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Biomedical subjects

B Roth

Publications and source records attributed to B Roth.

At least 91 records · Page 5Linked to original sources

The significance of oncometry for infusion therapy during pediatric heart surgery.

The colloid osmotic pressure (COP) is not routinely assessed during pediatric heart surgery. Two cases of unrecognized hyperoncotic states associated with renal failure have been observed after pediatric heart surgery. We studied the hypothesis that the COP cannot be estimated from the total plasma protein (TPP) or albumin level. The course of COP and its correlation to the TPP and albumin level were investigated in 25 children undergoing elective heart surgery. Infusion therapy was performed solely on the basis of clinical parameters and TPP/albumin levels. COP values were determined in a blinded fashion at the end of the study. No correlation between TPP/albumin and the COP could be determined preoperatively. On arrival at the ICU correlation was strong. A weak correlation was observed at 24 hours and 48 hours after surgery. However, the observed wide range of the confidential bands indicates that the COP cannot be estimated correctly, neither from the TPP, nor from the albumin level. Due to colloidal oversubstitution COP was significantly increased compared to preoperative level at 48 hrs following surgery. As estimation of COP from TPP or albumin level is inaccurate, oncometry should be performed during pediatric heart surgery.

Age Factors↗

Induction of apoptosis in Kaposi's sarcoma spindle cell cultures by the subunits of human chorionic gonadotropin.

OBJECTIVES: Elucidation of the mechanisms of the previously shown growth-inhibitory action of human chorionic gonadotropin (hCG) on Kaposi's sarcoma (KS) cells and the role of the luteinizing hormone/hCG receptor (hCGR). DESIGN AND METHODS: Analysis of KS tissues and cultured spindle-type KS cells for the presence of the hCGR using 125I-hCG binding and reverse transcriptase-polymerase chain reaction; analysis of several hCG preparations (urinary, recombinant, isolated alpha and beta subunits); analysis of apoptosis mechanisms by several assays including using z-Val-Ala-Asp-fluoromethylketone (zVAD-FMK), a known apoptosis-inhibitory drug. RESULTS: First, we found that some urinary preparations of hCG (e.g., CG-10, Steris Profasi) were indeed KS-killing but others (such as Pregnyl, Choragon, Serono Profasi) were not. Secondly, recombinant subunits (alpha as well as beta) of hCG were KS cell-killing but recombinant intact hCG was not. Thirdly, the hCGR message and protein were undetectable in KS. Fourthly, CG10-induced cell death occurred by apoptosis and KS cells could be rescued by preincubation with zVAD-FMK. Finally, we also found that normal peripheral blood lymphocytes (PBL) were killed by CG-10. CONCLUSION: It is proposed that the action of subunits or subunit fragments of hCG, mediated by a putative orphan receptor (as opposed to the hCGR) and executed by interleukin-1-converting enzyme (ICE)-like protease(s), constitutes a novel apoptosis mechanism effective towards KS cells, but PBLs and possibly other cells as well. These results provide a basis for testing in vitro the therapeutic efficacy of hCG preparations which, in turn, should improve current clinical trials with 'hCG' in patients who have KS.

Amino Acid Chloromethyl Ketones↗

Airway endoscopy in the interdisciplinary management of acute epiglottitis.

INTRODUCTION: Acute epiglottitis (AE) continues to cause life-threatening airway obstruction in children. The aim of this retrospective study was to evaluate deficiencies in the management of AE, to clarify the role of airway endoscopy, and to establish the cause of death in this disease. MATERIAL: The subjects of our retrospective study were 24 children with AE treated in the paediatric intensive care unit (PICU) of the University of Cologne between 1980 and 1994. The records of all patients were reviewed. RESULTS: Laryngoscopy with fibreoptic or small rigid endoscopes allowed accurate diagnosis of AE, particularly in patients presented with atypical clinical signs. Furthermore, endoscopic information of the degree of inflammation were helpful in the critical decision, whether artificial airway was required. The number of patients managed without intubation increased (8% vs. 45%) since airway endoscopy became available in 1989. No evidence of beta-lactamase-producing strains of Haemophilus influenzae was observed. The most remarkable finding was the high mortality in AE (12.5%). Affected children were admitted in poor post-hypoxia conditions following outdoor cardiorespiratory arrest. CONCLUSION: The most decisive factor to decrease mortality seems to be timely appropriate presentation at referring centres, if AE is suspected or stridor remains unclear. Fibreoptic airway endoscopy represents a major step forward in the management of acute epiglottitis, and this requires close interdisciplinary collaboration between paediatricians, anaesthetists and otorhinolaryngologists.

