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Biomedical subjects

P Bartmann

Publications and source records attributed to P Bartmann.

At least 37 records · Page 2Linked to original sources

Effects of dexamethasone on proliferation, chemotaxis, collagen I, and fibronectin-metabolism of human fetal lung fibroblasts.

Premature infants at risk for bronchopulmonary dysplasia (BPD) are often treated with dexamethasone (Dex), which has been shown to suppress inflammatory processes in the lung. To elucidate a possible direct influence on the fibroproliferative component of the disease, we studied the effects of Dex in therapeutic and supratherapeutic dosages (5-50 nmol/L) on proliferation, chemotaxis, procollagen I, and fibronectin metabolism of human fetal lung fibroblasts in vitro. Proliferation was inhibited by Dex in a dose-dependent manner. Chemotactic activity in response to conditioned medium of human fetal fibroblasts also showed a dose-dependent inhibition after pretreatment with Dex. The amount of procollagen I C-terminal propeptide and fibronectin per cell in the cell culture supernatant was increased in the presence of Dex. Our results show that Dex does not uniformly suppress the fibroproliferative activity of human fetal lung fibroblasts, which may explain in part the unsatisfactory long-term effects of Dex treatment in BPD.

Anti-Inflammatory Agents↗

Carbamazepine in phenobarbital-nonresponders: experience with ten preterm infants.

UNLABELLED: Carbamazepine is a standard anticonvulsant in children and adults. Until now there is only little information available on its use in neonates. We investigated the oral administration of carbamazepine in refractory neonatal seizures treated with phenobarbital. Ten preterm infants (gestational age 23 + 6-34 + 6 weeks, birth weight 640 g-3080 g) with neonatal seizures were refractory to a primary therapy with phenobarbital. All patients subsequently received carbamazepine exclusively as a second choice anticonvulsant. A daily dose of 7-23 mg/kg carbamazepine was administered orally in two to three aliquots. All patients reached therapeutic plasma drug levels (3-12 mg/l; 13-50 mumol/l). In nine out of ten patients (complete group of small preterms with gestational age under 30 weeks and weight less than 1000 g), therapeutic success was excellent. Carbamazepine was continued for 1-5 months. After termination of therapy no further seizures occurred, also on EEG recordings. Finally, no carbamazepine-induced adverse effects were observed. CONCLUSION: This is the first report on the use of carbamazepine in small preterm infants. Carbamazepine may provide a useful and effective oral maintenance therapy in the management of neonatal seizures in these patients.

Administration, Oral↗

Concentrations of thrombopoietin and interleukin-11 in the umbilical cord blood of patients with fetal alloimmune thrombocytopenia.

The objective of this study is to determine whether the fetus compensates for fetal alloimmune thrombocytopenia (FAITP) by increasing serum concentrations of thrombopoietin (TPO) and interleukin-11 (IL-11). TPO and IL-11 concentrations were measured in cord blood sera of 12 neonates with FAITP, and 35 preterm and 25 term controls. TPO concentrations in the 12 patients (median 129 pg/mL, range 73 to 325 pg/mL) were similar to those of 35 healthy preterm neonates (median 183 pg/mL, range 71 to 290 pg/mL) and the 25 term controls (median 180 pg/mL, range 93 to 302 pg/mL), although the platelet counts were significantly lower in FAITP. TPO concentrations did not correlate with the platelet counts, platelet nadir after birth, or time to recovery of normal platelet count. IL-11 reached detectable concentrations only in four patients with FAITP (median 54 pg/mL). After birth, these patients had a more rapid recovery of the platelet count. Cord blood serum concentrations of TPO are not significantly elevated in FAITP and do not predict the severity of the thrombocytopenia. Elevated IL-11 may signal a more rapid platelet recovery in FAITP.

Fetal Blood↗

Thyroid function in healthy and sick very-low-birth-weight infants--thyrotropin and free thyroxine levels until the sixth week of age.

Hypothyroxinemia in preterm infants without congenital hypothyroidism is associated with developmental delay. Longitudinal information on thyroid function in very-low-birth-weight (VLBW, <1,500 g birth weight) infants is limited: we present data on thyroid function in sick and healthy VLBW infants until 6 weeks of age. Free T(4) and TSH levels routinely obtained on days 14-21 and days 35-49 in 92 consecutive VLBW infants were correlated retrospectively with neonatal morbidity. Free T(4) levels were positively correlated with gestational age; an independent effect of neonatal disease on thyroid function was not detectable.

