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Biomedical subjects

B Bertram

Publications and source records attributed to B Bertram.

At least 91 records · Page 5Linked to original sources
PubMed1989

[Rheologic findings in patients with Eales disease].

In a retrospective analysis of findings in 12 patients with Eales' disease significant changes in blood fluidity were established. The six female and six male patients, aged between 15 and 59, were examined in the acute and subclinical stages and when a recurrence occurred. The rheologic parameters plasma viscosity, erythrocyte rigidity, and erythrocyte aggregation were significantly increased in the acute stage and when there was a recurrence, while in the subclinical stage the rheologic values improved to normal. No correlation could be found between the severity of the clinical picture in the various phases and the rheologic values. None of the other biochemical, microbiologic, and immunologic parameters were pathologic in any stage of the disease. In particular, virus serology, protein, immune, and hemoglobin electrophoresis were normal in all patients. While the etiology of Eales' disease remains unknown, deteroration in erythrocyte rigidity appears to play a part in the pathophysiology of the disease.

Adolescent↗
PubMed1989

[Retinal hemodynamics and morphologic findings in patients with occlusion of the internal carotid artery].

Only a minor percentage of patients with occlusion of the internal carotid artery develops the clinical symptoms of ischemic ophthalmopathy. The degree of functional collateralization that mirrors the alteration in ocular perfusion seems to be of importance for its development. We employed video fluorescein angiography to determine the degree of minor retinal perfusion in 33 patients. With a picture analyzer (Microvideomat 3, Zeiss) we quantified the arm-retina time (ART), the arteriovenous passage time (AVP) and the arterial dye bolus velocity. In these patients retinal perfusion was significantly decreased compared to a normal control group. The AVP of 18 patients was more than triple the average normal value (1.45 +/- 4.0 s); 3 of these patients showed morphological signs of ischemic ophthalmopathy with extensive non-perfusion areas: they showed a change in retinal hemodynamics and a massive deficiency in vasomotor response to CO2 stimulation. After panretinal laser coagulation their retinal hemodynamics, morphological alterations and subjective complaints improved. Our results show that using video fluorescein angiography on patients suffering from occlusion of the internal carotic artery analyzing the retinal hemodynamics can help to determine whether ischemic ophthalmopathy is developing or not.

Adolescent↗
PubMed1988

[Video fluorescence angiography follow-up of patients with retinal stasis syndrome].

Forty-four patients were examined by video-fluorescein angiography. With the onset of the first symptoms a significant decrease in retinal blood flow was determined by prolonged arteriovenous passage time (AVP) and diminution of mean dye bolus velocity (MDV). No correlation could be found between the extent of impeded retinal perfusion in the acute phase and the severity of the clinical appearance. In 35 of the 44 patients a favorable clinical course was observed. An initially markedly reduced retinal perfusion improved under treatment by isovolemic or hypervolemic hemodilution, fibrinolysis, and panretinal laser coagulation, and remained stationary during the further course of time. Complete normalization of the AVP and the MDV could not be found in any of these patients. Sixteen percent of the patients with retinal stasis syndrome developed hemorrhagic central venous thrombosis. In the authors' opinion videoangiographic follow-up of patients with retinal stasis syndrome is essential for early detection of further-reduced retinal perfusion. It may thus be possible to prevent the transition to hemorrhagic central retinal vein occlusion in these cases by early treatment.

Adult↗
PubMed1988

Influence of thiocompounds on the metabolism of N-nitrosodiethylamine.

Diethyldithiocarbaminate (DDTC), mercaptoethanesulfonate (MESNA) and ethylxanthate (PEX) were tested for their influence on N-nitrosodiethylamine (NDEA) metabolism. The exhalation rate of 14CO2 released from [14C]NDEA was decreased by PEX, but not by MESNA or DDTC. The sulfur compounds led to an increased excretion of unchanged NDEA in urine in the order PEX greater than DDTC much greater than MESNA. The activity of NDEA-deethylase in liver microsomal system was decreased only after DDTC or PEX treatment. Glutathione content and glutathione-S-transferase activity were not affected significantly by any of the tested compounds. NDEA-induced single-strand breaks in liver cell DNA were inhibited after PEX treatment.

