DNA methylation and gene expression patterns in adipose tissue differ significantly within young adult monozygotic BMI-discordant twin pairs.

BACKGROUND: Little is known about epigenetic alterations associated with subcutaneous adipose tissue (SAT) in obesity. Our aim was to study genome-wide DNA methylation and gene expression differences in SAT in monozygotic (MZ) twin pairs who are discordant for body mass index (BMI). This design completely matches lean and obese groups for genetic background, age, gender and shared environment. METHODS: 14We analyzed DNA methylome and gene expression from SAT, together with body composition (magnetic resonance imaging/spectroscopy) and glucose tolerance test, lipids and C-reactive protein from 26 rare BMI-discordant (intrapair difference in BMI ⩾3 kg m(-2)) MZ twin pairs identified from 10 birth cohorts of young adult Finnish twins. RESULTS: We found 17 novel obesity-associated genes that were differentially methylated across the genome between heavy and lean co-twins. Nine of them were also differentially expressed. Pathway analyses indicated that dysregulation of SAT in obesity includes a paradoxical downregulation of lipo/adipogenesis and upregulation of inflammation and extracellular matrix remodeling. Furthermore, CpG sites whose methylation correlated with metabolically harmful fat depots (intra-abdominal and liver fat) also correlated with measures of insulin resistance, dyslipidemia and low-grade inflammation, thus suggesting that epigenetic alterations in SAT are associated with the development of unhealthy obesity. CONCLUSION: This is the first study in BMI-discordant MZ twin pairs reporting genome-wide DNA methylation and expression profiles in SAT. We found a number of novel genes and pathways whose methylation and expression patterns differ within the twin pairs, suggesting that the pathological adaptation of SAT to obesity is, at least in part, epigenetically regulated.

Prospective evaluation of external ocular microbial growth and aqueous humor contamination during cataract surgery.

PURPOSE: To analyze the route of aqueous humor contamination leading to the development of postoperative endophthalmitis. SETTING: Department of Ophthalmology, University of Helsinki, Finland. METHODS: Forty-nine eyes of 49 patients (31 having phacoemulsification and 18 extracapsular cataract extraction [ECCE]) participated in the study. Four bacterial cultures were taken: preoperative conjunctival swab, lid margin culture, intraoperative lacrimal lake sample, and immediate postoperative anterior chamber fluid sample. RESULTS: Preoperative lid margin cultures were positive in 59.2% of eyes, conjunctival cultures in 69.4%, and lacrimal lake cultures in 24.9%. Four aqueous humor samples (8.2%) showed bacterial growth in the anterior chamber aspirate: 3 in the phacoemulsification and 1 in the ECCE group. The bacteria isolated in this study, Staphylococcus epidermidis and Propionibacterium acnes (2 positive isolates each) were sensitive to the preoperative topical antibiotics used. No aqueous humor sample or any from other locations showed gram-negative microbe growth. The most frequently recovered microbes in all samples collected from the 3 other sources were S epidermidis and other coagulase-negative staphylococcus species, followed by P acnes and other propionibacterium species. Staphylococcus aureus, and diptheroids. CONCLUSION: The ocular surface significantly contributed to the transmission of microbes into the eye during cataract surgery. These microbes could not be eradicated by topical preoperative antibiotics. However, no patient developed postoperative endophthalmitis. Natural defense mechanisms appear to fend off a minor inoculum with these microbes of relatively low pathogenicity.

Effect of zopiclone on sleep quality, morning stiffness, widespread tenderness and pain and general discomfort in primary fibromyalgia patients. A double-blind randomized trial.