Aging↗

Erythropoietin gene expression in different areas of the developing human central nervous system.

UNLABELLED: Evidence from cell culture and animal experiments suggests a neuroprotective and neurotrophic function of erythropoietin (EPO). We have quantitated the distribution of EPO mRNA expression in the developing human central nervous system (CNS). PATIENTS AND METHODS: Up to seven biopsies from different areas of the CNS of four preterm fetuses (gestational age 23-37 weeks) were obtained at routine postmortem examinations. EPO mRNA was quantitated by competitive PCR in samples from the CNS, the kidneys, and the liver where the EPO gene is predominantly expressed at this gestational age. RESULTS: EPO mRNA was most abundant in one sample from the cerebellum (0.29 amol/microg total RNA [amol=10(-18)mol]) and two from the pituitary gland (0.23 amol/microg total RNA), but levels varied considerably. EPO mRNA in the cortex cerebri (median 0.12 amol/microg total RNA; n=4) dominated over the expression in the corpora amygdala (median 0.05 amol/microg total RNA; n=4), the hippocampus (median 0.03 amol/microg total RNA; n=4), or the basal ganglia (median 0.01 amol/microg total RNA; n=3). Only little EPO mRNA (<0.01 and 0.06 amol/microg total RNA) was found in the spinal cord. EPO mRNA levels in the cerebellum, pituitary gland, or the cerebral cortex were within the same range as in the liver (0.03-1.67 amol/microg total RNA; n=4), or the kidneys (0.06-0.79 amol/microg total RNA; n=4). CONCLUSION: We found the EPO gene expressed throughout the fetal human CNS. Our data provide the basis to discuss a function for EPO in the brain of humans as well.

Central Nervous System↗

Yunis-Varon syndrome: evidence for a lysosomal storage disease.

We present clinical and neuropathological findings in a female infant with Yunis-Varon syndrome (YVS) comprising absence of thumbs and halluces, aphalangia of fingers and toes, hypoplasia of clavicles, severely undermineralized skeleton (especially skull), microcephaly, and multiple nonskeletal anomalies. The patient also had a Dandy-Walker malformation, hydrocephalus, and hypertension, which were not reported previously in YVS. The infant excreted an abnormal unidentified oligosaccharide. The patient died at day 108 with severe neurological impairment. Autopsy showed prominent intraneuronal inclusions with vacuolar degeneration, mainly in the thalamic, dentate nuclei, cerebellar cortex, and inferior olivary nuclei. No storage phenomena were observed in other tissues. These findings strongly suggest that a lysosomal storage disorder is involved in the pathogenesis of Yunis-Varon syndrome.

Abnormalities, Multiple↗

Phospholipase A secreted by Legionella pneumophila destroys alveolar surfactant phospholipids.

Destruction of alveolar surfactant phospholipids by bacterial phospholipases is suggested to be a major virulence factor involved in bacterial pneumonia. Since Legionella pneumophila secretes phospholipase A, we analyzed phospholipid degradation in natural bovine surfactant by L. pneumophila. Phospholipids were reduced in amount after incubation with bacteria or culture supernatant of L. pneumophila serogroup 6. Free fatty acids and lysophosphatidylcholine were formed, the latter is known to be highly cytotoxic. Surface tension of surfactant as determined by pulsating bubble surfactometer increased significantly compared to the control. Phospholipase A activity seems to be a powerful agent of legionellae in causing lung disease.

Animals↗

Fentanyl-induced chest wall rigidity and laryngospasm in preterm and term infants.

