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Biomedical subjects

O Linderkamp

Publications and source records attributed to O Linderkamp.

At least 19 recordsLinked to original sources
PubMed2002

Alpha-tocopherol transfer protein is specifically localized at the implantation site of pregnant mouse uterus.

Alpha-tocopherol transfer protein (alpha-TTP) was first described to play a major role in maintaining alpha-tocopherol levels in plasma, while alpha-tocopherol was primarily reported to be a factor relevant for reproduction. Expression of alpha-TTP is not only seen in the liver, from where it was first isolated, but also in mouse uterus, depending on its state of pregnancy, stressing the importance of alpha-TTP for embryogenesis and fetal development. The cellular localization of alpha-TTP in mouse uterus is reported here. By immunohistochemistry, alpha-TTP could be localized in the secretory columnar epithelial cells of the pregnant uterus on Days 4.5 and 6.5 postcoitum as well as in the glandular epithelial cells and the inner decidual reaction zone surrounding the implantation site. On Days 8.5 and 10.5 postcoitum (midterm of mouse pregnancy), alpha-TTP could still be detected in the uterine secretory columnar epithelial cells, while in alpha-TTP knockout mice, no immunostaining was visible. It is suggested that alpha-TTP plays a major role in supplying the placenta and consecutively the fetus with alpha-tocopherol throughout pregnancy. We conclude that alpha-tocopherol plays a role in the process of implantation and that alpha-TTP may be necessary for adequate alpha-tocopherol status of the fetus.

Animals↗
PubMed2001

L-selectin tyrosine phosphorylates cbl and induces association of tyrosine-phosphorylated cbl with crkl and grb2.

L-Selectin-mediated rolling of leukocytes on endothelial cells is an important step for lymphocyte homing and an early event in the immune response to pathogens or inflammatory stimuli. We have previously elucidated intracellular signaling cascades upon L-selectin engagement resulting in activation of Ras, Rac and JNK as well as cytoskeletal changes, oxygen release, ceramide synthesis and receptor capping. Activation of the src-tyrosine kinase p56lck is followed by phosphorylation of the L-selectin molecule and MAP-K. Here we show a tyrosine kinase dependent phosphorylation of the Cbl adapter protein after L-selectin engagement in lymphocytes. Phosphorylation of Cbl was absent in Jurkat cells that are pharmacologically treated with tyrosine kinase inhibitors and in lck-deficient JCaM cells. There is an activation induced association of tyrosine phosphorylated Cbl with Grb2 and CrkL, respectively, but not CrkII. Therefore, the adapter protein Cbl plays a role in L-selectin signaling and might modulate immune function by the specific recruitment of signaling molecules to multiprotein complexes.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Restrictive dermopathy: case report, subject review with Kaplan-Meier analysis, and differential diagnosis of the lethal congenital contractural syndromes.

We report on a 34-week-old infant with restrictive dermopathy (RD), a rare lethal genodermatosis, characterized by an abnormal skin growth and differentiation with thin, tightly adherent skin that causes a dysmorphic face, generalized flexion joint contractures, and respiratory insufficiency. Kaplan-Meier analysis of 32 previously well-described infants affected with RD showed a median survival of 132 hours. Lethal congenital contractural syndromes, including Pena-Shokeir phenotype, cerebro-oculo facio-skeletal syndrome, and lethal multiple pterygium syndrome, should be considered first in the differential diagnosis. Other lethal contractural syndromes are discussed.

Contracture↗
PubMed2001

Hepatic failure with neonatal tissue siderosis of hemochromatotic type in an infant presenting with meconium ileus. Case report and differential diagnosis of the perinatal iron storage disorders.