Acute Disease↗

Lipid deposition in Kupffer cells after parenteral fat nutrition in rats: a biochemical and ultrastructural study.

OBJECTIVE: To study fat metabolism and evaluate lipid deposition in hepatocytes and Kupffer cells during parenteral nutrition (PN) with or without fat. DESIGN: 20 male Sprague-Dawley rats, divided into four groups, were investigated. Rats fed orally were used as a reference group and compared to three groups of rats receiving PN either without fat or with 33% of non-protein energy as fat or with 66% of non-protein energy as fat. The PN regimens were equicaloric and administered continuously via a jugular catheter for 7 days. INTERVENTIONS: After suffocation, blood was collected for determination of serum lipids. Epididymal fat and heart were collected for analysis of lipoprotein lipase activities, and pieces of liver were saved for analyses of liver triglyceride concentration and hepatic lipase activity. Light and electron microscopy were used for examination of lipid deposition in Kupffer cells. RESULTS: Directly after termination of parenteral feeding, the serum levels of triglycerides were similar in all PN groups, while the levels of non-high-density lipoprotein (HDL) cholesterol and non-HDL phospholipids were significantly increased in parallel with increased doses of fat. Lipid-free PN resulted in significantly less liver steatosis than high-fat PN. Lipid PN also resulted in downregulated hepatic lipase activity, signs of lipid accumulation in Kupffer cells and hepatocytes and an increased number of phagosomes in Kupffer cells. CONCLUSIONS: Fat vacuoles were found in Kupffer cells after lipid PN, although serum levels of triglycerides were not elevated and lipoprotein lipase activity were not depressed. The cells were distended by fat vacuoles after administration of PN solutions with a high fat concentration. Morphological signs of increased Kupffer cell activity were also found, suggesting that intravenous fat emulsions may activate macrophages.

Animals↗

Renal failure associated with unrecognized hyperoncotic states after pediatric heart surgery.

Despite severe alteration of transcapillary fluid exchange during cardiopulmonary bypass, colloid osmotic pressure is not routinely assessed. Infusion therapy during pediatric heart surgery is determined by clinical parameters and on the basis of total plasma protein level alone. Following this concept, postoperative renal dysfunction associated with unrecognized hyperoncotic disturbances has been observed in two children. Hyperoncotic states may not be identified by routine laboratory parameters.

Acute Kidney Injury↗

Verocytotoxin-producing Escherichia coli infection in hemolytic uremic syndrome in part of western Europe.

UNLABELLED: From September 1989 until September 1993, stool specimens and sera from 113 children with diarrhoea-associated haemolytic uraemic syndrome (HUS) from the Netherlands, two university hospitals in Belgium and one university hospital in Germany were examined for the presence of verocytotoxin-producing Escherichia coli (VTEC) infection. Evidence for VTEC infection was observed in 88 (78%) patients with HUS compared to 2 (3%) of the 65 children with acute gastro-enteritis Serotype O157 was the causative agent in 76 (86%) of these 88 patients with VTEC-associated HUS and verocytotoxin-2 (VT-2) was the most frequent toxin produced. Serological testing for antibodies to O157 O-antigen yielded the highest number of positive results compared to the other test methods. Antibodies to O157 were found in sera of 71 (65%) of 110 patients with HUS and one control serum. Stool and sera examination for VTEC in 95 family contacts of 28 patients with HUS demonstrated an evidence for VTEC infection 33 (35%). In contrast, in patients with HUS serological antibodies to O157 O-antigen were found in only 3 (4%) of 85 family contacts. CONCLUSION: In this part of Western Europe, VT2-producing Escherichia coli, mainly those belonging to serogroup O157, are the major cause of HUS in childhood.

