Occupational exposure to hexachlorocyclohexane

Summary Metabolism of -Hexachlorocyclohexane (HCH) was studied examining 21 workers producing this insecticide. Using gas chromatography in combination with ECD and mass spectrometry 14 mono-, di-, tri- and tetrachlorophenols were identified in the urine samples of the workers. Seven dihydroxychlorobenzenes of still unknown configuration were detected by mass spectrometry. Ten of the more abundant metabolites, di-, tri- and tetrachlorophenols were determined quantitatively in all urine samples. 2,4,6-; 2,3,5- and 2,4,5-trichlorophenol turned out to be the main metabolites of -HCH. They were excreted in nearly equal quantities. On account of their potential liver toxicity, the determination of chlorophenols in urine should be part of a biological monitoring program of HCH-exposed persons.     

Assessment of occupational exposure to 4,4′-methylene-bis-(2-chloroaniline) “MOCA” by a new sensitive method for biological monitoring

Summary A new specific and sensitive method for the urinary determination of 4,4-methylene-bis-(2-chloroaniline) (MOCA), a known carcinogen in rats, mice and dogs, has been developed. After a brief study on rats to determine some peculiarities in MOCA urinary excretion, this method was used to assess occupational exposure in French industrial firms. Both the manufacture of MOCA and its use as a curing agent in the production of polyurethane elastomers were surveyed. MOCA excretion levels were distributed from non-detectable (<0.5 g/l) up to 1600 g/l. Concentrations of N-acetyl metabolites, when present, were largely lower than MOCA levels. The results seemed to reflect workers' overall exposure fairly. Preventive measures following analytical determinations often led to an obvious lowering of excretion levels.     

Decreased excretion of thioethers in urine of smokers after the use of β-carotene

Summary Epidemiologic studies have demonstrated an inverse relation between vitamin A intake and lung cancer rate. There is strong evidence that the provitamin A, -carotene, plays a more important role in the protective effect than vitamin A itself. The anticarcinogenic properties of -carotene have so far been attributed to its scavenger properties in deactivating or trapping reactive chemical species such as singlet oxygen and certain organic free radicals. Smoking results in increased excretion of detoxification products of electrophilic agents (mercapturic acids) in urine. Since reactive electrophilic intermediates are involved in carcinogenesis, we performed a double-blind, placebo-controlled intervention trial to investigate whether the intake of -carotene by smokers would affect urinary thioether excretion. Before the intervention the -carotene group (n = 62) and the placebo group (n = 61) had similar thioether excretion levels in urine (4.2 vs 4.3mmolSH/molcreatinine). During the intervention (20 mg -carotene daily for 14 weeks) the placebo group showed a 12% increase, whereas the -carotene group showed a 5% decrease (P=0.004). After the intervention the -carotene group had a 15% lower thioether excretion level than the placebo group (4.1 vs 4.7 mmol SH/mol creatinine; P=0.0017). Our study shows that urinary thioether excretion varies considerably over time, and that smokers have a decreased excretion of thioethers in urine after the use of -carotene. This latter observation suggests a role of -carotene in the detoxification of tobacco smoke constituents. Our observations warrant further studies on the involvement of -carotene in the generation and detoxification of electrophilic intermediates.     

Mutagenicity of 4,4′-methylene-bis-(2-chloroaniline) “MOCA” and its N-acetyl derivatives in S. typhimurium

Summary 4,4-methylene-bis-(2-chloroaniline) (MOCA) and two identified urinary N-acetyl and N,N-diacetyl derivatives were tested in a Salmonella/mammalian microsome assay. No mutagenic activity was observed without rat liver S9 mix activation. In the presence of rat liver S9 mix, the chemicals were mutagens, but the mutagenicity of N-acetyl derivatives to strain TA 100 was reduced when compared to that of MOCA, and a greater amount of S9 was required to exhibit the mutagenicity of the N,N-diacetyl-MOCA. These data suggest that N-acetylation does not account for the mutagenic effectiveness of MOCA.     