Animals↗
PubMed1988

[Treatment trials of plasminogen activator (rt-PA) in central vein thrombosis of the retina].

Five patients with central retinal vein occlusion were treated by fibrinolysis using recombinant tissue plasminogen activator (rt-PA). Three patients received 70 mg of rt-PA within 90 minutes followed by 1000 I.U. of heparin per hour. The retinal blood flow was measured by videofluorescence angiography. The arterio-venous passage time initially prolonged was diminished after the fibrinolysis. Also the vision and the plasma viscosity were improved. However, this beneficial effect lasted only for a few days. Therefore, two other patients were treated for three days by daily infusions of 70 mg rt-PA. This longterm lysis did not improve vision, arterio-venous passage time or plasma viscosity. No side effects of this fibrinolytic therapy were observed. But ten days later, all of these patients had to be treated by photocoagulation.

Adult↗
PubMed1986

Use of diethyldithiocarbamate as a probe to detect stable intermediates during the decomposition of several mutagenic and nonmutagenic N-nitroso compounds.

By showing that methyldiethyldithiocarbamate is formed from the reaction of methylnitrosourea and disulfiram, we demonstrated in previous experiments that one of the anticarcinogenic/antimutagenic mechanisms of disulfiram is the scavenging of reactive species. We propose that this reaction may be employed additionally as a model for elucidating the following: (a) possible reactions between alkylating species and nucleophilic sites within the cell, and (b) the existence of stable intermediates during the metabolism of N-nitroso compounds. With structurally related pairs of nitrosoureas (n-propyl/isopropyl; cyclopropyl/allyl; 2-phenylethyl/l-phenylethyl), for which each alkylating group of the first compound can spontaneously rearrange to form the alkylating group of the second isomer, we investigated whether the alkylation proceeds via a monomolecular (sn1) or a bimolecular substitution (sn2). For this, we comparatively determined the relative mutagenic activities of each isomer in Salmonella typhimurium TA 1535, as well as their reactivities towards diethyldithiocarbamate (DDTC) by identifying the reaction products. These studies were aimed at revealing the possible formation of a free carbonium ion in the decomposition of several nitrosoureas in the rat liver supernatant fraction. Our system showed that DDTC reacts by two competing mechanisms: attack at the diazonium ion and at the free carbonium ion. Therefore the striking differences which were observed in the mutagenic potency of cyclopropylnitrosourea and N-nitrosoallylurea as well as of N-nitroso-2-phenylethylurea and N-nitroso-1-phenylethylurea cannot be explained only by the different electrophilic reactivities of the respective intermediates.

Animals↗
PubMed1985

Influence of a prolonged treatment with disulfiram and D(-)penicillamine on nitrosodiethylamine-induced biological and biochemical effects in rats. I. Investigations on the drug metabolizing system.

The influence of a prolonged treatment with disulfiram (DSF) and D(-)penicillamine (PA) on biological and biochemical effects induced by nitrosodiethylamine (NDEA) was studied in rats. The combination of NDEA and DSF led to a massive and early development of esophageal tumors, which were fatal to the animals. No liver tumors were observed in this group, whereas PA in combination with NDEA led to an increased development of liver tumors compared with NDEA alone. In the last two groups, only incidental tumors of the esophagus were observed. Nasal cavity tumors also appeared earlier in the animals treated with DSF and NDEA than in animals treated with NDEA alone or with NDEA plus PA. At a biochemical level, DSF led to a significant inhibition of hepatic anilinehydroxylase and nitroso-dimethylaminedemethylase in contrast to PA, which had no influence on these enzymes. The reduced activities of these drug-metabolizing enzymes did not appear to be related to gross cytochrome P450 content. Highly significant increases in glutathione content and glutathione-S-transferase activity (GSH/GST) were induced by DSF but not by PA. Because N-nitrosodiethylamine requires enzymatic activation to form the ultimate carcinogen, it is suggested that the observed inhibition of nitrosamine-transforming enzymes in the liver during DSF treatment leads to an increased amount of intact nitrosamines in other organs, e.g., in the esophagus, where it could be transformed to the ultimate carcinogen. DSF treatment alone or in combination with NDEA leads to an accumulation of trace elements in the liver, whereas PA eliminated copper and cobalt. The possible influence of these elements on tumor development is discussed in part II of this study.

