The importance of ST elevation in V2-4 ECG leads in athletes.

BACKGROUND: Early repolarization in the anterior ECG leads (ERV2-4) is considered to be a sign of right ventricular (RV) remodeling, but its etiology and importance are unclear. METHODS: A total of 243 top-level endurance-trained athletes (ETA; 183 men and 60 women, weekly training hours: 15-20) and 120 leisure-time athletes (LTA; 71 men and 49 women, weekly training hours: 5-6) were investigated. The ERV2-4 sign was evaluated concerning type of sport, gender, transthoracic echocardiographic parameters, and ECG changes, which can indicate elevated RV systolic pressure [left atrium enlargement (LAE), right atrium enlargement (RAE), RV conduction defect (RVcd)]. RESULTS: Stroke volume and left ventricular mass were higher in ETAs vs. LTAs in both genders (p < 0.01). Prevalence of the ERV2-4 sign was significantly higher in men than in women [p = 0.000, odds ratio (OR) = 36.4] and in ETAs than in LTAs (p = 0.000). The highest ERV2-4 prevalence appeared in the most highly trained triathlonists and canoe and kayak paddlers (OR = 13.8 and 5.2, respectively). Within the ETA group, the post-exercise LAE, RAE, and RVcd changes developed more frequently in cases with than without ERV2-4 (LAE: men: p < 0.05, females: p < 0.005; RAE: men: p < 0.05, females: p < 0.005; RVcd: N.S.). These post-exercise appearing LAE, RAE, and RVcd are associated with the ERV2-4 sign (OR = 4.0, 3.7, and 3.8, respectively). CONCLUSIONS: According to these results, ERV2-4 develops mainly in male ETAs due to long-lasting and repeated endurance training. The ERV2-4 sign indicates RV's adaptation to maintain higher compensatory pulmonary pressure and flow during exercise but its danger regarding malignant arrhythmias is unclear.

Some signal effects in human erythrocytes on specific binding of free doxorubicin and doxorubicin conjugates with magnetite nanoparticles.

Binding of doxorubicin (DOX) immobilized on nanodispersed magnetite (DOX-M conjugates with loading in the range of 0.16-25.1 mg DOX/g carrier) to intact human erythrocytes in concurrence with free DOX was investigated. Two specific binding sites for doxorubicin were revealed at the plasma membrane of human erythrocytes. Changes in the ordering of the DOX-M nanoparticles according to small angle scattering data are consistent with their specific binding at the plasma membrane upon incubation with erythrocytes. Free and conjugated doxorubicin modulated signal transduction in erythrocytes in a similar way. Both up-regulate nitric oxide and cyclic GMP and down-regulate cyclic AMP production and stabilize the membranes of oxidatively damaged erythrocytes.

Major phase I biotransformation pathways of Trichostatin a in rat hepatocytes and in rat and human liver microsomes.

Phase I biotransformation of Trichostatin A (TSA), a histone deacetylase inhibitor with promising antifibrotic and antitumoral properties, was investigated in rat and human liver microsomes and in suspensions of rat hepatocytes. TSA (50 micro M) was readily and completely metabolized by rat hepatocytes in suspension (2 x 10(6) cells/ml), whereafter its phase I metabolites were separated by high-performance liquid chromatography and detected with simultaneous UV and electrospray ionization mass spectrometry (ESI-MS). ESI tandem mass spectrometry (ESI-MS/MS) was used to identify the metabolites. Two major phase I biotransformation pathways in rat hepatocytes were shown to be N-demethylation and reduction of the hydroxamic acid function to its corresponding amide. N-monodemethylated TSA and TSA amide were preferentially formed during the first 20 min of exposure, and N-monodemethylated TSA amide appeared as the main metabolite after a 30 min incubation period. At this time, virtually all TSA had been metabolized. Trichostatic acid, N-monodemethylated Trichostatic acid, and N-didemethylated TSA were identified as minor metabolites. Longer incubation led to the formation of N-didemethylated TSA amide as the main metabolite. Lower concentrations of TSA (5 and 25 micro M) formed relatively higher amounts of N-demethylated, nonreduced metabolites. Incubations of TSA with rat and human microsomal suspensions, however, led to an incomplete biotransformation with the formation of two major metabolites, N-mono- and N-didemethylated TSA. Traces of Trichostatic acid, TSA amide, N-mono- and N-didemethylated TSA amide were also detected. This study is the first to show that TSA undergoes intensive phase I biotransformation in rat hepatocytes. This has important consequences for its potential development as a drug, since rapid biotransformation resulting in a short exposure to the pharmacologically active parent compound, and a complex mixture of metabolites is usually not desired. Further biotransformation studies of TSA and structural analogs with antitumoral and antifibrotic properties need to be performed in cultured intact hepatocytes, in particular since one of the major phase I biotransformation pathways is catalyzed by nonmicrosomal enzymes.