Bacterial Toxins↗

[Interdisciplinary therapeutic concept in severe bacterial infections of the central respiratory tract in childhood].

BACKGROUND: Apart from all advances made in the management of central airway infections, Acute Epiglottitis (AE) and Bacterial Tracheitis (BT) continue to be causes of life-threatening airway obstruction in children. The aim of this retrospective study was to evaluate deficiencies in the diagnostical protocol, to clarify the role of airway endoscopy in acute childhood stridor, and to identify current reasons for fatalities in these diseases. MATERIAL: In the observation period between 1980-92, we found 12 patients suffering from BT and 21 from AE managed in close cooperation of the involved disciplines at the pediatric intensive care unit of the University of Cologne. RESULTS: Laryngoscopy with fiberoptic or small rigid endoscopes allowed in awake cooperative children accurate diagnose of AE, and the exclusion of supraglottic inflammation in BT without complications. Furthermore, additional endoscopic information of the degree of inflammation was helpful in the next critical decision, whether artificial airway or rigid tracheobronchoscopy was required. Nasotracheal intubation was necessary in 76% of our patients, in one child tracheostomy was performed (5%). Premature extubation necessitating reintubation occurred in 33% of the children suffering from BT. In these patients, our method of advancing a flexible endoscope for tracheoscopy through the respiration tube failed because of a low tube diameter. Another remarkable finding was the high mortality in AE (14%). Affected children were admitted in poor post-hypoxia conditions following outdoor cardiorespiratory arrest. CONCLUSION: In the analysis of the clinical course we found three decisive turning points in managing the disorder; First, the confirmation of the correct admission diagnosis; second, the decision, as to whether an artificial airway should be established; and third, the proper time of extubation. The most decisive factor in decreasing mortality seems to be timely, appropriate presentation at referral centers if AE or BT is suspected. Clinically, progressive management of childhood stridor requires close cooperation between the Pediatric, Anesthesiologic, and ENT Departments. Fiberoptic endoscopy as a guide to current airway management is a major step forward and should be a part of every established protocol.

Airway Obstruction↗

Effects of heparin and low molecular weight heparin on lipid transport during parenteral feeding in the rat.

BACKGROUND: Treatment with heparin has been reported to interfere with lipid metabolism by release of Lipoprotein Lipase (LPL) into the circulation. The purpose of the present study was to determine the effects on LPL activity by anticoagulants in combination with total parenteral nutrition (TPN) in the rat. In an earlier investigation we could show that TPN, per se, caused a three-fold increase of triglyceride content in liver tissue, retention of lipids in the circulation and disturbed cholesterol metabolism with accumulation of cholesterol in the non High Density Lipoprotein (HDL) fraction of lipoproteins. The activity of Hepatic Lipase (HL) was decreased, while the activities of LPL in adipose tissue and heart were up-regulated. METHODS: Effects on lipid metabolism by TPN for seven days with or without simultaneous administration of heparin or Low Molecular Weight Heparin (LMWH) were studied in 52 healthy male Sprague-Dawley rats. Combinations of Heparin or LMWH and discontinuous or continuous administration of TPN solutions (including approximately 8 g triglycerides/kg body weight daily) were investigated. RESULTS: Addition of LMWH, but not heparin, to treatment with TPN resulted in significant up-regulation of LPL activity in the heart. Combination of heparin and continuous administration of TPN solutions was followed by modest, but significant, increases of S-Triglycerides and HDL-Triglycerides. No differences between the TPN groups were observed concerning liver steatosis, cholesterol metabolism, phospholipid metabolism or HL activity. CONCLUSION: Treatment with LMWH during TPN resulted in up-regulated LPL activity in the heart, which might represent a compensatory mechanism for enzyme release from the capillary walls induced by anticoagulants. Administration of heparin, a more effective lipase-releasing agent, was not associated with increased LPL activity. Heparin treatment in combination with continuous TPN administration was followed by increased levels of triglycerides in blood and HDL particles, suggesting that treatment with heparin might have impaired the capacity for LPL up-regulation, resulting in the development of hyperlipidemia. Further investigations are necessary for evaluation of the mechanisms. Depletion of LPL activity could not be demonstrated by this study in healthy rats.