Thirty-three patients fulfilling the diagnostic criteria for primary fibromyalgia completed an eight-week double-blind treatment trial with the drug zopiclone. Of outcome measures studied a score expressing subjective sleep quality showed improvement in more than ninety percent of zopiclone patients at 4 weeks and nearly eighty percent at 8 weeks, but similar improvement was also reported by more than sixty percent of the patients on placebo. Patient self-assessment of a treatment effect also showed an advantage for zopiclone, with most patients in the placebo group considering their state as unchanged at 8 weeks. According to examiner assessment, however, half the patients in both groups showed improvement at 8 weeks. For other assessment variables, e.g. dolorimeter assessment of widespread tenderness, visual analogue scales and pain drawings for pain and other subjective feelings of discomfort, the effects of zopiclone treatment were at the same level as those of placebo.

Early rehabilitation after small incision cataract surgery.

BACKGROUND: The use of smaller cataract incision is thought to induce less astigmatism, resulting in a more stable refraction and more stable wound. METHODS: We have analyzed the early astigmatic changes and rehabilitation in 20 eyes of 16 patients operated with advanced phacoemulsification techniques. The patients operated with small-incision surgery (incision 4.0 mm) were compared to those with large-incision surgery (incision 7.5 mm). Keratometric values and visual acuity data were evaluated up to 6 months postoperatively. RESULTS: Less initial induced astigmatism was demonstrated at day 7 postoperatively with a 4.0-millimeter incision (0.1 +/- 0.53 D) compared with a 7.5-millimeter incision (1.90 +/- 1.97). Similar but not statistically significant changes were seen at days 1 and 30 postoperatively. Visual rehabilitation was also faster in the small-incision group and 70% of the eyes gave uncorrected visual acuity of 20/40 or better in this group as early as the first postoperative day. Only 11% of the eyes showed that uncorrected visual acuity after large-incision surgery at first postoperative day. CONCLUSION: The low amount of induced cylinder, rapid stabilization of the wound, and faster visual rehabilitation confirms the advantage of small-incision cataract surgery to large-incision surgery.

Mortality, disability and changes in occupation among aging municipal employees.

During a four-year follow-up period the indicators of work load, individual factors, and stress reactions predicting mortality, disability, and change of occupation were studied. In 1981, 6257 active workers aged 44-58 years answered a questionnaire. The study was repeated in 1985 when 1% of the subjects had died, 9% had become disabled, and 5% had changed their occupation. These changes had occurred the most often in occupations which included muscular work, poor work postures, and a poor physical environment. The highest mortality rate was observed for the male installation and auxiliary workers who had reported the presence of cardiovascular, but no musculoskeletal, disease four years earlier. The highest disability rate was well predicted by a poor index of work ability. Major diseases leading to disability included malignant tumor, coronary artery disease, congestive heart failure, rheumatoid arthritis, bronchitis or bronchial asthma, and mental disease. Work-related stress reactions were associated with both mortality and disability.

Mortality and disability among cotton mill workers.

The mortality and disability of cotton mill workers were studied in five Finnish cotton mills. The population under study comprised all 1065 women exposed to raw cotton dust who had been hired between 1950 and 1971. The minimum exposure period was five years. For the study on disability, the cohort was followed up until the end of 1981. The follow up period for the mortality analysis was from 1950 to 1985. At the end of 1981 the observed number of prevalent disability pensions for respiratory disease was 15, whereas 3.9 were expected (p less than 0.01) on the basis of the national figures for women. There were 46 musculoskeletal diseases (27.7 expected, p less than 0.01), of which 24 were osteoarthritis (14.5 expected) and 13 rheumatoid arthritis (6.6 expected). The incidence rates of disability pensions were calculated for the period 1969-81. Comparison of incidence rates between cotton mill workers and the Finnish female population showed excessive rates for both respiratory diseases (p less than 0.001) and musculoskeletal diseases (p less than 0.01), with an excess of new cases of rheumatoid arthritis (p less than 0.05). By the end of 1985 the number of person-years was 31,678 and the number of deaths 95. The standardised mortality ratios for the total period of follow up (1950-85) showed no excess for respiratory diseases. Mortality from cardiovascular diseases was also lower than expected. The observed number of tumours was 33, the corresponding expected number 32.0. Thirteen tumours were in the digestive organs (6.6 expected, p<0.05) and three were lung cancers (1.9 expected). Five workers had died from renal disease; the expected number was 1.5 (p<0.05).