We report on a female preterm infant with hepatic failure and neonatal tissue siderosis of hemochromatotic type diagnosed by using both histochemistry and atomic absorption spectroscopy. The infant presented with meconium ileus, signs of rapidly progressive hepatic failure, and hyperferritinemia (7132 ng/ml). Despite surgery and intensive care the infant died 32 days after birth. Postmortem examination showed a wrinkled liver with extensive collapse of the hepatic architecture and regenerating nodules as well as hepatic and extrahepatic iron accumulation of hemochromatotic type, sparing the reticuloendothelial system. Atomic absorption spectroscopy confirmed an increase in the iron content of various organs: liver, heart, pancreas, oral salivary gland, kidney, and adrenal gland. The increase in the iron content of various organs was determined by comparing the analysis of the propositus with those of 5 gestationally age-related preterm infants who had died in the intensive care unit: 2 died of meconium aspiration syndrome, the other 3 of hyaline membrane disease, bronchopulmonary dysplasia, and immaturity, respectively. We also compared the analysis of 15 fetuses having a a condition predisposing to iron accumulation (trisomy 21, trisomy 18, cytomegalovirus, amnion infection syndrome, Rhesus- and ABO-incompatibility, congenital hemolysis, anti-phospholipid syndrome, congenital heart disease). Delta F508, the most frequent mutation seen in cystic fibrosis patients, was excluded by gene sequencing. Different noxae causing iron accumulation in the neonatal period have led to the statement that neonatal hemochromatosis may collect different etiologies, such as metabolic disorders, infections, chromosomal aberrations, and immunological disorders. In this study, we report the singular evidence of neonatal iron accumulation of hemochromatotic type in an infant presenting with meconium ileus and propose a classification of the neonatal disorders associated with iron accumulation.

DNA↗
PubMed2001

Postnatal changes in neonatal acylcarnitine profile.

++Electrospray-tandem mass spectrometry represents a powerful method for detection of inborn errors of fatty acid metabolism. In the present study, it was used to examine neonatal carnitine metabolism, which reflects fatty acid metabolism. In 70 healthy neonates, blood samples were taken from the umbilical cord and by heel-stick puncture in full-term neonates on postnatal d 5. Cord blood specimens were also obtained from 15 preterm and 10 small-for-gestational-age infants. Acylcarnitine concentrations were measured in dried blood spots by electrospray tandem mass spectrometry. Compared with cord blood, the levels of nearly all acylcarnitine species were significantly higher on the postnatal d 5, whereas free carnitine remained unchanged. Total acylcarnitine/free carnitine-ratio increased, whereas the free carnitine/total carnitine-ratio (0.54 +/- 0.05; p < 0.01) further decreased. A reduced availability of free carnitine in the early neonatal period may affect fatty acid oxidation and thus be of potential pathophysiological relevance under conditions with higher energy demands, e.g. in sepsis. Cord blood concentrations of free carnitine, total carnitine, and total acylcarnitines were strongly related to birth weight (p < 0.01). Lower umbilical artery pH, i.e. mild hypoxia, caused accumulation of mainly long-chain acylcarnitines. This implicates that long-chain acylcarnitines could serve as a parameter of perinatal asphyxia.

Carnitine↗
PubMed2001

Effect of caffeine on oxygen consumption and metabolic rate in very low birth weight infants with idiopathic apnea.

OBJECTIVE: Methylxanthines are among the most commonly prescribed drugs in neonatal intensive care. This study evaluates the effect of caffeine on oxygen consumption and metabolic rate in premature infants with idiopathic apnea. METHODS: Eighteen preterm infants at gestational ages from 28 to 33 weeks and birth weights of 890 to 1680 g were enrolled in the study. Nine preterm infants received caffeine therapy, and 9 served as a control group. Oxygen consumption and energy expenditure were examined before, during, and after caffeine treatment. RESULTS: Oxygen consumption increased significantly from 7.0 +/- 0.9 before caffeine to 8.8 +/- 0.7 mL/kg/min after 48 hours of caffeine therapy, and energy expenditure increased from 2.1 +/- 0.3 to 3.0 +/- 0.2 kcal/kg/hour. During the observation period of 4 weeks of caffeine treatment, oxygen consumption increased significantly in the caffeine group compared with the control patients. In the caffeine group, a lower environmental temperature was sufficient to maintain a normal body temperature. With similar caloric intake in both groups during the study period, daily weight gain in the control group was significantly higher (21 +/- 4 vs 42 +/- 2 g/d). None of the other parameters recorded changed during caffeine therapy. CONCLUSION: Long-term administration of caffeine in preterm infants is associated with an increase in oxygen consumption and with a reduction of weight gain. This may have implications for clinical practice as nutritional regimens need to be adjusted during this therapy.

Apnea↗
PubMed2000

[Acute retinpathia praematurorum. Is plasma prorenin level of prognostic value?].

