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Biomedical subjects

B Roth

Publications and source records attributed to B Roth.

At least 127 records · Page 7Linked to original sources
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↗
PubMed1991

[Responders and non-responders of surfactant therapy of very small premature infants. A clinical, histopathologic and immunohistochemical analysis].

The administration of surfactants is highly effective and yields an immediate clinical response in cases of a lack of surfactant in the premature lung of preterm infants. The administration of surfactants might diminish the need for intensive care and artificial ventilation thereby also reducing or preventing the severe side effects associated with these therapeutic measures. However, the lack of clear clinical features precludes a reliable predictive forecast of the therapeutic outcome. Only the therapeutic follow-up period can disclose possible damage due to the administration of surfactants. Histological preparations of lung specimens from non-responding infants reveal cellular inflammatory infiltrations, destruction of the alveolo-capillary basement membrane and monocytic phagocytosis.

Antibodies, Heterophile↗
PubMed1991

[Ureaplasma urealyticum--a new problem pathogen in neonatology].

Some previous studies showed that Ureaplasma urealyticum is the most common germ that appears in the birthway of pregnant women and which is also frequently found in skin swabs and secretions of newborn and premature babies. The colonization of pregnant women by Ureaplasma urealyticum makes a premature birth more likely. Another factor of risk for a premature infant is a premature rupture of membranes for more than 24 hours which also makes an infection possible. There exists an association between pulmonary infection by Ureaplasma urealyticum and the development of a bronchopulmonary dysplasia especially for premature babies. According to our observations acute exacerbations of severe pneumonia can appear even after month. An attempt of therapy of pulmonary infection should be undertaken with erythromycin, if sensitive serotypes are present. In the case of erythromycin resistance chloramphenicol can be used but only under frequent controls of blood levels. We were able to observe rapid improvements with this effective therapy.

Anti-Bacterial Agents↗
PubMed1990

Phospholipid specificity of bovine heart bc1 complex.

Bovine heart bc1 complex was reversibly inactivated by a new simple and effective chromatographic delipidation method. Upon phospholipid replenishment, catalytic activity increased from values near zero to values 2-6-times higher than those of the original preparation. Compared to original preparations maximally activated by additional phospholipid, the degree of reactivation was up to 100%. By this delipidation method, the 6.4-kDa protein subunit was removed with the phospholipid. The loss of this protein neither diminished electron transport activity nor abolished proton translocation. Two requirements were necessary to obtain quantitative data: (a) only bc1 complexes, homogeneously dissolved before and after relipidation had to be used and (b) the phospholipid bound to the complex had to be determined. The correlation of catalytic activity to bound phospholipid was studied in the range of low phospholipid/protein ratios, which had previously been insufficiently resolved. Catalytic activity increased linearly with added phospholipid up to a molar ratio of 80-100 lipid molecules/dimeric complex. This corresponds to the number of phospholipid molecules that complete a single bilayer annulus. The activating effect of phospholipid is not merely due to a hydrophobic phase effect, since it strongly depends on the nature of the polar head group of the added phospholipid. Of the three major phospholipids bound to the bc1 complex, only phosphatidylethanolamine and phosphatidylcholine activated when added as sole phospholipid. Tightly bound diphosphatidylglycerol was needed for preservation of the native complex structure.

Animals↗
PubMed1990

[Hypersomnia with sleep apnea. I].

The author gives an account of present knowledge on the syndrome of hypersomnia with sleep apnea (HSA). After a historical introduction he deals with the incidence of this syndrome in Czechoslovakia; there are few accounts of this syndrome in the Czech literature. The author holds the view that this affection which is very frequent in other countries frequently escapes diagnosis in this country because the patients are not examined by sleep polygraphy which is essential for the diagnosis of HSA. The author describes also individual symptoms of the affection, i.e. hypersomnia, impaired respiration during sleep with frequent apnoic intervals, obesity, cardiovascular disorders and psychic changes. He emphasizes also the frequent incidence of tissue hyperplasia in the oropharyngeal area which leads to stenosis in this area.

Humans↗
PubMed1990

[Hypersomnia with sleep apnea. II].

