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Biomedical subjects

M Radke

Publications and source records attributed to M Radke.

At least 19 recordsLinked to original sources

Influence of nutrition level on digestibility in high yielding cows and effects on energy evaluation systems.

The objective of the study was to determine the effect of nutrition level (NL, multiples of maintenance energy requirement) on the digestibility of nutrients for dairy cows regarding the energy supply of the animal. The digestion of nutrients and energy was investigated in two trials using lactating dairy cows. The NL varied from 2.7 to 5.0 using diets similar composition. In addition, sheep were given the same feed with a NL of 1.4. Digestibility of dry matter (DM) and all specific measures of dietary components declined significantly as NL increased. Digestibility of energy decreased by 4.1% for each increase in NL. The metabolizable energy, the ability to metabolize energy (metabolizable energy/gross energy), and the content of net energy for lactation (NE(L)) per kilogram of DM intake were calculated for NL from 1 to 6 on the basis of these relationships and as well as the gross energy, methane energy, and urine energy. Accordingly the NEL content declined by 0.11 MJ/kg of DM intake or 1.6% as the NL increased by one unit. It means that the NE(L) requirement above the maintenance requirement increased by 0.07 MJ of NE(L) per kilogram of fat-corrected milk, if the NL increased by one unit.

Animal Nutritional Physiological Phenomena↗

Omeprazole for treatment of chronic erosive esophagitis in children: a multicenter study of efficacy, safety, tolerability and dose requirements. International Pediatric Omeprazole Study Group.

OBJECTIVES: To determine the efficacy, safety, and tolerability of omeprazole in children and to determine the doses required to heal chronic, severe esophagitis. STUDY DESIGN: Open multicenter study in children aged 1 to 16 years with erosive reflux esophagitis. The healing dose of omeprazole used was that with which the duration of acid reflux was <6% of a 24-hour intraesophageal pH study. Follow-up endoscopy was performed after 3 months of treatment with the healing dose. RESULTS: At entry, two thirds of 57 patients who completed the study had esophagitis grade 3 or 4 (scale 0-4); some 50% had neurologic impairment or repaired esophageal atresia. Of the 57 patients, 54 healed; 3 did not heal and left the study, and 3 healed with a second course. Doses required for healing were 0.7 to 3.5 mg/kg/d: 0.7 mg/kg/d in 44% of patients and 1.4 mg/kg/d in another 28%. Healing dose correlated with grade of esophagitis but not with age or underlying disease. Reflux symptoms improved dramatically in almost all of the 57 patients, including the unhealed patients. CONCLUSIONS: Omeprazole is well tolerated, highly effective, and safe for treatment of erosive esophagitis and symptoms of gastroesophageal reflux in children, including children in whom antireflux surgery or other medical therapy has failed. On a per-kilogram basis, the doses of omeprazole required to heal erosive esophagitis are much greater than those required for adults.

Adolescent↗

Pharmacokinetics of orally administered omeprazole in children. International Pediatric Omeprazole Pharmacokinetic Group.

OBJECTIVES: The aim of this study was to examine the pharmacokinetics of orally administered omeprazole in children. METHODS: Plasma concentrations of omeprazole were measured at steady state over a 6-h period after administration of the drug. Patients were a subset of those in a multicenter study to determine the dose, safety, efficacy, and tolerability of omeprazole in the treatment of erosive reflux esophagitis in children. Children were 1-16 yr of age, with erosive esophagitis and pathological acid reflux on 24 h-intraesophageal pH study. The "healing dose" of omeprazole was that at which subsequent intraesophageal pH study normalized. Children remained on this dose for 3 months, and during this period the pharmacokinetics were measured. RESULTS: A total of 57 children were enrolled in the overall healing phase of the study. Pharmacokinetic study was optional for subjects and was performed in 25 of the 57 enrolled. The doses of omeprazole required were substantially higher doses per kilogram of body weight than in adults. Values of the pharmacokinetic parameters of omeprazole were generally within the ranges previously reported in adults. However, the plasma levels, area under the plasma concentration versus time curve (AUC), plasma half-life (t(1/2)), and maximal plasma concentration (Cmax), were lower in the younger age group, when the AUC and Cmax were normalized to a dose of 1 mg/kg. Furthermore, within the group as a whole, these values showed a gradation from lowest in the children 1-6 yr of age to higher in the older age groups. CONCLUSIONS: The pharmacokinetics of omeprazole in children showed a trend toward higher metabolic capacity with decreasing age, being highest at 1-6 yr of age. This may explain the need for higher doses of omeprazole on a per kilogram basis, not only in children overall compared with adults but, in many cases, particularly in younger children.

Administration, Oral↗

Triglyceride oxidation in cystic fibrosis: a comparison between different 13C-labeled tracer substances.

