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B Roth

Publications and source records attributed to B Roth.

At least 19 recordsLinked to original sources
PubMed2000

Oligonucleotide-conjugated beads for transdominant genetic experiments.

Transdominant genetics using expression libraries can identify proteins and peptides that affect cell division. In conjunction with these libraries, oligo-nucleotide-conjugated beads and flow cytometry were used to test a strategy that potentially expands the range of such genetic studies. The experimental approach involved creation of tagged expression libraries, introduction of these libraries into cells, growth of the cultured cells for several generations and recovery on oligonucleotide-conjugated beads of sequences that encode growth-modulatory proteins or peptides. Experiments in Saccharomyces cerevisiae demonstrating the feasibility of the strategy are presented.

Base Sequence↗
PubMed1999

Chromosomal imbalances in noninvasive papillary bladder neoplasms (pTa).

Almost 70% of urinary bladder neoplasms present as low-grade papillary noninvasive tumors (stage pTa). To determine which genomic alterations can occur in pTa tumors of different grades and to evaluate the prognostic significance of chromosomal imbalances, we analyzed 113 pTa tumors (40 grade 1, 55 grade 2, 18 grade 3) by comparative genomic hybridization. pTaG1 (1.9 +/- 2.0) and pTaG2 (3.1 +/- 2.9) tumors had only few genomic alterations with 9q- (44%), 9p- (36%), and -Y (21%) being most prevalent. Neither the total number of aberrations nor any individual alteration was linked to the risk of recurrence in 95 pTaG1/G2 tumors with clinical follow-up information. pTaG3 tumors were characterized by a high number of alterations (7.7 +/- 4.5; P < 0.0001 for G3 versus G2). Several chromosomal imbalances that have previously been reported to be typical for invasive bladder neoplasms were significantly more frequent in pTaG3 than in pTaG2 tumors, including 2q-, 5p+, 5q-, 6q-, 8p-, 10q-, 18q-, and 20q+. A malfunction of genes at these loci may contribute to the development of high-grade urothelial neoplasias. However, there is no evidence for a direct role of these alterations for development of invasive tumor growth.

Carcinoma in Situ↗
PubMed1999

Management of acute inflammatory childhood stridor.

BACKGROUND AND OBJECTIVE: Acute epiglottitis, bacterial tracheitis, and severe viral laryngotracheobronchitis continue to cause life-threatening airway obstruction in children. The aim of this retrospective study was to evaluate deficiencies in treatment, to clarify the role of airway endoscopy, and to identify current reasons for fatalities in these diseases. MATERIALS AND PATIENTS: During the observation period from 1980 to 1996, we identified 61 patients treated in the pediatric intensive care unit of the University Hospital of Cologne for severe inflammatory airway obstruction. RESULTS: Critical points in the appropriate airway management were (1) the confirmation of the admission diagnosis, (2) whether an artificial airway or rigid tracheobronchoscopy was required; and (3) appropriate timing of extubation. Since 1989 airway evaluation with flexible or small, rigid endoscopes was used to confirm the diagnosis and to determine the appropriate management. Endoscopic findings were extremely helpful to decide not to intubate and to monitor in the pediatric intensive care unit first. Three patients with acute epiglottitis died after out-of-hospital cardiorespiratory arrest. CONCLUSION: Endoscopy should be a part of every established treatment protocol of childhood stridor. The most decisive factor to decrease mortality seems to be timely presentation to a referral center.

Airway Obstruction↗
PubMed1999

Early metabolic acidosis and coma after acetaminophen ingestion.

Metabolic acidosis and coma may develop in patients who experience severe hepatic injury after acetaminophen poisoning. The onset of acidosis and coma soon after acetaminophen overdose, but preceding manifest hepatic injury, contrasts with the typical course of poisoning. This pattern has been reported in a limited number of cases. Coingestions and the rare occurrence of these findings after an overdose have engendered controversy as to whether acetaminophen alone is the cause of early coma and acidosis. We describe 4 separate overdoses among 3 patients who arrived at the emergency department comatose with a metabolic acidosis soon after ingesting large amounts of acetaminophen without evidence of toxic liver injury. Our cases support the view that early metabolic acidosis with coma does indeed occur after acetaminophen poisoning, independent of hepatic failure or its complications.

Acetaminophen↗
PubMed1999

Characterization of radioactive metabolites of 5-HT2A receptor PET ligand [18F]altanserin in human and rodent.

