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Biomedical subjects

F Schweinsberg

Publications and source records attributed to F Schweinsberg.

At least 37 records · Page 2Linked to original sources
PubMed1991

[Morphological and toxicological findings after intravenous injection of metallic mercury].

At the autopsy of a 25-year-old man who had died from combined morphine and cocaine intoxication, depositions of metallic mercury were incidentally found in the myocardium of the right ventricular septum and posterior wall. Deposits, toxicologically identified as mercury, were also found radiologically and histologically in the lungs. All these deposits were probably the result of intravenous injections of mercury many months previously, as is known to be done occasionally by addicts. Judging by the histological picture the greatest proportion of the mercury collected in the right ventricular cavity after injection, a smaller amount by embolization in the small pulmonary arteries. The mercury spheres which came to lie in the right ventricle then penetrated into the myocardium, moving outward and causing a chronic and partly transmural inflammatory response.

Adult↗
PubMed1991

Tripotassium dicitrato bismuthate: absorption and urinary excretion of bismuth in patients with normal and impaired renal function.

We have investigated the absorption and urinary excretion of tripotassium dicitrato bismuthate during a treatment course of 4 weeks in 7 patients with normal renal function (creatinine clearance 115 +/- 29 ml/min; mean +/- S.D.), in 7 patients with impaired renal function (creatinine clearance = 34 +/- 19 ml/min) and in 4 dialysed patients. Following the first dose of tripotassium dicitrato bismuthate (216 mg bismuth b.d.), and after 2 and 4 weeks of treatment (dialysed patients received only 108 mg/b.d.), plasma and urine concentrations of bismuth were monitored for 2 and 24 h, respectively. After stopping therapy plasma and urine concentrations of bismuth were followed for 4 and 6 weeks, respectively. In all three groups of patients small amounts of bismuth (mean values 0.26 to 0.28% of dose) were rapidly (transient mean peak concentrations between 40 and 134 micrograms/L) reached within about 30 to 40 min, absorbed and plasma levels demonstrated a wide intra- and inter-individual variability. Absorption profiles were not altered during the treatment course; however, the trough plasma concentration of bismuth demonstrated an about 3- to 5-fold accumulation (correlated to creatinine clearance) from about 5 micrograms/L to 15 micrograms/L (normal renal function) or to 20-25 micrograms/L (impaired renal function). Pre-study bismuth levels could be detected within 2 to 4 weeks after stopping therapy in all subjects whereas urinary concentrations were still elevated 6 weeks after the course of treatment. Our results indicate that tripotassium dicitrato bismuthate is absorbed in very low amounts during standard therapy. However, dependent on renal function, accumulation to non-toxic levels does occur during a course of treatment. It appears prudent to halve tripotassium dicitrato bismuthate dosage in patients with severe renal insufficiency (creatinine clearance less than or equal to 20 ml/min) to avoid any possible toxic risks. In such patients monitoring of the plasma bismuth concentration might be helpful, especially if longer or repeated treatment is anticipated.

Absorption↗
PubMed1990

[Threshold values for chemicals to prevent disease].

Proper interpretation of threshold limit values should always take into account that such limits are not absolute, but rather subject to change depending on advances in scientific knowledge. Threshold limit values derived from toxicologic study are best suited to evaluation of health risks of chemicals in the environment. Although more toxicologic information than is currently available would be desirable for the establishment of limit values, this should not prevent agreement on limits for more substances. "Better" threshold limit values would be forthcoming from epidemiologic studies, which are particularly rare in the FRG. Prospective studies measure current exposure; but appearance of detrimental health effects generally requires a lengthy latency period (e.g., decades in the case of cancer or cardiovascular disease). Threshold limit values permit monitoring and, if necessary, restriction of anthropogenic activity. Such restrictions are necessary, as shown by severe health damage which has occurred in the past (e.g., angiosarcoma due to vinyl chloride or neurogenic damage due to mercury in the workplace, tumors due to arsenic in drinking water, and methemoglobinemia in infants due to nitrite or renal damage due to cadmium in food). Evaluation of potential detrimental health effects for threshold limit values in environmental media is difficult because the effective dose cannot be determined. Monitoring of such limit values, which have already been incorporated into West German law, is relatively easy to implement, however (e.g. continuous outdoor air quality sampling and measurement, and periodic analysis of drinking water and foodstuffs). Since such monitoring may be performed close to the source, preventive measures should be easy to implement. Biological threshold limit values (biological monitoring) are essential to effective evaluation of the health effects of chemicals. Such limits should be established for more substances. When biological limit values are exceeded, however, it is generally difficult to determine the source(s) of exposure. Since individuals themselves cause the most damage to their own health e.g., through consumption of alcoholic beverages, cigarette smoking, or poor eating habits; the establishment of threshold limit values designed to protect individuals from themselves would be the most effective method of preventing environmental disease.