Animals↗
PubMed1985

Influence of a prolonged treatment with disulfiram and D-penicillamine on nitrosodiethylamine-induced biological and biochemical effects. II. Investigations on trace elements in the liver.

The influence of a 28-week treatment with disulfiram (DSF), D-penicillamine (PA), and nitrosodiethylamine (NDEA), as well as with a combination of DSF or PA with NDEA on the concentrations of eight essential trace elements in the whole liver tissue of rats was measured by means of neutron activation analysis. While NDEA treatment lowered the Zn content of the liver, DSF alone or in combination with NDEA enhanced the Zn and Se concentration by 50%-80%. Co, Cu, and Cd levels were increased by factors of 10, 60, and 110, respectively. The Mo concentration was decreased by 50% after DSF administration. PA reduced Cu, Co, and Zn in the liver. PA/NDEA treatment also lowered Cu, Co, and Zn content, but there was no strengthening effect of PA on the decrease in Zn observed with NDEA. The change of trace element concentrations, especially of Cu, is discussed with regard to the observed tumor induction in the liver, which tended to be increased by a combined NDEA/PA administration compared with NDEA treatment alone, whereas a protective action of DSF against NDEA induced liver tumors could not be established.

Animals↗
PubMed1985

Reduced glutathione inhibits the alkylation by N-nitrosodimethylamine of liver DNA in vivo and microsomal fraction in vitro.

The transfer of radioactivity from N-nitroso-[14C]dimethylamine to trichloroacetic acid precipitable macromolecules in the microsomal fraction of rat liver was investigated. This transfer was found to depend on N-nitrosodimethylamine being metabolized. Cytosolic fraction and cytosol enriched with reduced glutathione inhibited the binding of radioactivity to acid insoluble proteins. Depletion of glutathione in rat liver with diethylmaleate prior to i.v. administration of 10 mg N-nitroso-[14C]dimethylamine/kg led to an increase in O6-methylguanine and N-7-methylguanine in DNA. If rats were fed disulfiram for 6 days (2 g/kg feed), glutathione and glutathione S-transferase were enhanced, and the degree of methylation of guanine by N-nitrosodimethylamine was greatly reduced, as was the metabolism of N-nitrosodimethylamine in the intact animal. Fasting rats for 24 h did not change the N-nitrosodimethylamine-demethylase activity in vitro but greatly enhanced the methylation of guanine in vivo, while the glutathione content and glutathione S-transferase activity were not changed compared to fed animals.

Alkylation↗
PubMed1984

[Coronary vessel dilatation using guided balloon catheters. Experiences with the first 100 dilatations in stable and unstable angina pectoris].

Between April and December 1983 100 transluminal coronary dilatations in 98 patients were performed using new steerable balloon catheter systems. The primary success rate (diameter enlargement greater than 20%) overall was 87%, in stenoses of the anterior interventricular branch 88.1% (59 out of 67 interventions), in stenoses of the right coronary artery 88.9% (16 out of 18), and in circumflex branch stenoses 84.6% (11 out of 13). Within the first 50 interventions the success rate was 80%. Among the second 50 cases it was improved to 94%, mainly due to the increasing experience of the investigators. Emergency bypass operations had to be performed in two patients in whom coronary vascular occlusion had occurred. No patient died and in only one a small infarction occurred, probably due to occlusion of a side branch with an increase of creatine kinase to a maximum of 120 U/l. These figures show that steerable balloon systems clearly improve the primary success rate despite broadening of indications and diminish serious complications.

