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Biomedical subjects

E Kunz

Publications and source records attributed to E Kunz.

At least 19 recordsLinked to original sources

Reactivation of a Trypanosoma cruzi infection in a rhesus monkey (Macaca mulatta) experimentally infected with SIV.

Trypanosoma cruzi-like flagellates were incidentally noted in blood smears of a routinely monitored rhesus monkey experimentally infected with the simian immunodeficiency virus (SIV). Immunodeficiency in the course of the SIV infection reactivated a chronic infection of Chagas' disease that had been unnoticed when the macaque was imported to Europe. The animal developed no specific clinical symptoms of American trypanosomiasis, but histologically a chagasic myocarditis was detected. Analysis of the small subunit rRNA gene of the trypanosome identified the protozoan as T. cruzi.

Animals↗

Radon exposure and lung cancer risk--Czech cohort study on residential radon.

Epidemiological evidence of lung cancer risk from radon is based mainly on studies of men employed underground in mines where exposures are relatively high in comparison to indoor exposure. Nevertheless, direct evidence of risk from residential radon is desirable. In 1990, a study was started comprising 12,000 inhabitants of an area with elevated radon concentrations. The mean level in the houses was higher than general mean of the country by a factor of five. In the period 1961-1995, a total of 173 lung cancers were observed. Comparing to nationally expected numbers (E), the observed number (O) of cases is elevated (O/E = 1.11), in contrast to generally low figures for cancers other than lung (O/E = 0.85). Lung cancer risk related to cumulative exposures experienced in the past 5-24 or 5-35 years were both significant. In relation to standard radon progeny concentration 100 Bq/m3, the excess relative risk coefficient was 0.103 (95% CI, 0.039-0.168), the value somewhat lower than findings in other indoor studies.

Air Pollutants, Radioactive↗

Experimental Helicobacter pylori infection of rhesus macaques (Macaca mulatta).

The aim of the present study was to establish an animal model for Helicobacter pylori (H. pylori) infection at the German Primate Centre in rhesus monkeys (Macaca mulatta). During the experiments the susceptibility of three animals to different H. pylori strains of human origin was tested. In a follow-up study gastric biopsies from three different sites were investigated in regular intervals using microbiological, histological, electron microscopical and molecular biological methods to evaluate the presence of bacterial colonization and the occurrence of gastritis. It was possible to establish a persistent experimental infection. The rather long follow-up period of 18 months offered the possibility to demonstrate a permanent H. pylori infection in the gastric mucosa of the test animals. The three animals have now been successfully colonized with H. pylori for 18 months and presented a chronic active gastritis confirmed by microbiological and histological methods. By molecular typing, the identity of the isolates recovered from the animals was shown. It was possible to demonstrate that one infection strain outcompeted the second one. Taken together, prerequisites exist for making use of an attractive and useful animal model in rhesus monkeys especially for long term observations.

Animals↗

Study of lung cancer and residential radon in the Czech Republic.

Epidemiological evidence of lung cancer risk from radon is based mainly on studies of men employed underground in mines where exposures are relatively high in comparison to indoor exposure. Risk from residential radon can be estimated from occupational studies. Nevertheless, as such extrapolations depend on a number of assumptions, direct estimation of the risk is needed. The present study of lung cancer mortality was designed as a follow-up of a population (N = 12,004) in a radon prone area of the Czech Republic covering the period 1960-1999. Information on vital status and causes of death were obtained mostly from local authorities and from the national population registry. Exposure estimates were based on one year measurements of radon progeny in most houses of the study area (74%). Exposures outside the area (16%) were based on country radon mapping. Mean concentration of 509 Bq/m3 is higher than the country estimate by a factor of 5. By 1999, a total of 210 lung cancers were observed, somewhat more than the nationally expected number (O/E = 1.10) in comparison to generally low numbers corresponding to cancers other than lung (O/E = 0.81). The excess relative risk per standard radon concentration (100 Bq/m3) was 0.087 (90% CI: 0.017-0.208). This value is consistent with risk coefficients derived in other indoor studies. The present follow-up demonstrated that increased incidence of lung cancer depends linearly on exposure in terms of average radon concentration in the course of previous 5-34 years. Adjustment for smoking did not substantially change this estimate, although the risk coefficient for non-smokers (0.130) was higher in comparison to that for ever smokers (0.069), but not statistically different.

