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Biomedical subjects

P Bartmann

Publications and source records attributed to P Bartmann.

At least 55 records · Page 3Linked to original sources

Erythropoietin mRNA expression in human fetal and neonatal tissue.

Based on animal experiments, a switch of the erythropoietin (EPO) production site from the liver in the fetus to the kidneys in the adult has been postulated. To study the switch in humans, we have quantitated EPO mRNA expression in liver, kidney, spleen, and bone marrow of human fetuses and neonates by means of a competitive polymerase chain reaction (PCR). Tissue samples from 66 routine postmortem examinations were obtained. EPO mRNA was expressed in 97% of the tissue specimen derived from the liver (n = 66) and in 93% of those from the kidneys (17 weeks of gestation until 18 months after birth; n = 59). For the first time the EPO gene was found expressed in vivo in human spleen (96% of 64 samples) and in fetal and neonatal bone marrow (81% of 21 samples). EPO mRNA expression in the kidneys increased significantly beyond 30 weeks of gestation (P < .05). Although there was a slight decrease in EPO mRNA content per g liver tissue towards birth, the liver accounted for about 80% of the total body EPO mRNA. The contribution of the spleen and bone marrow were minor compared with liver and kidneys. Our results indicate that in humans the liver is the primary site of EPO gene expression not only in fetal, but also in neonatal life. A significant increase of renal EPO mRNA expression after 30 weeks of gestation might indicate the beginning switch.

Bone Marrow↗

Prevention of necrotizing enterocolitis in extremely low birth weight infants by IgG feeding?

UNLABELLED: Oral immunoglobulin has been described as preventing necrotizing enterocolitis(NEC) in preterm infants. To prevent NEC in extremely low birth weight infants (ELBW), we have carried out oral IgG prophylaxis since April 1991. The efficacy of this prophylaxis was examined in a study comparing historical cohorts. ELBW infants delivered in the Department of Obstetrics and Gynaecology of the University of Ulm and treated until day 28 in the level III intensive care nursery, Division of Neonatology, University of Ulm were included. Cohort 1, born between 1.1.1988 and 31.3.1991, received no oral IgG and served as a control [n = 84, gestational age: median 26 weeks, range 24-34; birth weight: 811 g, 490-990], cohort 2, born between 1.4.1991 and 31.12.1995 [n= 137, gestational age: 26 weeks, 22-32; birth weight: 760 g, 362-995], received 6 x 100 mg/kg human IgG (Beriglobin) orally on days 1-28. NEC, stage 2a and higher according to the modified classification of Bell, was observed in 9 of 84 (10.7%) infants of cohort 1 and in 11 of 137 (8%) infants of cohort 2 until day 28. The difference did not reach statistical significance (P = 0.63 Fisher's exact test). CONCLUSION: In this historical cohort study, ELBW infants were not protected against NEC by oral IgG. The present published evidence does not allow recommendation of oral human IgG administration in preterm infants as a prophylactic measure against NEC.

Enterocolitis, Necrotizing↗

Triplet pregnancy with acardius acranius after preimplantation diagnosis.

OBJECTIVE: To report the first case of fetal malformation after preimplantation diagnosis for Duchenne muscular dystrophy (DMD). DESIGN: Case report. SETTING: Perinatal center in a university hospital. PATIENT(S): A conductor for DMD in her third pregnancy. INTERVENTION(S): Preimplantation diagnosis was performed in an outside hospital. In our center, a dichorionic triplet pregnancy with acardius acranius was diagnosed. The anastomosis between the "pump"-twin and the fetus with acardius was embolized with histoacryl to prevent worsening cardiac insufficiency of the "pump"-twin. MAIN OUTCOME MEASURE(S): Pregnancy outcome. RESULT(S): The anastomosis between the "pump"-twin and the fetus with acardius was occluded successfully. Premature preterm rupture of membranes led to rapid labor and delivery at 24 + 5 weeks' gestation. The smaller girl died of severe hyaline membrane disease, whereas the other infant had no major clinical problems and has developed well. CONCLUSION(S): There might be an association between embryo biopsy and fetal malformations. The setting up of a birth register after embryo biopsy is strongly recommended.

Abnormalities, Multiple↗

Response to diphtheria and tetanus booster vaccination in pediatric renal transplant recipients.

