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BACKGROUND: Although alcohol abuse is known to create a variety of adverse effects on hematopoiesis, the associations between ethanol consumption and hematological abnormalities have not been fully established. METHODS: We studied 144 consecutive adult patients who underwent clinical and bone marrow examinations due to abnormal findings in peripheral blood cell counts or red blood cell indices without previously established diagnoses of specific hematological diseases, malignancies, or infections. Assessment included the amount of alcohol consumption, complete blood cell counts, morphological review of peripheral blood and bone marrow, markers of liver status, and erythrocyte folate and serum vitamin B12 levels. RESULTS: There were 57 (40%) patients who showed a history of hazardous drinking and 87 patients who were either nondrinkers or social drinkers. The incidence of anemia was 51% in the alcohol abusers, as compared with 69% of the nonalcoholics (p < 0.05). A diverse pattern of hematological effects was observed in the alcohol abusers. Abnormal platelet and leukocyte levels were common, especially in the anemic alcoholics. Both increased mean cell volume of erythrocytes (macrocytosis; 67 vs. 18%; p < 0.0001) and mean cell hemoglobin (63 vs. 22%; p < 0.0001) were more frequent in the alcoholics than in the nonalcoholics. Reticulocytosis (37%), thrombocytopenia (41%), and combined cytopenias (34-38%) were also common findings in the alcoholic patients. The blood smears from such patients typically showed round macrocytes, stomatocytes, and knizocytes. Bone marrow aspirates revealed vacuolization of pronormoblasts in 24% of the alcoholic patients. Interestingly, megakaryocytes in the cell periphery were also vacuolized in 20% of the alcohol abusers, especially in those with recent intoxication. CONCLUSIONS: Our findings suggest that alcohol abuse results in diverse patterns of hematological effects and affects several cell lines. Therefore, in patients undergoing bone marrow examinations due to cytopenias, the probabilities for likely findings seem to be different between alcoholics and nonalcoholics. Information on ethanol consumption should be systematically included in the clinical assessment of such patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the long-term time trends of the prevalence of asthma, allergic rhinitis and atopic eczema in young Finnish men.A retrospective analysis was carried out on cross-sectional data from the Finnish Defence Forces taken from call-up examinations of candidates for military conscription and examinations of conscripts discharged from service because of poor health. Roughly 1.7 million men aged 18‒19 years (98% of men of conscription age) were examined from 1966 to 2017. A proportional but unknown number of young men were examined from 1926 to 1961.The main outcome measures were asthma recorded at call-up examination as the main diagnosis in 1926‒2017 and any diagnosis in 1997‒2017, exemption or discharge from military service due to asthma, and allergic rhinitis and atopic eczema recorded as the main diagnosis in 1966‒2017 and any diagnosis in 1997‒2017.During 1926-1961 the prevalence of asthma remained low at between 0.02% and 0.08%. A linear rise began between 1961 and 1966, with a 12-fold increase in the prevalence from 0.29% in 1966 to 3.44% in 2001. Thereafter, the prevalence of asthma as the main diagnosis stabilised but continued to increase to 5.19% in 2017 if secondary diagnoses of asthma were included. Exemption rates from military service due to asthma have similarly increased but fluctuated more. The prevalence of allergic rhinitis increased from 0.06% to 10.70% and atopic eczema from 0.15% to 2.90% during the period 1966‒2017.In Finland, an increase in asthma and allergic conditions among young men became evident in the mid-1960s. The increase slowed in the 2000s and may be levelling off in the 2020s., Competing Interests: Conflict of interest: J. Reijula has nothing to disclose. Conflict of interest: J. Latvala has nothing to disclose. Conflict of interest: M. Mäkelä has nothing to disclose. Conflict of interest: S. Siitonen has nothing to disclose. Conflict of interest: M. Saario has nothing to disclose. Conflict of interest: T. Haahtela has nothing to disclose., (Copyright ©ERS 2020.)

This field study evaluated the level of muscular, cardiorespiratory and thermal strain of mast and pole workers. We measured the muscular strain using electromyography (EMG), expressed as a percentage in relation to maximal EMG activity (%MEMG). Oxygen consumption (VO2) was indirectly estimated from HR measured during work and expressed as a percentage of maximum VO2 (%VO2max). Skin and deep body temperatures were measured to quantify thermal strain. The highest average muscular strain was found in the wrist flexor (24 ± 1.5%MEMG) and extensor (21 ± 1.0%MEMG) muscles, exceeding the recommendation of 14%MEMG. Average cardiorespiratory strain was 48 ± 3%VO2max. Nearly half (40%) of the participants exceeded the recommended 50%VO2max level. The core body temperature varied between 36.8°C and 37.6°C and mean skin temperature between 28.6°C and 33.4°C indicating possible occasional superficial cooling. Both muscular and cardiorespiratory strain may pose a risk of local and systemic overloading and thus reduced work efficiency. Thermal strain remained at a tolerable level.

