Impaired vitamin B12 metabolic status in healthcare workers occupationally exposed to nitrous oxide.

BACKGROUND: Previous studies demonstrated inactivation of vitamin B12 by nitrous oxide (N(2)O). The intraoperative exposure to N(2)O was shown to induce megaloblastic anaemia and myelopathy in subjects with subclinical vitamin B12 deficiency. In contrast, no data concerning the influence of occupational exposure to N(2)O on vitamin B12 metabolic status are available to date. In the present study, the vitamin B12 status in operating theatre personnel was assessed in relation to the extent of exposure. METHODS: Ninety-five operating theatre nurses with the history of exposure to N(2)O and 90 unexposed counterparts were examined. Vitamin B12 and folic acid were measured by immunoassay. Total homocysteine (tHcy), an indicator of impaired vitamin B12 metabolism, was determined by high performance liquid chromatography. N(2)O concentration was monitored by adsorption gas chromatography and mass spectrometry. RESULTS: No significant differences were found between both groups with respect to haematological parameters and folic acid. However, subjects exposed to N(2)O presented with lower vitamin B12 [372.8 (12.1) vs 436.8 (13.2) pmol litre(-1), P<0.001] and higher tHcy [11.2 (0.5) vs 8.9 (0.5) micromol litre(-1), P=0.006]. The changes in vitamin B12 status were aggravated in subjects exposed to N(2)O in concentrations substantially exceeding occupational exposure limit (180 mg m(-3)) [vitamin B12: 341.9 (17.7) vs 436.8 (13.2) pmol litre(-1), P=0.006; tHcy: 12.9 (0.7) vs 8.9 (0.5) micromol litre(-1), P=0.047]. CONCLUSIONS: Exposure to N(2)O in healthcare workers is associated with alterations of vitamin B12 metabolic status, the extent of which depends on the level of exposure.

Alagille syndrome associated with a paracentric inversion 20p12.2p13 disrupting the JAG1 gene.

Mutations in the human gene Jagged1 (JAG1) localized in 20p12 have been recently identified as causal for the anomalies found in patients with Alagille syndrome (AGS). This gene encodes a ligand for the Notch1 transmembrane receptor, which plays a key role in cell-to-cell signaling during differentiation and is conserved from C. elegans to human. We report a paracentric inversion (PAI) of chromosome 20p12.2p13 in an individual with AGS who also had alpha-1-antitrypsin deficiency. To our knowledge, this is the first published case of PAI involving the short arm of chromosome 20. Using FISH, fiberFISH, and molecular studies with a approximately 40 kb cosmid clone encompassing the entire 36 kb JAG1 gene, we demonstrate that the gene was disrupted by the inversion breakpoint between exons 5 and 6. An unusual association between two most common causes of chronic liver disease in childhood, AGS and alpha-1-antitrypsin deficiency, as well as their influence on the proband's abnormal phenotype are discussed.

[Use of hypoprothrombinemia provocation test for early diagnosis of liver disease caused by harmful environmental agents]. / Zastosowanie próby hipoprotrombinemii prowokowanej we wczesnej diagnostyce chorób watroby wywolanych przez czynniki srodowiskowe.

The aim of this work has been to assess the feasibility of using Prothrombin Time (PT) Assay before and after administration of Pelentan (Hypoprothrombinemia Provocation (HPP) Test) for early detection of subclinical toxic hepatic injuries. The proposed modification of PT Assay is based on the observation that people with slight hepatic injury receiving small doses of Pelentan (diethylcoumarol) display remarkably longer PT than healthy people receiving similar doses of the chemical. The test group comprised 37 people occupationally exposed to hepatotoxic agents, 85 males permanently abusing alcohol, while 24 clinically healthy people, not exposed occupationally to the toxic agents served as the control. In addition, 26 hepatitis B and/or C virus carriers were also examined. The results show that: 1. HPP test enables assessment of hepatic function in patients with suspected hepatic injury and in people permanently abusing alcohol; 2. low value of serum prothrombin index 24 h and 48 h after the administration of Pelentan is indicative of the positive result of the test; 3. HPP test provides more information on the functional condition of liver than single PT determination by the Quick assay.

Determination of blood serum oncoprotein NEU and antioncoprotein p-53--molecular biomarkers in various types of occupational exposure.