In the submitted paper the author gives an account of different affection associated with the syndrome of hypersomnia with sleep apnea. They include diseases and malformations with stenosis of the upper airways in the oropharyngeal area, particularly marked during sleep. They comprise also affections of nervous structures which innervate muscles in this area. The author pays attention to the frequent incidence of this syndrome in children with hypertrophic tonsils and adenoid vegetations. In this connection he mentions the cot death syndrome where very often death occurs during the apnoic interval as a result of immaturity of nervous structures which regulate respiration during sleep. The author describes also pathophysiological mechanisms of development of HSA and the diagnosis of this affection where examination by sleep polygraphy is essential. In the subsequent part of the work the author reviews contemporary conservative and surgical treatment of HSA.

Child↗
PubMed1990

[Pregnancy outcome with intensified insulin therapy in manifest diabetes].

In 1981, the intensified insulin therapy for achievement of euglycaemia in pregnant diabetics was introduced at the University Department of Obstetrics and Gynaecology in Cologne. This study compares the results of 112 pregnancies in women with overt diabetes monitored before (1971-1980) or after (1981-1988) changing the therapeutic regimen. In the period from 1981 to 1988, the proportion of euglycaemic patients (preconceptionally 19%, before delivery 79%) was clearly higher than from 1971 to 1980 (n = 42; 7% and 9%, respectively). The tight blood glucose control resulted in a doubling of hypoglycaemic episodes during pregnancy. The proportion of preterm deliveries was reduced from 47% to 24%. The rate of caesarean sections was nearly constant (1971-1980: 38%, 1981-1988: 34%). The marked success of therapy was the decrease of perinatal mortality from 20.9% to 2.9%. The perinatal morbidity also diminished, as shown by the decreasing rates (30-90%) of foetopathy, macrosomy, respiratory distress syndrome, birth trauma, hypoglycaemia, hypocalcaemia and polycythaemia. The malformation rate, however, remained high (1971-1980 = 7%, 1981-1988 = 11%). The results demonstrate the necessity of a strict blood glucose control during pregnancy, beginning before the time of conception.

Adult↗
PubMed1990

Effects of kallikrein on sperm motility, capillary tube test, and pregnancy rate in an AIH program.

From 1984 to 1986, 172 couples were enrolled in an artificial insemination homologous (AIH) program, because of negative postcoital test, fair PT, positive PT with unexplained infertility, and impotentia coeundi. Patients were randomly assigned to the following procedures: AIH with native semen (N, n = 68), washed sperm (V, n = 50), semen mixed with kallikrein (K, 5 IE/ml semen, n = 45), and timed intercourse. The overall pregnancy rate (PR) was 22% per couple (13% inseminations, 9% spontaneous). PR from insemination (spontaneous) was 13% (8), 13% (13), 23% (0) in PT negative, fair, and positive patients, respectively, and 18% (9), 13% (7), and 11% (9) in AIH groups N, V, and K. Among in vitro studies with K added semen, an improvement of sperm motility was demonstrated in half of the specimens. In the capillary tube test (CTT), with wives' cervical mucus, a deterioration was more frequently seen than an improvement after 2 h, independent of the early effect of K in semen, K induced changes of CTT were less pronounced when donors' cervical mucus was used. The results of the in vitro studies offer an explanation for the low PR in the AIH program with K.

Adult↗
PubMed1990

[The status of computerized tomography and conventional tomography in the assessment of endobronchial growth and extension of central bronchial cancer].

In comparison with endoscopy, computed tomography can produce excellent results with respect to the endobronchial spread of central bronchial carcinomas. Used for the same purpose, conventional tomography of the central bronchial system is greatly inferior. With respect to an evaluation of the endobronchial tumour growth configuration, computed tomography of the chest showed agreement with the endoscopic findings in only 56 per cent of all cases. This would seem to indicate that for the planning of palliative bronchological measures, such as, for example, laser therapy and afterloading treatment, prior endoscopic inspection is indispensable. By themselves, the results obtained with the imaging procedures described in this article are not adequate.

Bronchi↗