Gamma-hydroxybutyrate versus chlorprothixene/phenobarbital sedation in children undergoing MRI studies.

BACKGROUND: Few clinical studies have assessed gamma-hydroxybutyrate and chlorprothixene/phenobarbital sedation in children. This prospective trial compared the two regimes in children, in particular concerning differences in recovery time. METHODS: 28 pediatric oncology patients undergoing elective MRI studies at a university hospital were randomly assigned to either receive gamma-hydroxybutyrate or chlorprothixene/phenobarbital sedation. Time to induce deep sedation (Ramsay score of 5) and recovery time, the incidence of failure of sedation, the frequency of side effects, the need for therapeutic interventions, and the number of patients receiving additional midazolam were recorded. Analysis of hemodynamic parameters was performed at five defined time points. RESULTS: All 28 MRI studies were successfully completed. Recovery time was significantly shorter with gamma-hydroxybutyrate (p < 0.01). There were more side effects with chlorprothixene/phenobarbital, in particular tachycardia and hyperexcitation. Vomiting was the side effect most often seen in gamma-hydroxybutyrate sedation. Therapeutic interventions were not required in any patient. Additional midazolam was necessary to maintain satisfactory sedation in six children receiving gamma-hydroxybutyrate and four receiving chlorprothixene/phenobarbital. CONCLUSIONS: Due to its significantly shorter recovery time, gamma-hydroxybutyrate is a reasonable sedative drug for children undergoing non-invasive diagnostic procedures, and is superior to chlorprothixene/phenobarbital. In pediatric oncology patients gamma-hydroxybutyrate appears to be associated more often with vomiting. The long recovery time and its great variability make chlorprothixene/phenobarbital a less valuable alternative.

[Ultrasonography of hips in neonates].

For evaluation of the development of the hip joints in young infants, between Jun., 1988 and Oct., 1991, 522 hips of the infants under 4 months of age were studied by ultrasonography based on the method well described by Graf. The results revealed only 48% of the hips of neonatal group was type I (stable type). But this percentage increased with age: 90% in the group under 2 months of age; 97% in the group under 4 months of age. Compared with the findings of other studies in Europe, the development and the stability of the hips of our neonatal group seemed poorer. But this condition improved much within 2 months after birth. So we concluded that, except the high risk group, the ultrasonographic screening approach should be performed after 2 months of age, but not in neonatal period under considering the cost-benefit.

[Value of serum sialic acid determination in children]. / Wertigkeit der Sialinsäurebestimmung im Serum bei Kindern.

In order to find out whether sialic acid (SA) is suitable as a tumor marker this compound was determined in the sera of 48 healthy and of 168 sick children. In healthy children under six months of age lower concentrations of SA were found (x = 41 +/- 5 mg/dl) than in subjects aged six months to 18 years (x = 68 +/- 8 mg/dl). Inflammatory diseases of various etiologies lead to a significant increase in both age groups (x = 93 +/- 28 mg/dl), the same could be observed in subjects up to 14 days after surgery. In children with malignant disorders the concentration of SA was significantly higher (x = 83 +/- 27 mg/dl) than in the healthy subjects, but not higher than in patients with inflammatory diseases. We conclude that SA might play a role in the follow up protocol of patients with malignant tumors.

[Clinical evaluation of a test strip for measuring creatinine in capillary blood of children]. / Klinische Erprobung eines Teststreifens zur Messung des Kreatinins im Kapillarblut von Kindern.

Basing on an enzymatic method for determining creatinine, the new reagent strip "Reflotron Creatinin" of the Reflotron system recently was presented. In this study, it will be compared with another enzymatic test (Creatinin-PAP) and with a Jaffe-based assay (Creatinin-Jaffe for Hitachi 737). The quality control (within-days and within-series) yielded a sufficient accuracy and precision (CV = 4%) for the charge of used test strips. The recovery of double measured values was very good (r greater than 0.94). As regards the method comparison, differences in both charges were seen. The values of the former charge lay 7% on an average below the Jaffe-values, those of the latter 28% below. The slope of the latter regression line was considerably steeper. Comparing both enzymatic tests, the regression analysis gave poor results (y = -0.33 + 1.35 x). Bilirubin had not remarkable influences, whereas an evelated hematocrit slightly depressed the values. It seems necessary to start further studies to clear up the difference in test strip charges and to check more capillary blood samples of newborn and children with a pathologic creatinine level.