Air Pollution↗
PubMed1989

[A literature review of the concentrations of arsenic, lead, cadmium, and mercury in body fluids and tissues to establish normal levels and to detect exposure. 3. Mercury].

The 3rd of 4 communications on metal concentrations in human body media deals with mercury. Publications obtained from a comprehensive data bank search from January 1980 to April 1984 are listed in tables; study groups have been assigned to the following categories: normal, exposed; and exposed, exhibiting adverse health effects. Quality and strength of evidence of analytical procedures and reported data are discussed, particularly in light of adverse health effects. General methods and individual analytical procedures were presented in the 1st communication, a summary of mean exposure levels, critically elevated levels, and references will be published in the 4th communication.

Humans↗
PubMed1989

[A literature review of concentrations of arsenic, lead, cadmium and mercury in body fluids and tissues for establishing normal values and detection of body burden. 4. Lead, summary of average values for As, Cd, Hg and literature references].

The last of 4 communications on metal concentrations in human body media deals with lead. It includes also a summary of mean exposure levels, critically elevated levels, and references. Publications obtained from a comprehensive data bank search from January 1980 to April 1984 are listed in tables; study groups have been assigned to the following categories: normal; exposed; and exposed, exhibiting adverse health effects. Quality and strength of evidence of analytical procedures and reported data are discussed, particularly in light of adverse health effects. General methods and individual analytical procedures were presented in the 1st communication.

Arsenic↗
PubMed1989

[Correlation of blood pressure and cadmium and lead content of the hair in nonsmoking males].

In developed countries, hypertension represents one of the most frequent diseases and is one of the most important risk factors of arteriosclerotic vascular disease e.g. to myocardial infarction or cerebral apoplexy. The etiology of hypertension is unknown in about 90% of cases. The heavy metals cadmium and lead occur in increasing amounts in the human environment. Numerous epidemiological studies and investigations using experimental animals have dealt with the putative relationship between cadmium and lead, and hypertension. The results to date have been quite controversial; thus the issue appears to be unresolved at present. In the present study scalp hair samples were collected from 100 non-smoking 30-to-50-year-old men. After washing, the samples were digested with a mixture of nitric and sulfuric acid in a teflon bomb and analyzed by flameless atomic absorption spectroscopy. For 90% of the test persons the cadmium hair values were in the range of 0 to 1400 micrograms/kg; the corresponding range for hair lead was 0 to 13,000 micrograms/kg. Correlation with diastolic or systolic blood pressure was neither found for cadmium or lead. The test persons with the highest cadmium or lead load were not hypertensive. Some factors should be considered when comparing the present results with those of other investigators reporting a positive correlation in the question under consideration. 1. Previous studies in man frequently did not sufficiently take smoking habits into account. This is essential, however, because, in addition to cadmium and lead, nicotine and carbon monoxide are also constituents of tobacco smoke and contribute to an increase in blood pressure. 2. Previous investigations generally employed blood samples, which is disadvantageous in comparison with the analysis of hair because blood samples do not reflect long-term exposition, which is important in the etiology of chronic diseases. Correlation between hypertension and levels of long-term cadmium and lead exposure in man seem to be unlikely in light of the present results. Nevertheless, numerous potential effects should be considered to obtain further insight in the complex pathogenesis of hypertension.

Adult↗
PubMed1988

[A study of the literature on the concentrations of arsenic, lead, cadmium and mercury in body fluids and tissues to define normal values and detection of overload. 1. Description of analytical methods and arsenic].

