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Biomedical subjects

B Roth

Publications and source records attributed to B Roth.

At least 37 records · Page 2Linked to original sources
PubMed1998

Enantiomers of thalidomide: blood distribution and the influence of serum albumin on chiral inversion and hydrolysis.

The aim of this investigation was to elucidate the distribution and reactions of the enantiomers of thalidomide at their main site of biotransformation in vivo, i.e., in human blood. Plasma protein binding, erythrocyte: plasma distribution, and the kinetics of chiral inversion and degradation in buffer, plasma, and solutions of human serum albumin (HSA) were studied by means of a stereospecific HPLC assay. The enantiomers of thalidomide were not extensively bound to blood or plasma components. The geometric mean plasma protein binding was 55% and 66%, respectively, for (+)-(R)- and (-)-(S)-thalidomide. The corresponding geometric mean blood:plasma concentration ratios were 0.86 and 0.95 (at a haematocrit of 0.37) and erythrocyte:plasma distributions were 0.58 and 0.87. The rates of inversion and hydrolysis of the enantiomers increased with pH over the range 7.0-7.5. HSA, and to a lesser extent human plasma, catalysed the chiral inversion, but not the degradation, of (+)-(R)- and (-)-(S)-thalidomide. The addition of capric acid or preincubation of HSA with acetylsalicylic acid or physostigmine impaired the catalysis to varying extents. Correction for distribution in blood enhances previously observed differences between the pharmacokinetics of the enantiomers in vivo. The findings also support the notion that chiral inversion in vivo takes place mainly in the circulation and in albumin-rich extravascular spaces while hydrolysis occurs more uniformly in the body. In addition, the chiral inversion and hydrolysis of thalidomide apparently occur by several different mechanisms.

Blood Proteins↗
PubMed1998

[Etiology of moderate and profound deafness in childhood].

UNLABELLED: The present study sought to determine the etiology of bilateral profound hearing losses in children living in Germany. Additionally, a comparison with the data of previous investigations in the available literature was used to update causes now known through medical progress. PATIENTS AND METHODS: The medical charts of 314 profoundly hearing-impaired pupils at schools for the deaf in Cologne, Germany, were reviewed. All available data on possible etiological factors were collected. In addition, the families of these children were interviewed using a standardized questionnaire. RESULTS: Sixty children were found to have bilateral sensorineural hearing losses averaging 30 to 60dBHL within the frequency ranges of 500-2000 HZ, while 254 had bilateral hearing impairments of 60 dBHL or greater. The etiology of the hearing disorder could be determined in 218 of the children. Eighty-two children suffered from hereditary deafness and 136 from acquired hearing losses. The etiology could not be determined in 96 children. Hereditary causes included 34 children with mendelian autosomal dominant losses, 46 with autosomal recessive losses and two children with genetic but non-mendelian causes. Immigrants to Germany (mostly from Turkey and the former Soviet Union) were found significantly more frequently among the students of these schools, than among the total population of the Cologne area. In this group of students, autosomal recessive deafness was particularly common as compared to the overall native population. Acquired hearing disorders were broken down into three subgroups: prenatal, perinatal and postnatal disorders. A prenatal etiology was considered in 32 children, 21 of whom had known congenital rubella infection. This entity was significantly less common among younger children. A perinatal etiology was considered in 60 children. Causative factors were birth asphyxia, apnea and/or hyperbilirubinemia. Forty-four children had deafness attributed to postnatal causes, with bacterial meningitis (n = 31) being the most important single factor. The findings reported indicate changing trends for causes of hearing loss in children with severe hearing impairment in Germany.

Adolescent↗
PubMed1998

Biochemical and ultra-structural reactions to parenteral nutrition with two different fat emulsions in rats.