[The effect of methotrexate pharmacokinetics and of leucovorin rescue on the prognosis of osteosarcoma]. / Einfluss der Methotrexatpharmakokinetik und des Leukovorinrescues auf die Prognose des Osteosarkoms.

A total of 129 high-dosage methotrexate therapies performed in 19 patients with osteosarcoma were retrospectively analyzed. Serum methotrexate peak concentrations were found to vary widely, both inter-individually as well as in the same patient. The measured MTX peak concentrations correlated closely with pharmacokinetic data such as area under the curve and total body clearance. No correlations were found between the serum MTX correlations and different times after methotrexate administration. Increase in leucovorin rescue or low MTX peak concentrations were associated with poor prognosis. High-dosage methotrexate therapies with leucovorin rescue need to be further optimized in accordance with biochemical knowledge of the mode of action and the individual pharmacokinetic data of methotrexate. Such optimization may be expected to improve the prognosis for osteosarcoma. Serum methotrexate concentrations should be determined not only 24, 48, and 72 hours after methotrexate administration, in order to avoid elevated toxicity of the therapy, but also at the start of methotrexate infusion, in order to influence MTX peak concentrations at an early stage if necessary. Measurement of L-leucovorin in serum will be necessary, to enable a restrictive leucovorin rescue to be performed safely.

[The clinical significance of pseudouridine determination of the urine in children and adolescents]. / Die klinische Bedeutung der Pseudouridinbestimmung im Urin von Kindern und Jugendlichen.

A HPLC-method is described to determine the Pseudouridine/creatinine ratio in spontaneous urine samples in infancy and childhood. The urines of 74 healthy children between 1 and 18 years of age and of 231 children with different diseases were examined for this ratio, making 1097 measurements. 157 children suffered from a malignant disease, 66 of them having an acute leukemia. Those patients, who remain in remission of the leukemia showed normal values, whereas the others had elevated ratios, reflecting the activity of the leukemia, when they were followed up by multiple determinations. Perhaps it is also possible to detect preclinical stages of leukemia by measuring the pseudouridine/creatinine ratio routinously over a long period of time. Today no strict correlation between the prognosis of leukemia and the level of this ratio can be drawn. Similar behaviour of the pseudouridine/creatinine ratio is seen in other malignant diseases with exception of brain tumors. The difference to leukemias is, that all other malignant tumors show more often normal values in patients with a remaining tumor. A pathological value of pseudouridine may also be seen in others than malignant diseases.

[Selenium concentration in the cerebrospinal fluid of children]. / Die Selenkonzentration im Liquor cerebrospinalis von Kindern.

Following a wet digestion of 0.5-2.0 ml cerebrospinal fluid in an open system using 2.0 ml nitric acid and 1.0 ml perchloric acid (240 degrees C) and a reduction step with 1.0 ml hydrochloric acid, Selenium can be determined polarographically after adding 100 micrograms Copper(II)-ions to the analyte (15 ml; water/perchloric acid). Selenium concentrations in cerebrospinal fluid of children younger than one year (2.49 +/- 1.67 ng/ml) are significantly higher (p = 0.0074) than those of older children (1.28 +/- 0.97 ng/ml). Independent of the children age and diseases the Selenium concentrations correlate distinctly with cell numbers and protein contents. A correlation between Selenium content and cell numbers alone could not be proved. The nonsignificant differences between the Selenium concentrations in cerebrospinal fluids of children with hydrocephalus, leukemia (with or without involvement of the central nervous system), and other diseases, respectively, may be interpreted by considering the protein content of the cerebrospinal fluid and the age of the children.

[Selenium concentration in the cerebrospinal fluid of children]. / Die Selenkonzentration im Liquor cerebrospinalis von Kindern.