Application of various diagnostic tests for occupational cancer risk monitoring is associated with the fact that gene mutations and changes in gene expression correspond to the earliest stages of carcinogenesis, namely early stages of the promotion process. The changes in protooncogenes and suppressor genes can be detected either at the genome level, at the level of transferring the genetic information from DNA to protein, or at the level of protein synthesis controlled by genes (oncogenes or antioncogenes). In the latter instance, as the concentrations of these proteins are considerably increased, their quantities in blood serum can be determined by the immunochemical methods. In our work, blood serum p-53 and NEU proteins were determined in 32 workers exposed to asbestos and in 57 workers exposed to PAHs. The proteins were also determined in 99 patients with overt cancer and in 47 controls. The data obtained in this work show positive values of oncoprotein NEU or antioncoprotein p-53 in 17.3% to 31.8% of workers exposed to PAHs or asbestos. The percentage of positive values for the examined proteins in the patients with overt cancer ranged from 12.5% to 42.5%. It should be noted that positive values of the oncoproteins detected in the biomaterial of the persons exposed do not mean that people must necessarily develop cancer, nevertheless the elevated values should be regarded as a warning and an implication for undertaking suitable preventive steps.

Determination of tissue polypeptide antigens (TPA) and carcinoembryonic antigen (CEA) in serum: its value in the preliminary cancer risk assessment in asbestos exposed workers.

Seeking the changes at the cellular level or at the level of cellular metabolism products, present in the biological fluids, in order to detect early stages of the carcinogenic process is an essential step in preventing cancer development among asbestos exposed workers. Carcinogenic biomarkers such as tissue polypeptide antigens (TPA) and carcinoembryonic antigen (CEA) were found very useful in this attempt. The objective of this work was to identify individuals at critical cancer risk in the population of workers exposed to asbestos and to evaluate the value of TPA and CEA determinations for this particular purpose. The study was carried out in the group of workers exposed to asbestos (n = 274). Age, exposure duration, smoking habits and the kind of job performed, were considered in the analysis of the results. To sum up, it should be concluded that in 22 persons exposed to asbestos TPA values exceeded the cut off concentrations, established on the basis of the studies performed in the control group, and CEA value accounted for 10 ng/lm. Statistically significant differences in the percentage of TPA increased values between two groups under study were indicated. Such a relationship did not apply to CEA. In the exposed group, an evident effect of the age and exposure duration on the number of persons with TPA concentrations above the cut off, was also revealed. These changes show a growing tendency and statistical significance for TPA only. Smoking had a great impact on the occurrence of TPA increased concentrations. Three kinds of jobs were considered: operation of the production line, white collar workers and miscellaneous'. The significant differences in TPA concentrations between the operators and miscellaneous, and between white collar workers and miscellaneous were found. Therefore, it may be concluded that a similar percentage of TPA increased values was observed in the group of operators and white collar workers. The study allowed to identify, among those exposed to asbestos, 22 persons who should be covered with target medical care. It also indicated that TPA determination was more useful than that of CEA in this kind of investigations.

[Exposure to asbestos and levels of selected tumor biomarkers]. / Ekspozycja na azbest a stezenia wybranych biomarkerów nowotworowych.

Occupational exposure to asbestos, a recognised carcinogen, poses a risk for such diseases as asbestosis, lung cancer and mesothelioma. It is thought that asbestos fibres may damage microphages which undergo neoplastic transformation as well as fibroblast, while partial phagocytosis may generate free oxygenic radicals which induce cellular peroxidase and damage macromolecules. A search for cellular changes or changes in cellular metabolism products, present in biological fluids, in order to detect early stages of a neoplastic process is an important factor in the prophylaxis of workers exposed to asbestos. Neoplastic biomarkers such as tissue polypeptide antigen (TPA) or carcinoembryonic antigen (CEA) are now used for this purpose. The aim of the work was to identify workers exposed to asbestos in the population, especially high risk groups neoplastic diseases and to evaluate the usefulness of TPA and CEA determinations. The study covered a group of asbestos exposed workers (n = 4000 and the control group of workers (n = 135) nonexposed to any toxic factor at work. Age, exposure time, smoking habits and workpost characteristics were taken into consideration in the analysis of the results. It was revealed that in 38 persons exposed to asbestos, TPA values were above the concentration limit set on the basis of studies carried out in the control group, and elevated CEA values applied to 13 persons. Significant differences between groups under study were found in the proportion of pathological TPA values. Such a relationship was not observed in regard to CEA values. In the exposed group the results also indicated an evident effect of age and exposure time on the number of persons with TPA values above concentration limit. There is a growing tendency in those changes but only in regard to TPA values. The effect of smoking on the frequency of pathological TPA values was also clear-cut in workers exposed to asbestos. Taking into account three types of employment: blue collar workers, white collar workers and other personnel, the analysis indicated significant differences in TPA values between blue collar workers and other personnel; and between white collar workers and other personnel. This means a similar percentage of pathological TPA values in the group of blue collar and white collar workers. The study carried out allowed to identify persons exposed to asbestos who should be covered with targeted medical care. They also proved that TPA biomarker is better than CEA one for this kind of studies.

Alpha-1-antitrypsin subtypes in Polish newborns.