Background: During military service young men (age 19-21 years) are exposed to many predisposing factors for asthma. We aimed to study the short-term prognosis of asthma after the military service., Methods: All 216 men with verified asthma in 2004-2005 from the register of the Central Military Hospital were included in the study. A questionnaire was mailed to them in autumn 2007 and the 146 responders (68%) formed the final study population. Asthma severity was evaluated during military service according to the medical records of the subjects and two years later based on the questionnaire using modified GINA guidelines. The results on lung function and allergy tests during military service and asthma history were used as predictors of asthma severity at two-year follow-up., Results: Two groups of asthmatics were identified: those who already had asthma when entering the military service (n=71, 48.6%) and those, who had a new onset of asthma during the service (n=75, 51.4%). Overall asthma was less severe at two-year follow-up than during military service (p=0.036). Both during military service and at two-year follow-up, asthma was milder among the men, who had a new onset of asthma during military service. Atopy (p=0.002), number of positive skin-prick tests (p=0.005) and higher total serum IgE (p=0.001) were significant predictors for persistent asthma at follow-up., Conclusions: Asthma, which had aggravated or started during military service, was significantly less severe two years later. The degree of atopy was a major determinant of the two-year prognosis of asthma after military service.

Background: Alcohol abuse has been shown to result in the production of antibodies against acetaldehyde-modified epitopes in proteins. However, as yet, only limited information has been available on the clinical usefulness of such responses as markers of hazardous drinking., Methods: We developed an ELISA to measure specific IgAs against acetaldehyde-protein adducts. This method was evaluated in cross-sectional and follow-up studies on male heavy drinkers with a current ethanol consumption of 40 to 540 g/d (n=40), moderate drinkers consuming 1 to 40 g/d (n=25), and abstainers (n=16). The clinical assessments included detailed interviews on the amounts and patterns of ethanol consumption and various biochemical markers of alcohol abuse and liver function., Results: The mean antiadduct IgAs (198+/-28 U/L) in the alcohol abusers were significantly higher than those in the moderate drinkers (58+/-11 U/L, p<0.001) or abstainers (28+/-8 U/L, p<0.001). The values of moderate drinkers were also higher than those in abstainers (p<0.05). The amount of ethanol consumed during the period of 1 month preceding blood sampling correlated strongly with antiadduct IgAs (r=0.67, p<0.001). The sensitivity (73%) and specificity (94%) of this marker were found to exceed those of the conventional laboratory markers of alcohol abuse in comparisons contrasting heavy drinkers with abstainers although not in comparisons contrasting heavy drinkers with moderate drinkers. During abstinence, antiadduct IgAs disappeared with a mean rate of 3% per day. In additional analyses of possible marker combinations, antiadduct IgAs, together with CDT, were found to provide the highest sensitivity and specificity., Conclusions: Measurements of antiadduct IgAs may provide a new clinically useful marker of alcohol abuse, providing a close relationship between marker levels and the actual amounts of recent ethanol ingestion.

Objectives: Excessive alcohol consumption is associated with the generation of antibodies against neoantigens induced by ethanol metabolism. However, the associations between such immune responses, ethanol consumption, and liver injury remain unclear., Methods: Eight-six male alcoholics with (n=54) or without (n=32) liver disease, and 20 male volunteers (6 abstainers, 14 moderate drinkers) underwent clinical, morphological, and biochemical assessments of liver status and ethanol consumption., Results: Antiacetaldehyde adduct IgAs in both groups of alcoholics were significantly higher than those in the controls. Elevated IgGs occurred in patients with liver disease, whereas IgMs were high in the heavy drinkers without apparent liver disease. Liver disease patients had high levels of both proinflammatory (IL-2, IL-6, IL-8, TNF-alpha) and antiinflammatory (IL-10) cytokines, whereas those without liver disease showed elevated IL-6, IL-8, and IL-10 only. Ethanol consumption correlated significantly with antiadduct IgA and IL-6 levels, which also showed parallel changes upon abstinence., Conclusions: Alcoholic liver disease is associated with the generation of IgAs and IgGs against acetaldehyde-derived antigens and enhanced levels of both pro- and antiinflammatory cytokines, whereas elevated IgA, IL-6, and IL-10 characterize alcoholics without liver disease. These data suggest that immunological mechanisms may play a role in the sequence of events leading to liver disease in some patients with excessive drinking.