β-carotene bioavailability from differently processed carrot meals in human ileostomy volunteers

Summary. Background: Carotenoids contribute to the beneficial effects of fruits and vegetables consumption; however, the bioavailability of these compounds from fresh or processed foods is not well established. Aim of the study: We evaluated the bioavailability of -carotene (15 mg) from a single meal composed of cooked, pureed carrots and compared it to raw, chopped carrots. Methods: Test meals were given to overnight-fastedileostomy volunteers (n = 8) along with skimmed-milk yogurt containing 40 g of added sunflower oil. Blood and complete ileal effluent samples were collected over a 24 h period. Samples were solvent-extracted and the -carotene content measured by HPLC. Results: Kinetics of excretion of cis and trans -carotene were similar. More -carotene was absorbed from puree as compared to raw carrots. Carotenoid mass-balance calculations indicated that 65.1 ± 7.4% of the -carotene was absorbed from cooked pureed carrot meals, vs. 41.4 ± 7.4 % from raw, chopped carrot meals. Gastrointestinal transit parameters did not differ significantly among the volunteers. As expected, the calculated lag phase was five times longer for raw vs. cooked carrots. Mean t-end, t-1/2 and rate of mass transit resulted in similar values for both raw and cooked carrot meals. A moderate response in carotenoid plasma profile was observed for cooked carrot test meals. Conclusions: Significantly more -carotene was absorbed from meals containing cooked, pureed carrots than from meals containing the raw vegetable. Moderate carotenoid plasma response was detected within 6 h following the administration of cooked processed carotenoid-containing single meal.     

Correlation between work process-related exposure to polycyclic aromatic hydrocarbons and urinary levels of α-naphthol, β-naphthylamine and 1-hydroxypyrene in iron foundry workers

Summary In two Danish iron foundries the concentration of polycyclic aromatic hydrocarbons (PAH) in 24 personal air samples of workers employed in selected processes, i.e. melters, melted iron transporters, casters, machine molders, hand molders, shake-out workers and finishing workers, were measured and correlated to levels of 1-hydroxypyrene, -naphthol and -naphthylamine in the urine of exposed workers. The highest total airborne PAH concentrations (sum of 15 selected PAH compounds: 9.6–11.2 g/m³) were associated with casting, machine molding, and shake-out. The highest concentrations of the sum of six selected airborne carcinogenic PAH compounds were found for melting, casting and machine and hand molding. As seen in other working environments involving low-level PAH exposure, the content of naphthalene was high, in general exceeding 85% of the total content of PAH compounds. The present study demonstrates that 1-hydroxypyrene is a useful and direct biomarker of low-dose occupational exposure to PAH compounds. Molding and casting had the highest pyrene levels in iron foundries. Furthermore, the data shows that levels of -naphthylamine in urine are significantly elevated in iron foundry workers. Hand molders, finishing workers and truck drivers tended to have the highest levels. Concerning -naphthol the highest concentrations were measured in urine from casters and shake-out workers. With regard to epidemiologic studies demonstrating that molders and casters have a higher risk of lung cancer, the present study suggests that the elevated risk may be due to exposure to carcinogenic PAH compounds in iron foundries, particularly in some high-risk work processes, e.g. casting and molding. In addition, the present study suggests that biological monitoring of 1-hydroxypyrene and -naphthylamine may be used to estimate the individual exposure, which seems to be correlated with exposure during individual work processes.     

Blood toluene as a biological index of environmental toluene exposure in the “normal” population and in occupationally exposed workers immediately after exposure and 16 hours later

Blood toluene was measured in a group of 100 workers occupationally exposed to a mean 8-h environmental toluene concentration of 128 g/l (34 ppm), and in a group of 269 normal subjects without occupational exposure to toluene. The mean blood toluene of the workers at the end of the shift and the following morning, after 16 h, was 457 and 38 g/l, respectively. The normal subjects had a blood toluene level of 1.1 g/l. On the basis of the highly significant correlation between blood toluene and occupational exposure, it can be calculated that environmental toluene exposure of 188 and 377 g/l (50 and 100 ppm) gives end-of-shift blood toluene levels of 690 and 1390 g/l, respectively. The corresponding blood toluene levels on the following morning are 50 and 100 /l, respectively.     