BACKGROUND: In patients with diabetes mellitus an elevated level of plasma prorenin (PP) may be associated with proliferative diabetic retinopathy. Although retinopathy of prematurity (ROP) is also characterized by retinal vasoproliferation, no study on PP in ROP appears to have been carried out. This study investigated PP prospectively in preterm infants with high risk of ROP. PATIENTS AND METHODS: In 304 preterm infants (gestational age 24-36 weeks, mean +/- SD 29.8 +/- 2.6 weeks; birth weight 570-1750 g, 1180 +/- 294 g) PP was examined prospectively between 3 and 14 weeks postnatally. Renin and total renin (after cryoactivation) were determined by radioimmunoassay. Total renin minus renin is the PP level; PP was correlated with the presence of ROP, stage of ROP, gestational age, birth weight, and postnatal age. RESULTS: There was no significant difference between mean PP in 112 preterm infants with ROP (682 +/- 666 ng/l) and that in 192 preterm infants without ROP (622 +/- 454 ng/l). There was no correlation between PP and the stage of ROP, gestational age, or birth weight. Mean PP decreased with increasing postnatal age (postnatal age 3-4 weeks: 906 +/- 587 ng/l; 7-8 weeks: 585 +/- 423 ng/l; 13-14 weeks: 326 +/- 205 ng/l). CONCLUSION: This study found no significant difference in PP between preterm infants with and those without ROP. Thus PP is not a valid predictor or indicator of ROP. However, the study showed a hitherto unknown correlation between PP and postnatal age in preterm infants.

Birth Weight↗
PubMed2000

Visual-motor function of very low birth weight and full-term children at 3 1/2 to 4 years of age.

Improvements in perinatal and neonatal management have not only led to a higher survival rate of very low birth weight infants (VLBW; < or = 1,500 g or < 32 weeks gestational age), but also to a better outcome of these children. However the percentage of VLBW children who need special education because of later school problems remains high even in children considered neurologically normal during infancy. We assessed 40 VLBW children and 83 healthy full-term children at age 3 to 4 years by means of a simple and short test for visual-motor deficits. The test included the copying and cutting-out of geometric shapes, the building of models, the recognition of colours and the observation of the concentration and cooperation during the test. All VLBW children had had a good perinatal outcome and had been considered neurologically normal at one year of age. Most VLBW children scored within 1 standard deviation (S.D.) of the test mean, but on average the VLBW children scored significantly lower than the full-term infants in the copying of figures, the cutting-out of geometric forms, the building of models and in the overall concentration and cooperation during the test. Children who attended a nursery school achieved significantly better test results. Girls tended to have better results, but this was not statistically significant. Social factors and age had a significantly greater impact on results than perinatal factors. In summary, VLBW children scored significantly less in almost every test item compared to their term peers. Our test battery could serve as a short introductory test to screen for deficits in visual-motor skills, especially in VLBW children.

Adolescent↗
PubMed2000

Decrease of cholestasis under "continuous extracorporeal stool transport (CEST)" in prematures and neonates with stomas.

According to recent studies, the percentage of neonates suffering a combination of very low birth weight (VLBW) and intestinal malformation or diseases that require surgery has increased. As opposed to mature newborn, split stoma is the therapy of choice in VLBW infants. These neonates and patients with other causes for a congenital or acquired short-bowel syndrome usually require parenteral nutrition and have a high risk of a cholestasis. Until 1993, stoma patients were treated with a special diet in our department, but depending of the stoma site often required parenteral nutrition, while the non-used distal bowel was irrigated with an isotonic electrolyte solution. With this regime, up to 38.5% of the treated patients (10126) were found to have a hyperbilirubinemia (> 3 mg/dl) after the 21st day of life. 1994, we started to use a device that continuously transfers the intestinal chylus from the proximal into the aboral bowel via a pump like a continuous extracorporeal stool transport (CEST). In this study, we evaluated the risk of cholestasis by comparison of the prospectively investigated group (CEST-group 1994-1998) of 33 infants with the results of the retrospectively studied group of 26 patients operated on between 1987 and 1993. We found a significantly lower risk of cholestasis in the CEST-Group (12.9% versus 38.5%; p<0.04). Only 3% of our patients with CEST (one patient) required permanent parenteral nutrition, compared to 50% of the conventionally treated patients.

Bilirubin↗
PubMed2000

Influence of the endothelial glycocalyx on cerebral blood flow in mice.