Animals↗

Positron emission tomography and magnetic resonance spectroscopy of cerebral glycolysis in children with congenital lactic acidosis.

Congenital lactic acidosis with neurological symptoms may be due to a variety of disorders of energy metabolism. We investigated whether positron emission tomography (PET) and proton magnetic resonance spectroscopy (1H MRS) are capable of demonstrating specific changes to facilitate diagnosis. A corresponding increase of cerebral lactate (with MRS) and rate of glycolysis (with PET) was observed in 2 children with biochemical evidence of defective mitochondrial respiration. No such increase was noted in a child with lactic acidosis due to stress and exercise but normal respiratory chain activity, and in a control case with an epilepsy syndrome without evidence of primary changes of energy metabolism. The results suggest that defects of oxidative phosphorylation may cause a massive increase of glycolysis to cover energy requirements, with corresponding accumulation of lactate in brain tissue. This mechanism can now be demonstrated in vivo and, with further experience, may potentially be used as a diagnostic marker of respiratory chain disorders in brain tissue.

Acidosis, Lactic↗

Stereospecific determination, chiral inversion in vitro and pharmacokinetics in humans of the enantiomers of thalidomide.

The purposes of this work were (1) to develop a high performance liquid chromatographic (HPLC) assay for the enantiomers of thalidomide in blood, (2) to study their inversion and degradation in human blood, and (3) to study the pharmacokinetics of (+)-(R)- and (-)-(S)-thalidomide after oral administration of the separate enantiomers or of the racemate to healthy male volunteers. The enantiomers of thalidomide were determined by direct resolution on a tribenzoyl cellulose column. Mean rate constants of chiral inversion of (+)-(R)-thalidomide and (-)-(S)-thalidomide in blood at 37 degrees C were 0.30 and 0.31 h-1, respectively. Rate constants of degradation were 0.17 and 0.18 h-1. There was rapid interconversion in vivo in humans, the (+)-(R)-enantiomer predominating at equilibrium. The pharmacokinetics of (+)-(R)- and (-)-(S)-thalidomide could be characterized by means of two one-compartment models connected by rate constants for chiral inversion. Mean rate constants for in vivo inversion were 0.17 h-1 (R to S) and 0.12 h-1 (S to R) and for elimination 0.079 h-1 (R) and 0.24 h-1 (S), i.e., a considerably faster rate of elimination of the (-)-(S)-enantiomer. Putative differences in therapeutic or adverse effects between (+)-(R)- and (-)-(S)-thalidomide would to a large extent be abolished by rapid interconversion in vivo.

Adult↗

Proton magnetic resonance spectroscopy reflects metabolic decompensation in maple syrup urine disease.

Using localized proton magnetic resonance spectroscopy (1H-MRS), accumulation of branched-chain amino acids (BCAA) and their corresponding 2-oxo acids (BCOA) could be non-invasively demonstrated in the brain of a 9-year-old girl suffering from classical maple syrup urine disease. During acute metabolic decompensation, the compounds caused a signal at a chemical shift of 0.9 ppm which was assigned by in vitro experiments. The brain tissue concentration of the sum of BCAA and BCOA could be estimated as 0.9 mmol/l. Localized 1H-MRS of the brain appears to be suitable for examining patients suffering from maple syrup urine disease in different metabolic states.

Adolescent↗

Ketamine and strychnine treatment of an infant with nonketotic hyperglycinaemia.