This study was performed to identify and characterize the radiometabolites of the serotonin 5-HT2A receptor ligand [18F]altanserin in supporting quantification of the target receptors by positron emission tomography. In analogy to its analog ketanserin, we postulated 4-(4-fluorobenzoyl)piperidine (FBP) and altanserinol for the previously observed two polar radiometabolites, corresponding to dealkylation at the piperidine nitrogen and reduction at the ketone, respectively. To test this hypothesis and characterize the in vivo and in vitro behavior of the radiometabolites, we synthesized nonradioactive authentic compounds altanserinol, 1-(4-fluorophenyl)-1-(piperidin-4-yl)methanol (FBPOH), and isolated nonradioactive FBP metabolite from monkey plasma. [18F]Altanserinol was obtained by NaBH4 reduction of [18F]altanserin, followed by acid hydrolysis. Identification of radiometabolites was carried out by high performance liquid chromatography and thin layer chromatography comparison of the radioactive plasma after injection of tracers with five authentic compounds. Human studies revealed that at least four radiometabolites, one identified as [18F]altanserinol, resulted from reduction of the ketone functionality. The N-dealkylation product [18F]FBP was not detectable; however, a radiometabolite of FBP was present in plasma after administration of [18F]altanserin. Monkey studies showed nonradioactive FBP was converted rapidly to a less polar metabolite. In rat, altanserin and altanserinol were converted to each other in vivo, and all the radiometabolites likely penetrated the blood-brain barrier and entered the brain. Displacement binding of altanserin to cloned serotonin 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7 receptors showed Ki values of 0.3, 6.0, 1,756, and 15 nM; the binding of FBP and altanserinol to these four 5-HT subtypes was negligible. We conclude from these studies that the radiometabolites of [18F]altanserin from N-dealkylation and ketone reduction should not interfere with specific receptor quantification in an equilibrium paradigm.

Animals↗
PubMed1999

Vinblastine versus vinblastine plus oral estramustine phosphate for patients with hormone-refractory prostate cancer: A Hoosier Oncology Group and Fox Chase Network phase III trial.

PURPOSE: To compare vinblastine versus the combination of vinblastine plus estramustine as treatment for patients with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: A total of 201 patients with metastatic prostate cancer, progressive after hormonal therapy and antiandrogen withdrawal (if prior antiandrogen treatment), were randomized to receive vinblastine (V) 4 mg/m(2) by intravenous bolus weekly for 6 weeks followed by 2 weeks off, either alone or together with estramustine phosphate (EM-V) 600 mg/m(2) PO days 1 through 42, repeated every 8 weeks. Of 193 eligible patients, 98 received V, and 95 received EM-V. RESULTS: Overall survival trended in favor of EM-V but was not significantly different as determined by Kaplan-Meier analysis (P =.08). Median survival was 11.9 months for EM-V and 9.2 months for V. EM-V was superior to V for secondary end points of time to progression (P <. 001, stratified log rank test; median 3.7 v 2.2 months, respectively) and for proportion of patients with >/= 50% prostate-specific antigen (PSA) decline sustained for at least 3 monthly measurements (25.2% v 3.2%, respectively; P <.0001). Granulocytopenia was significantly less for EM-V compared with V (grade 2, 3, and 4 = 7%, 7%, and 1% v 27%, 18% and 9%, respectively; P <.0001); however, grade 2 or worse nausea (26% v 7%, respectively; P =.0002) and extremity edema (22% v 8%, respectively; P =.005) were more frequent for EM-V. CONCLUSION: Although overall survival was not significantly greater for the combination, EM-V was superior to V for time to progression and PSA improvement. These results encourage further study of estramustine-based antimicrotubule drug combinations in HRPC.

Administration, Oral↗
PubMed1999

Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group.

PURPOSE: Prostate-specific antigen (PSA) is a glycoprotein that is found almost exclusively in normal and neoplastic prostate cells. For patients with metastatic disease, changes in PSA will often antedate changes in bone scan. Furthermore, many but not all investigators have observed an association between a decline in PSA levels of 50% or greater and survival. Since the majority of phase II clinical trials for patients with androgen-independent prostate cancer (AIPC) have used PSA as a marker, we believed it was important for investigators to agree on definitions and values for a minimum set of parameters for eligibility and PSA declines and to develop a common approach to outcome analysis and reporting. We held a consensus conference with 26 leading investigators in the field of AIPC to define these parameters. RESULT: We defined four patient groups: (1) progressive measurable disease, (2) progressive bone metastasis, (3) stable metastases and a rising PSA, and (4) rising PSA and no other evidence of metastatic disease. The purpose of determining the number of patients whose PSA level drops in a phase II trial of AIPC is to guide the selection of agents for further testing and phase III trials. We propose that investigators report at a minimum a PSA decline of at least 50% and this must be confirmed by a second PSA value 4 or more weeks later. Patients may not demonstrate clinical or radiographic evidence of disease progression during this time period. Some investigators may want to report additional measures of PSA changes (ie, 75% decline, 90% decline). Response duration and the time to PSA progression may also be important clinical end point. CONCLUSION: Through this consensus conference, we believe we have developed practical guidelines for using PSA as a measurement of outcome. Furthermore, the use of common standards is important as we determine which agents should progress to randomized trials which will use survival as an end point.