Adult↗
PubMed1984

Chemical interaction of disulfiram with nitrosodimethylamine after in vitro enzymatic activation.

The in vitro reaction between disulfiram (DSF) and N-nitroso[14C]dimethylamine [( 14C]NDMA) was studied. Incubations of DSF with [14C]NDMA were carried out in the presence of rat liver microsomes, control 9000 g (S9) supernatant fraction and phenobarbital-induced S9 fraction. H.p.l.c. analysis and liquid scintillation measurement provided evidence for the formation of methyldiethyldithiocarbamate (MeDDTC) as a product of the reaction between diethyldithiocarbamate (DDTC), the main active metabolite of DSF and the 'methyl-cation' released by NDMA after enzymatic activation. The amount of MeDDTC found here was consistent with the rate of oxidation of NDMA to formaldehyde. Scintillation counting confirmed that other radioactive peaks, not due to MeDDTC, were unrelated to the methylation of L-cysteine by [14C]NDMA.

Animals↗
PubMed1982

Effects of disulfiram on mixed function oxidase system and trace element concentration in the liver of rats.

Disulfiram (DSF), an inhibitor of chemically induced carcinogenesis, and its metabolite diethyldithiocarbamate (DDTC) have been investigated for their influence on trace element distribution and on certain enzymes of the drug metabolizing system in the livers of phenobarbital (PB) treated rats. Both substances diminished the PB induced enzyme response in liver microsomes, DDTC being more effective (-85%) than DSF (-60%). The copper, cobalt and zinc content of the livers of DSF treated animals were increased by factors of 6, 3 and 1.5 respectively as compared to controls, while DDTC treatment had no influence on liver trace element content. A correlation between enzyme inhibition and enhanced trace element uptake of the liver after DSF administration could not be observed. The change of trace element transport into the liver during DSF treatment is discussed.

Animals↗
PubMed1982

In vitro formation of methyldiethyldithiocarbamate after the reaction of nitrosoacetoxymethylmethylamine or methylnitrosourea with disulfiram.

Analysis by scintillation measurement, mass spectrometry and h.p.l.c. showed that diethyldithiocarbamic acid (DDTC), the main metabolite of disulfiram (DSF), forms methyldithiocarbamate (MeDDTC) when incubated with [14C]nitrosoacetoxymethylmethylamine ([14C]NAMM) or [14C]methylnitrosourea ([14C]MNU) in different media (bacteria, esterases, rat liver 9000 x g supernatant fraction and microsomes). When DSF instead of DDTC was used, MeDDTC was formed only when soluble enzymes were present which are required to split DSF into two DDTC moieties. No physiological methylation of DDTC takes place as was shown by experiments with [3H]MNU. [14C]Methanol, formed by the decay of [14C]NAMM and [14C]MNU was shown to have no alkylating properties.

Animals↗
PubMed1982

Mutagenicity and synthesis of alpha-substituted N-nitrosamines: derivatives with dithiocarbamic acid.

Disulfiram (DSF) can considerably alter the organotropy of chemical carcinogens. For N-nitrosodimethylamine and for N-nitrosodiethylamine the organotropy is shifted from the liver to the nasal cavity or the oesophagus, respectively. Whereas the influence of DSF or its metabolites on enzyme systems has been studied, little is known about its interaction with the carcinogens at a molecular level. Therefore, postulated reaction products of a series of alpha-hydroxylated N-nitroso-dialkylamines and dithiocarbamate were synthesized and tested for mutagenicity in Salmonella typhimurium TA 1535. The results show that the compounds conjugated at a primary alpha-C-atom are not mutagenic, whereas those conjugated at a secondary alpha-C-atom are active. The primary N-nitroso-dithiocarbamates represent unique examples of inactivated dialkyl-nitrosamine derivatives. In addition, their formation in vitro was indirectly demonstrated. The possible role these inactivated compounds may play during the DSF-modulation of carcinogenesis will be discussed.

Chemical Phenomena↗