Cancer mortality of granite workers 1940-1985.

A retrospective cohort study was undertaken to investigate the cancer mortality of granite workers. The study comprised 1026 workers who took up such work between 1940 and 1971. The number of person-years was 23,434, and the number of deaths was 296. During the total follow-up period, 59 tumours were observed as compared with 54.4 expected. An excess mortality from tumours was observed in workers followed up for 20 years or more. Of the 59 tumours, 31 were lung cancers (expected 19.9), and 18 gastrointestinal cancers (expected 11.6), nine of which were stomach cancers (expected 7.1). Mortality from lung cancer was excessive for workers followed up for at least 15 years (28 observed, 12.7 expected). The results indicate that granite exposure per se may be an etiological factor in the initiation or promotion of malignant neoplasms.

Mortality and disability among granite workers.

The objective of the present study was to investigate the mortality, disability, and long-term morbidity of granite workers. The study included 1,026 workers hired between 1940 and 1971 and followed until the end of 1981. The total number of deaths was 235, and the expected number was 229.7. Excess mortality rates were observed for respiratory diseases (observed/expected = 28/13.9). The number of tumor deaths was 46 (expected 44.9). Excess lung cancer mortality was evident at 15 to 35 years of latency; the observed number of lung cancer deaths for the follow-up period of 25 to 29 years was 8, while 2.1 were expected. Mortality from cardiovascular diseases and violent deaths was slightly less than expected. The results for disability and long-term morbidity showed elevated incidence and prevalence rates for respiratory diseases and rheumatoid arthritis. The observed number of disability pensions due to rheumatoid arthritis in 1981 was 10 observed versus 1.8 expected, and the observed number of patients granted free medication was 19 versus 8.1 expected. The results indicate that granite dust exposure per se may be an etiologic and pathogenetic factor for lung cancer, cancer of the gastrointestinal tract, and some extrapulmonary nonmalignant chronic diseases.

Cancer mortality of granite workers.

A retrospective cohort study was undertaken to investigate the cancer mortality of granite workers. The study comprised 1,026 workers hired between 1940 and 1971. The number of person-years was 20,165, and the number of deaths 235. During the total follow-up 46 tumors were observed and 44.9 were expected. An excess mortality from tumors was observed for the workers followed for 20 years or more, the greatest excess occurring during the follow-up period of 25-29 years (observed 11, expected 5.2). Of the 46 tumors, 22 were lung cancers (expected 17.1) and 15 were gastrointestinal cancers (expected 9.7), nine of which were cancers of the stomach (expected 6.0). Mortality from lung cancer was excessive for workers with at least 15 years since entry into granite work (latency) (21 observed and 9.5 expected), being highest during the follow-up period of 25-29 years (observed 8, expected 2.1). The results indicate that granite exposure per se may be an etiologic factor in the initiation or promotion of malignant neoplasms.

Municipal employees' cardiovascular diseases and occupational stress factors in Finland.

The occupational stress factors related to specific cardiovascular diseases were studied by a questionnaire mailed to 6213 municipal employees aged 45 to 58 years, (response rate 85%) and by a specific job analysis of certain municipal occupations. The highest prevalences of self-reported chronic hypertension were found among male transport workers (19%), technical supervisors (19%) and auxiliary workers (15%), as well as among female domestic helpers (18%) and auxiliary workers (18%). Among men the prevalence of coronary heart disease varied from 9% for dump workers to 0% for dentists (mean 5%) and among women from 4% for kitchen supervisors to 0% for physicians (mean 3%). In the work profile groups with the highest rates of reported, specific cardiovascular diseases, the stress factors of women's work (domestic help and auxiliary work) were high energy demands, heavy dynamic and static work with high application of strength, poor postures, and uncomfortable climatic conditions. These stress factors were also typical among men doing auxiliary work. Other common stress factors among men included sensory-motor work done alone in static, monotonous sitting postures, exposured to vibration, drafts, and continuous alertness of the senses (transport work) and to processing and organization of information together with time pressure linked to decision-making and the need for accurate sensory perception (technical supervision work).