OBJECTIVE: To assess the occurrence of muscle rigidity after fentanyl administration in premature and term neonates. DESIGN: Prospective case series, observational study. SETTING: A university hospital neonatal intensive care unit. PATIENTS: 8/89 preterm and term infants (25-40 wks gestational age) who received fentanyl for perioperative analgesia and sedation or intensive care procedures. INTERVENTIONS: Mechanical or bag mask ventilation and antagonization with naloxone. MEASUREMENTS AND MAIN RESULTS: We observed chest wall rigidity in 8 patients after low dosage of fentanyl (3-5 microg/kg body weight). All patients presented with respiratory distress, hypercapnia, and hypoxemia leading to bradycardia. In two patients, laryngospasm was noted and associated with muscle rigidity, thus making intubation impossible. Naloxone (20-40 microg/kg body weight) reversed the laryngospasm and muscle rigidity immediately, allowing restitution within 1 min. In our patient population, we found fentanyl-induced chest wall rigidity in 4% of neonates after fentanyl administration. CONCLUSION: Even low doses of fentanyl can lead to thoracic rigidity in neonates. Additionally, we observed laryngospasm in two patients and speculate that it might be a variant of muscle rigidity.

Fentanyl↗

Novel phospholipase A activity secreted by Legionella species.

Bacterial phospholipases are regarded as a major virulence factor in infection. In bacteria associated with pneumonia, destruction of lung surfactant and host cell membranes by bacterial phospholipases secreted during infection is thought to contribute to the disease. Phospholipase C (PLC) activity has been described in several Legionella species (W. B. Baine, J. Gen. Microbiol. 134:489-498, 1988; W. B. Baine, J. Gen. Microbiol. 131:1383-1391, 1985). By using detection methods such as thin-layer chromatography and mass spectrometry, PLC activity could not be detected in several strains of Legionella pneumophila. Instead, phospholipid degradation was identified to be caused by a novel PLA activity. We could demonstrate that PLA secretion starts at the mid-exponential-growth phase when bacteria were grown in liquid culture. Several Legionella species secreted different amounts of PLA. Legionella PLA may act as a powerful agent in the mediation of pathogenicity due to destruction of lung surfactant and epithelial cells.

Chromatography, Thin Layer↗

Thyroid function in very low birthweight infants after intravenous administration of the iodinated contrast medium iopromide.

BACKGROUND: Thyroid function disorders have often been observed in preterm infants after intravenous administration of iodinated contrast medium. The effect on thyroid function depends on the dosage, but the choice of the contrast medium may be equally important, as there are appreciable pharmacological differences between them. METHOD: Thyroid function was analysed in 20 very low birthweight infants of gestational age less than 30 weeks after injection of iopromide, a monomeric non-ionic iodinated contrast medium. Levels of free thyroxine and thyroid stimulating hormone were compared with those in 26 control infants. RESULTS: Free thyroxine levels in all study infants ranged from 9.0 to 25.7 pmol/l (days 14-21) and 9.0 to 23.2 pmol/l (days 35-49), and thyroid stimulating hormone levels ranged from 0.13 to 0.26 mU/l (days 14-21) and 0.26 to 11.11 mU/l (days 35-49). These levels were not altered after injection of iopromide. CONCLUSION: The risk of transient hypothyroidism or hyperthyrotropinaemia may be reduced with the use of iopromide compared with other contrast media.

Case-Control Studies↗

Agenesis of the ductus venosus and its correlation to hydrops fetalis.

Absence of the ductus venosus is a rare vascular anomaly. We report a late onset of a hydrops fetalis seen in a fetus at 34 completed weeks of gestation. A persistence of the cranial parts of the left and right umbilical veins and of the paired cranial vitelline veins with an absent ductus venosus led to a bilateral hydrothorax, ascites and skin-edema. Postnatally the hydrops resolved within 7 days most probably due to the change from the fetal to the adult circulation. The abnormal venous system was confirmed by angiography. Agenesis of the ductus venosus can manifest in two different morphologic patterns: The umbilical vein drains exclusively into the left branch of the intrahepatic portal vein or the umbilical vein drains into the inferior vena cava or directly into the right atrium by-passing the liver completely. In both patterns, the preferential direction of the flow towards the foramen ovale is not present. While the first pattern leads to hyperperfusion of the liver parenchyma, the latter would result in reduced perfusion and oxygenation. Our findings suggest that agenesis of ductus venosus might induce hydrops fetalis. We conclude, that in every case of hydrops fetalis the venous system should be evaluated by ultrasonography prenatally and/or immediately postnatally.

Adult↗

Determination of total interleukin-8 in whole blood after cell lysis.