Diversity of β-lactamases among Klebsiella pneumoniae strains isolated in a university hospital in Greece

Among 48 clinical strains of Klebsiella pneumoniae isolated in a university hospital in Northern Greece, 29 (60.4%) exhibited resistance to third generation cephalosporins (3GC) and aztreonam. Thirty-two (66.7%) of the isolates were found resistant to the combination of ampicillin/sulbactam and six (12.5%) exhibited resistance to all the above antibiotics plus cefoxitin. Resistance to 3GC was related mostly with the presence of a -lactamase exhibiting pI 8.2 and substrate profile of an SHV-5 type enzyme and rarely (in two of the cefoxitin resistant strains) with the presence of plasmid-mediated class C cephalosporinases. Resistance to the ampicillin/sulbactam combination was associated with the presence of a -lactamase with pI 5.4, presumably representing a TEM-1 -lactamase. These findings record a diversity of -lactamases and explain, at least partly, the various -lactam resistance patterns observed in our K. pneumoniae sample.     

Blood retinol and β-carotene levels in rural Guatemalan preschool children

Plasma retinol and -carotene levels were measured in 502 preschool Guatemalan children from five rural hamlets. Their ages ranged from 6 to 78 months (mean: 42.9±19.2 months); 45% males and 55% females. The mean retinol value in the whole group was 0.9±0.4 µmol/1 (range: 0.1 to 8.4 µmol/1). There was no significant difference between sexes in retinol mean values nor in the incidence of retinol values less than 0.7 µmol/1 (22% in males, 18% in females). When grouped by age and community, significant low retinol mean values were found in two hamlets in the youngest age group (12 to 23 months) as compared to the other age-groups (p<0.05). In the other two hamlets, there were no significant differences among retinol means by age-group. The highest prevalence of deficient retinol values by age-group was in the 12 to 23 months group (40%), and decreased as age increased. The mean value for -carotene in the whole group was 0.13±0.18 µmol/1 (range: 0.01 to 2.23 µmol/1). There were no significant differences in -carotene means between sexes in the whole group. Stratifying the -carotene data by age-groups and community, values were significantly higher in the 48–59 months and 72–83 months groups, as compared with the other age groups in two of the communities (p<0.05). Significant differences across communities for -carotene were found only in the 12 to 23 months group.     

Kinetics of gastro-intestinal transit and carotenoid absorption and disposal in ileostomy volunteers fed spinach meals

Summary.Background: Reports of low carotenoid absorption from food sources has undermined their postulated protective role as one of the active agents in diets rich in vegetable matter.Aim of the study: This study quantified -carotene and lutein absorption from a representative green vegetable with different degrees of processing, using both mass balance and metabolic modelling of triglyceride-rich lipoprotein plasma fraction (TRL) response.Methods: Whole or chopped-leaf cooked spinach was fed to volunteers (n = 7, paired) with vegetable oil (40 g) in yoghurt. Blood and ileal effluent samples were collected for up to 24 h. Effluent and TRL samples were analysed for lutein and -carotene by HPLC. A digesta transit model was used to describe meal transit and a single compartment model used to predict percentage absorption from the plasma TRL response.Results: Mass balance showed 25% of lutein and -carotene were absorbed from chopped spinach, compared with 25% -carotene and 40 % lutein from whole-leaf spinach. Increased lutein absorption correlated to slower gastrointestinal (GI) transit for the whole-leaf meal. An area under the curve (AUC) response for the TRL fraction, found in 50% of cases, was not confined to those with the greatest percentage absorption. Absorption by mass balance and TRL AUC indicate a half-life of newly absorbed carotenoid around 11 minConclusion: GI residence time appears to have an effect on the absorption of lutein but not -carotene. Rapid clearance is probably the main reason for absence of measurable plasma concentration excursions. Lack of plasma response cannot be interpreted as lack of carotenoid absorption without knowledge of the absorption and disposal kinetics.Abbreviations AUC Area under the curve - BMI Body mass index - GI Gastro-intestinal - HDL High-density lipoproteins - HPLC High performance liquid chromatography - LDL Low-density lipoproteins - SD Standard deviation - SI Small intestine - TGWM Total gastrointestinal washout method - TRL Triglyceride rich lipoproteins - VLDL Very low density lipoproteins - IV Intravenous     

