month history of anaemia and low gastro-intestinal bleeding. Abdominal sonography and small bowel series showed a submucosal mass in the proximal jejunum. On surgery, a submucosal tumour was excised and histological examination suggested a diagnosis of “smooth muscle tumour of undetermined malignant potential”. There were no recurrence of symptoms for 4 years after the operation. Conclusion Jejunal leiomyoma should be considered in a child with neurofibromatosis presenting with gastro-intestinal bleeding.
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  • 96
    ISSN: 1432-1076
    Keywords: Key words Respiratory chain ; Mitochondria ; Children ; Infancy ; Liver failure ; AbbreviationsMRCD mitochondrial respiratory chain disease ; OLT orthotopic ; liver transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mitochondrial respiratory chain disease may lead to neonatal or late onset liver failure, requiring liver transplantation. In rare cases, the disease is restricted to the liver and the patient is cured after surgery. More frequently, other organs are simultaneously involved and neuromuscular or other extra-hepatic symptoms may pre-exist, or appear in the post-transplant follow up. Pre-transplant evaluation should aim to rule out neurological disease, which may be difficult to differentiate from signs accompanying liver insufficiency. Cerebrospinal fluid lactic acid levels, compared to blood lactate, may be suggestive of central nervous system involvement. Of 11 cases with respiratory chain disorders who had liver transplantation in various centres, 4 are alive and well on follow up, and 6 died, three of them having developed neurological disease post orthotopic liver transplantation. All three patients with initial liver and gastro-intestinal disease died early after transplantation, indicating that these may be poor candidates for this procedure. Conclusion Liver transplantation is feasible in hepatic respiratory chain disorders, but extra-hepatic disease should be ruled out before transplantation. Extra-hepatic manifestations may, however, appear and cause patient death despite successful transplantation.
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  • 97
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    European journal of pediatrics 158 (1999), S. S085 
    ISSN: 1432-1076
    Keywords: Key wordsα1-Antitrypsin ; Liver disease ; Liver transplantation ; Children ; AbbreviationsAATα1-antitrypsin deficiency ; OLT orthotopic liver transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Only a minority of infants born with α1-antitrypsin deficiency will develop serious liver disease during childhood, mostly but not always after neonatal cholestasis. Early prognosis is difficult and all children have to be followed up carefully. The liver disease progresses with varying speed and it lacks specific features. At the time of liver transplantation the young patients have no pulmonary disease induced by the deficiency and in those with renal involvement, the kidney problems can mostly be dealt with by conservative therapy. The peri- and postoperative care of the patients who undergo liver transplantation does not differ from the usual routines.
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  • 98
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    European journal of pediatrics 158 (1999), S. 298-301 
    ISSN: 1432-1076
    Keywords: Key words Isolated ; Sphenoid ; Sinusitis ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acute isolated infectious sphenoiditis is an uncommon, potentially dangerous condition which is often misdiagnosed because of its nonspecific symptoms and paucity of clinical signs. We present eight children with isolated sphenoiditis who were managed in our medical centre during the last 2 years and review the literature. All the patients were adolescents or pre-adolescents and all experienced moderate to severe refractory oppressive headache. Four had a history of sinusitis or allergic rhinitis. None had fever or any other directing clinical sign. Diagnosis was made by cranial computer tomography. All were treated with antibiotics and recovered completely without infectious or neurological complications. Conclusion Acute isolated infectious sphenoiditis should be considered in adolescents and pre-adolescents who present with constant moderate to severe oppressive headache. Awareness of this entity will enable early diagnosis and initiation of antibiotic treatment which is essential to avoid complications and surgical intervention.
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  • 99
    ISSN: 1432-1076
    Keywords: Key words Heparin treatment ; Heparin-induced thrombocytopenia ; HIT antibodies ; Children ; Catheter patency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The immunological form of heparin-induced thrombocytopenia (HIT) is a potentially life-threatening adverse reaction of heparin medication. It is mediated by multimolecular complexes consisting of platelet factor 4 (PF4)-heparin-IgG which bind to platelets via platelet Fcγ receptors. Cross-linking of multiple Fcγ receptors results in platelet activation, platelet aggregation and enhanced thrombin generation with a increasing risk of developing new thrombosis. In children, data on HIT are sparse. This review of the literature reports on 8 children aged 3 months to 15 years and 14 newborns suffering from HIT. Additionally, we report one new case treated with danaparoid sodium. Thrombotic complications were venous (n = 12) and arterial (n = 15). The children received heparin either for a spontaneous thrombotic event, for severe cardiac diseases or to maintain patency of intravascular catheters which are used for nutrition, blood sampling, and for application of medication. After diagnosis of HIT they were further anticoagulated with aspirin, warfarin, danaparoid sodium, lepirudin or low molecular weight heparin. Conclusion Although HIT is less frequently reported in newborns and children, paediatricians should be aware of HIT in childhood as a potential complication of heparin application. The widespread practice of flushing catheters with heparin should also be debated in view of the risk of triggering the primary immune-response of HIT. In 1999, treatment options for further parenteral anticoagulation of HIT patients are danaparoid sodium (a low-molecular weight heparinoid) and lepirudin (a direct thrombin inhibitor).
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  • 100
    ISSN: 1432-1076
    Keywords: Key words Factor V G1691A ; Prothrombin G20210A ; Lipoprotein (a) ; Central venous lines ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate the role of inherited thrombophilia in the development of central venous line (CVL)-related thrombosis, the following parameters were determined in 77 pediatric-oncologic patients with CVL: activated protein C (APC)-ratio, factor V (FV) G1691A and prothrombin G20210A mutation, protein C, protein S, antithrombin, coagulation factor XII, lipoprotein (a) and homocysteine. An inherited prothrombotic risk factor was found in 17 patients (23%). Four out of 14 patients with a single defect (hyperlipoproteinemia, heterozygous FV G1691A and prothrombin G20210A mutation, protein C deficiency type I) and all three patients with combined defects (heterozygous FV G1691A mutation combined with heterozygous prothrombin G20210A variant, protein S deficiency or hyperlipoproteinemia) suffered from CVL-related thrombosis. In 11 out of 77 patients (14%) a CVL-related thrombosis was detected. In 2 children thrombosis occurred a few days after asparaginase therapy and in another three thrombosis was associated with CVL-related septicemia caused by Staphylococcus epidermidis. After removal of CVL, thrombosis was detected in 5 children, in 2 without clinical symptoms but in the presence of inherited prothrombotic risk factors. Conclusion The present study demonstrates the clinical importance of CVL in combination with inherited thrombophilia in the development of thrombosis in pediatric-oncologic patients. Before or shortly after insertion of CVL, patients should be tested for the presence of factor V G1691A mutation, prothrombin G20210A variant and increased lipoprotein (a) values.
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