BACKGROUND: Although inactivated vaccines are recommended for immunocompromized patients, efficacy and safety of diphtheria and tetanus immunization in renal transplant recipients have received little attention so far. The aim of the study was to investigate the response to a standard diphtheria and tetanus booster vaccination in pediatric renal transplant recipients. METHODS: Forty-two children, median age 13.2 years (range, 7.8-18.9 years) with complete primary immunization 9.2 years (0.9-15.4 years) before transplantation were enrolled. Immunosuppression consisted of cyclosporine plus prednisolone in 15 (36%), cyclosporine, azathioprine, and prednisolone in 24 (57%), and tacrolimus plus prednisolone in 3 (7%). Antibodies were measured by enzyme-linked immunosorbent assay before and 1, 6, and 12 months after vaccination. RESULTS: Before vaccination, protective antibody concentrations exceeding 0.1 IU/ml against diphtheria were found in 16 children (38%). Thirty-eight (90%) had protective antibody concentrations against tetanus. After booster immunization, the protection rate against diphtheria rose to 95% at 1 month with a decline to 93% at 6 and 76% at 12 months. Protection against tetanus was complete after vaccination and persisted over the observation. Antibody concentrations were comparable to those reported for healthy children. Statistical analysis showed no influence of allograft function, immunosuppressive regimen, previous cytotoxic therapy, or time between primary immunization and end-stage renal failure on antibody response. Immunization was well tolerated and kidney function remained unaffected in patients with stable allograft function. CONCLUSIONS: Diphtheria and tetanus vaccination can be performed effectively and safely in renal transplant recipients as generally recommended.

Adolescent↗

Seroprevalence of Helicobacter pylori in German infants and children.

BACKGROUND: The purpose of the study was to evaluate the serological prevalence of Helicobacter pylori (H. pylori) infection during infancy and childhood in Germany. PATIENTS AND METHODS: We quantified specific IgG antibody titers against H. pylori by enzyme-linked immunosorbent assay (ELISA) technique (BIO-RAD G.A.P. IgG-test) from healthy children under 18 years (n = 216) admitted to hospital for minor surgical procedures. All patients were age 0-18 years and lived in the southern part of Germany (Bavaria and Baden-Wuerttemberg). For each age group, 12 different sera were obtained and were determined in duplicate. We analyzed the 216 sera within 6 age groups of equal size. Mean titers > 19 U/ml were considered positive for H. pylori infection. RESULTS: None of the sera of 48 children less than 4 years old were positive for anti-H. pylori specific IgG antibodies. Titers above 19 U/ml were found in 8.3% (3/36 sera each, CI 95% 1-21.7%) in the children age three to five and nine to 11 years. Six- to eight-year-old children showed a 19.4% seroprevalence (7/36 sera, CI 95% 8.2-48%) and children 12-14 years old showed a seropositivity of 16.7% (6/36 sera, CI 95% 6.6-46.1%). In contrast, 47.2% (17/36 sera, CI 26.5-70.3%) of the adolescents older than 14 years had positive H. pylori antibody titers (p < .01, compared to the age-group 12-14 years). The test for linear trend (seropositivity and age) was significant with p < .001. The overall incidence increase with age in prevalence of H. pylori infection was found to be 0.9% per year within this population. CONCLUSIONS: In contrast to published data from other European and non-European countries, we could not detect H. pylori infection in German infants less than four years old by measurement of IgG antibodies. In the older subjects, seropositivity increased significantly and linearly with age.

Adolescent↗

Prenatal contact with inhalant allergens.

Pollen contact in early infancy may enhance the risk for subsequent pollen allergy. In this study likelihood of a prenatal antigen contact, as a result of inhalation of pollen allergens by the mother, was investigated. Due to the seasonal occurrence of allergens studied, the date of priming can be estimated, and this can supply data about the maturation of the fetal immune system. Proliferative responses of umbilical cord blood mononuclear cells (UCB MNCs) to the recombinant major allergens of birch (rBet v 1) and timothy grass (rPhl p 1) were analyzed throughout the whole year. A positive proliferative response was regarded as the criterion for a prenatal contact of the immune system with the allergen. Prenatal priming with both allergens was observed. Timothy grass pollen displayed considerably higher antigenicity than did birch pollen. The susceptibility of the fetal immune system to be primed by these allergens varies during the gestation period. The majority of positive responses to rPhl p 1 and rBet v 1 were found in UCB samples in which antigen contact (the respective pollen season) took place in the first 6 mo of pregnancy. Our results offer indirect evidence that, shortly after migration of T cell precursors to the epithelial thymus, T cells are mature enough for priming with antigens. No relationship was found between the susceptibility of the fetal immune system to be primed by these allergens and the clinical history of the family concerning type I allergy.