BACKGROUND: It has been shown that a high percentage of interleukin-8 (IL-8) in blood is cell associated. Recently, a simple method for determination of cell-associated IL-8 in whole blood after cell lysis has been described. The purpose of this study was to evaluate this method, to examine the influence of preanalytic sample handling, and to establish the concentration range of total IL-8 and its relation to age and sex in healthy subjects. METHODS: Total IL-8 content of whole blood was determined after lysing blood cells with Milenia((R)) cell lysis solution. IL-8 in the resulting blood lysate was measured with the IMMULITE((R)) IL-8 immunoassay. RESULTS: When freshly drawn blood was stored up to 48 h on ice, no significant changes in total IL-8 were measured in the subsequently prepared lysate, whereas with storage at room temperature, total IL-8 increased after 3 h from 94 +/- 13 ng/L to 114 +/- 16 ng/L (n = 10). In lysate stored for 48 h at 4 degrees C, marginal changes of the IL-8 concentration were noted, with storage at room temperature, only 76% +/- 5% (n = 12) of initial concentration was recovered. From lysate frozen at -20 and -80 degrees C, respectively, 84% +/- 4% and 93% +/- 2% of initial IL-8 was recovered after 70 days (n = 10). IL-8 was measured with comparable precision in plasma (CV, 3. 2-4.2%) and blood lysate (CV, 3.7-4.1%). When plasma was diluted with cell lysis solution, a slightly overestimated recovery (125% +/- 3%) was observed; for lysate specimens with a cell lysis solution content >/=75%, the recovery after dilution was 98% +/- 2%. In lysate prepared from 12 blood samples with exogenous IL-8 added, IL-8 recovery was 104% +/- 2% (recovery from plasma <35%). The median total IL-8 in blood lysates from 103 healthy subjects (22-61 years) was 83 ng/L of blood (2.5-97.5 percentile range, 49-202 ng/L of blood). In females but not in males, total IL-8 increased significantly with advancing age (P: <0.002). We found grossly increased total IL-8 in six pregnant women with amniotic infection syndrome. CONCLUSIONS: The evaluated method allows the assessment of total IL-8 in blood with good performance when appropriate conditions of sample pretreatment are considered. The values in healthy volunteers all were above the detection limit of the IL-8 assay; therefore, slight changes of total IL-8 could be noted. Thus, the present method is a suitable tool to study the diagnostic relevance of total IL-8 in blood.

Adult↗

Expression of the thrombopoietin gene in human fetal and neonatal tissues.

Thrombopoietin (TPO) regulates megakaryopoiesis and platelet production. In the adult, TPO is mainly produced by the liver and the kidneys. This study focuses on fetal and neonatal TPO mRNA expression. In 26 human fetuses and preterm neonates, samples from liver, kidney, spleen, lung, and bone marrow were extracted for total RNA. We measured platelet counts, TPO serum concentrations by enzyme-linked immunosorbent assay, and TPO mRNA contents by reverse transcription/competitive polymerase chain reaction. TPO mRNA concentrations per microgram total RNA were similar in liver, spleen, and bone marrow, slightly lower in kidney, and significantly lower in lung. When related to gram tissue, TPO mRNA levels were highest in the liver. Considering the total amount of TPO mRNA produced in liver, kidney, and spleen, the liver accounted for 95.3%. No correlations between TPO mRNA expression and serum TPO concentration, blood platelet count, or gestational age were observed. In conclusion, the liver is the primary site of TPO gene expression in human fetuses and neonates. The spleen may contribute to TPO production during fetal life. Like in the adult, TPO mRNA is expressed in fetal bone marrow.

Adult↗

Pulmonary function at school-age in surfactant-treated preterm infants.