Air Pollutants↗

[Swiss 1992/1993 publications in the area of cardiovascular diseases with reference to "good clinical practice"].

BACKGROUND: For most readers, the publication is the only source of information about a study, and therefore the quality of a publication is particularly important. On January 1, 1995, new guidelines on "Good clinical practice" were implemented in Switzerland. GOAL: Quality assessments of Swiss publications in the field of clinical cardiovascular research in the light of these new guidelines. METHODS: A catalogue of 119 questions was applied to 65 cardiovascular publications that appeared during the years 1992/93. The answers were quantified with the use of a point scale. RESULTS: Publication practice as represented by the years 1992/93 can be improved on most notably in the "methods" and "results" sections of the publications, as well as with regard to medical-ethical and statistical issues. The biggest improvements in quality seem to be achievable by more precise documentation of statistical and other methodology, precise definition of the variables examined, and adaptation of the number of cases to the number of variables. In addition, description of treatment modalities and of allowed and forbidden concurrent treatments should be more precise.

Cardiovascular Diseases↗

Estimating lung cancer mortality from residential radon using data for low exposures of miners.

Some recent estimates of lung cancer risk from exposure to radon progeny in homes have been based on models developed from a pooled analysis of 11 cohorts of underground miners exposed to radon. While some miners were exposed to over 10,000 working level months (WLM), mean exposure among exposed miners was 162 WLM, about 10 times the exposure from lifetime residence in an average house and about three times the exposure from lifetime residence at the "action level" suggested by the U.S. Environmental Protection Agency. The extrapolation of lung cancer risk from the higher exposures in the miners to the generally lower exposures in the home is a substantial source of uncertainty in the assessment of the risk of indoor radon. Using the pooled data for the miners, analyses of lung cancer risk were carried out on data restricted to lower exposures, either <50 WLM or <100 WLM. In the pooled data, there were 115 lung cancer cases among workers with no occupational WLM exposure and 2,674 among exposed miners, with 353 and 562 lung cancer cases in miners with <50 WLM and <100 WLM, respectively. Relative risks (RRs) for categories of WLM based on deciles exhibited a statistically significant increasing trend with exposure in each of the restricted data sets. In the restricted data, there was little evidence of departures from a linear excess relative risk model in cumulative exposure, although power to assess alternative exposure-response trends was limited. The general patterns of declining excess RR per WLM with attained age, time since exposure and exposure rate seen in the unrestricted data were similar to the patterns found in the restricted data. Risk models based on the unrestricted data for miners provided an excellent fit to the restricted data, suggesting substantial internal validity in the projection of risk from miners with high exposures to those with low exposures. Estimates of attributable risk for lung cancer (10-14%) in the U.S. from residential radon based on models from the unrestricted data were similar to estimates based on the data for miners receiving low exposures.

Air Pollutants, Radioactive↗

[Injury sequelae and late damage of dislocation fracture of the head of the tibia].

Consequences of injury as well as succeeding joint-impairment after fracture dislocation of the tibial head are analysed. Of 38 patients who had undergone operative therapy for fracture dislocation of the tibial head between 1982 and 1991, 30 were followed up after a mean of 6.3 years. With an average age of 46.8 years and a distribution between sexes of 26 men vs. 12 women, types II (17) and V (14) (classification acc. to Moore) clearly outweighed types III (3) and IV (3) as well as type I (1). Causes of injury were dominated by traffic accidents (22/38), 9 patients suffered from accompanying ipsi-, another 9 from contralateral injuries of their lower extremities. For evaluating follow-up results, both Lysholmscore and IKDC-knee-evaluation-form were employed. The latter qualifies the overall result as "normal", "nearly normal", "abnormal" or "severely abnormal". None of the knee-joints assessed was evaluated normal. There were only 2 patients to be qualified nearly normal, whereas 5 had to be assessed abnormal and 23 severely abnormal. These poor results were mainly due to persistent symptoms (pain, swelling, giving-way) (30/30), limited range of motion (27/30) as well as impairment of joint-stability (25/30). Our results stress the need for sophisticated operative and p.op. therapy of these complex injuries.