Education, Practice and Bioethics: Growing Barriers to Ethical Practice

While Bioethics is now taught at all medical colleges in the United States as well as in other nations, and while discussions about Bioethics have become frequent in most medical journals there are increasing barriers to teaching and incorporating what has been taught into daily practice. I shall discuss some of these barriers and suggest that integrating the teaching of Bioethics throughout the curriculum after presenting some of the basic theory and methodology is the most effective way of teaching this vital subject. Furthermore, courses in health care ethics are often taught as something distinct and distinguishable from one's medical practice. I shall emphasize what I consider to be the failure of Bioethics to participate effectively in creating a context whereby what has been taught can be put into praxis. In this brief article I will discuss such barriers and suggest several approaches and remedies.     

Patterns of sexual arousal and history in a “normal” sample of young men

Sexual histories and arousal patterns of 60 college men were sampled in a rural area to better evaluate the role of sexual arousal in males typically used as nonoffender controls in sex research. Nearly two-thirds of the sample (65%) had engaged in some form of sexual misconduct in the past, ranging from sexual contacts with children and coercive sex with women to voyeurism and frottage. Even more subjects expressed a desire for such activities. Previous experience with frottage, obscene phone calls, and pedophilic contacts was associated with higher subjective arousal to depictions of these activities. Previous experience with coercive sex or voyeurism did not appear to be associated with greater arousal to these activities. There was considerable variability in the arousability of subjects to the variety of deviant stimuli presented, thus blurring the distinction between pathological and normal arousal patterns. These results suggest that young men are easily aroused sexually by a variety of stimuli, and seek out a variety of sexual experiences, some of which are punishable by law.     

UrinaryN-acetyl-β-d-glucosaminidase and β-aminoisobutyric acid in workers occupationally exposed to metals such as chromium,nickel, and iron

Summary To examine the relationships between the urinary excretion ofN-acetyl--d-glucosaminidase (NAG) and -aminoisobutyric acid (AIBA) as a metabolite of thymine, and exposure to chromium, nickel, and iron, we determined these parameters in 58 workers engaged in the cutting and grinding of stainless steel or iron-steel plates. A significant increase in urinary NAG activity or urinary AIBA excretion was found in some of these workers. However, we could not find a significant positive correlation between the urinary excretion of NAG or AIBA and the urinary concentration of chromium, nickel, or iron as an indicator of internal dose.     

Rise and fall of asthma-related mortality in Italy and sales of β2-agonists, 1980–1994

We performed this study with the aims of describing the trend of asthma-related mortality in Italy between 1980 and 1994, and to evaluate the relationship between sale estimates of ₂-agonists drugs and mortality from asthma. For asthma mortality we used data provided by National Institute of Statistics, for sale estimates of ₂-agonists we used data provided by IMS HEALTH. We calculated the gender specific age-standardized incidence rates of asthma-related deaths for all ages and for age classes. We found that estimates for asthma-related mortality steadily increased between 1980 and 1987 in both sexes, and thereafter decreased. In people, aged between 34 and 64 and over 64, death rates in males were significantly higher than in females while the rates in those aged less than 34, were mostly similar in both gender. The overall exposure to ₂-agonists (alone and in combination) increased from 1980 to 1990, remained stable between 1990 and 1993, and increased steeply in 1994. We conclude that asthma-related death rates have declined since the mid-1980's. This decline has been more pronounced in males and in the older ages, while the rates in younger patients of both genders have remained nearly unchanged. Our data do not substantiate the hypothesis of an increased risk of asthma-related mortality associated to the use of inhaled ₂-agonists in general nor fenoterol or salbutamol in particular.     