OBJECTIVE: To compare the effects on fat metabolism and Kupffer cell morphology by total parenteral nutrition (TPN) with two different fat emulsions. DESIGN: Thirty-two male Sprague-Dawley rats, divided into three groups, were investigated. Rats fed orally were used as a reference group, and a group of rats receiving TPN with fat emulsions containing pure long-chain triglycerides (LCT) was compared to a group of rats receiving fat emulsions containing both long-chain triglycerides and medium-chain triglycerides (MCT/LCT). The TPN regimens were equicaloric and administered continuously via a jugular catheter for 10 days. INTERVENTIONS: After suffocation, blood of the rats was collected for the determination of serum lipids. Epididymal fat and heart were collected for the analysis of lipoprotein lipase (LPL) activities, and liver specimens were saved for analyses of hepatic triglyceride concentration, as well as activities of hepatic lipase (HL) and lysosomal enzymes. Light and electron microscopy were used for examination of the Kupffer cell reaction. RESULTS: Directly after termination of parenteral feeding, the levels of serum triglycerides and high density lipoprotein (HDL) triglycerides were higher in the MCT/LCT group than in the LCT group, while no differences concerning cholesterol and phospholipid concentrations were found. No significant difference in liver steatosis was found between the two TPN groups. Comparison of the TPN groups showed that the MCT/ LCT group had significantly decreased LPL activity in adipose tissue, while the LCT group had significantly increased LPL activity in the heart. The activity of HL was low in both groups, but significantly lower in the LCT group. Lipid accumulation and an increased number of lysosomes were found in all Kupffer cell when TPN with LCTemulsions was used. Moreover, TPN induced a pronounced increase in various liver lysosomal enzyme activities, but there was no notable difference between LCT and MCT/LCT effects. CONCLUSIONS: Compared to treatment with pure LCTemulsions, treatment with MCT/LCT emulsions evoked weaker biochemical reactions in terms of lower activity of lipoprotein lipase in fat and heart together with higher serum and HDL triglyceride levels. Morphological signs of increased Kupffer cell activity such as the appearance of multiple lysosomes and fat vacuoles in the cytoplasm followed treatment with pure LCT emulsions. However, both TPN groups showed a marked increase in activities of liver lysosomal enzymes.

Animals↗
PubMed1998

A prospective, randomized, multicenter trial of high-frequency oscillatory ventilation compared with conventional ventilation in preterm infants with respiratory distress syndrome receiving surfactant.

OBJECTIVES: To compare high-frequency oscillatory ventilation (HFOV) and intermittent positive pressure ventilation (IPPV) as a primary ventilation mode in preterm infants with respiratory distress syndrome. Primary end points were survival and maintenance of the randomized ventilation mode. STUDY DESIGN: Prospective, multicenter, randomized clinical trial. SETTING: Level III neonatal intensive care units at three university children's hospitals. PATIENTS: Ninety-six premature infants (gestational age < 32 weeks) randomly assigned to HFOV or IPPV within the first 2 hours of life. All patients received a natural surfactant. No differences were found between the study groups with respect to the demographic data or the severity of respiratory distress syndrome. Infants were stratified at randomization, by birth weight, into two groups: 750 to 1000 gm (n = 32) and 1001 to 1500 gm (n = 64). The centers involved complied with a study protocol that planned a reduction in respiratory pressures when the infant's oxygen requirement had reached a fractional concentration of inspired oxygen of 0.6. RESULTS: Five patients in the HFOV group died, and eight patients did not respond to the randomized ventilation mode; whereas four patients in the IPPV group died, and nine were switched to HFOV. No differences were found in gas exchange or ventilator support over the first 72 hours. Premature infants with a birth weight < 1000 gm had a significantly shorter course to reach fractional concentration of inspired oxygen of 0.21 while receiving IPPV than those receiving HFOV (9.3+/-4.5 days vs 27.5+/-10.2 days, p = 0.01). No differences were found between the groups in extraalveolar air (HFOV seven; IPPV, seven) and intracranial bleeding (HFOV, nine; IPPV, eight). CONCLUSION: After surfactant treatment, HFOV, as a primary ventilation mode in premature infants with respiratory distress syndrome, is as safe and efficacious as conventional ventilation.

Female↗
PubMed1998

Jaw lift--a simple and effective method to open the airway in children.

Assessment of breathing during resuscitation of children is important. Misjudgement due to failure to open the airway may lead to mouth-to-mouth ventilation in unconscious children who have retained spontaneous breathing efforts, and might lead to completely ineffective ventilation with gastric distension. The efficiency of the standard head tilt-chin lift manoeuvre (HT-CL) and the jaw lift manoeuvre (JL) for opening of the airway in children was investigated. Fifty children between 1 and 9 years of age breathing spontaneously during deep anaesthesia were studied. Both manoeuvres were randomly performed in all children by nurse anaesthetists. The time for opening and the quality of the airway was determined by a blind folded anaesthesiologist listening to the breathing sounds. The standard HT-CL manoeuvre was insufficient in 12% of the children. JL was more effective than HT-CL in opening the airway in unconscious children who had retained attempts at spontaneous breathing. The JL manoeuvre may, therefore, be recommended in situations when the HT-CL manoeuvre is insufficient.