Synthesis of oxytocin antagonists containing conformationally constrained amino acids in position 2.

Analogues of oxytocin containing D-Trp, 2-amino-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid (Atc) or 1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (Car) with R or S configurations in position 2 were synthetized, and their receptor bindings were tested on isolated guinea-pig uterus, rat liver and rat kidney inner medulla plasma membranes. The peptides were synthetized in the solid phase by using racemates of Car and Atc. The resulting diastereomeric mixtures were separated by means of RP-HPLC. The binding to the oxytocin receptor was somewhat decreased for the Atc isomers and dramatically decreased for both R- and S-Car, while the D-Trp-containing analogue displayed a relatively high receptor affinity. However, the V1 receptor affinities were almost the same as those of the parent peptide for the Car-containing analogues and dramatically decreased for the S-Atc substituted analogue, which has a relatively high OT/V1 receptor selectivity of 44.5.

[The use of a radial osteocutaneous flap in mandibular reconstruction]. / Allkapocspótlás radiális osteocutan szabad lebennyel.

The authors make known the indications and method of the free osteocutaneous forearm flap. They have established from the literature data, and by their own experience of 4 cases, that the use of free osteocutaneous forearm flap seems to be the most ideal method when the bone defect is not bigger than 6-8 cm and only the replacement of mucosa is required.

[Effects of fecal bile acids on experimental colon carcinogenesis]. / Die Wirkung der Fäkalgallensäure auf die experimentelle Kolonkarzinogenese.

Because of the in a controversial way held discussion on an possibly existing connection between bile acid metabolism and the development of colonic carcinomas experimental researches on this problems were carried out with Wistar rats. Two test series with altogether 130 animals manifested independently from each other the result of a provable connection. During model tests small bowel resections and colon exclusion operations were realized. The carcinoma protection was accomplished by 1.2 dimethylhydrazine administered for 14 weeks in a doses of 20 mg/kg body weight. The carcinoma was proved after a 32-weeks-period. It was shown that in case of shortening the ileum more than in case of reduction of the jejunum on the left-side colon adenocarcinomas develop and the amount of the excreted fecal bile acids is the highest one. In bypassing the left-side section of the colon carcinomas develop also on the left side of the colon. But their number is significantly lower than of those on the right side. The test results indicate a causal connection.

Cytogenetic effect of the thiocarbamate herbicides butylate, molinate and vernolate in the mouse bone marrow micronucleus test.

Three thiocarbamate herbicides, butylate (S-ethyl-diisobutylthiocarbamate), vernolate (S-propyl dipropylthiocarbamate) and molinate (S-ethyl-N,N-hexamethylenethiocarbamate) were assayed for cytogenetic effect in the mouse bone marrow micronucleus test. Butylate was inactive in bone marrow, vernolate caused a marginal increase in the incidence of micronucleated polychromatic erythrocytes only at a high toxic dose level. Molinate, the N,N-hexamethylene derivative was, however, strongly active in the bone marrow, causing a high frequency of micronucleated erythrocytes, even at subtoxic concentrations.

Effect of small bowel resection on fecal bile acid excretion and on experimental colon tumour in rats.

Ileal and jejunal resections were carried out to investigate their effect on the faecal bile acid excretion and on the development of 1,2-dimethylhydrazine (DMH)-induced colonic cancer in rats. Both resection types raise the total daily faecal bile acid level compared to the control sham-operated group, whereas ileal resection has a more pronounced effect. The incidence of tumours was found higher in groups with enhanced faecal bile acid level. Our findings show a connection between the daily faecal bile acid excretion and the incidence of DMH-induced colonic cancer.

Long-term carcinogenicity bioassay of the herbicide atrazine in F344 rats.