Allergens↗

C-reactive protein is a useful marker for guiding duration of antibiotic therapy in suspected neonatal bacterial infection.

OBJECTIVE: To determine whether C-reactive protein (CRP) can be used as a parameter to identify the time point when antibiotic treatment can safely be discontinued in a defined major subgroup of neonates treated for suspected bacterial infection. PATIENTS: One hundred seventy-six newborns with birth weights of greater than 1500 g and without central lines and mechanical ventilation who had suspected bacterial infection were enrolled in a prospective study. SETTING: Tertiary care neonatal reference center. DESIGN: Serum concentrations of CRP were determined 24 to 48 hours after the first dose of antibiotics. If CRP levels were less than 10 mg/L, infants were considered unlikely to be infected, and the antibiotic treatment was stopped using CRP as the single decision criterion in 84 of 94 newborns (group 1). Infants with CRP levels of 10 mg/L or greater were considered likely to be infected and randomized to two study groups. In 38 of 39 neonates (group 2a), CRP was determined daily, and antibiotic therapy was discontinued as soon as CRP returned to less than 10 mg/L. Forty-three neonates with likely infection (group 2b) were treated for at least 5 days, and relapse rates of bacterial infections were compared between groups 2a and 2b. OUTCOME MEASURES: The primary outcome variable of the study was the number of infectious relapses of the primary infection. This was assessed by the need for a second course of antibiotics within 4 weeks of the first one. The value of CRP for guiding treatment duration was determined by calculating the negative predictive value of CRP with respect to further treatment in study groups 1 and 2a. Treatment durations and relapse incidence in the two groups of neonates with likely infection (groups 2a and 2b) were compared. RESULTS: Within the 4-week follow-up period, one infant in group 1 and no infant in group 2a received a second course of antibiotics for bacterial infection. CRP levels of less than 10 mg/L determined later than 24 hours after beginning the antibiotic treatment thus correctly identified 120 of 121 infants as not needing further antibiotics. This corresponds to a negative predictive value with respect to further treatment of 99% (95% confidence interval, 95.4% to 99.9%). The mean treatment duration was 3.7 (median, 4; range, 3 to 6) days in the CRP-guided group and 5.5 (median, 5; range, 5 to 7) days in the at least 5-day study group. In the latter group, one infant was treated for a potential relapse, and one infant was treated for a likely relapse. The low relapse rates in both treatment groups are a preliminary indication that relapses may not occur more frequently if patients are treated until CRP is negative rather than for a 5-day or longer treatment period. CONCLUSIONS: We conclude that CRP could be a key parameter for individually guiding the duration of antibiotic treatment in a major subgroup of newborns with suspected bacterial infection. This approach would allow considerably shorter courses of antibiotic therapy.

Anti-Bacterial Agents↗

In vitro studies on clonal growth of chondrocytes in thanatophoric dysplasia.

Thanatophoric dysplasia (TD) is characterized by a disorganized growth plate with markedly reduced proliferative and hypertrophic cartilage zones. Therefore, we studied in vitro the proliferation rates of articular chondrocytes from five TD patients and age-matched controls in response to bFGF, IGF-I, IGF-II, and TGF-beta 1. In human fetal controls bFGF was the most potent growth factor. Clonal growth the articular chondrocytes in response to bFGF was reduced in two of five TD patients and slightly below the range of controls in a third case. Stimulation of chondrocyte proliferation by IGF I and II was reduced in the patient whose response to bFGF was most markedly impaired. The effect of TGF-beta 1 ranged from normal to slightly elevated values in TD fetuses. These results indicate heterogeneity of the underlying defects in TD. Low proliferative responses of chondrocytes to bFGF and IGF-I/II are likely to play a key role in the pathogenesis of some cases. In two of five patients studied, the mechanisms of bFGF and IGF-signal transduction are candidates for the primary molecular defect.

Cartilage, Articular↗

Effects of different surfactant preparations on bacterial growth in vitro.

Several lines of evidence suggest that surfactant and surfactant proteins may have direct effects on inhaled bacteria and are able to interact with lung defence mechanisms in many ways. We examined the effect of three different surfactant preparations (Alveofact, Survanta and Exosurf) approved for treatment of the infant respiratory distress syndrome on different strains of Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus agalactiae which are important neonatal pathogens and on Legionella pneumophila serogroup I as a frequent cause of pneumonia in adults. Addition of Survanta to saline seemed to delay the reduction of viable bacteria in sterile saline and induced a considerably accelerated growth of all examined E. coli strains. As opposed to this, addition of surfactant did not influence the kinetics of bacterial growth in brain-heart infusion or buffered yeast extract both with the exception of Exosurf which exerted an inhibitory effect on the multiplication of group B streptococci. Though the exact mechanisms underlying these effects remain to be determined, the influence of surfactant therapy on the growth of bacteria within the respiratory tract should be taken into account.