Alpha-1-antitrypsin phenotypes of umbilical cord serum from 741 Polish newborns were studied by isoelectric focusing. The frequencies of the PI alleles were: PI*M1 = 0.7199, PI*M2 = 0.1613, PI*M3 = 0.0965, PI*S = 0.0094, PI*Z = 0.0067, and PI*Var(F,I,L) = 0.0060. The data obtained for Poland were compared to those for other European populations.

[Alpha 1-antitrypsin phenotypes and their role in the development of early and late cirrhosis of the liver]. / Fenotypy alpha 1-antytrypsyny i ich rola w rozwoju wczesnej i póznej marskosci watroby.

On the basis of cooperation with the Children's Health Centre the role was analysed of certain phenotypes of alpha 1-antitrypsin (alpha 1-AT), mainly Pi Z and Pi MZ phenotypes in the development of infantile cirrhosis. A significant participation was demonstrated of the latter phenotype in patients developing infantile cirrhosis. The preliminary analysis of the incidence of pathological alpha 1-AT phenotypes in the group of patients with cirrhosis manifested at the adult age seems to indicate the higher incidence of the Pi MZ phenotype as compared with the general population. The genetically determined low serum alpha 1-AT activity is probably one out of many factors determining the development of this disease. Further studies will be aimed at explaining whether the combination of action of two factors: alpha 1-AT deficiency and exposure to hepatotoxic agents is not accelerating the appearance of the disease and is not potentiating its clinical intensity.

Inherited defect of alpha-1-antitrypsin associated with chronic liver and respiratory tract diseases in children.

The frequency of occurrence of alpha-1-antitrypsin (A1AT) deficiency among total of 3228 Polish children with chronic liver diseases and chronic disease of respiratory tract was determined. It was observed that among children with chronic liver diseases which disclosed more frequent defect (concentration of A1AT below 150 mg/dl was found in 10.3% of children), the highest occurrence of deficiency was in children with neonatal hepatitis (23.1%). The deficiency was connected with the presence of ZZ and MZ phenotypes of A1AT.

[The role of screening studies in epidemiology and occupational medicine]. / Rola badan skriningowych w epidemiologii i medycynie pracy.

Discussed in the paper are the conditions underlying the planning of screening tests for early diagnosis of diseases--at the asymptomatic stage--and the detection of higher risk groups. The so called "early diagnosis" can be established with various strategies: specific examinations for all those spontaneously coming to physicians, periodic examinations for industrial workers, genetic screening ensuring the protection against exposures to work environment hazards for those exhibiting genetically conditioned biochemical abnormalities. Screening tests in a specific population should be preceded by extensive epidemiological studies aimed at the determination of such basic parameters as: the rate of feature marker in a population, incidence of the disease resulting from the marker's presence, determination of the relative risk coefficient.

[Alpha 1-antitrypsin phenotypes and their role in medical diagnosis]. / Fenotypy alfa-1-antytrypsyny i ich rola w diagnostyce medycznej.

Alpha-1-antitrypsin is a glycoprotein of blood exhibiting the properties of a proteolytic enzymes inhibitor. It occurs in a number of polymorphic variants transmitted genetically, the differentiation of which enables to use electrophoretic methods. The authors surveys literature, involving also her own experience, on the diagnostic use of alpha-1-antitrypsin phenotypes. The variants related to alpha-1-AT deficiency are associated with an increased incidence of certain diseases: obstructive pulmonary disease, liver cirrhosis in children, cancer. An early establishment of alpha-1-antitrypsin phenotype may be significant for occupational prevention, furthermore, it may be helpful in the highlighting of etiology of certain liver diseases in early childhood.

[Laboratory procedures in the detection of deficiencies and the determination of alpha 1-antitrypsin phenotypes in the blood serum]. / Postepowanie laboratoryjne w celu wykrycia niedoborów i okreslenia fenotypów alfa-1-antytrypsyny w surowicy krwi.

Eriksson's method was analysed and an attempt was made to determine the probability of the occurrence of phenotypes predisposing to emphysema and obstructive catarrhs, when low alpha-1-AT values were found using gelatinous film or immunochemical methods. The authoresses propose a three-stage system for the detection of all those susceptible to emphysema.

[Screening methods for the detection of alpha-1-antitrypsin deficiency in blood serum]. / Metody screeningowe dla wykrywania niedoborów alfa-1-antytrypsyny w surowicy krwi

In order to spread in occupational medicine the simple screening test allowing to detect the alpha-1-antitrypsin deficiency, the conformability of four procedures with the method of radial immunodiffusion has been analysed. From the received data it results that for the preliminary diagnostics of deficiency in mass examinations methods based on separation of proteins on the agar gel, determination on the gelatinous membrane and the method of rocket immunodiffusion are suitable.