In Fischer F344/LATI rats of both sexes the herbicide atrazine was given in the diet at concentrations of 0, 375 and 750 ppm for 126 weeks. Food and water consumption was similar in the treated and control groups. Feeding of atrazine resulted in dose-dependent depression of body weight gain in both sexes. There was no difference in the survival among the females. The males in the treated groups lived significantly longer than the controls. Exposure to atrazine resulted in significantly increased incidence of mammary tumors in the high dose male group. Uterine carcinomas were observed at a dose-related, significantly increased incidence. The number of combined leukemias/lymphomas increased in the treated males and females, but it was statistically significant only for females. The total number of malignant tumors showed a dose-related increase in both sexes. Other tumors and nontumorous lesions occurred at background level and were not influenced by treatment.

Mutagenicity of emission and immission samples around industrial areas.

Urban air particulates (suspended particles and settling dusts), as well as dusts emitted by a Söderberg aluminium production plant and a coal-burning power plant, in the industrial town of Ajka were analysed for polycyclic aromatic hydrocarbon (PAH) content (liquid chromatography) and mutagenicity (Salmonella microsome test). The same parameters for air particulates from Pápa (a town of similar size without much heavy industry) were analysed and compared to those from Ajka. The dust content, PAH concentration and the mutagenic potency of the air in Ajka were higher than in Pápa. Mutagenicity of airborne particulates showed a clear seasonality with a winter maximum and a summer minimum in both towns. The mutagenic potency of air correlated well with the benzo[a]pyrene (BP) and PAH content in Ajka but not in Pápa. The amounts of extractable organic material and mutagenic potency, as calculated for unit quantity of airborne particulate matter, were higher in the Pápa samples. Similar differences between the two towns were observed in the case of deposited dust. As regards the emission dusts, the aluminium plant emissions are responsible for much more of the mutagenicity of the urban air than the power plant emission, which is the main component of air dust pollution in Ajka.

Effect of change of fecal bile acid excretion achieved by operative procedures on 1,2-dimethylhydrazine-induced colon cancer in rats.

The effect of bile on the development of 1,2-dimethylhydrazine (DMH)-induced colon cancer was studied in male Wistar rats. Experimental operative models were created, in which in Group 1, the half intestinal tract, the ileum, and the right side of colon were released from bile. In Group 2, both sides of the colon contained bile. The sham operated animals formed Group 3. These techniques changed the concentration of bile acid in different parts of the colon, and the daily total fecal bile acid excretion as well. After DMH treatment, the relationship between these changes of bile acid level and the development of colon cancer was studied. Significantly more tumors than in the control group were found if the daily total bile acid level and the bile acid concentration in the left side of the colon were increased. Our findings show an unambiguous connection between the fecal bile acid level and the incidence of DMH-induced colon cancer.

[The role of bile in the development of colon cancer induced by 1,2-dimethyl hydrazine in rats]. / Az epe szerepe az 1,2-dimetilhidrazin-indukálta vastagbéldaganatok kialakulásában, patkányban.

Experimental operative models were created in order to investigate the role of the bile acids in the development of colon cancer in rats. These techniques changed the concentration of bile acids in different parts of the colon, and the daily fecal total bile acid levels. The relationship between these changes and the development of 1,2-dimethylhydrazin-induced colon cancer was studied. Significantly more tumors than in the control group were found if the daily total bile acid level and the concentration of bile acids in the left subsite of the large bowel was increased. Our results suggest that bile acids, as promoting factors, may play a role in the development of colon cancer in rats.

Pediatric update #8. Acute hematogenous osteomyelitis in children. Long-term results of surgical treatment.

A retrospective review (1970-1982) of the clinical experience of 68 children with acute hematogenous osteomyelitis (AHO) is presented. Analysis of the epidemiologic, clinical, laboratory, radiologic and bacteriologic findings is made. Our series was treated mainly by an aggressive primary surgical protocol which is described in detail. Seventeen percent developed chronic osteomyelitis. The role of surgery in the treatment of AHO is discussed. It is our belief that surgical treatment has definite advantages over the conservative regime and it remains our treatment of choice.

Genotoxicity of selected herbicides.

Twenty-two herbicides were studied in 67 tests for induction of DNA damage, gene mutation and chromosomal changes in vitro and in vivo. Triazine and urea-type herbicides were found to be inactive in all but one test. Of 4 thiocarbamates, molinate and vernolate caused chromosomal changes, namely increased incidence of sister chromatid exchanges and chromosomal aberrations in vitro and increased frequency of micronucleated polychromatic erythrocytes in mouse bone marrow. These compounds, however, did not cause gene mutation and only molinate gave equivocal positive result in bacterial repair test. Out of 11 miscellaneous herbicides, ethofumesate, alachlor, dichlorprop and fluorodifen proved to be positive only in one or two tests. In the light of clastogenicity of some thiocarbamates, serious consideration should be given to start animal carcinogenicity studies with these chemicals.