Age Factors↗
PubMed1998

Oxalate, citrate, and sulfate concentration in human milk compared with formula preparations: influence on urinary anion excretion.

BACKGROUND: Nephrocalcinosis is not uncommon in preterm infants, and elevated urinary oxalate excretion is known to be one of the main risk factors. When oxalate excretion was found to be higher in formula-fed than in human milk-fed infants, the formulas' oxalate content was thought to be responsible. METHODS: The oxalate concentration in human milk (21 samples obtained during lactogenesis; 17 samples obtained during established lactation) and of 16 formula preparations was examined. Citrate and sulfate concentrations were also measured, because both anions influence urinary saturation. RESULTS: The mean (+/- SE) oxalate content of human milk increased approximately 27% from early lactogenesis (70.4 +/- 6.4 micromol/1) to established lactation (96.4 +/- 9.5 micromol/l; p < 0.05). The latter was not different from the mean oxalate concentration of formula (98.2 +/- 11.4 micromol/l), however a fourfold range of measurements was recorded in both groups. The mean citrate content of human milk increased only slightly after early lactogenesis (2.66 +/- 0.22 mmol/l), but remained significantly lower than in formula (3.34 +/- 0.23 mmol/l; p < 0.05). The mean sulfate concentration did not increase and was 13 times lower in human milk (52.1 +/- 9.5 micromol/l) than in formula (688.7 +/- 95.4 micromol/l; p < 0.0001). CONCLUSIONS: The higher oxalate excretion in formula-fed infants is not because of the milk's oxalate concentration. Urinary citrate and sulfate excretion may be influenced by their higher concentrations in formula preparations, which may be of clinical importance in the population that is at risk for development of nephrocalcinosis.

Anions↗
PubMed1998

Hydroxylated metabolites of thalidomide: formation in-vitro and in-vivo in man.

There is renewed interest in the clinical use of thalidomide, because of its unique immunomodulating action. Because data on the metabolism of thalidomide in man are very sparse, the aim of this study was to develop HPLC assays for the 5-hydroxy, 5,6-dihydroxy, 4,5-dihydroxy and 5'-hydroxy metabolites of thalidomide and to investigate their possible formation in man-in-vitro in liver homogenates and in-vivo in healthy volunteers. Reversed-phase HPLC assays with UV detection were developed for quantification of the metabolites in the low ng mL(-1) range in plasma and incubate samples. The stability of the metabolites was investigated and degradation was avoided by rapid chilling and acidification of the samples. After incubation of thalidomide with fraction S9 from human liver, formation of the 5-hydroxy and 5'-hydroxy metabolites could be demonstrated. The 5'-hydroxy metabolite was found, in low concentrations, in plasma samples from eight healthy male volunteers who had received thalidomide orally. The other three metabolites could not be found by HPLC with detection limits of 1-2 ng mL(-1). Thus the formation of two hydroxylated metabolites of thalidomide in the liver in man was demonstrated, but only one of these could be detected in the circulation.

Biotransformation↗
PubMed1998

Proton MR spectroscopy in infants with cerebral energy deficiency due to hypoxia and metabolic disorders.

PURPOSE: To investigate the similarities and differences of cellular energy deficiencies due to asphyxia and to impaired oxidative phosphorylation caused by enzyme deficiencies using localized 1H-MR spectroscopy of the brain. MATERIAL AND METHODS: In 35 neonates and infants with a postconceptional age of 36.4-153 weeks, 1H-MR spectra were obtained from the basal ganglia. Of the 35 children, 14 served as a control group, 12 suffered from hypoxic-ischemic disease (HIE), and 9 had congenital enzymatic disorders. RESULTS: Eleven of the 12 children with HIE showed low N-acetyl aspartate (NAA) to trimethylamine (TMA) ratios, indicating neuronal damage. Lactate (Lac) to TMA ratios correlated with the HIE grade. Children with congenital disorders of energy metabolism had NAA/TMA ratios ranging from severely decreased to normal, but 7 of the 9 had high Lac signals, even in brains with normal NAA/TMA. CONCLUSION: High Lac/TMA even with normal NAA/TMA in children with enzyme deficiencies, in contrast to Lac/TMA that correlates with clinical grade and low NAA/TMA in asphyxic children, hints at different mechanisms of cell damage in the two disease groups.