BACKGROUND: For indirect evaluation of pancreatic lipase activity in cystic fibrosis, different 13C-labeled triglycerides may be used. METHODS: Triglyceride oxidation in patients with cystic fibrosis was investigated after administration of different 13C-labeled triglycerides by comparing 13CO2 breath exhalation. In the comparative study, five patients with cystic fibrosis (age, 8-15 years; body weight, 22.5-39.8 kg) were treated with Pangrol (individual dosages: 1-3 capsules per morning meal; Berlin-Chemie, Berlin, Germany). [1,1,1-13C3]Glyceryl tripalmitate and [1,1,1-13C3]glyceryl trioleate were administered as a single oral pulse at 8:00 A.M. (dosage, 4 mg/kg each) with the standard diet Fresubin (dosage, 10 ml/kg; Fresenius, Bad Homburg, Germany). Alternately, the same subjects were given the synthetic mixed triglyceride 1,3-distearyl, 2[13C]octanoyl glycerol (dosage, 12.5 mg/kg) contained in the standard diet Nutri-Mix (dosage, 10 ml/kg; Nutricia, Zoetemeer, The Netherlands). Breath samples were taken in 15- and 30-minute intervals over 8 hours. The 13CO2 enrichment was measured by continuous-flow isotope ratio mass spectrometry. RESULTS: After administration of the 13C-labeled tripalmitin-triolein mixture and the mixed triglyceride, mean maximum 13CO2 enrichments were 4.70 and 7.37 delta over baseline, occurring at 7.0 and 3.5 hours, respectively. The corresponding percentage cumulative 13CO2 exhalations were 12.25% and 29.19%, respectively, and differed significantly in the five paired subjects (p = 0.003). CONCLUSIONS: After using different 13C-labeled triglycerides the resultant 13CO2 exhalation reflected the triglyceride hydrolysis and subsequent oxidation. It is concluded that the different cumulative 13CO2 exhalations were mainly caused by the rate-limiting step of triglyceride hydrolysis to free fatty acids and 2-monoglycerides and by fat deposition. Noninvasive 13C breath tests using different 13C-labeled triglycerides can be used for evaluation of pancreatic lipase activity before and during enzyme supplementation.

Adolescent↗

Lymphotoxin-alpha is an autocrine growth factor for chronic lymphocytic leukemia B cells.

Lymphotoxin-alpha (LT), also called TNF-beta, which belongs to the 'TNF family' was originally isolated from a lymphoblastoid cell line. LT enhances the proliferation of activated B cells and augments B cell proliferation induced by IL-2. It functions as an autocrine growth factor for EBV-infected B cell lines and has been implicated in the pathogenesis of B cell malignancies. We tested the expression of LT mRNA in B-CLL and found that LT was expressed in highly purified leukemic cells in 11 out of 11 patients examined. Regulation of expression of LT mRNA is aberrant in B-CLL cells, since LT mRNA expression was not detected in fresh peripheral blood mononuclear cells or B cells identified in seven out of seven normal individuals. In addition, LT mRNA expression was detected for up to 6 days in purified unstimulated in vitro cultures of B-CLL cells. Glucocorticosteroids, that have been effectively used in the treatment of lymphoid malignancies, were added to the cultures and abrogated the LT mRNA expression after an incubation time of 12 h. Addition of recombinant LT to cultures increased proliferation of B-CLL cells while proliferation of these cells was inhibited by antisense oligonucleotides against LT mRNA. B-CLL cells cultured with LT antisense oligonucleotides (asLT) as well as glucocorticoid-treated cells showed reduced viability and a DNA fragmentation ladder characteristic of apoptosis suggesting a relationship between down-regulation of LT mRNA expression and the induction of apoptosis. These studies support the role of LT in the growth regulation and development of B-CLL cells.

Aged↗

Cloning and sequence analysis of the immediate promoter region and cDNA of porcine granulocyte colony-stimulating factor.

Granulocyte colony-stimulating factor (G-CSF) is a cytokine that stimulates the proliferation and differentiation of hematopoietic progenitor cells committed to the neutrophil/granulocyte lineage. Recombinant G-CSF (rG-CSF) is routinely used in the prevention of chemotherapy-induced neutropenia and in the setting of bone marrow transplantation. Chronic idiopathic and congenital neutropenic disorders also show improvement after rG-CSF injections. Applications of either rG-CSF or G-CSF gene transfected cells into mice give rise to leukocytosis, which can be measured easily. This makes G-CSF a versatile tool for studying systemic effects of therapeutic proteins delivered by genetically modified cells in vivo. Although the biological activity of G-CSF is not species-specific, studies on long-term expression would require the use of species-identical proteins in order to avoid host immune reactions against the foreign gene product. Because of the physiological and immunological similarity of pigs and human, the pig has become an important large-animal model for biomedical research. We have therefore cloned porcine G-CSF cDNA from RNA isolated from pig PBLs. Pig G-CSF is a 195-amino-acid polypeptide that shares a high degree of homology to human (78%), murine (71%) as well as rat (68%) G-CSF. In contrast to human and murine, but not to rat G-CSF, a different ATG translation start codon is used, resulting in a shorter, but still functional signal sequence.