A follow-up study was conducted in 40 children who had been enrolled in a prospective randomized study of exogenous surfactant therapy for respiratory distress syndrome (RDS) (n = 22; S) or placebo (n = 18; P) to determine long-term pulmonary sequelae of surfactant treatment in premature infants with RDS. At follow-up, mean (SD) age was 6.63 (0.18) and 6.55 (0.23) years for S and P, respectively. Complete lung function tests (LFT) were attempted in all patients. Satisfactory data were obtained in 17/22 surfactant-treated and in 12/18 control children. There was no significant difference between groups for any of the parameters measured. Mean (SD) functional residual capacity (FRC) was 92% (16%) and 90% (21%) predicted, mean (SD) airway resistance (R(aw,exp)) was 122% (25%) and 127% (61%), and mean (SD) forced expiratory volume in 1 s (FEV1) was 104% (12%) and 99% (17%) predicted for S and P. Only maximal expiratory flow at 25% vital capacity (L/s) was significantly below the predicted range in S and P groups, with 74% (23%) and 77% (28%), respectively. To test bronchial hyperreactivity, a simple standardized running test was performed: 4 children in S and 5 in P showed a significant response as defined by clinical airway obstruction or changes in FEV1 and/or R(aw), with no significant difference between groups. Although we found no major abnormalities in lung function and no difference between S and P at early school-age, lack of cooperation during lung function tests makes further follow-up necessary.

Adolescent↗

Homozygous alpha-thalassaemia and hypospadias--common aetiology or incidental association? Long-term survival of Hb Bart's hydrops syndrome leads to new aspects for counselling of alpha-thalassaemic traits.

UNLABELLED: Fetuses with homozygous alpha-thalassaemia develop Hb Bart's hydrops fetalis syndrome, which usually leads either to abortion or fetal/neonatal death. We report diagnosis, intrauterine transfusion therapy, neonatal intensive care management and long-term follow-up of a Vietnamese infant who survived Hb Bart's hydrops fetalis syndrome. During the first 2 years the child had normal development. In addition, the patient exhibited penoscrotal hypospadias. Despite a thorough endocrinological work-up the aetiology of genital ambiguity could not be elucidated. A review of the literature showed an association of homozygous alpha-thalassaemia and hypospadias in all surviving male children, suggesting a common aetiology for both entities. CONCLUSION: On the basis of our findings, we speculate that an unknown gene on chromosome 16 responsible for genital formation is altered in homozygous alpha-thalassaemia.

Chromosomes, Human, Pair 16↗

Perinatal hypophosphatasia: diagnosis and detection of heterozygote carriers within the family.

We report on two families in which one or two children had a severe disorder of skeletal development detected by prenatal ultrasonography. The children died postnatally and showed typical radiological and biochemical findings of perinatal hypophosphatasia. Biochemical analysis revealed a low activity of alkaline phosphatase (AP) and a high value of pyridoxal-5-phosphate (PLP), one of its natural substrates. The screening for mutations of the tissue nonspecific alkaline phosphatase (TNSALP) gene showed homozygosity for a point mutation (G 317 --> D) in the two affected children of the first family. The affected child of the second family was homozygous for a nonsense mutation (R 411 --> X). Family screening revealed that the determination of AP and PLP is helpful for detection of heterozygotes. However, heterozygote children had values of AP in the lower normal range during phases of rapid growth. The determination of PLP proved to be more sensitive in these cases. It should be kept in mind that during the last trimester of gestation there is an increase in maternal AP activity and a normalization of PLP due to placental AP, which is not affected. Therefore, in the course of a prenatal diagnosis in an index case, paternal blood should be analyzed in parallel. For detailed genetic counseling and early prenatal diagnosis in following pregnancies, the possibility of mutation analysis should be used.

Alkaline Phosphatase↗

Congenital intrapulmonary bronchogenic cyst in the neonate--perinatal management.

Approximately 50% of all congenital lung malformations are pulmonary and mediastinal bronchogenic cysts (BC). Therefore, their diagnosis and management is of clinical importance. Usually asymptomatic in the first months of life, bronchogenic cysts are frequently clinically inapparent even adulthood. Early diagnosis and elective surgery can prevent late complications such as pneumothorax, pulmonary hypertension, and recurrent infections; prognosis after surgery is excellent. If mediastinal shifting is present, fetal thoracocentesis is indicated to prevent cardiovascular insufficiency. We report a case of a prenatally diagnosed intrapulmonary BC of the right lung. Following in utero thoracocentesis of the cyst and transient spontaneous regression postnatal onset of severe clinical symptoms due to rapidly developing hyperinflation and mediastinal shifting within the first days of life required early surgical intervention.

Bronchial Diseases↗