Aspartic Acid↗
PubMed1998

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: As estimation of COP from TPP or albumin level is inaccurate, oncometry should be performed during pediatric heart surgery.

Blood Proteins↗
PubMed1998

A 12-year-old boy with fatal hemolytic-uremic-syndrome, excessive neutrophilia and elevated endogenous granulocyte-colony-stimulating-factor serum concentrations.

We report the case of a 12-year-old boy with fatal enteropathic hemolytic-uremic syndrome who developed excessive neutrophilia in the course of his disease, his leukocyte count exceeding 200,000/mm3. Neutrophilia, as it was observed in this case, is an extreme manifestation of a phenomenon, that is commonly observed in hemolytic-uremic syndrome [Salzmann et al. 1991]. Neutrophilia is suspected to be correlated with a bad prognosis [Walters et al. 1989], but further explanation of this phenomenon is needed. Other underlying diseases related with neutrophilia, especially hematologic malignancies, could be ruled out by far. We examined endogenous G-CSF serum concentrations of the HUS patient from day 6 to 13 in the course of the disease. The assayed concentrations were found to be elevated in the first two samples taken (peak level 340 pg/ml). In the samples taken after plasmapheresis had started, G-CSF concentrations were not found to be elevated. The peak of neutrophilia was reached short before death on day 13 of the disease. We also measured the serum G-CSF concentrations of 28 children aged 3 months to 12 years, who were treated with various infectious and noninfectious diseases in our hospital. In none of the examined samples was there a G-CSF serum concentration exceeding 50 pg/ml. The reported case shows evidence that the commonly observed coincidence of leukocytosis and HUS may reflect the role of G-CSF (and other cytokines) in the inflammatory process underlying the HUS.

Child↗
PubMed1997

Neonatal haemochromatosis: report of a patient with favourable outcome.

UNLABELLED: A male newborn was referred on the 2nd day of life because of suspected sepsis. The child became comatose and ventilator dependent owing to progressive hepatic failure with hyperammonaemia. Diagnostic studies revealed an highly elevated ferritin level. The family history was remarkable in that an aunt and a great aunt on his mother's side have idiopathic haemochromatosis. Open liver biopsy showed advanced cirrhosis with cholestasis and excessive hepatocellular siderosis. Concentrations of iron in liver tissue were highly elevated. The child's status improved unexpectedly, and excretory and synthetic liver function gradually returned to normal. CONCLUSION: Neonatal haemochromatosis is not an irreversible disease of iron metabolism but rather a distinct outcome of fetal liver disease which predisposes by an yet unknown mechanism to a derangement of fetoplacental iron handling. If patients survive the initial phase of liver failure, prognosis is largely dependent upon liver cirrhosis and its sequels. The iron overload in this type of haemochromatosis is reversible and not progressive.

Diagnosis, Differential↗
PubMed1997

Influence of nutrition on urinary oxalate and calcium in preterm and term infants.

Few data for normal urinary oxalate (Ox) and calcium (Ca) excretion related both to gestational age and nutritional factors have been reported in preterm or term infants. We therefore determined the molar Ox and Ca to creatinine (Cr) ratios in spot urines from 64 preterm and 37 term infants aged 1-60 days, either fed formula or human milk (HM). Only vitamin D was supplemented; renal or metabolic diseases were excluded. Urinary Ox/Cr ratio was higher in preterm than in term infants, both when formula fed (1st month 253 vs. 180 mmol/mol and 2nd month 306 vs. 212 mmol/mol; P<0.05) or HM fed (206 vs. 169 mmol/ mol and 283* vs. 232 mmol/mol; *P<0.05). Ox/Cr was also higher in formula- than HM-fed preterm infants. The ratio increased during the first 2 months of life irrespective of nutrition. Urinary Ca/Cr ratio was comparable in all groups during the 1st month of life, except for a lower (P < 0.05) value in term infants fed HM (0.10 mol/mol). It increased in all groups during the 2nd month of life, being highest in HM-fed preterm infants (1.86 mol/mol). In conclusion, urinary Ox and Ca excretion is influenced by both gestational age and nutrient intake in preterm and term infants.

Breast Feeding↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