Adult↗

[Problematic aspects of the Structural Health Regulation and minimal invasive surgery].

Decisions in surgery will have to consider economic obligations more than ever before. Consequences are evident: the assessment of surgical efficiency will be insufficient when only considering the accuracy and results of a clinical study. We actually will have to document, moreover, the economic impact of therapeutic procedures, particularly with respect to minimally invasive surgery.

Cost-Benefit Analysis↗

Lung cancer in radon-exposed miners and estimation of risk from indoor exposure.

BACKGROUND: Radioactive radon is an inert gas that can migrate from soils and rocks and accumulate in enclosed areas, such as homes and underground mines. Studies of miners show that exposure to radon decay products causes lung cancer. Consequently, it is of public health interest to estimate accurately the consequences of daily, low-level exposure in homes to this known carcinogen. Epidemiologic studies of residential radon exposure are burdened by an inability to estimate exposure accurately, low total exposure, and subsequent small excess risks. As a result, the studies have been inconclusive to date. Estimates of the hazard posed by residential radon have been based on analyses of data on miners, with recent estimates based on a pooling of four occupational cohort studies of miners, including 360 lung cancer deaths. PURPOSE: To more fully describe the lung cancer risk in radon-exposed miners, we pooled original data from 11 studies of radon-exposed underground miners, conducted a comprehensive analysis, and developed models for estimating radon-associated lung cancer risk. METHODS: We pooled original data from 11 cohort studies of radon-exposed underground miners, including 65,000 men and more than 2700 lung cancer deaths, and fit various relative risk (RR) regression models. RESULTS: The RR relationship for cumulative radon progeny exposure was consistently linear in the range of miner exposures, suggesting that exposures at lower levels, such as in homes, would carry some risk. The exposure-response trend for never-smokers was threefold the trend for smokers, indicating a greater RR for exposure in never-smokers. The RR from exposure diminished with time since the exposure occurred. For equal total exposure, exposures of long duration (and low rate) were more harmful than exposures of short duration (and high rate). CONCLUSIONS: In the miners, about 40% of all lung cancer deaths may be due to radon progeny exposure, 70% of lung cancer deaths in never-smokers, and 39% of lung cancer deaths in smokers. In the United States, 10% of all lung cancer deaths might be due to indoor radon exposure, 11% of lung cancer deaths in smokers, and 30% of lung cancer deaths in never-smokers. This risk model estimates that reducing radon in all homes exceeding the U. S. Environmental Protection Agency's recommended action level may reduce lung cancer deaths about 2%-4%. These estimates should be interpreted with caution, because concomitant exposures of miners to agents such as arsenic or diesel exhaust may modify the radon effect and, when considered together with other differences between homes and mines, might reduce the generalizability of findings in miners.

Adult↗

[Resorbable osteosynthesis rods. An experimental study of the biomechanics and degradation of various rods of polyglycolide and poly (-L-lactide)].

Six different polyglycolide and poly(-L-lactide) rods were tested biomechanically: native, in vitro and in vivo. They were Biofix-C and Biofix-CG rods and 4 poly(-L-lactide) rods with a molecular weight between 70,000 and 700,000. Their flexual strength and elasticity module were determined by the 3-point flexion test. A total of 70 pins were implanted in the soft tissue and intramedullary to splint tibial osteotomies of 30 rabbits. The Biofix rods' flexural strength was high. There was no difference due to coating (346 to 402 N/mm2). In vitro experiments showed a rapid loss strength by 75 and 90%, equivalent to 2 to 3 weeks' implantation. The initial strength of the lactide pins was about 60% lower than that of the polyglycolid rods. The stability of the former after implantation decreased at a lower rate, with 25% of the initial strength being retained after 14 weeks. The histological findings were commensurate with the loss of flexural strength.

Animals↗

Radon-exposed underground miners and inverse dose-rate (protraction enhancement) effects.