Following a wet digestion of 0.5-2.0 ml cerebrospinal fluid in an open system using 2.0 ml nitric acid and 1.0 ml perchloric acid (240 degrees C) and a reduction step with 1.0 ml hydrochloric acid, Selenium can be determined polarographically after adding 100 micrograms Copper(II)-ions to the analyte (15 ml; water/perchloric acid). Selenium concentrations in cerebrospinal fluid of children younger than one year (2.49 +/- 1.67 ng/ml) are significantly higher (p = 0.0074) than those of older children (1.28 +/- 0.97 ng/ml). Independent of the childrens age and diseases the Selenium concentrations correlate distinctly with cell numbers and protein contents. A correlation between Selenium content and cell numbers alone could not be proved. The non-significant differences between the Selenium concentrations in cerebrospinal fluids of children with hydrocephalus, leukemia (with or without involvement of the central nervous system), and other diseases, respectively, may be interpreted by considering the protein content of the cerebrospinal fluid and the age of the children.

[Behavior of glucosephosphate isomerase in children with malignant diseases]. / Verhalten der Glucose-Phosphat-Isomerase bei Kindern mit malignen Erkrankungen.

The normal range of glucose-phosphate-isomerase (GPI) in the plasma of children during the first month of life is up to 80 U/l; until the end of the second year of life between 11 and 50 U/l; thereafter the upper limit is 46 U/l. In osteogenic sarcoma or medulloblastoma there is a good correlation between activity of GPI in plasma and clinical tumor stage. In a lot of other tumors sensitivity of this enzyme is either very low as in Ewing-sarcoma or myeloic leukemia or there is no consistent relation to the extent of the tumor. High activities of GPI are equally obtained in children suffering from cystic fibrosis, diabetes mellitus or muscular dystrophy. GPI is not valid as a tumor marker even being raised in sarcoma and medulloblastoma as mentioned. So it is not necessary to check GPI activity as a part of routine enzyme chemistry.

Generalised glucosephosphate isomerase (GPI) deficiency causing haemolytic anaemia, neuromuscular symptoms and impairment of granulocytic function: a new syndrome due to a new stable GPI variant with diminished specific activity (GPI Homburg).

A new glucosephosphate isomerase (GPI) variant is described which is characterised by very low specific activity in erythrocytes, granulocytes and muscle tissue, nearly normal stability, normal kinetic properties and a decreased electrophoretic mobility. The propositus suffers from a complex syndrome involving erythrocytes (congenital haemolytic anaemia), granulocytes (decreased production of superoxide anion and reduced bactericidal activity in vitro) and the neuromuscular system (myopathy, mental retardation). It is suggested that the clinical syndrome results from generalised GPI deficiency due to a decreased specific activity of the variant enzyme, which cannot be compensated by an increase of de-novo synthesis of GPI protein even in cells exhibiting active protein synthesis such as granulocytes and muscle cells.

[Determination of chymotrypsin in the feces by a new photometric method]. / Bestimmung des Chymotrypsins im Stuhl mit einer neuen photometrischen Methode.

Fecal chymotrypsin (FCT) was determined in stool specimens of healthy children and those with gastro-intestinal disease, by a new photometric method. The values are comparable with chymotrypsin concentrations found by pH-stat method. The new test is cheap, reliable and easy to perform. For this reasons and for the sensitivity of all tubeless pancreatic function tests (NBT-PABA, FDL, FCT) is rather low (60-70%), the FCT-test may be preferred as diagnostic marker for differential diagnosis of exocrine pancreatic insufficiency.

[Immunoreactive trypsin in the serum of normal children and children with gastrointestinal diseases]. / Immunreaktives Trypsin im Serum gesunder Kinder und solcher mit gastrointestinalen Erkrankungen.

Serum immunoreactive trypsin (IRT) was measured in cord blood and blood specimens of 156 healthy children of different age. These results were compared with the IRT of children with gastrointestinal disease. While IRT from newborn is significantly elevated, mean trypsin levels form older children do not differ from those found in adults. In acute pancreatitis too, as in renal failure, trypsin is elevated. Low trypsin values were estimated in acute hepatitis and Crohn's disease. In cystic fibrosis (CF) serum trypsin levels depend on the exocrine function of the pancreas. The IRT assay on dried blood-spots, seems to become a reliable and convenient neonatal screening test for CF in newborns.

[N-acetyl-cystein-(NAC)-activated creatinkinase (CK) and isoenzyme CK-MB in the serum of children]. / N-Acetyl-Cystein-(NAC)-aktivierte Kreatinkinase (CK) und Isoenzym CK-MB im Serum von Kindern.