Levels of β-HCH,HCB, p,p′-DDE,p,p′-DDT and PCBs in human milk from a continental town in Croatia,Yugoslavia

Summary Concentrations of -HCH, HCB, p,p-DDE, p,p-DDT and PCBs were determined by gas chromatography in 50 human milk samples collected from the general population during 1981/1982 in a continental town in Croatia (Yugoslavia). The samples were collected between one and 22 weeks after delivery from mothers breast-feeding one child only. The mothers' age was 18 to 31 years, and they were nursing their first or second child. All 50 samples contained -HCH, HCB, p,p-DDE and PCBs, whereas p,p-DDT was present in 37 samples. The concentrations of -HCH, HCB, p,p-DDE, p,p-DDT and PCBs expressed on a whole milk basis were (median in g/kg): 11, 7.1, 67, 7.3 and 22 respectively, and expressed on a fat basis (median in mg/kg): 0.28, 0.21, 1.9, 0.18 and 0.62 respectively. The fat content was 3.7% (median). PCBs were present in a mixture containing penta-, hexa- and heptachlorobiphenyls.     

Lack of nephrotoxicity of styrene at current TLV level (50 ppm)

Summary Biochemical markers of kidney damage were examined in 37 female workers exposed to an average concentration of 225 mg/m³ of styrene. The concentration of mandelic acid in urine was on the average 759 mg/g creatinine. The mean duration of employment of the exposed subjects was 11 years. The results were compared to those obtained in 35 control female workers matched for age and a number of demographic and lifestyle factors and with no history of exposure to organic solvents. No difference was found in the urinary excretion of albumin, beta₂-microglobulin, retinol-binding protein, total proteins, glucose, lysozyme, lactate dehydrogenase and beta-N-acetyld-glucosaminidase. The present study provides thus further evidence that exposure to styrene at the current TLV (215 mg/m³) does not entail any detectable risk for the renal function.     

Effects of a new low dose soy protein/β-sitosterol association on plasma lipid levels and oxidation

Summary. Background: High doses of soy protein are able to decrease plasma cholesterolemia significantly, but they unbalance daily protein intake and strongly modify nutritional habits in patients. Aim of the study: To evaluate the antihypercholesterolemic efficacy of a low dose soy protein product with added -sitosterol (rapport = 4:1) in 36 moderately hypercholesterolemic subjects. Methods: The study was divided into 3 separate periods of 40 days each: a stabilization diet period, followed by a treatment period during which all subjects took 10 g of the test product once daily and, finally, a wash out period. The following parameters were monitored: weight, dietary habits, plasma lipid levels, glycemia, uric acid, fibrinogenemia and antibodies against oxidized LDL (ox-LDL Ab). Results: From the end of the stabilization diet period to the end of the supplementation with the soy protein product with added -sitosterol we observed a 19.64 ± 20.32 mg/dL, 8.47 ± 54.61 mg/dL, 1.69 ± 10.92 mg/dL, and 7.06 ± 16.66 mg/dL mean ± SD decrease respectively in LDL-C (p < 0.001), TG (p = 0.358), VLDLs (p = 0.358) and apoB (p = 0.016) levels, associated with a 1.31 ± 8.08 mg/dL and 1.03 ± 19.09 mg/dL mean increase respectively in HDLC (p = 0.251) and apoAI (p = 0.749) plasma concentrations. The dietary supplementation did not influence Lp(a) (p = 0.984) and ox-LDL Ab (p = 0.953) plasma levels. A statistically significant correlation was observed for LDL-C plasma levels, between the end of the stabilization diet period and the end of the period of supplementation with soy proteins with added -sitosterols (p < 0.001). Conclusion: Although further long-term clinical studies are necessary before claims can be made regarding the therapeutic effects of the tested formulation, the preliminary findings regarding its efficacy and safety as an antihypercholesterolemic agent are encouraging.     