Adult↗

Characterization of coagulase-negative staphylococci causing nosocomial infections in preterm infants.

The species spectrum, antibiotic susceptibility, and genomic profile of coagulase-negative staphylococci (CNS) isolated from infected preterm infants were compared with those obtained in CNS from nursery personnel. Staphylococcus epidermidis was the predominant species in the 66 investigated preterm infants (171 isolates), accounting for 64% of all isolates. A high proportion of Staphylococcus haemolyticus (32%) could be detected. In contrast to the results in patients, the spectrum in nursery personnel was broad and included more species of CNS. All isolates of CNS from preterm infants demonstrated a low rate of susceptibility to the beta-lactam antibiotics (2% sensitivity to penicillin and 6% sensitivity to oxacillin). Sensitivity to gentamicin (9%) was also rare. An unexpected observation was susceptibility to teicoplanin in only 70% of all CNS isolated from patients due to the high proportion of Staphylococcus haemolyticus. Analysis of the genomic profile of 33 isolates of Staphylococcus haemolyticus by pulsed-field gel electrophoresis revealed a relationship between the strains. An outbreak of one particular strain of Staphylococcus haemolyticus in the neonatal intensive care unit investigated can therefore not be excluded.

Coagulase↗

Sporadic ALS/MND: a global neurodegeneration with retroviral involvement?

Sporadic amyotrophic lateral sclerosis may be an aetiologically heterogenous disease. We confirmed elevated circulating IgG immune complexes, and altered IgG seroreactivities against human retroviral antigens (HIV-2 and HTLV immunoblots) in overlapping subgroups of patients. Together with preliminary findings of a positive polymerase chain reactivity for human T-lymphotropic virus (HTLV.tax/rex) in blood leukocytes of 5 out of 14 sALS patients, we interpret this as evidence for a retroviral involvement in this relentlessly progressive, often asymmetrically spreading neurodegeneration. The possibility of a secondary phenomenon seems unlikely, yet cannot be completely ruled out.

Adult↗

Measurements of sodium and potassium in newborns and prematures by ion-selective electrodes and flame photometry: influence of lipid and protein content of blood.

The alternative use of flame photometry and ion selective electrodes for electrolyte determinations in neonatology led to the question how the two methods agree. 104 routine blood samples were taken as matched pairs for a comparison of sodium and potassium determinations. Pre-analytical error was avoided by the mode of blood collection. The influence of the protein and lipid content of blood on the differences between the methods was determined by calculating its water content and making a post-correction of the flame values. Thus the differences for sodium could be reduced, whereas the differences for potassium slightly increased. As long as the imprecision of sodium determination is a meaningful methodological problem, the influence of the protein and lipid content of neonatal blood is not the main factor for differences between ISE and flame photometry.

Bilirubin↗

Immunoglobulin-G isotype changes in human sporadic amyotrophic lateral sclerosis (ALS).

Out of 50 patients with sporadic amyotrophic lateral sclerosis (sALS), excluding 8 patients with recent immunosuppressive medication or low total IgG, we examined all available 92 sera of 11 women and 31 men nephelometrically for serum immunoglobulin concentrations including IgG isotypes IgG1-4. Mean serum levels of IgA and IgM remained within references in all cases. Isotypes IgG1 and IgG3 were the most frequently altered immunoglobulins. Without specific treatment, 34 out of 42 patients (= 80%) and 58 out of 92 sera (= 63%) demonstrated low IgG3 concentrations (< 0.41 g/l), while 14 patients (= 33%) and 20 sera (= 22%) demonstrated low IgG1 serum levels (< 4.22 g/l). In patients with normal total IgG, isotypes IgG1 and IgG2 often changed in a complementary way, and IgG1/IgG2 serum concentrations correlated significantly (rs = -0.518, P < 0.001). In four longitudinally monitored patients, the IgG3 isotype ranged from 1.3% to 8.2% of serum IgG and demonstrated a remarkable individual variability over time, corresponding to the relatively short half-life of IgG3. Since elevated circulating immune complexes may fluctuate rapidly, altered serum immunoglobulin isotypes could become more convenient parameters in a still enigmatic disease. To assess their role and relevance, their association with clinical course, cerebrospinal fluid and circulating immune complexes has to be examined.