We have examined the variation of creatinekinase levels (NAC-activated) with age in 170 children. The subjects included 40 neonates, 18 premature neonates, 40 small babies, 32 infants and 40 schoolchildren. The enzyme activity of CK-MM was very high in the first hours after delivery and remained high for a few days. The isoenzyme MB in healthy newborns also showed a higher catalytic concentration. These values (about 2-12 U/l) reached normal levels of adults within 4 months of life (0.5-5 U/l). The same rule applied to CK-MM: enzyme activities of 160 U/l and more in the first days of life declined to 16-75 U/l during the first 4 months. No correlation between birth trauma and the increase in serum-CK was found. Because of the increased CK-MM (and CK-MB) found in normal newborns screening for Duchenne-type muscular dystrophy should be postponed for a few weeks after delivery. In view of the relatively high endogenous serum CK-MB in the neonates (release of CK-MB from the skeletal muscle) the test lacks the specificity for cardiac damage. Intramuscular injections of several drugs lead to a distinct increase in CK activity. A rise of CK-MM was seen 4-24 h after catheterization of the heart.

[New culture method for the diagnosis of bacteriurias]. / Neues kulturelles Verfahren zum Nachweis von Bakteriurien.

The aim of this study is to check the clinical relevance of a new cultural method for the detection of urinary tract infection especially in urine samples containing residue of antimicrobial agents. The new procedure concerns a urine collecting and cultivating cup (UCCC Biotest Serum Institute), containing a recovery agar (RA5) with incorporated chemotherapeutica antagonists. The efficiency of the UCCC is compared with the familiar dip slide coated with cystein lactose electrolyte deficient (CLED) agar and MacConkey agar. A collective of 305 children is considered in this study. The investigation was carried out before starting, three to five days after starting and three to five days after stopping the chemotherapy. The highest correlation between the microbial count in urine samples and the whole clinical diagnosis was achieved with RA5. The lowest correlation was attained with MacConkey agar. With CLED agar a good correlation was determined before starting therapy, a modest correlation during therapy and very good correlation after stopping therapy. Regarding relapses and reinfections the detection quote of relevant bacteriuria during therapy amounted to 90% as RA5 was used, 62% with CLED agar and 34,5% with MacConkey. RA5 proved very useful for follow-up purposes, especially during treatment with antimicrobial agents and may be considered as a susceptibility testing in vivo.

[Examination of pancreatic function in children with special reference to the PABA-test (author's transl)]. / Pankreasfunktionsdiagnostik, insbesondere PABA-Test, im Kindesalter.

To establish the diagnosis of acute pancreatitis the estimation of amylase in serum and urine, lipase and radio-immunoreactive trypsin in the serum are useful. Lipase estimations are more helpful than measuring amylase values. Trypsin-RIA-tests are increasingly important adults. But in chronic pancreatitis and inborn secretory insufficiencies of the pancreas these methods are less helpful. PABA-test, pancreolauryl-test (PLT), and the estimation of chymotrypsin in faeces are screening procedures, although their results correlate well amongst each other. As compared to the chymotrypsin estimation in faeces PABA test and PLT allow for some semiquantitative estimation of the secretory function and dynamics of the gland. The influence of malabsorption, liver and kidney diseases on these parameters is not yet quite clarified. Besides screening they are undoubtedly of value for judging the course and therapy of cystic fibrosis, Shwachman-syndrome, iatrogenic lesions by cytostatics (immunosuppressives and corticosteroids). Quantitative estimations of fat in faces and the pancreozymin test are no longer of significance.

[Generalized mycobacterium avium infection in an infant (author's transl)]. / Generalisierte Mycobacterium avium-Infektion bei einem Kleinkind

In a 3-year-old girl, who was admitted to our hospital with marked splenomegaly, a swollen abdomen and progressive loss of weight, the difficulty in establishing the correct diagnosis, namely a very rare generalized infection with Mycobacterium avium (serum type III), and the lengthy course of the disease are demonstrated. Norcardiosis, sarcoidosis and BCG-granulomatosis were excluded. From the spleen, lymphatic nodes, gastric juice, stools and urine of the child, who had not been vaccinated with BCG vaccine, masses of acid-fast bacilli were isolated. The generalisation of the disease was promoted by an immunological deficiency. At autopsy an atrophic thymus was discovered. The extensive clinical and immunological investigations pointed to a partial deficiency of the cell-mediated immune systeme. The patient died 8 months after admission.