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Biomedical subjects

B Roth

Publications and source records attributed to B Roth.

At least 19 recordsLinked to original sources
PubMed1992

Postnatal development of the rat organ of Corti. I. General morphology, basilar membrane, tectorial membrane and border cells.

The development of the rat organ of Corti was studied during the first postnatal weeks. The temporal and the spatial patterns of cochlear development were investigated between 4 and 24 days after birth by means of semi-thin sections at approx. ten equidistant positions along the entire cochlear duct. At all examined positions width, thickness and cross sectional area of basilar membrane, cross-sectional area of tectorial membrane, of cells of Hensen, Claudius and Boettcher and of the organ of Corti were quantitatively analyzed. The most conspicuous maturational changes occur between 8 and 12 days after birth. These are the detachment of the tectorial membrane, the first appearance of filaments within the basilar membrane, the formation of the tunnel of Corti and the opening of the inner spiral sulcus. Quantitative analysis revealed that structures of a given position along the cochlear duct do not develop synchronously. Width of the basilar membrane and cross-sectional area of the tectorial membrane are already mature at the onset of hearing (10-12 days after birth). Length, thickness and cross-sectional area of the basilar membrane as well as cross-sectional area of the organ of Corti and of the cells of Hensen, Claudius and Boettcher still develop after the onset of hearing (up to 20-24 days after birth). We suggest that basic cochlear function is established by structures which are mature before the onset of hearing. Cochlear structures which develop after the onset of hearing might be involved in this improvement during this period.

Animals↗
PubMed1992

Postnatal development of the rat organ of Corti. II. Hair cell receptors and their supporting elements.

The development of cochlear receptor cells and their supporting elements was studied by means of semi-thin and ultra-thin sections during the first postnatal weeks in the rat. The temporal and spatial patterns of the receptor cell development were investigated between the 4th and 24th days after birth. At approx. ten equidistant positions along the entire cochlear duct length of inner and outer hair cells, width of outer hair cell triad and stereocilia-length of the outer hair cells were quantitatively analyzed. Striking maturational changes take place before the 12th day after birth, that is, when the onset of hearing occurs. These changes are the formation of the tunnel of Corti, of the Nuel spaces, the appearance of filaments within the supporting elements and the change in cell shape of the hair cells. Between 4 days and 20 days after birth the maturation of outer hair cells is characterized by a decrease of organelles in the cytoplasm and establishment of the subsurface cistern. The quantitative analysis revealed a unique developmental pattern of the length of the outer hair cells, the width of the outer hair cell triad and the stereocilia length of the outer hair cells. Shortly after birth these structures have an almost constant size along the whole cochlear duct, but with increasing age the structures shorten at the cochlear base and enlarge at the apex. This pattern results in the establishment of a baso-apical gradient of the above mentioned structures. We assume that this baso-apical gradient is of central importance for the frequency representation.

Animals↗
PubMed1992

Cerebral reperfusion in brain death of a newborn. Case report.

A case of "sudden infant death" after 15 minutes of successful resuscitation of cardiovascular function is presented. While apnoic cranial nerve areflexia and electrocerebral silence persisted, angiography and transcranial Doppler sonography demonstrated nearly normal cerebral perfusion, which even increased day by day inspite of the persistence of other signs of brain death. The phenomenon "cerebral reperfusion" is concluded to be compatible with the diagnosis of brain death.

Blood Flow Velocity↗
PubMed1992

Ketamine and midazolam decrease cerebral blood flow and consequently their own rate of transport to the brain: an application of mass balance pharmacokinetics with a changing regional blood flow.

Mass balance pharmacokinetics, with simultaneous blood sampling from an artery and the internal jugular vein, was used to characterize the cerebral uptake of ketamine, norketamine, and midazolam in normoventilated pigs. Intravenous injections of ketamine or midazolam decreased the cerebral blood flow (CBF) by one third, as measured by intermittent 133Xe washout. By means of pharmacodynamic models, the effects on the CBF could be predicted from the arterial drug concentrations. The high-resolution CBF vs. time curves thus generated allowed the calculation of cerebral drug levels from arterio-venous concentration gradients in spite of a continuously changing regional blood flow. By their effects on the CBF, ketamine and midazolam decrease their own rate of transport to the brain, the immediate 30-35% drops in CBF giving similar reductions in initial net influx of drug. Physiological pharmacokinetic models assuming a constant regional blood flow are therefore not appropriate. Under clinical conditions, the CBF is determined mainly by the effects of the anesthetics and by the arterial CO2 tension. CBF changes in either direction influence the transport of drugs to the brain and may consequently result in impaired or exaggerated drug effects.

