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Biomedical subjects

B Roth

Publications and source records attributed to B Roth.

At least 55 records · Page 3Linked to original sources

Disposable CO2-detector, a reliable tool for determination of correct tracheal tube position during resuscitation of a neonate.

Undetected displacement of the endotracheal tube may lead to death of the patient. The present report illustrates the benefits of using a disposable carbon dioxide detector, designed for adults, also in a new-nate during resuscitation. The infant had asystole after delivery by caesarean section. The trachea was intubated, but the tube was displaced soon after return of spontaneous circulation. The oesophageal position of the tube was, however, discovered before bradycardia had occurred, thanks to the use of the CO2 detector.

Adult↗

Metastatic bladder cancer: advances in treatment.

At present, a combination of cisplatin, methotrexate, vinblastine and doxorubicin is the most widely used chemotherapy for metastatic bladder cancer. However, long-term follow-up shows that this combination may have little effect on survival. In addition, this regimen is toxic. New agents are needed which combine efficacy with good safety profiles. Agents which have been investigated include gallium nitrate, interferon-alpha and paclitaxel both as single agents and in combination with established cytotoxic drugs. A number of studies have been conducted in bladder cancer with the novel nucleoside analogue, gemcitabine. Response rates of up to 33% have been recorded in two phase II studies. Gemcitabine was well tolerated in both studies with few of the side-effects normally associated with cytotoxic drugs. A third study is ongoing.

Adult↗

Phase II study of single-agent gemcitabine in previously untreated patients with metastatic urothelial cancer.

PURPOSE: To determine the activity of single-agent gemcitabine in previously untreated patients with metastatic transitional cell cancer. METHODS: Forty patients with measurable disease and a Karnofsky performance status > or = 60% were enrolled at five institutions between March 1994 and October 1995. Treatment consisted of gemcitabine (1,200 mg/m2) administered weekly times three on a 4-week cycle. One patient was ineligible for response evaluation because pathology review showed a metastatic melanoma. Responses were confirmed by all investigators and an independent radiologist and were maintained for at least 4 weeks. RESULTS: There were four complete and seven partial responses, for an overall response rate of 28%. Responses were seen at all sites, including liver. Median progression-free and overall survival times were 20 and 54 weeks, respectively. Toxicity was mild, with only two grade 4 toxicities. Twenty-five percent of patients experienced grade 3 neutropenia or thrombocytopenia that was rapidly reversible. CONCLUSION: Gemcitabine exhibits significant activity in metastatic transitional cell cancer with minimal toxicity, but survival remains short. Trials of gemcitabine in combination with other active agents are thus suggested.

Adult↗

Mindfulness meditation-based stress reduction: experience with a bilingual inner-city program.

This article describes a bilingual mindfulness meditation-based stress reduction program in an inner-city setting. Mindfulness meditation is defined, and the practices of breathing meditation, eating meditation, walking meditation, and mindful yoga are described. Data analysis examined compliance, medical and psychologic symptom reduction, and changes in self-esteem, of English- and Spanish-speaking patients who completed the 8-week Stress Reduction and Relaxation Program at the Community Health Center in Meriden, Conn. Statistically significant decreases in medical and psychologic symptoms and improvement in self-esteem were found. Many program completers reported dramatic changes in attitudes, beliefs, habits, and behaviors. Despite the limitations of the research design, these findings suggest that a mindfulness meditation course can be an effective health care intervention when utilized by English- and Spanish-speaking patients in an inner-city community health center. The article includes a discussion of factors to be considered when establishing a mindfulness meditation-based stress reduction program in a health care setting.

Adult↗

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↗