Adolescent↗

The use of intravenous immunoglobulins in symptomatic HIV infection. Results of a randomized study.

To study the efficacy of intravenous immunoglobulin in symptomatic infection with human immunodeficiency virus (HIV) we enrolled 35 patients with CD4 lymphocyte counts below 300/microliter in a randomized three-arm study. In addition to standard HIV treatment (e.g., zidovudine, aerosolized pentamidine), 13 patients were treated with 7.5 g and 11 with 40 g of a 7 S intravenous IgG preparation every 4 weeks over a period of 1 year. A control group of 11 patients remained on standard treatment. Clinical and laboratory parameters, including lymphocyte proliferation and in vitro immunoglobulin synthesis were evaluated prior to intravenous IgG administration. HIV-specific immunological abnormalities such as increased B-cell activation and B-cell immaturity were observed in all three study groups at the beginning of the study. Mitogen-induced lymphocyte proliferation was diminished. These disturbances were not influenced by intravenous IgG treatment. Further laboratory data and the course of the HIV infection (fever, antibiotic treatment, hospitalization, Candida and herpes simplex or cytomegalovirus infection) remained unchanged. Thus, our data with an observation period of 12 months do not support the use of intravenous IgG treatment in adult symptomatic HIV-infected patients with CD4 counts lower than 300/microliter.

AIDS-Related Opportunistic Infections↗

High-dose versus low-dose bovine surfactant treatment in very premature infants.

The aim of the study was to determine if high-dose bovine surfactant (Alveofact, initially 100 mg/kg birth weight) would improve oxygenation compared with low-dose surfactant (50 mg/kg birth weight) administered intratracheally within 1 h after birth. Inclusion criteria included gestational age 24-29 weeks and birth weight 500-1500 g, intubation and mechanical ventilation, absence of congenital malformations and bacterial infections. Retreatment was considered if the fraction of inspired oxygen (FiO2) was > 0.4 (dose 50 mg/kg birth weight). The primary endpoint was level of oxygenation (PaO2/FiO2) 2 h after treatment. The study design was a sequential analysis using a triangular test with alpha = 0.05 and 95% power to detect a 25% improvement in the endpoint. Oxygenation was improved significantly with high-dose (n = 42) compared to low-dose treatment (n = 48): 30.9 +/- 15.0 kPa (231.5 +/- 112.7 mmHg) versus 24.1 +/- 15.7 kPa (180.6 +/- 118.0 mmHg) (mean +/- SD). The survival rate was 83% in both groups and the incidence of pulmonary interstitial emphysema was 33% versus 14% with the high-dose treatment. We conclude that high-dose surfactant significantly improved oxygenation and reduced lung barotrauma. An initial dose greater than 50 mg/kg birth weight of surfactant is required for optimal acute response.

Dose-Response Relationship, Drug↗

Influence of dexamethasone on lymphocyte proliferation in whole blood cultures of neonates.

The lymphocyte proliferative response to mitogen stimulation was measured in cord blood cultures of term and preterm neonates. The lymphocyte proliferative response increased 150- to 400-fold above baseline after stimulation with mitogens. Dexamethasone suppressed the lymphocyte proliferative response in a concentration-dependent manner with considerable suppression at concentrations applied during treatment of preterm neonates for bronchopulmonary dysplasia (BPD). Dexamethasone and other corticosteroids tested in equipotent glucocorticoid concentrations suppressed the lymphocyte proliferative response to the same extent. We conclude that dexamethasone treatment for BPD may well compromise immune functions of preterm neonates.

Adrenal Cortex Hormones↗

The effect of three surfactant preparations on in vitro lymphocyte functions.

Respiratory distress can be successfully treated by endotracheal surfactant replacement therapy. The effects of two natural surfactant preparations, Alveofact and Survanta, and one synthetic, Exosurf, on lymphocyte functions were investigated. Peripheral blood lymphocytes from cord blood or buffy coat from adult healthy donors were stimulated with mitogens (PHA-P, Con A), allogenic cells (MLC) or antigen (SEB), and the proliferative response was measured by the uptake of tritiated thymidine. Immunoglobulin synthesis was stimulated by PWM and determined by an ELISA. Stimulation of lymphocytes in the presence of variable surfactant concentrations resulted in a concentration dependent suppression of the investigated lymphocyte function, with different results for the three products. Complex immunological function such as proliferation in response to allogenic cells were more sensitive to surfactant induced suppression than mitogen induced proliferation. Thus, it can not be excluded that surfactant replacement therapy may influence the local immune response of the lung.

Adult↗