Animals↗
PubMed1992

Application of the polymerase chain reaction in the diagnosis of pulmonary toxoplasmosis in immunocompromised patients.

Bronchoalveolar lavage (BAL) fluid from 47 immunocompromised patients (26 with AIDS and 21 patients on immunosuppressive therapy) was analysed for the presence of Toxoplasma gondii DNA by means of the polymerase chain reaction (PCR). Specific target DNA derived from the B1 and P30 gene of Toxoplasma gondii was detected in BAL fluids from three patients with AIDS (6.4%). Pneumonia as the presenting feature of disseminated toxoplasmosis was confirmed by both clinical findings and by detection of Toxoplasma gondii DNA in blood obtained from two patients. The findings indicate that PCR has potential value in the detection of Toxoplasma gondii as an etiologic agent of atypical pneumonia in immunocompromised patients.

Animals↗
PubMed1992

Calcium homeostasis and hypercalciuria in hyperprostaglandin E syndrome.

Children with hyperprostaglandin E syndrome, a neonatal variant of Bartter syndrome with enhanced renal and systemic formation of prostaglandin E2, have hypercalciuria, nephrocalcinosis, and osteopenia. Because prostaglandin E2 affects tubular calcium handling, stimulates the formation of calcitriol in vitro, and has osteolytic activity, we studied calcium homeostasis and the influence of prostaglandin E2 formation on hypercalciuria in nine patients with hyperprostaglandin E syndrome during long-term indomethacin treatment and after its withdrawal. Suppression of prostaglandin E2 formation by indomethacin resulted in improvement of biochemical and clinical features of hyperprostaglandin E syndrome. However, hypercalciuria, osteopenia, and nephrocalcinosis did not completely resolve. Despite a low calcium diet, daily urinary calcium excretion was enhanced during and after withdrawal of indomethacin treatment (median 6.3, range 5.3 to 14, and median 9.4, range 4.4 to 38 mg/kg per day, respectively). Daily urinary calcium excretion was greater after withdrawal than during indomethacin treatment. Urinary calcium excretion was not correlated with urinary prostaglandin E2 excretion. Plasma levels of intact parathyroid hormone (median 11, range 6.8 to 12 pmol/L) and calcitriol (median 157, range 108 to 236 pg/ml) were elevated during indomethacin treatment and decreased after withdrawal of indomethacin. These data suggest that hypercalciuria in hyperprostaglandin E syndrome is mainly due to a renal leak of calcium, which is caused by enhanced renal formation of prostaglandin E2 and a tubular defect not related to prostaglandin E2 formation. There is no evidence for prostaglandin-stimulated calcitriol formation. Decreasing plasma levels of parathyroid hormone in the presence of renal calcium losses after withdrawal of indomethacin treatment may be due to a bone resorption process caused by systemic prostaglandin formation; the process may contribute to hypercalciuria in the patient not receiving indomethacin.

Bone Diseases, Metabolic↗
PubMed1992

High-dose intravenous immune globulin therapy for hyperbilirubinemia caused by Rh hemolytic disease.

We conducted a multicenter controlled trial to test the hypothesis that high-dose intravenous immune globulin (HDivIG) therapy can modulate bilirubin production and reduce the frequency of exchange transfusions in newborn infants with Rh hemolytic disease. Thirty-four patients with Rh incompatibility proved by positive direct antiglobulin test (Coombs test) results were randomly assigned to receive conventional treatment including phototherapy, with or without additional HDivIG therapy at 500 mg/kg given for a 2-hour period as soon as the diagnosis was established. Exchange transfusions were performed if serum bilirubin concentrations exceeded the modified curves of Polácek by more than 2 mg/dl. Two patients were excluded because of protocol violations. The results in 32 infants were analyzed. In the HDivIG group, 2 (12.5%) of 16 children required exchange transfusions, whereas it became necessary in 11 (69%) of 16 children in the control group (p less than 0.005). Bilirubin levels in the HDivIG group were lower despite reduced frequency of exchange transfusions. No side effects of HDivIG treatment were observed. We conclude that HDivIG therapy by a yet unknown mechanism reduces serum bilirubin levels and the need for blood exchange transfusions in children with Rh hemolytic disease.

Anemia↗
PubMed1991

ChAT-like immunoreactivity of olivocochlear fibres on rat outer hair cells during the postnatal development.