Reliability and validity testing of a Chinese-translated version of the 39-item Parkinson’s Disease Questionnaire (PDQ-39)

The trend toward international cooperation in research projects emphasizes the need to translate existing validated tools into local languages. The purpose of this study was to test the reliability and validity of a Chinese-translated version of the 39-item Parkinsons Disease Questionnaire (PDQ-39). Seventy-three Taiwanese individuals with Parkinsons disease were consecutively recruited. The internal consistency reliability was satisfactory for all domains (Cronbachs =0.80–0.96), except for the social support, cognition, and bodily discomfort domains (=0.58–0.63). The convergent validity was also supported by strong correlations between domains measuring related constructs of the PDQ-39 and Unified Parkinsons Disease Rating Scale (r=0.81–0.86), and between those of the PDQ-39 and SF-36 (r=–0.70––0.93). Except for the bodily discomfort domain, all domains of the PDQ-39 significantly discriminated patients at different stages, as indicated by the Hoehn and Yahr scale. Overall, the results of this study are consistent with the reports of the PDQ-39 in other countries (e.g., UK, Spain, US, and Greece), which suggests that the PDQ-39 is appropriate for use among Taiwanese individuals with PD. This study lays the foundation for future combinations and comparisons of data cross-nationally.     

Circulation in Italy of β-lactamase-producing strains within the major groups of bacterial pathogens

A multicenter study was undertaken in Italy to assess the circulation of -lactamase-producing organisms and their current incidence within the major groups of bacterial pathogens. Almost four thousand strains, all freshly isolated from clinical material, were examined at four centers serving different areas of Italy. Despite some significant center-to-center differences, this survey documented the occurrence of a large overall circulation of -lactamase-producing organisms among clinical bacterial isolates. In particular, ampicillin resistance was recorded in one third to one half of the isolates of some Enterobacteriaceae, including Escherichia coli, Proteus, and Citrobacter species, and 80–90% of these resistant strains proved to be B-lactamase producers. Both ampicillin resistance and -lactamase production were almost the rule in other Enterobacteriaceae, including Klebsiella, Enterobacter, and Serratia species. -lactamase was also produced by about 80% of glucose-non-fermenting gram-negative bacteria and Aeromonas hydrophila strains, by all of the isolates of Branhamella catarrhalis manifesting ampicillin resistance (i.e. more than half the total number of isolates), and by about two thirds of the ampicillin-resistantffaemophilus strains (which accounted for 20–25% of all Haemophilus isolates examined). In contrast, no B-lactamase producers were observed among Neisseria gonorrhoeae isolates.     

Occurrence of plasmids in “Campylobacter upsaliensis” (catalase negative or weak group) from geographically diverse patients with gastroenteritis or bacteraemia

The natural occurrence of plasmids in Campylobacter upsaliensis (catalase negative or weak campylobacters: CNW group) was investigated. The 62 strains isolated from patients with gastroenteritis or bacteraemia in five countries (South Africa, Belgium, Sweden, UK and Australia) were screened for plasmid DNA, which was detected in 54 (87%) of them. Plasmids were of various sizes between 1.4 and 90-Md and up to three or possibly four plasmids were present in 26 (42%) strains. A total of 15 different plasmid profile types were identified. Strains of profile type 2, containing 2.8-, 34- and 60-Md plasmids and a less distinct 5-Md plasmid, were the most frequently encountered (22 strains) and they exhibited a wide geograhical distribution. Overall the 34- and 2.8-Md plasmids were the commonest occurring in 58 and 55% of plasmid containing strains respectively. Nine strains from dog faeces were also examined and some had identical profiles to human isolates, suggesting a possible animal to man transmission route. These findings show that plasmid profiling has considerable potential as a typing method for C. upsaliensis.