Androgens↗
PubMed1999

Scrofuloderma of the lower extremity treated with wide resection: a case report and review of the literature.

Scrofuloderma is tuberculosis of subcutaneous tissue that ulcerates and drains through the overlying skin. It most commonly occurs in the neck from a cervical lymph node source. Although such lymphatic spread is the usual clinical picture, there are sporadic reports in the literature of direct hematogenous seeding of subcutaneous tissue forming a tuberculoma, or "cold abscess." Definitive diagnosis requires the identification of Mycobacterium tuberculosis within the suspect lesion. Surgical intervention is necessary in any draining lesion and should be accompanied by appropriate antituberculous chemotherapy. Accounts of bone and joint involvement are numerous, but the orthopedic surgeon must also be aware of the soft-tissue manifestations of tuberculosis and the indications for surgery. We report on an immunocompromised patient who presented with a rare case of scrofuloderma of the lower extremity, which was treated with wide resection.

Adult↗
PubMed1998

Attenuated hematopoietic response to granulocyte-macrophage colony-stimulating factor in patients with acquired pulmonary alveolar proteinosis.

The pathogenesis of acquired pulmonary alveolar proteinosis (PAP), a rare lung disease characterized by excessive surfactant accumulation within the alveolar space, remains obscure. Gene-targeted mice lacking the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) or the signal-transducing beta-common chain of the GM-CSF receptor have impaired surfactant clearance and pulmonary pathology resembling human PAP. We therefore investigated the hematopoietic effects of GM-CSF in patients with PAP. The hematologic response of 5 infants with congenital PAP to 5 microgram/kg/d was of normal magnitude. By contrast, despite normal expression of GM-CSF receptor alpha- and beta-common chains on peripheral blood myelomonocytic cells (n = 6) and normal binding affinity of bone marrow mononuclear cells for GM-CSF (n = 3), each of the 12 patients with acquired PAP treated displayed impaired responses to GM-CSF; 5 microgram/kg/d produced only minor eosinophilia, and doses of 7.5 to 20 microgram/kg were required to induce >/=1.5-fold neutrophil increments in the 3 patients who underwent dose-escalation. However, neutrophilic responses to 5 microgram/kg granulocyte colony-stimulating factor (G-CSF) were normal (n = 4). In vitro, the proportion of hematopoietic progenitors responsive to GM-CSF (16.1% +/- 8.9%; P = .042) or interleukin-3 (IL-3; 19.3% +/- 7.7%; P = .063), both of which utilize the beta-common chain of the GM-CSF receptor complex, were reduced among patients with acquired PAP (n = 4) compared with normal bone marrow donor controls (47.2% +/- 25.9% and 40.9% +/- 18.6%, respectively). In the one individual who had complete resolution of lung disease during the period of study, this was temporally associated with correction of this defective in vitro response to GM-CSF and IL-3 on serial assessment. These data establish that patients with acquired PAP have an associated impaired responsiveness to GM-CSF that is potentially pathogenic in the development of their lung disease. Based on these observations, we propose a model of the pathogenesis of acquired PAP that suggests the disease arises as a consequence of an acquired clonal disorder within the hematopoietic progenitor cell compartment.

Adolescent↗
PubMed1998

Epidemiology and etiology of acquired hearing disorders in childhood in the Cologne area.

Because of their serious consequences for all aspects of development, severe hearing disorders in children are an important clinical entity. A better understanding of the epidemiology and etiology of acquired hearing disorders may potentially lead to more effective prevention. Marked differences in the epidemiology of acquired hearing disorders are reported in the literature. In order to illuminate the problem of acquired disorders and to define current etiological causes with special regard to ethnological factors in the Cologne area, we started a retrospective study. A total of 314 children in residence at the school for hearing impaired children in Cologne were investigated. We also obtained concise data on the structure of the population in order to determine prevalence of acquired hearing disorders in the German and immigrant portions of the population. We found an overall prevalence of 0.43 per thousand for severe hearing disorders and deafness. German children were most frequently affected by acquired, and non-German children by hereditary hearing disorders. The most common causes of acquired severe hearing disorder were the perinatal complex of premature delivery, anoxia and hyperbilirubinuria or kernicterus. Other causes were congenital rubella infections and meningitis in early childhood. The accumulation of perinatal etiologies seems to be the reason for the remarkable majority of acquired hearing disorders among German children. One reason might be progress in neonatology which exerts two effects. It decreases perinatal mortality but increases perinatal complications like acquired hearing impairment. The incidence of congenital rubella in Germany has decreased during recent years, reaching a low level.

Child↗
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↗