UNLABELLED: Non-ketotic hyperglycinaemia (NKH) is a severe seizure disorder associated with high glycine levels. Glycine is a major inhibitory neurotransmitter in the CNS, but has also modulating effects at one of the glutamate receptors, the N-methyl-D-aspartate-(NMDA) receptor. Based on this knowledge we treated a female newborn suffering from severe NKH with the NMDA receptor blocker ketamine in association with strychnine and magnesium supplementation. This treatment led to cessation of seizures, reappearance of swallowing and sucking and improved the neurological status. Some pharmacokinetic data of strychnine and ketamine in the infant are given. CONCLUSION: Ketamine in combination with strychnine may be beneficial in non-ketotic hyperglycinaemia.

Amino Acid Metabolism, Inborn Errors↗

[Obstetric prognostic factors of newborn infants with very low birth weight (< or = 1,500 gram) with reference to survival rate and early childhood development].

Prognostic factors influencing survival in 235 very low birthweight prematures (< or = 1500 g) born between 1986 and 15.11. 1993 at the Department of Obstetrics and Gynaecology, University Hospital of Cologne, were retrospectively evaluated. Chromosomal anomalies and severe congenital malformations were excluded. Of 180 singletons 84 were classified as appropriate-for-gestational-age (AGA) and 96 as small-for-gestational-age (SGA). By interrogating the attending paediatricians data regarding the early development of 62/65 surviving singletons born between 1986 to 1990 were recorded (follow-up rate 95%). Survival was significantly correlated to singleton pregnancy (p < 0.05), female sex (p = 0.001) and in the AGA-prematures to prenatal corticoid prophylaxis. With similar mean birthweight SGA-singletons showed a three weeks higher mean gestational age; the mortality showed an inverse correlation to birthweight and gestational age being 11% higher in the AGA-group compared with the SGA-group (32% versus 21%). At the age of between 11 months and 6 years severe handicaps and developmental retardations were found more often in previous AGA-prematures (6/26) than in previous SGA-prematures (4/36); type and degree of later handicap were not correlated to birthweight. According to our results survival rates of very low birthweight prematures are strongly influenced by singleton pregnancy, by fetal sex, by gestational age and in the AGA-group by prenatal corticoid prophylaxis; mortality shows an inverted correlation to birthweight and gestational age, whereas the later prognosis of survivors does not seem to be influenced by birthweight or gestational age.

Adult↗

The importance of colloid osmotic pressure measurements to prevent oncotic overdosage during cardiac surgery.

OBJECTIVE: Colloidal infusion therapy during cardiac surgery has changed from the principal use of human albumin to the preference for synthetic colloids. Despite the possible interference of synthetic plasma expanders with the biuret determination of total plasma protein (TPP), perioperative infusion therapy is frequently directed on the basis of TPP and albumin levels. The hypothesis that the level of TPP or albumin does not reflect the plasma colloid osmotic pressure (COP) if synthetic plasma expanders are used was studied. MATERIALS AND METHODS: In 61 patients undergoing elective cardiac surgery the course of COP and its correlation to the TPP and albumin levels were investigated. Natural and artificial colloids were used for colloidal infusion therapy. RESULTS: No correlation between TPP/albumin levels and COP was found preoperatively and on arrival at the ICU, only a weak correlation was observed at 24 hours and 48 hours postoperatively. The wide range of the confidential interval indicates that the COP cannot be estimated correctly neither from the TPP nor the albumin level. The postoperative COP was significantly increased compared to the preoperative levels indicating oncotic overdosage. CONCLUSIONS: In order to avoid oncotic disturbances, indication for colloidal volume replacement during cardiac surgery should be controlled by oncometry if natural and synthetic colloids are administered.

Blood Proteins↗

Clinical experiences with high-frequency oscillatory ventilation in newborns with severe respiratory distress syndrome.