Recent models for radon-induced lung cancer assume that at high levels of cumulative exposure, as experienced historically by many underground miners of uranium and other ores, the risk of lung cancer follows an inverse dose-rate (protraction enhancement) pattern. That is, for equal total dose, a greater risk is incurred by those whose total dose is accumulated at a lower rate over a longer duration than at a higher rate over a shorter duration. This inverse dose-rate effect is hypothesized to be the consequence of multiple traversals of the nucleus of a target cell by alpha particles. It has recently been concluded, however, that for low total doses, as in most residential settings, the inverse dose-rate effect should diminish and perhaps even disappear, since at very low doses the probability that more than one alpha particle would traverse a cell is small and there would be no possibility for interactions from multiple hits. Pooling original data from 11 cohort studies of underground miners, including nearly 1.2 million person-y of observation and 2,701 lung cancer deaths, we evaluate the presence of an inverse dose-rate effect and its modification by total dose. An inverse dose-rate effect was confirmed in each cohort, except one, and overall in the pooled data. There also appears to be a diminution of the inverse dose-rate effect below 50 Working Level Months (WLM), although analyses were necessarily hampered by a limited range of exposure rates at low total WLM. These data support both the presence of an inverse dose-rate effect, as well as its diminution at low total dose. As a consequence, assessment of risks of radon progeny exposure in homes (on average 15-20 WLM for a lifetime) using miner-based models should not assume an ever-increasing risk per unit dose. Rather, it is more appropriate to apply risk models that take into account protraction enhancement and its diminution.

Humans↗

[The risk of splenectomy].

BACKGROUND: The controversely discussed effect of splenic loss and disturbances of the general state of health are to be reported by means of several check sheets. There is a control group for comparison and statistic evaluation. The results will be considered in relation to laboratory serum parameters. PATIENTS AND METHOD: 111 patients splenectomized for various reasons could be examined 3 to 17 years following surgery. We applied the depression check sheet by Beck, the Giessen complaint check sheet, and a specific splenectomy check sheet. The latter served to inquire an additional control group of statistic twins who underwent comparable upper abdominal surgery, but not splenectomy. Furthermore, 42 laboratory serum parameters were determined in every splenectomized patient. RESULTS: Compared to random tests with the Federal Republic's population, the Giessen complaint check sheet detected a more frequently disturbed state of health in "spleenless". An evaluation of the specific splenectomy check sheet detected an increased trend for infections after splenectomy (p = 0.0000001) compared to those after upper abdominal surgery. There was no statistical proof for other typical symptoms such as incompatibility with alcohol or vegetative dystonia. There was no significant anomaly in the 42 parameters measured. CONCLUSION: Every other splenectomized patient complained about frequent infections and, consequently, disturbed state of health (physical weakness, early exhaustion). These complaints did not correlate to the measured laboratory serum parameters.

Adult↗

Probability of causation for lung cancer after exposure to radon progeny: a comparison of models and data.

The estimates of lung cancer risk due to the exposure to radon decay products are based on different data sets from underground mining and on different mathematical models that are used to fit the data. Diagrams of the excess relative rate per 100 working level months in its dependence on age at exposure and age attained are shown to be a useful tool to elucidate the influence that is due to the choice of the model, and to assess the differences between the data from the major western cohorts and those from the Czech uranium miners. It is seen that the influence of the choice of the model is minor compared to the difference between the data sets. The results are used to derive attributable lifetime risks and probabilities of causation for lung cancer following radon progeny exposures.

Adult↗

Mortality in uranium miners in west Bohemia: a long-term cohort study.