Mutagenicity and PAH content of airborn particulates and of fallen dusts from two Hungarian towns and emission samples from aluminum reduction and power plants.

Urban air particulates (suspended particles and settling dust), furthermore dust emitted by a Soderberg aluminum reduction plant and a coal burning power plant from an industrial town, Ajka (30,000 inhabitants) were analysed for PAH content (liquid chromatography) and mutagenicity (Salmonella microsome test). Air particulates from Papa--a town of similar size without considerable heavy industry--and corresponding plant emission from Inota, a third town in the study, served as controls. The dust content and the PAH concentration, as well as the mutagenic potency of the air in Ajka were higher than in Papa. Mutagenicity of the airborne particulates showed a clear seasonality with a winter maximum and a summer minimum in both towns. The mutagenic potency of air correlated well with the air BaP and total PAH content in Ajka, but not in Papa. The amounts of extractable organic material and mutagenic potency as calculated for unit quantity of airborne particulate matter was higher in the Papa samples. Similar differences between the two towns were observed in the case of fallen dust, too. On the basis of examination of emitted dust, it can be stated, that in the mutagenicity of urban air, the aluminum plant emission plays a considerably higher role than the power plant emission, which is the main component of air dust pollution in Ajka.

Transnitrosating activity of N-nitroso-N-methyl-p-toluenesulfonamide in rats and human gastric juice.

N-nitroso-N-methyl-p-toluenesulfonamide (NMTS, diazald, CAS 80-11-5) is a widely used compound for laboratory production of diazomethane. The present results showed that the noncarcinogenic NMTS reacts as a transnitrosating agent with amino nitrogen of secondary amines and amide both in vitro (human gastric juice) and in vivo (rats) to yield N-nitroso compounds. Since all compounds formed (NMOR, NDMA, NPIP, NPZ, NMU) are known animal carcinogens, caution should be taken by users handling NMTS.

Congenital dislocation of the hip without acetabular dysplasia.

Congenital dislocation of the hip and acetabular dysplasia apparently are not constant features of the same disease. Cases of congenital dislocation of the hip with well-developed acetabula are reported periodically. The causative factors are genetically determined or unknown. In routine clinical work, a well-developed acetabulum improves the prognosis, even in the presence of severe dislocation. An acetabular operation is often unnecessary and the reduction is more stable. Once reduction is achieved, acetabular growth seems to continue at its usual pace in these patients.

Agriculturally-related carcinogenic risk.

Although all people are exposed throughout life to pesticides (during manufacture and use, in the environment, via the food chain), with the exception of vinyl chloride and the arsenic compounds, no human carcinogen pesticide is known. In experimental animals and short-term tests, however, many pesticides have proved to be carcinogenic or genotoxic. In order to elucidate possible modes of action related to genotoxicity (short-term tests) and carcinogenicity, data on 83 pesticides were analysed. A definitive promoter effect was demonstrated for five compounds, and a suspected promoter effect could be attributed to 16 compounds. Almost all were organohalogens. Ethylenthiourea and aminotriazole are also carcinogens, which induce tumours through hormonal imbalance. Ethylenthiourea is the degradation product and metabolite of certain ethylene-bisdithiocarbamate pesticides. Chlorphenol and chlorophenoxyacetic acid-type pesticides contain 2,3,7,8-tetrachlorodibenzo-paradioxin (TCDD) as a contaminant. TCDD has definite promoter action. Seventeen tumorigenic pesticides could be regarded as genotoxic, and similar activity could be suspected in three other carcinogenic pesticides. Many pesticides contain N-nitroso impurities in various amounts. Nitrosation of the original pesticide or its derivative, such as dialkylamines, alkyl-arylamines, methyleneimines, gives rise to the formation of N-nitroso compounds. Amides containing secondary amines, such as ethylcarbamate and alkylurea, could be nitrosated in vivo and in vitro. Most nitrosated pesticides are strong genotoxic carcinogens.

Primary liposarcoma of bone. Case report and review of the literature.

Although liposarcoma is a common tumor of the soft tissues of the body, it rarely occurs as a primary neoplasm of bone. An extensive review of the literature from 1930-1980 uncovered fewer than 35 cases. The authors discuss the diagnosis and treatment of a case of primary liposarcoma of bone in the right femur of a 34-year-old Bedouin man.