Several studies present a great deal of information about putative efferent neurotransmitters and their distribution in the adult and developing cochlea. Anatomical mapping of outer hair cell efferent fibres during ontogeny is still not available. Using quantitative electron microscopy in combination with immunocytochemistry, the distribution of ChAT-like immunoreactivity in the developing rat was investigated. Adult-like immunoreactivity in the whole cochlea is first observed in 30-day-old rats. We localized the adult-like immunoreactivity in all efferent fibres and synapses of the outer hair cells along the entire cochlear duct. An adult-like reaction in the whole cochlea could be observed on the 25th day after birth in two out of three cases. On the 20th postnatal day, no adult-like ChAT immunoreactivity was found, with the exception of one case where labelling was seen in the basal region only. The adult-like ChAT immunoreactivity on the 30th day, 2-3 weeks after the onset of hearing, is the latest maturation of all features of the organ of Corti so far investigated. Synaptogenesis of the outer hair cell efferents reaches an adult-like appearance already on the 16th day after birth.

Animals↗
PubMed1991

Anatomical mapping of choline acetyltransferase (ChAT)-like and glutamate decarboxylase (GAD)-like immunoreactivity in outer hair cell efferents in adult rats.

The distribution of choline acetyltransferase (ChAT)-like and glutamate decarboxylase (GAD)-like immunoreactivity in the cochleae of 15 adult Wistar white rats was investigated using the peroxidase-antiperoxidase (PAP) technique. A monoclonal antibody to ChAT and a polyclonal antiserum to GAD were used. Immunoreaction was investigated quantitatively, in the electron microscope, on tangential sections of the tunnel of Corti and the rows of outer hair cells. ChAT-like and GAD-like immunoreactivity was found in all efferent nerve fibres in the tunnel of Corti and in all efferent synapses on the outer hair cells. A coexistence of ChAT and GAD in the efferent system to the outer hair cells of the rat is therefore assumed.

Age Factors↗
PubMed1991

Clinical experience with continuous intravenous sedation using midazolam and fentanyl in the paediatric intensive care unit.

Twenty-four patients in a paediatric intensive care unit mostly undergoing cardiac surgery, received a midazolam dosage between 50-400 micrograms/kg per hour as a continuous intravenous infusion partly in combination with fentanyl [0,5-2,5 micrograms/kg per hour] for analgesia and sedation. The mean duration of midazolam infusion was 11.6 days (range 38 h-40 days). Blood samples for the HPLC assay of serum midazolam concentration were taken and the clearance estimated. The efficiency of sedation in correlation to the midazolam concentration was evaluated by a clinical sedation score. Serum midazolam concentrations between 100-400 micrograms/l were sufficient for sedation. Dosage had to be increased during therapy according to an increased midazolam clearance. The evaluation of the sedation score showed that sedation of artificially ventilated infants and young children can be established by continuous intravenous infusion of midazolam.

Child, Preschool↗
PubMed1991

2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 14. 2,3-Dihydro-1-(2,4-diamino-5-pyrimidyl)-1H-indenes as conformationally restricted analogues of trimethoprim.

A conformationally restricted analogue of trimethoprim (1a) has been prepared by connecting the ortho position of the benzene ring to the methylene linkage with two methylene groups, thus forming a dihydroindene derivative (2b). The chemistry involved the condensation of barbituric acid with an indanone derivative, followed by a three-step conversion to a 2,4-diaminopyrimidine. The S isomer of 2b was found to have a minimum-energy conformation very similar to that of 1a when bound to Escherichia coli dihydrofolate reductase, in contrast to that of 1a in vertebrate DHFR. Theoretically such a derivative might have increased specificity and activity against the bacterial enzyme. Molecular modeling experiments suggested that the actual decreased activity was due to crowding in the enzyme, caused by the extra atoms needed to restrict the conformation.

Animals↗
PubMed1991

Receptor-based design of novel dihydrofolate reductase inhibitors: benzimidazole and indole derivatives.