The endothelial surface layer (glycocalyx) of cerebral capillaries may increase resistance to blood flow. This hypothesis was investigated in mice by intravenous administration of heparinase (2500 IU/kg body weight in saline), which cleaves proteoglycan junctions of the glycocalyx. Morphology was investigated by transmission electron microscopy. Cerebral perfusion velocity was recorded before and during heparinase or saline treatment using laser-Doppler flowmetry. In addition, cerebral blood flow (CBF) was measured 10 minutes after heparinase or saline treatment using the iodo[14C]antipyrine method. Laser-Doppler flowmetry and CBF measurements were performed during normocapnia and severe hypercapnia (PCO2: 120 mm Hg). After heparinase, morphology showed a reduced thickness of the glycocalyx in cortical microvessels by 43% (P < 0.05) compared with saline-treated controls. Under normocapnic conditions, a 15% (P < 0.05) transient increase of cerebral flow velocity occurred 2.5 to 5 minutes after heparinase injection. Laser-Doppler flow and CBF returned to control values ten minutes after the injection. However, during severe hypercapnia, heparinase treatment resulted in a persisting increase in laser-Doppler flow (6%, P < 0.05) and CBF (30%, P < 0.05). These observations indicate the existence of a flow resistance in cerebral capillaries exerted by the glycocalyx. The transient nature of the CBF increase during normocapnia may be explained by a vascular compensation that is exhausted during severe hypercapnia.

Adaptation, Physiological↗
PubMed2000

Risk factors in retinopathy of prematurity. a multivariate statistical analysis.

OBJECTIVE: To analyze risk factors in retinopathy of prematurity (ROP). PATIENTS AND METHODS: Four hundred forty-seven surviving very-low-birth-weight infants (birth weight </=1,500 g) were enrolled in a retrospective study. Clinical data underwent multivariate analysis using stepwise logistic forward regression. RESULTS: For 402 of the babies a complete dataset of 38 possible risk factors was available. Multivariate analysis showed 10 factors to be independently significant variables. Low birth weight, low gestational age, artificial ventilation for more than 7 days, high volume of blood transfusion and surfactant therapy were risk factors associated with higher rates of ROP. Necrotizing enterocolitis, maternal pre-eclampsia, lung maturation by antepartum betamethasone application, vitamin E and phototherapy were accompanied by a lower incidence of ROP. CONCLUSIONS: This study confirms several risk factors recognized by previous statistical analysis. In addition, this study reveals maternal pre-eclampsia, which is associated with chronic intrauterine stress, as a statistically independent factor and as having an influence on the incidence of ROP.

Female↗
PubMed2000

Surfactant modulates intracellular signaling of the adhesion receptor L-selectin.

Intraalveolar leukocyte accumulation is one of the hallmarks during respiratory distress. In the intraalveolar space, leukocyte activation is mediated by pathogens, cytokines, and different ligands binding to adhesion molecules. Leukocyte stimulation via the adhesion molecule L-selectin is specifically induced by ligands expressed on leukocytes, platelets, endothelial cells, or lipopolysaccharide. Recently, we have demonstrated that leukocyte activation by L-selectin transmits several intracellular signaling cascades resulting in capping and cytoskeletal changes, the activation of kinases and neutral sphingomyelinase, the recruitment of adaptor proteins to the cell membrane, the activation of the small G-proteins Ras and Rac, and the release of oxygen. In the present study, we examined the effects of surfactant on L-selectin-induced signal transduction in leukocytes. Using fluorescence microscopy, we provide evidence that preincubation of leukocytes with surfactant significantly inhibits receptor capping; 28+/-7% of cells show capping after L-selectin stimulation versus 8+/-5% and 3+/-1% of cells after preincubation with Exosurf and Curosurf, respectively (p < 0.05). The activity of the neutral sphingomyelinase in cell lysates is also modulated by surfactant. In addition, we show that the activation of the tyrosine kinase p56lck is diminished by approximately 50% after surfactant treatment. This results in inhibition in tyrosine phosphorylation of certain intracellular proteins. The interaction of the L-selectin molecule with its antibody was not influenced by surfactant as shown by flow cytometry. Surfactant inhibits intracellular signaling events of the L-selectin receptor in leukocytes and might therefore contribute to the modulatory effects of surfactant on immune function.

Humans↗
PubMed2000

Decreased mechanical stability of neonatal red cell membrane quantified by measurement of the elastic area compressibility modulus.

Previous studies suggest that early loss of membrane might account for the shortened life-span of neonatal red blood cells (RBC). The elastic area compressibility modulus describes the force required to achieve a defined expansion of the membrane and is thus a suitable intrinsic material property to describe mechanical stability of the RBC membrane. We studied RBC in eight cord blood samples (representing fetal blood), ten 5-day old full-term neonates and seven healthy adults. The RBC were suspended in hypotonic buffer solution and investigated using a modification of the micropipet technique by Evans et al. Cord blood RBC (204+/-33 dyn/cm) and neonatal RBC (209+/-11 dyn/cm) showed a 25% lower elastic area compressibility modulus than adult cells (278+/-26 dyn/cm; p < 0.05). Thus, less force was necessary for expansion of neonatal RBC membrane. We conclude that neonatal RBC are more susceptible to mechanical damage of their membrane than adult cells.