OBJECTIVE: To generate hypotheses about which subgroups of newborns with severe respiratory distress syndrome might benefit most from high-frequency oscillatory ventilation. DESIGN: Retrospective analysis of a case series of newborns with severe respiratory distress syndrome who were treated in our department with high-frequency oscillatory ventilation. SETTING: Referral center for neonatal and pediatric intensive care medicine. PATIENTS: All newborns (n = 18), admitted between June 1991 and February 1993, of various gestational ages (26 to 41 wks), with severe respiratory distress syndrome caused by various underlying pulmonary diseases who did not respond to conventional therapy and who thus were treated with high-frequency oscillatory ventilation. MAIN OUTCOME MEASURES: Survival until discharge from our unit and persistent improvement of gas exchange. RESULTS: Eight (44%) of 18 patients survived; ten (55%) patients died. Four (22%) survivors showed marked clinical improvement with the initiation of high-frequency oscillatory ventilation. Four (22%) survivors did not respond to high-frequency oscillatory ventilation. The responder group consisted of term or near-term neonates (gestational age at least 35 wks) with pulmonary disease that was complicated by persistent pulmonary hypertension. The group of premature neonates with a gestational age of < 35 wks did not respond to high-frequency oscillatory ventilation. CONCLUSIONS: As a result of our analysis, we hypothesize that term newborns with severe respiratory distress syndrome complicated by persistent pulmonary hypertension and hypercarbia can benefit from high-frequency oscillatory ventilation. Premature neonates with ventilation-induced lung injury are not likely to respond to high-frequency oscillatory ventilation.

Female↗

Value of PCR for evaluating occurrence of parasitemia in immunocompromised patients with cerebral and extracerebral toxoplasmosis.

PCR was used to evaluate the occurrence of Toxoplasma gondii parasitemia by detection of the B1 gene in blood samples in two groups of immunosuppressed patients (148 subjects) suspected of having cerebral or extracerebral infection, respectively. Group I consisted of 52 patients with AIDS with suspected cerebral toxoplasmosis. The diagnosis was clinically proven in 15 cases. Parasitemia was detected by PCR in only two of these patients (13.3%), both showing evidence of disseminated infection. Group II consisted of 96 immunocompromised patients, either with AIDS or receiving iatrogenic immunosuppressive therapy. Of these patients, 65 (34 with AIDS and 31 others) showed abnormalities only in chest radiography and were first screened for the presence of Toxoplasma DNA in bronchoalveolar lavage fluid. Blood was then analyzed when the parasite was detected in the bronchoalveolar lavage fluid. The remaining 31 subjects (22 with AIDS and 9 others) were suspected of having extracerebral, pulmonary, or disseminated toxoplasmosis, and blood was studied directly in these cases. Among the nine patients with clinically diagnosed extracerebral infection in group II, the parasite was detected by PCR in the blood of five patients (55.5%), all having pulmonary toxoplasmosis. If all patients with clinical manifestations of extracerebral toxoplasmosis (from both groups) who had not received antitoxoplasma therapy when the samples were collected are considered, PCR detected parasitemia in seven of the nine cases (77.8%). The present study indicates that examination of blood by PCR may be valuable in cases of extracerebral toxoplasmosis because of the disseminated nature of the disease. Since most cases of cerebral toxoplasmosis result from the local reactivation of latent brain cysts, detection of parasitemia by PCR is useful only in cases associated with severe cerebral infection or dissemination of this disease.

Acquired Immunodeficiency Syndrome↗

Misuse of metered-dose inhalers in hospitalized patients.

Metered-dose inhalers (MDIs) have been associated with a high rate of misuse. Medical personnel also have a poor understanding of MDI technique. Hospitalized patients had their MDI technique observed before and after a series of inservices were provided to hospital personnel on correct MDI use. The rate of misuse did not change with 55 of 72 (76 percent) patients making errors in the first group before, and 45 of 55 (82 percent) patients making errors in the second group after staff education (p = 0.46). The average number of errors per patient was 2.39 in group 1 and 2.45 in group 2 (p = 0.93). Alternatives to deal with this high rate of MDI misuse are discussed.

Administration, Inhalation↗