Objectives: Asthma prevalence is increasing in many countries. Some recent articles, however, claim that this tendency is drawing to an end. Hence, the incidence of persistent asthma was drawn from a birth cohort study in Finland., Materials and Methods: A cohort of 6107 men and 5839 women was followed from 1981 to 2004. The participants were members of the Northern Finland Birth Cohort 1966 Study (NFBC-66). The single-year birth cohort was followed from the age of 15 to 38 years by means of a complete register held by the national Social Insurance Institute (SII) in Finland. Within the register data, an incident case of asthma was defined by the received right for reimbursement for asthma medication from the SII., Results: Over a 23-year follow-up period, persistent asthma occurred in 466 study participants of whom 54% were women. The incidence of persistent asthma increased from the rate of 10 cases per 10 000 person-years at the age of 15-20 years to 21 cases per 10 000 person-years at the age of 36-38 years. In females, a peak of incidence rate was found between the age of 31 and 35 years, up to 27 cases per 10 000 person-years., Conclusions: The follow-up of a population-based birth cohort among young working aged Finns shows the increasing incidence rate of persistent asthma. In recent years, however, a decline in new cases of asthma occurred in females aged between 36 and 38 years.

Objectives: Previous studies have paid little attention to the occurrence of frostbites and related risk factors. The purpose of this study is to analyse the life-time occurrence of frostbite in young men and its association with the cold-provoked white finger syndrome (CPWF), smoking and hand vibration., Methods: The study population consisted of 5839 Finnish men aged 17-30 years entering military service. Data was collected for cases of first-degree, or more severe, frostbite affecting the head and extremities. Logistic analysis was used to assess the risk of frostbite with respect to CPWF, smoking and hand vibration., Results: The life-time and annual occurrences of frostbite were 44% and 2.2%, respectively (n = 2555). 2333 subjects (41%) had suffered first-degree freezing injury and 671 (12%) suffered severe injury at some time in their lives. The sites most prone to frostbite were the head, 1668 cases (31%), followed by the hands, 1154 (20%), and the feet, 810 (15%). The risk for frostbite in different body parts was increased among the subjects with CPWF (95% CI: 1.66 to 3.87), regular smokers (95% CI: 1.02 to 3.15) and those exposed to vibration (95% CI: 1.07 to 4.03)., Conclusions: A synergistic increase of frostbite was reported between CPWF and regular smokers, and between CPWF and hand/arm vibration in both exposure classes analysed. The life-time occurrence of frostbite among young healthy men was high. Frostbite, and its association with CPWF, smoking and hand/arm vibration should be noted by the health care personnel in circumpolar countries.

Aims: There are only limited data comparing the diagnostic characteristics of carbohydrate-deficient transferrin (CDT) measurements in assays for excessive alcohol consumption under controlled conditions., Methods: We compared different CDT assays and the conventional laboratory markers of ethanol consumption, gamma-glutamyl transferase (gamma-GT) aspartate aminotransferase (AST) and mean corpuscular volume (MCV) in the assessment and follow-up of 36 alcoholics (31 men, five women, mean age 44 years), who were admitted for detoxification. Detailed interviews to assess the amount of alcohol consumption were carried out for each patient. A hospital follow-up with supervised abstinence for 8 +/- 4 days (range 5-19 days) was carried out for 17 patients. Controls were 30 apparently healthy individuals (22 men, eight women, mean age 49 years), who had no history of hazardous drinking., Results: At the time of admission, the %CDT method, which excludes the trisialotransferrin isoform from the measurement, yielded elevated values in 69% of the patients, compared to 61% for CDTect. The corresponding sensitivities for gamma-GT, AST and MCV were 61, 56 and 47%, respectively. The self-reported alcohol consumption for a period of 1 month prior to admission showed a stronger correlation with the %CDT results (r = 0.59, P = 0.0003) than with the CDTect results (r = 0.36, P = 0.04), GT (r = 0.40, P = 0.02) or AST (r = 0.35, P = 0.05). During follow-up with supervised abstinence the mean %CDT values were found to show a slower rate to normalization (mean 14 +/- 4 days) than the CDT values measured with the CDTect method (mean 10 +/- 5 days) (P < 0.05)., Conclusions: The data indicate distinct differences and method-dependent rates of normalization in CDT assays, possibly reflecting different degrees of transferrin desialylation in the alcoholics. The present findings should be considered in studies on alcohol markers for monitoring abstinence.