A cohort of 4320 uranium miners in West Bohemia who started work at the mines during 1948 to 1959 and worked there for at least four years were followed up to the end of 1990 to determine cause specific mortality risks in relation to exposures in the mines. The miners had experienced high radon exposures, on average 219 working level months during their uranium mining careers, for which detailed measurements were available. They had also been exposed to high arsenic levels in one of the two major mines, and to dust. New follow up methods, not previously used for occupational cohorts in Czechoslovakia, were utilised. By the end of follow up 2415 (56%) of the cohort were known to have died. Overall mortality was significantly raised compared with that in the general population (relative risk (RR) = 1.56, 95% confidence interval (95% CI) 1.50-1.63), with significantly raised risks of lung cancer (RR = 5.08, 95% CI 4.71-5.47), accidents (RR = 1.59, 95% CI 1.34-1.87), homicide (RR = 5.57, 95% CI 2.66-10.21), mental disorders (RR = 5.18, 95% CI 2.83-8.70), cirrhosis (RR = 1.51, 95% CI 1.16-1.94), and non-rheumatic circulatory diseases (RR = 1.16, 95% CI 1.08-1.25). The relative risk of lung cancer was greatest four to 14 years after entry to the mines. Relative risks for homicide and accidents were raised up to 25 years from entry but not after this. Substantial significantly raised risks at 15 to 24 years after entry occurred for cirrhosis, non-rheumatic circulatory diseases,a nd pneumonia and other respiratory infections. Sizeable significantly raised risks at 25 and more years after entry, but not earlier, were present for mental disorders, tuberculosis, and non-malignant non-infectious respiratory conditions. No specific causes showed risks significantly related to age at entry to mining. Risk of lung cancer was significantly positively related to radon exposure, estimated arsenic exposure, and duration of work in the mines, but no other cause was significantly positively related to these variables. The raised risk of lung cancer in uranium miners, which is well established, is related aetiologically to radon exposure, and in the present cohort it may also in part have been due to exposure to arsenic. The raised risks of accidents, tuberculosis, and non-infectious respiratory diseases have also been seen in other uranium mining cohorts, and are likely to reflect the dangerous and dusty working conditions and the confined spaces in which work occurred. The cirrhosis and homicide deaths probably related to the lifestyle associated with mining. The raised risk of circulatory diseases does not seem to be related to radon or arsenic exposure; its causes are unclear. The use of multiple follow up methods was found to be mortality in the cohort.

Adolescent↗

Detection of RET proto-oncogene point mutations in paraffin-embedded pheochromocytoma specimens by nonradioactive single-strand conformation polymorphism analysis and direct sequencing.

The suitability of formalin-fixed and paraffin-embedded tumor material was evaluated for molecular analysis of the RET proto-oncogene. We analyzed exons 10, 11, and 16 for point mutations in seven sporadic and six multiple endocrine neoplasia (MEN) 2A-associated pheochromocytomas by a nonradioactive single-strand conformation polymorphism assay followed by nonradioactive direct sequencing of PCR-amplified DNA using an automated DNA sequencer. All MEN 2A-associated pheochromocytomas contained a heterozygous missense germline mutation within cystine codons of the cysteine-rich extracellular domain encoded by exons 10 and 11. Mutations were located in codon 619 (TGC-->TCC; Cys-->Ser) in one, in codon 635 (TGC-->CGC; Cys--Arg) in three, and in codon 635 (TGC-->TAC; Cys-->Tyr) in two pheochromocytomas. No tumor-specific (somatic) mutations were detected in exons 10, 11, and 16 of the sporadic pheochromocytomas. These data support recent findings that germline point mutations that are clustered in distinct cysteine codons of the RET proto-oncogene are involved in the neoplastic phenotype of the MEN 2A syndrome. Our results demonstrate that both nonradioactive single-strand conformation polymorphism and direct sequencing are suitable methods to detect single base substitutions in DNA extracted from archival material.

Adolescent↗

[Differential indications for intramedullary nailing of the tibia with the reamed and unreamed technique].

The principle of unreamed intramedullary nailing in tibial fractures is theoretically convincing: regarding the almost fully maintained endosteal blood supply, this concept of biological osteosynthesis implies a lower rate of postoperative complications such as non- or malunion and infection. In our clinic, 89 patients underwent intramedullary nailing of the tibia since August 1988 using the "AO-Universal-Nagel" in 63 and the Russell-Taylor unreamed nail in 26 cases. With primary data (type of fracture and grade of soft tissue injury) being comparable, we found an almost identical rate of infection for both techniques. In RT nailing, however, rates were significantly higher for non- or malunion (AO 10.3%, RT 27.6%) and implant complications such as interlocking screw or nail breakage (AO 6.2%, RT 17.2%). Thus indicating less mechanical stability, for RT- nail we allowed full weight bearing after 6-8 weeks only, whereas for AO-nail this was performed approximately 14 days p. op. after satisfying soft tissue conditions had occurred. Subsequently, this worse mechanical properties of an unreamed nail mean loss of comfort for patients, which is not fully equalized by biological advantages in all cases. We therefore champion a differentiated indication for the unreamed technique, determined by the grade of soft tissue injury: treatment of Gustilo type II and III a and b open tibial fractures by either primarily performing biological osteosynthesis or early changing from external fixation. Finally, unreamed nailing has been established as monorail procedure treating defect fractures by means of segmental transport.