The present review covers 208 papers dealing with determination of the metals arsenic, cadmium, lead and mercury in human biologic material. A comprehensive data bank survey of the literature from January 1980 to April 1984 was conducted and supplemented by review of some earlier publications. As shown by comparison of the results from a number of papers, the various state-of-the-art methods for determining metal content in biologic materials (e.g., atomic absorption spectrophotometry, neutron activation analysis, and x-ray fluorescent analysis) appear to be equally sensitive and reliable. These detection methods are suited to determination of the above metals in the following media: arsenic in urine, hair; cadmium in blood, urine, hair, renal cortex; lead in blood, hair; mercury in blood, urine, hair. To permit better comparison of the results presented in various publications, agreement must be reached on use of uniform concentration units and participation in quality control programs. Safe levels of chronic biological exposure overlap with concentrations which cause health effects or measurable impairment of body function over a wide range. Individual sensitivity to biological exposure varies. In a number of studies, metal concentrations are measured in symptom-free persons which cause symptoms in persons examined in other studies. Due to differences in the sensitivity of detection of symptoms, the range of minimum levels of biological exposure considered to be associated with deleterious health effects (levels of critical exposure) is unacceptably broad. Minimum levels of critical exposure should protect against development of early symptoms of toxicity. If the lowest published critical levels of biological exposure are taken as a cutoff, then a sizable portion of the persons currently revealing metal exposure in any of the reported media exceeds such levels. Symptoms of detrimental effects should be detectable in such persons and should be investigated. In establishing and evaluating current minimum levels of critical chronic metal exposure, there is a general need for a quantitative increase in determinations and for a qualitative increase in the sensitivity of detection of symptoms and other health effects--in order to avoid dependence on reports of acute toxicity. When detected levels of a given metal are in a range held to be normal, exclusion of toxic effects and poisoning requires additional consideration of clinical findings.

Arsenic↗
PubMed1988

[A review of the literature on the concentration of arsenic, lead, cadmium and mercury in body fluids and tissues for the localization of normal values and the detection of body burden. 2. Cadmium].

The 2nd of 4 communications on metal concentrations in human body media deals with cadmium. Publications obtained from a comprehensive data bank search from January 1980 to April 1984 are listed in tables; study groups have been assigned to the following categories: normal; exposed; and exposed, exhibiting adverse health effects. Quality and strength of evidence of analytical procedures and reported data are discussed, particularly in light of adverse health effects. General methods and individual analytical procedures were presented in the 1st communication, a summary of mean exposure levels, critically elevated levels, and references will be published in the 4th communication.

Body Burden↗
PubMed1986

Modifying effects of disulfiram on DNA adduct formation and persistence of benzaldehyde in N-nitroso-N-methyl-benzylamine-induced carcinogenesis in rats.

Whereas disulfiram (DSF) is known to inhibit tumor formation resulting from a number of chemical carcinogens, such inhibition does not apply to nitrosamines. In the present study, biochemical and morphological findings were examined to elucidate the effect of DSF on long-term application of N-nitroso-N-methylbenzylamine (NMBA). HPLC and fluorescence detection were used to determine O6-methylguanine (O6-MG) in DNA obtained from the respiratory tract of rats subjected to long-term simultaneous application of DSF and NMBA. After 2 days of treatment, more O6-MG was detected in the proximal portion of the respiratory tract, including the trachea and main bronchi, than in the distal portion. The findings were reversed after 10 and 30 days, at which time formation of the DNA adduct was substantially higher in the distal portion of the respiratory tract, despite increases in both portions. The biochemical results corresponded to morphological findings. Initially, increased numbers of metabolizing goblet cells appeared in mucous cell hyperplasia in the proximal respiratory tract. Subsequently, the hyperplasia migrated to distal regions of the respiratory tract; at this stage, the goblet cells disappeared from the proximal portion, which now revealed toxic degeneration, atrophy and subsequent squamous metaplasia of the mucous lining and squamous papillomas. At various times during a 40-day period, 2 to 7 times more O6-MG in pulmonary DNA was detected in rats treated with DSF and NMBA, than with NMBA alone, whereby distinct amounts of O6-MG were found in the latter animals. In contrast to the above-mentioned morphological findings, no morphological alterations occurred in the respiratory tract of the animals treated with NMBA alone. It is therefore conceivable that the above pathological lesions resulted not merely from the presence of DNA adducts, but also from an additional, previously unspecified effect. As benzaldehyde (BA) is formed in equimolar amounts in NMBA metabolism and DSF has been demonstrated to inhibit aldehyde metabolism, this aldehyde is a possible candidate for such an effect. In the present study, rats were therefore treated with BA, DSF, or NMBA, or combinations thereof. Histomorphological evaluation of these experiments revealed that long-term application of BA alone led to the following alterations in the respiratory tract: goblet cell hyperplasia, hyperplasia of the peribronchial lymphatic system, mucous epithelial atrophy and accompanying perivasculitis--the same alterations seen under long-term application of NMBA and DSF.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Nitrite: a co-carcinogen?