Adult↗
PubMed2000

[Results of a survey on the use of guidelines in neonatology].

To assess the use of guidelines in neonatology we conducted a survey on hyperbilirubinemia in 185 German pediatric hospitals from June to September 1999. Of these 136 hospitals (73%) treating infants with hyperbilirubinemia responded. Specific standards or guidelines were used by 99% of participating hospitals. 49% of those used a hospital-based guideline, 54% the recommendations of the Gesellschaft für Neonatologie und pädiatrische Intensivmedizin, 24% another not further specified guideline. In 98% of the hospitals paper copies were used. In 21% of the hospitals the implemented guidelines were also electronically available. A coordinator for their guidelines was available in 51% of the hospitals, whereas 49% did not coordinate locally the use of their guidelines. In conclusion, guidelines should be well maintained and regularly updated in order that they do not lose their impact and significance. In addition, the potential of these concise summaries of medical expertise do not seem to be fully exploited.

Germany↗
PubMed1999

Impaired deformability of erythrocytes and neutrophils in children with newly diagnosed insulin-dependent diabetes mellitus.

AIMS/HYPOTHESIS: Abnormal rheological properties of erythrocytes, leucocytes and plasma may have a role in the development of diabetic microangiopathy. We hypothesized that changed haemorrheological variables may already be found in children with onset diabetes. METHODS: Erythrocyte deformation (rheoscope), neutrophil deformation (micropipette), erythrocyte aggregation, blood and plasma viscosity were measured in 15 children with insulin-dependent diabetes mellitus before initiation of insulin treatment and 4 to 6 weeks later, 15 diabetic children treated with insulin for 5 to 8 years, 15 healthy children and 15 healthy adults. RESULTS: At a low shear stress of 0.6 Pa, erythrocyte deformation was decreased in the diabetic children before (-28%), after 4 to 6 weeks (-22%) and after 5 to 8 years (-17%) of insulin treatment compared with healthy children. More active neutrophils were counted in the untreated diabetic children (9 +/- 6%) than in healthy children (3 +/- 2%). Deformability of passive neutrophils was greatly decreased in the children with onset diabetes and moderately reduced in the diabetic children who were treated with insulin. Neutrophil deformation (r = -0.52) and erythrocyte deformation at 0.6 Pa (r = -0.62) were inversely related to haemoglobin A1c. Haematocrit and blood viscosity were increased in the untreated children and in the children treated with insulin for 5 to 8 years. Plasma viscosity and erythrocyte aggregation were similar in the three groups of children. CONCLUSION/INTERPRETATION: Decreased erythrocyte deformation at low shear force, increased count of active neutrophils and impaired deformability of passive neutrophils may increase the risk for acute cerebro-vascular complications in children with uncontrolled insulin-dependent diabetes mellitus.

Adolescent↗
PubMed1999

Clinical symptoms, biochemical studies and therapeutic approaches in a sibship with a new congenital tubulopathy.

UNLABELLED: We report on two siblings suffering from a new congenital tubulopathy. Following normal pregnancies not complicated by polyhydramnios, severe renal losses of potassium, chloride, sodium and magnesium occurred in the first weeks after birth. Calcium metabolism was not affected. The distal tubular chloride reabsorption was considerably decreased in the two siblings (0.25 and 0.28, respectively). Secondary hyperaldosteronism, activation of the kallikrein-kinin system and elevated urinary prostaglandin excretion were observed. The effects of indomethacin, spironolactone and captopril on symptoms, electrolyte wasting, activation of renin-angiotensin-aldosterone and kallikrein-kinin system and prostaglandin synthesis were studied. In spite of persisting elevation of prostaglandin synthesis, captopril decreased electrolyte wasting, polyuria and hyperaldosteronism most effectively. CONCLUSION: We delineate an apparently new disorder characterized by a postnatal onset, an extremely decreased chloride reabsorption with extensive hyperchloriduria and hypermagnesiuria in the presence of normal calcium metabolism. The disorder can be distinguished from other tubulopathies with hypokalaemic alkalosis.

Absorption↗