Amino Acid Sequence↗

Evaluation of oro-coecal transit time: a comparison of the lactose-[13C, 15N]ureide 13CO2- and the lactulose H2-breath test in humans.

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

Breath Tests↗

alpha-Lactalbumin-enriched low-protein infant formulas: a comparison to breast milk feeding.

Tryptophan (TRP) is the limiting amino acid in low-protein infant formulas. This is mainly due to lower alpha-lactalbumin (alpha LA) content in cow's milk whey as compared with human milk protein. To study the effect of alpha LA-enrichment on the TRP supply, cross-over studies were carried out in 20 healthy infants up to 3 months of age. In this study, two protein-reduced (1.3%) infant formulas (moderate TRP content of 1.88% and higher TRP content of 2.10%) were alternately fed over a 2 week period in two groups of infants. Serum TRP levels of the formula-fed infants with the higher TRP content did not differ significantly from an exclusively breastfed control group of 11 infants (10.5 +/- 4.8 versus 10.9 +/- 4.7 mg l-1, p = 0.841), whereas levels of the formula-fed infants with the moderate TRP content were significantly lower (7.4 +/- 3.9, p = 0.038). The supplementation of alpha LA resulting in a higher TRP supply to low-protein diets is a further step towards the production of infant formulas more closely adapted to human breast milk.

Amino Acids↗

Tracer kinetic studies on a methionine-supplemented soy-based infant formula using 1-13C- and 15N-methionine as tracers.

A tracer-kinetic study using 1-13C- and 15N-labeled L-methionine was conducted in order to measure the retention rate of free methionine added to commercially-produced soy-based infant formulas. Twelve male infants, fed on a soy formula, received a single-pulse labeling by oral administration of L-1-13C-methionine (5 mg/kg) and L-15N-methionine (10 mg/kg). The abundance of expired 13C-labeled CO2 was measured up to 7 h after administration at 15-, 30-, and 60-min intervals. Additionally, enrichment of total 15N and 15N in urinary ammonia were determined up to 48 h after administration. Retention rates of the labeled carboxyl group amounted to an average of 91.2% (SD 4.1) of the intake. A similar retention rate was measured for the 15N-label of methionine (90.0%, SD 4.3). The data point at the efficacy of methionine supplementation of soy-based infant formulas.

Ammonia↗

Laparoscopic cholecystectomy in a young girl.

Laparoscopic cholecystectomy is now a widely used procedure in adults. However, reports on this procedure in infants and young children are rare. This paper reports a successful laparoscopic cholecystectomy in a young girl.

Child, Preschool↗

Response to sodium benzoate treatment in non-ketotic hyperglycinaemia.

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

Benzoates↗

[Sialic acid in breast milk and infant formula food].

OBJECTIVE: Sialic acid (N-acetylneuraminic acid, NANA) is an essential component of mucins, glycoproteins and gangliosides and therefore important for the function of cell membranes, membrane receptors and the normal development of the brain. The capacity of the metabolic pathway for the synthesis of sialic acid from glucose and other carbohydrate sources in preterm infants and term-born neonates is currently unknown. METHODS: In the present study the overall nutritional sialic acid supply of infants was analysed by means of HPLC-based determination of sialic acid concentrations in a total of 51 human milk samples obtained from nursing mothers at different stages of lactation. The data were compared with 3 commercial preterm infant formulas, 7 adapted infant formulas, 11 partially adapted infant formulas, 4 follow-up and 2 soy-based formulas. RESULTS: The sialic acid concentration in colostrum and transitory human milk was 1300 +/- 322 mg/l. After the 10th day of lactation the concentration dropped to 983 +/- 455 mg/l (p < 0.01). Preterm infant formulas contained 197 +/- 31, adapted formulas 190 +/- 31, partially adapted formulas 100 +/- 33, follow-up formulas 100 +/- 33 and soy-based formulas 34 +/- 9 mg sialic acid/l, respectively. CONCLUSIONS: Formula-fed infants obtain less than 20% of the amount of sialic acid supplied if breast-fed. A sufficient sialic acid supply may be essential in very-low-birth-weight infants and neonates at risk for the normal development of brain function.

Animals↗

[Quo vadis--infant nutrition in the European Community? A comment on the guideline of the EC Commission on initial infant and subsequent nutrition].

The new European Community guidelines on infant nutrition formulas, their contents and their declaration, effective since January 1993, do not indicate a scientifically sound progress in infant nutrition. Several of the contents listed (i.e. carbohydrates) may be of potential risk to health. In the future, European paediatricians will have to occupy themselves more concisely with the contents of marketed infant formulas. Individual solutions may have to be found for some patients.

Europe↗