Background: The detection of excessive alcohol consumption by laboratory methods continues to lack sensitivity and specificity. Recent studies have suggested that diagnostic improvement may be achieved by combining carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GT) measurements into a marker defined as gamma-CDT., Methods: We developed a new approach for determining gamma-CDT by using the data obtained from the Axis %CDT turbidimetric assays. Marker results were compared in the assessment of 65 alcoholics, who were either with (n=34) or without (n=31) liver disease, as analysed by clinical, laboratory, and morphological criteria. Reference individuals were 45 healthy volunteers who were either social drinkers or abstainers., Results: Gamma-GT and CDT results derived from both CDTect and %CDT measurements were used to calculate marker ratios as follows 0.8 x ln(GT)+1.3 x ln(CDT). With the established cut-off of 4.0 for the gamma-%CDT, the sensitivity of this method was 94% for men and 82% for women, as compared to 61% and 46% for %CDT and 70% and 73% for GT. The gamma-%CDT method was less dependent on liver status than the various other markers and showed the highest correlation with self-reported alcohol consumption (r=0.7254)., Conclusions: The data indicates that the new gamma-%CDT method yields improved diagnostic accuracy for the detection of excessive ethanol consumption.

Objectives: Respiratory symptoms and obstructive pulmonary diseases experienced during exercise and in cold weather were analysed in a large postal questionnaire study of a general adult population living in a cold climate. The aim of this study was to assess the prevalence of shortness of breath (SOB) during exercise, or in cold weather, and to find out if the risks (odds ratio=OR) for asthma, chronic bronchitis, or SOB during exercise, or in cold weather, were affected by recreational cross-country skiing, or by outdoor work in a cold climate., Results: Of the 7937 invited persons, 84% responded; 876 of them were outdoor workers and 1497 were recreational cross-country skiers. Of the non-smoking responders, asthmatic subjects had the highest prevalence of SOB during exercise in cold weather (78%-82%), but allergic and bronchitic persons also had significantly higher prevalence rates (22%-38% and 27%-59%, respectively) than healthy persons (10%-19%). In all categories, the prevalence of SOB was significantly higher among current smokers than among ex- or non-smokers. Risk factor analysis revealed increased risks for respiratory conditions among those who had a family history of obstructive airway disease, or allergy. Skiers did not have a significantly increased risk for asthma, or respiratory symptoms. Among outdoor workers the risk for SOB during exercise in cold weather, OR 1.23 (CI 1.03-1.47), and for chronic bronchitis, OR 1.77 (CI 1.21-2.60), was higher than among indoor workers., Conclusions: In conclusion, the risk for chronic bronchitis and bronchitic symptoms was elevated among outdoor workers, but not among regular recreational cross-country skiers, and the risk for asthma was not significantly elevated by regular exercising, or by working in a cold climate.

Background: Acetaldehyde-derived protein condensates (adducts) have been suggested as promising biological markers of alcohol abuse because they represent actual metabolites of ethanol. However, the detection of such condensates in vivo has been hampered by a lack of sensitive and specific methods., Methods: To develop new approaches for the detection of acetaldehyde adducts, we have raised antibodies against condensates with acetaldehyde and lipoproteins, which have previously been shown to be readily modified by acetaldehyde in vitro. The characteristics of these antibodies were compared with those raised against bovine serum albumin/acetaldehyde adduct and against other types of lipoprotein modifications, as induced by malondialdehyde, oxidation, and acetylation., Results: The antibodies raised against low-density lipoprotein (LDL)/acetaldehyde, very low density lipoprotein (VLDL)/acetaldehyde, and bovine serum albumin/acetaldehyde all reacted with protein adducts generated at physiologically relevant concentrations of acetaldehyde in vitro, whereas the antibodies raised against malondialdehyde/LDL, oxidized LDL, or acetylated LDL were not found to cross-react with the acetaldehyde-derived adducts. In assays for acetaldehyde adducts from erythrocyte and serum proteins of patients with excessive ethanol consumption (n = 32) and healthy control individuals (n = 22), the antibody prepared against the acetaldehyde/VLDL condensate was found to provide the most effective detection of acetaldehyde adducts in vivo., Conclusions: Current data indicate that acetaldehyde generates immunogenic adducts with lipoproteins in vivo. Antibodies raised against the VLDL/acetaldehyde may provide a basis for new diagnostic assays to examine excessive alcohol consumption.