Corneal endothelium after photocoagulation in diabetic patients.

The corneal endothelium was photographed through a wide-field specular microscope in 38 eyes, in 20 successive diabetic outpatients receiving laser therapy because of underlying proliferative or background retinopathy. Areas of 100 individual endothelial cells from each central cornea were analysed using a digitizer. No statistically significant correlations were observed between mean cell areas or standard deviations of mean and total amount of previous laser energy received. Laser therapy or the type of diabetes did not seem to cause statistically significant changes in the endothelial cell areas examined.

Completeness of occupational history and occurrences of work-related diseases.

The lack of complete occupational histories causes underestimates or overestimates of occupational mortality and morbidity. The problem is emphasized in cohorts with high turnover and in cross-sectional study designs. In the study of the effect of selective turnover on occupational mortality and morbidity complete occupational histories were acquired via questionnaire. The sample comprised 1 200 current and 1 800 alive former workers and the closest relatives of 450 deceased workers and was formed from three exposure-level cohorts (defined primarily according to the physical demands of the work) of 15 714 metal workers hired in 1950-1976. The occupational histories reported in the questionnaires were compared with those collected from employers' personnel records. The coverage of occupational histories was the most accurate for current and former workers with the longest duration of exposure and the least accurate for dead workers and the oldest age groups. The use of complete occupational histories and the combining of the similar levels of exposure through the lifetime produced clear differences in the occurrences of musculoskeletal, respiratory, and cardiovascular diseases between the three levels of exposure. The errors in person-years were smaller than the errors in the duration of exposure; the coverage varied from 51 to 94%. However, misclassification clearly caused cancer cases to be located in classes with too short a period of latency. About 30% of the deceased workers had reportedly entered the industry before the first follow-up year.

Effect of cohort definition and follow-up length on occupational mortality rates.

The purpose of this study was to clarify the effects of cohort formation, period of entry, and period of follow-up on occupational mortality figures. The study material comprised three cohorts of metal industry workers (6 415 iron foundry workers, 3 901 metal product workers, and 5 398 workers manufacturing electrical devices). The men, hired between 1950 and 1976, were followed until the end of 1978. The number of person-years was approximately 215 800. Different cohort formation criteria and variations in the follow-up modify the results of occupational mortality studies. A cross-sectionally based cohort (workers employed in a certain year or years) produces results different from those for an open cohort (new workers hired during a certain period of time) although the cohorts are formed from the same workplaces. The cohorts for retrospective cohort studies usually contain various periods of entry, periods of follow-up, and age structures. Increased or decreased mortality in a cohort depends on this internal structure. The structure of the cohort becomes especially important when a certain cause of death is concentrated in certain age classes and/or when a period of latency is required, as for tumors. In an attempt to reveal this internal structure the three cohorts were analyzed in five-year calendar periods and stratified according to the length of follow-up. The mortality pattern remained nearly unchanged when the number of periods of entry increased, and it was also comparable with the mortality pattern of the general male population.(ABSTRACT TRUNCATED AT 250 WORDS)

A cancer register-based case study of occupations of patients with acute myeloid leukemia.

All 636 cases of acute myeloid leukemia (AML) reported to the Finnish Cancer Registry between 1971 and 1977 inclusive were compared with patients with other forms of cancer (non-AML) from the same registry. We found no increasing trend in the incidence of AML for either sex, but we found some evidence for regional clusters in certain provinces of Finland. A statistically significant higher incidence was found for men than women in the age group of 50 to 80 years. Classification according to occupation at the time of diagnosis revealed no statistically significant differences between the leukemia cases and the patients with other forms of cancer, but forestry work was more common among the men with AML, and both health care and food industry work were more common among the women with AML. Classification for exposure to chemicals, solvents, or drugs did not yield any statistical differences. The results were inconclusive with regard to the possible role of occupational factors in the etiology of acute myeloid leukemia.