Although many thousands of inhibitors of the enzyme dihydrofolate reductase (DHFR) have been synthesized, all of the very active compounds have been 2,4-diaminopyrimidines or very close analogues. This paper describes 2,4-diamino-6-benzylbenzimidazole (3b) and the corresponding indole (4), as well as more complex tri- and tetracyclic derivatives (5 and 6). These were designed on the basis of molecular modeling to the known X-ray structure of Escherichia coli DHFR, in an effort to determine whether one could drastically alter the diamino configuration by placing one amino substituent in a 5-membered nitrogen-containing ring and the second in the ortho position of a fused ring and still inhibit DHFR significantly. Although the electronics and bond angles are quite different from that of a 2,4-diaminopyrimidine, the pKa values are in an appropriate range, and hydrogen-bond distances appear to be quite reasonable. The most active compound, 4, was very unstable and active only in the 10(-4) M range. Dihydroindenoimidazole derivatives such as 6 showed quite a good fit to the enzyme by modeling studies, but had low activity. Since the most active compound made was 2 orders of magnitude weaker as an inhibitor of bacterial DHFR than the unsubstituted 5-benzyl-2,4-diaminopyrimidine, we concluded that such a ring system was unlikely to produce the high inhibitory potency of trimethoprim (1), even with greatly improved hydrophobic contacts. Thus the 2,4-diaminopyrimidine system remains unparalleled to date for the competitive inhibition of this enzyme.

Animals↗
PubMed1991

Analysis of pancreatic serum markers in patients with cystic fibrosis.

The occurrence of increased serum concentrations of pancreatic tumor markers CA 19-9, CA 50 and elastase 1 in cystic fibrosis (CF) prompted us to investigate the pancreatic markers DU-PAN-2 and TATI. DU-PAN-2 was measured in serum samples of 48 CF patients, 42 pediatric control patients, and 51 parents of CF children by a competition radioimmunoassay (RIA). A commercially available RIA test kit was used to measure TATI serum levels of 38 CF patients and 40 control patients. Nineteen percent of CF patients, 0% of the control group, and 6% of the parents exceeded the DU-PAN-2 threshold value of 300 U/ml. TATI concentrations were increased (greater than 20 micrograms/L) in 24% of CF patients and in 17% of control patients. The sensitivity-specificity curve of DU-PAN-2 was similar to those of CA 50 and elastase 1 but less discriminating than that of CA 19-9. However, the sensitivity-specificity profile of CA 19-9 can only be marginally enhanced in a range of low specificity by simultaneously determining elastase 1 and/or DU-PAN-2 antigens. TATI does not provide any diagnostic use in CF.

Adult↗
PubMed1991

Analgesia and sedation in neonatal intensive care using fentanyl by continuous infusion.

To determine the effects of fentanyl in newborn and premature infants, we compared two groups of 20 newborn and premature babies under artificial ventilation for severe respiratory distress syndrome: a prospective group receiving fentanyl for analgesic and sedation and a historical control group, who did not receive fentanyl. Fentanyl serum levels during steady state were determined by radioimmunoassay. Average time of infusion was 86 +/- 47 h with a mean dosage of 0.68 +/- 0.24 micrograms/kg/h. The fentanyl group needed much less sedatives and catecholamines. Heart rate and blood pressure were not significantly changed by fentanyl. Meconium was excreted later, and higher values of bilirubin were reached earlier than in the control group. Although fentanyl proved to be helpful in the neonatal intensive care unit, the administration should remain under strict indication.

Bilirubin↗
PubMed1991

[Analgesia and sedation in neonatal-pediatric intensive care].

In pediatric intensive care, analgesia and sedation has become increasingly important for newborns as well as prematures in recent years. However, its importance is frequently not well recognized and sedation is confounded with analgesia. In our intensive-care unit (ICU), fentanyl and midazolam have proved to be useful. In newborn and premature infants, fentanyl alone has been sufficient because of its analgesic and sedative action. In a study on 20 newborns and prematures suffering from severe respiratory problems as compared with a historical group that did not receive fentanyl, we could show that in subjects receiving fentanyl, considerably less treatment with sedatives and other analgesics was necessary. Cardiopulmonary tolerance was satisfactory. The highest bilirubin values were reached about 1 day earlier and were slightly higher than those measured in the control group, but oral nutrition could be initiated sooner. In small infants, additional midazolam was given after cardiac surgery. During the first 72 h, we found a correlation between serum levels of midazolam and the depth of sedation; however, after 72 h of medication, the dose had to be raised because of an increase in metabolic clearance. During the concomitant administration of midazolam and fentanyl, significantly less midazolam was needed to achieve appropriate analog-sedation. Prior to the administration of analgesics and sedatives, care should be taken to ensure that circulatory conditions are stable and that there is no hypovolemia, and the drugs must be given slowly during several minutes. Especially in a pediatric ICU, light and noise should be diminished and contact between the parents and the child should be encouraged, even when the child is undergoing mechanical ventilation.

Analgesia↗