Background: Although alcohol abuse is known to cause a wide array of adverse effects on blood cell formation, the molecular mechanisms by which alcohol exerts its toxic actions remain poorly defined. We examine here the formation of acetaldehyde-derived protein modifications in erythrocytes and in their bone marrow precursors using antibodies specifically recognizing acetaldehyde-modified epitopes in proteins independently of the nature of the carrier protein., Materials and Methods: We studied 138 consecutive adult patients undergoing bone marrow aspiration due to macrocytosis (MCV values above 99 fL). Assessment included complete blood counts, morphologic review, assessment of alcohol consumption, and biochemical and immunocytochemical assays for acetaldehyde adducts., Results: There were 68 patients (49%) with a history of excessive alcohol consumption, 28 (20%) of whom were patients with severe dependence. The blood smears prepared from the alcoholic patients with macrocytosis also contained stomatocytes and knizocytes. Bone marrow aspirates from 12 alcoholic patients showed vacuolization of pronormoblasts and the presence of ring sideroblasts was noted in 8 cases. In immunocytochemical analyses of the peripheral blood erythrocytes, acetaldehyde-derived epitopes were found to occur both on the cell membrane and inside the erythrocytes. Bone marrow aspirates also showed positive staining for acetaldehyde adducts in the erythropoietic cells in 8 of 11 (73%) consecutive alcoholic patients. Separation of the erythrocyte proteins from the samples of alcoholics on HPLC-chromatography revealed the formation of fast-eluting hemoglobin fractions, which also reacted with antibodies against acetaldehyde adducts., Conclusions: Current data suggest that acetaldehyde-erythrocyte adducts are formed in vivo in blood and bone marrow of patients with excessive alcohol consumption. This may contribute to the generation of the erythrocyte abnormalities, which are frequently observed in alcoholic patients.

Lysyl hydroxylase (EC ) and glucosyltransferase (EC ) are enzymes involved in post-translational modifications during collagen biosynthesis. We reveal in this paper that the protein produced by the cDNA for human lysyl hydroxylase isoform 3 (LH3) has both lysyl hydroxylase and glucosyltransferase (GGT) activities. The other known lysyl hydroxylase isoforms, LH1, LH2a, and LH2b, have no GGT activity. Furthermore, antibodies recognizing the amino acid sequence of human LH3 and those against a highly purified chicken GGT partially inhibited the GGT activity. Similarly, a partial inhibition was observed when these antibodies were tested against GGT extracted from human skin fibroblasts. In vitro mutagenesis experiments demonstrate that the amino acids involved in the GGT active site differ from those required for LH3 activity.

Although a lot of attention is focused on problems of energy balance and nutrition in cold environment, water balance has received less attention. In a cold environment the water balance might be disturbed because the need of water could be increased, the use of water could be decreased and the redistribution of blood could change water volume in circulation. In dehydrated subjects, exercising at -15 degrees C at submaximal work level, both oxygen uptake and heart rate were significantly higher during water deprivation while the anaerobic threshold was lower. The time before reaching exhaustion was also shortened. However, maximal oxygen uptake and maximal muscle strength were not affected. The results suggest lower efficiency, higher physical strain and earlier exhaustion of dehydrated subjects in cold. After repletion of 1.8% body weight loss by an equal amount of fluid (5% sucrose solution) the oxygen uptake was significantly decreased at a submaximal work level at -20 degrees C, suggesting an improved mechanical efficiency and decreased physical strain. Although physical performance could be restored by rehydration, a rapid rehydration is not recommended because of increased diuresis, increased blood pressure and vigorous shivering stimulated by cold fluids. Instead, a continuous maintenance of water balance is recommended, with a fluid temperature above 25-30 degrees C and with a carbohydrate content below 7%.

Recent investigations have shown that the prevalence of bronchial asthma is higher among skiers exposed to cold and dry air than among nonskiers. The upper airway passages are responsible for warming and humidifying the inhaled air. During exercise in cold and dry air, warming and humidifying of the inhaled air continues in the bronchial tree. Under these conditions both nasal and bronchial mucosa are cooled by inspiratory air and remain cooled throughout the respiratory cycle. The air which reaches the bronchoalveolar air space is at body temperature and fully saturated in all conditions. In this article we briefly review the studies carried out regarding the effects of cold air inhalation on the upper respiratory tract.