Adult↗

Patterns of lung cancer mortality among uranium miners in West Bohemia with varying rates of exposure to radon and its progeny.

Lung cancer mortality in a cohort of 4320 miners first employed during 1948-1959 at the Jáchymov and Horní Slavkov uranium mines in West Bohemia and followed until 1 January 1991 has been studied to gain a greater understanding of the consequences of exposure to radon and its progeny. Among men whose exposure rates never exceeded 10 working levels, excess relative risks per unit exposure were greater in younger men, and exposures received in the periods 15-24, 25-34 and 35+ years previously were found to have 47, 24 and 0% of the effect of exposures 5-14 years previously. Within this low-exposure-rate group excess relative risk increased linearly with time-weighted cumulative exposure and did not depend on exposure rate or duration of exposure. For men who spent less than 20% of their employment at the Jáchymov mine the excess relative risk per working level month was 1.36% (95% confidence interval 0.52-3.54) in the baseline category (age group 55+ and exposure received 5-14 years previously). For men who spent more than 20% of their employment at Jáchymov, the corresponding excess relative risk per working level month was higher by a factor of 1.80 (95% confidence interval 1.27-2.97). The difference may be due to the fact that men who spent more than 20% of their employment at Jáchymov were exposed to the much higher levels of arsenic in the dust at the Jáchymov mine than at other mines. When men with exposure rates above 10 working levels were included in the analysis, patterns of risk were complex and depended on both exposure rate and duration of exposure in addition to the factors mentioned above. If these findings are confirmed elsewhere, calculation of risk estimates for extrapolation to modern occupational or environmental exposures should be based on miners with exposure rates below about 10 working levels. Further investigation is desirable of the influence of dusts containing arsenic on lung cancer risk in miners exposed to radon.

Adult↗

Radon exposure and cancers other than lung cancer among uranium miners in West Bohemia.

Recent observations have suggested that radon in the ambient air may cause cancers at sites other than the lung, but the evidence is indirect. We have studied site-specific cancer mortality in 4320 uranium miners in West Bohemia who have been followed-up for an average of 25 years, and in whom a four-fold radon-related excess of lung cancer has already been established. For all cancers other than lung cancer the number of deaths observed was slightly greater than that expected from national rates, but the increase was not significant statistically (ratio of observed to expected deaths [O/E] = 1.11, 95% confidence interval [CI] = 0.98-1.24) and mortality did not increase with duration of employment underground or with cumulative exposure to radon. Non-lung cancer mortality was significantly raised among men who started mining work aged under 25 but the increase was not related to cumulative radon exposure. When twenty-eight individual sites and types of cancer were examined, significantly increased risks were found for cancers of the liver (O/E = 1.67) and gallbladder and extrahepatic bile ducts (O/E = 2.26). For liver cancer, mortality did not increase with duration of employment underground or with cumulative radon exposure. For cancer of the gallbladder and extrahepatic bile ducts, mortality did not increase with duration of employment, but increased with cumulative exposure to radon. Mortality from multiple myeloma, although not significantly increased overall (O/E = 1.08), increased with cumulative exposure to radon. Mortality from leukaemia was not increased overall (O/E = 0.91) and was not related to cumulative radon exposure, but did increase with increasing duration of employment in the mines. There is no evidence in these miners that a radon-rich atmosphere increases the risk of any cancer other than lung cancer. Possible exceptions are cancer of the gallbladder and extrahepatic bile ducts and multiple myeloma but further study is needed before it can be concluded that the associations found are causal.

Adult↗