The concurrent administration of N-nitroso-N-methylbenzylamine (NMBA) (10 mg/l drinking water) and sodium nitrite (5 g or 1 g/kg basic diet) induces enhanced progression of esophageal tumors. Pathologic changes of the respiratory system, which do not occur with administration of NMBA alone, are also observed. These findings call for re-evaluation of the toxicological significance of nitrite.

Animals↗
PubMed1984

Effect of disulfiram on N-nitroso-N-methylbenzylamine metabolism. Biochemical aspects.

The present biochemical experiments show that disulfiram inhibits N-nitroso-N-methylbenzylamine metabolism in the rat. More N-nitroso-N-methylbenzylamine may therefore reach extrahepatic tissues. The pathological lesions observed in the lungs in the present system can be explained by the finding that alkylation of lung DNA is increased and repair processes are impaired by enhanced cell proliferation in this organ.

Animals↗
PubMed1984

Role of the respiratory system in metabolism of N-nitrosamines after simultaneous application of disulfiram.

Subsequent to modification of N-nitrosamine metabolism by disulfiram, mucus-producing cells and Clara cells in the respiratory tract are involved increasingly in detoxification as well as in bioactivation of N-nitroso-N-methylbenzylamine and N-nitrosodibutylamine. Overtaxing of these cells or local concentration of antigenic metabolites leads to cytolytic defects in tracheal, bronchial and bronchiolar epithelium, in addition to toxic degenerative lesions. The resulting continuous stimulation of proliferation leads to basal-cell hyperplasia, squamous-cell metaplasia and squamous papillomas. In areas with insufficient differentiation, due to cell proliferation, there is an increased probability that focal mutation, subsequent to alkylation of purine bases, will be passed from one cell generation to the next, with subsequent formation of tumours in the bronchiolo-alveolar region.

Animals↗
PubMed1982

Mechanism of esophageal tumor induction in rats by N-nitrosomethylbenzylamine and its ring-methylated analog N-nitrosomethyl(4-methylbenzyl)amine.

The metabolism of the esophageal carcinogen N-nitrosomethylbenzylamine (MBN) and its ring-methylated analog N-nitrosomethyl(4-methylbenzyl)amine (4-MeMBN) was investigated in male Wistar rats. When given in the drinking water, both compounds have been shown to induce a high incidence of esophageal carcinomas but, after systemic administration of equimolar doses, 4-MeMBN is considerably less toxic and carcinogenic than is MBN. Following a single i.v. injection, 4-MeMBN disappeared from serum faster than did MBN. After 5 hr, neither compound was detectable in serum. Within 12 hr after a single i.v. injection (0.017 mmol/kg) of [methyl-14C]-MBN, 49% of the radioactivity was exhaled as 14CO2, and less than 5% was in the urine, compared with only 13% as 14CO2 and 65% in the urine after an equimolar dose of 4-Me[methyl-14C]MBN. The urinary metabolite of 4-MeMBN was identified as its benzoic acid derivative. Methylation of DNA purines 4 hr after a single i.v. injection (0.017 mmol/kg) of [methyl-14C]MBN was highest in the esophagus (344 mumol 7-methylguanine per mol guanine), followed by liver, lung, and forestomach. Considerably less DNA methylation was produced by an equimolar dose of 4-MeMBN, with highest values in liver, followed by esophagus (22 mumol 7-methylguanine per mol guanine) and lung. However, s.c. injections of equitoxic doses of MBN (18 mg/kg) and 4-MeMBN (394 mg/kg) produced similar amounts of 7-methylguanine in esophageal nucleic acids. These data indicate that the lower toxicity and carcinogenicity of 4-MeMBN after systemic administration are due to the rapid formation (mainly in the liver) and excretion via the urine of its benzoic acid derivative. The strong carcinogenic effect of orally administered 4-MeMBN can be explained by direct uptake from the drinking water into the esophageal mucosa. Following a single i.v. injection (0.017 mmol/kg) of [methylene-14C]MBN and 4-Me[methylene-14C]MBN, no benzylated bases were detectable in rat tissues. This indicates that the bioactivation of these compounds is initiated predominantly by hydroxylation at the methylene bridge leading to a methylating rather than a benzylating intermediate as the ultimate carcinogen.

Animals↗