A cohort study on workers exposed to trichloroethylene.

The mortality of 2,117 workers exposed to trichloroethylene sometime between 1963 and 1976 was studied. Their names were collected from the files of one biochemical laboratory performing urinary trichloroacetic acid determinations and from the Occupational Disease Register of Finland. Both the total mortality (SMR 69) and the cancer mortality (SMR 77) were lower than expected. Because of the young age structure and the brief follow-up time the results should be interpreted with caution. They suggest, however, that given as short a latency period as 6 to 13 years, trichloroethylene is not a strong human carcinogen. The present material provides a cohort with defined exposure for further follow-up.

Lung cancer mortality among iron foundry workers.

The present study was designed to test earlier findings of increased risk of lung cancer among iron foundry workers and to define the cause of the risk. The subjects were 3,425 workers with at least one year's employment in an iron foundry sometime between 1918 and December 31, 1972. The number (51) of cases of lung cancer which occurred prior to December 31, 1976 was statistically significantly higher than that expected, i.e., 35.3 based on proportional mortality. Molders and casters were determined to have the highest excess risk in a case-control study among the cohort. The worker groups with high exposure to polycyclic aromatic hydrocarbons (PAH) experienced a lung cancer risk higher than that of other groups, but the difference was not statistically significant.

Work conditions and health of locomotive engineers. II. Questionnaire study, mortality and disability.

A questionnaire study on work conditions, work organization, leisure time, social problems, and health was directed toward active and retired locomotive engineers. This article mainly presents responses of the active engineers. The active locomotive engineers quoted the irregular work hours as the worst occupational problem. They judged noise and vibration in the locomotive cabs as disturbing. The majority of the desired changes in the work and work conditions concerned work time. The most common complaints given on the questionnaire were back trouble, hypertension and dermatitis. Tiredness and exhaustion were the most prevalent neuropsychological symptoms. A retrospective follow-up survey on invalidity and mortality was made. Trainmen and railroad clerks were used as reference cohorts.The engineers had relatively high invalidity and mortality rates in comparison to the reference groups, especially with respect to cardiovascular diseases and malignant tumors. Higher rates for disease of the digestive system and hearing loss were also suggested by the results.

A mortality study of foundry workers.

The mortality of foundry workers was studied from a sample of all those men employed in 20 representative iron, steel, and nonferrous foundries for any period of time during 1950 through 1972. A statistical sample of 3,876 men from all those 15,401 workers with at least 3 months' exposure formed the cohort under study. The actual number of person-years of follow-up became 47,160. Total and cause-specific mortality was studied in the entire cohort and in different categories based on exposure time and occupation. The foundry workers' experience was compared to that expected on the basis of the general male population's death rates in Finland, and different categories of the cohort were compared to each other through direct standardization. During the period from 1950 through 1973, there had occurred 224 deaths. The mortality approached the expected value computed from the age-adjusted general male population, the standardized mortality ratio (SMR) being 90 for all foundry workers and 95 for workers in "typical" foundry occupations. The corresponding standard mortality ratios based on the estimated total number of person-years, after the application of corrections for sampling fractions, were 86 and 95, respectively. There was a slight shift of the age of death towards younger age groups among the casters, fettlers, and furnace tenders. Mortality from coronary heart disease showed a standardized mortality ratio of 80 for the whole cohort; no significant differences were found for any occupational category. Lung cancer mortality was higher than expected (SMR 150) in the entire cohort; closer analysis revealed that the excess was confined to iron foundries, and especially to molders with more than 5 years of exposure. There were no more violent deaths than expected, not even from work accidents. Because most occupational cohorts have standardized mortality ratios that are well below 90, the present results were interpreted as probably indicating slightly elevated mortality. The most important finding was the concentration of lung cancer among molders in iron foundries.