Knee injuries account for the sports-related increased risk of knee osteoarthritis.

Increased risk of osteoarthritis has been found among athletes active in different kinds of sports. Knee injury is an established risk factor for knee osteoarthritis. In this population-based case-control study we investigated the risk of knee osteoarthritis with respect to sports activity and previous knee injuries. A total of 825 cases with x-ray-verified femorotibial osteoarthritis were identified at six hospitals in southern Sweden. The cases were matched (age, sex and residential area) with 825 controls from the general population. Mailed questionnaire data on sports activity for more than 1 year after the age of 16, knee injuries and confounding variables (weight, height, heredity, smoking and occupation) were collected and analyzed using logistic regression models. The response frequency was 89%. Among men knee osteoarthritis was related to soccer (odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1-2.2), ice hockey (OR 1.9, 95% CI 1.2-3.0) and tennis (OR 2.0, 95% CI 1.1-3.8) but not to track and field sports, cross-country skiing, and orienteering. After adjustment for confounding variables soccer and ice hockey remained significantly related to knee osteoarthritis, but after adjustment for knee injuries no significant relation remained. The sports-related increased risk for knee osteoarthritis was explained by knee injuries.

Knee osteoarthritis and body mass index: a population-based case-control study.

OBJECTIVE: It is well established that overweight is related to osteoarthritis of the knees. The aim of this study was to investigate the risk of knee osteoarthritis for men and women in relation to body mass index (BMI) within the normal weight range and to assess the effect of former versus current weight. METHODS: A population-based case-control study was carried out in the southern part of Sweden, including 825 cases with X-ray verified femorotibial osteoarthritis and 825 age-, sex-, and county-matched population controls. Mailed questionnaire data on weight, height, and confounding factors (heredity, smoking, knee injuries, and physical activity) were collected and analysed using logistic regression models. The response frequency was 89%. RESULTS: Mean age of the participants was 63 years, and 57% were women. The adjusted risk of knee osteoarthritis was increased fourfold in men with a current BMI 23 to < 25 kg/m2 as compared to men with BMI < 23 kg/m2 (OR 4.0, 95% CI 1.7-9.5). The commensurate risk for women was 1.6 (95% CI 0.9-3.1). BMI at 30 years of age was similarly related to knee osteoarthritis. CONCLUSION: A moderate increase in BMI, within the normal weight range, was significantly related to knee osteoarthritis among men. Overweight at any time was related to knee osteoarthritis.

Fatalities in farming and forestry: an examination of the registry information used in the Swedish national statistics, 1988-1997.

In Sweden, work-related injuries are filed in the ISA, a national information system. The Occupational Safety and Health Administration is responsible for this registry, and local units of the ISA and the Labor Inspectorate provide the information. The risk of dying in a work-related accident is greatestfor those employed in farming and forestry. At the same time, small-scale industries such as farms and other entrepreneurial businesses have difficulties in reporting accidents. It is therefore possible that the registry is incomplete and/or has many errors with respect to this kind of occupational activity. Thus, it is of interest to study the ISA in this area. This study was carried out using information obtainedfrom the Labor Inspectorate (LI), the police, the occupational health service, and local persons. Errors were traced in 28 cases (17%), and at least one piece of necessary information was missing in 165 cases of a total of 167. Approximately 14% of the cases had such fundamental errors that the case should be withdrawn from the registry. Most of the errors concerned the victim's occupation/profession and the kind of work being done at the time of the accident. In order to be an adequate instrument for use in prevention work, the ISA files must be more complete. This is of special importance with respect to the characteristics of the events. At the same time, the number of errors should be reduced.

Early amniocentesis and congenital foot deformities.

OBJECTIVE: Several studies have shown an increased risk of congenital foot derformities after early amniocentesis. These studies have comprised amniocenteses performed before 13 completed gestational weeks. In this study, the risk of foot deformities after amniocentesis performed at 12-14 completed gestational weeks was determined. METHODS: 3,469 genetic amniocenteses in singleton pregnancies performed before 15 completed gestational weeks were studied. The intention was to perform the amniocenteses at 12-14 weeks of gestation, but 32 amniocenteses were performed at the gestational age 11 weeks + 5 days or 11 weeks + 6 days. The pregnancies were followed up with regard to fetal loss and leakage of amniotic fluid. After birth, newborns with a diagnosis of foot deformity were identified from the Swedish Medical Birth Registry. The observed number of foot deformities was then compared with the expected number which was calculated stratified for delivery hospital, year of birth, and maternal age. RESULTS: The observed number of foot deformities was significantly higher than the expected: exact odds ratio 1.74 (exact 95% confidence interval 1.06-2.69). The rate of spontaneous abortions after the procedure was 1.8%, and the rate of leakage of amniotic fluid was 1.9%. There was a significant trend for all complications to decrease with increasing gestational age at amniocentesis. CONCLUSION: Women undergoing amniocentesis at 11+5 to 14+6 gestational weeks have an increased risk of giving birth to a child with a congenital foot deformity.

Blood lipid levels in a rural male population.

OBJECTIVES: Farmers have a low risk for cardiovascular disease, which may be related to a favourable blood lipid profile. In order to study the blood lipid levels and evaluate the effect of other cardiovascular risk factors on the blood lipid profile, this cross-sectional study was made. MATERIAL AND METHODS: A total of 1013 farmers and 769 non-farming rural men in nine different Swedish counties were examined, interviewed, and replied to questionnaires. The inter-relationships between different risk factors were analysed using a multivariate linear regression model. RESULTS: The farmers had a significantly more favourable blood lipid profile than the non-farmers although the total cholesterol levels were almost the same for the two groups. In the total study population there were significant positive relationships between total cholesterol level and body mass index (BMI), diastolic blood pressure and smoking. The high-density lipoprotein (HDL) level was positively related to physical workload and alcohol consumption, and negatively related to BMI, waist/hip ratio and smoking. Triglyceride levels showed a positive relationship to BMI, waist/hip ratio and blood pressure. Differences between farmers and other rural males were seen, especially with respect to the effect of physical activity and psychosocial factors. Among the farmers, a negative correlation between the Karasek-Theorell authority over work index and total cholesterol, the low-density lipoprotein (LDL)/HDL ratio and triglyceride levels was observed. CONCLUSIONS: This study indicated that diet is of minor significance for the blood lipid profile, whereas factors such as physical activity, body weight and the waist/hip ratio, smoking, alcohol consumption, and perhaps psychosocial working conditions are major independent factors affecting the blood lipid profile most prominently among farmers, but also among non-farming rural men.

Monitoring of the subtraction process in solid-phase representational difference analysis: characterization of a candidate drug.

In this study, we have applied and evaluated a modified cDNA representational difference analysis (RDA) protocol based on magnetic bead technology to study the molecular effects of a candidate drug (N,N'-diacetyl-L-cystine, DiNAC) in a model for atherosclerosis. Alterations in a gene expression profile induced by DiNAC were investigated in a human monocytic cell line (THP-1) differentiated into macrophage-like cells by lipopolysaccharide and further exposed to DiNAC. Three rounds of subtraction have been performed and the difference products from the second and third rounds have been characterized in detail by analysis of over 1000 gene sequences. Two protocols for analysis of the subtraction products have been evaluated, a shotgun approach and size selection of both distinct fragments and band-patterned smear. We demonstrate that in order to obtain a representative view of the most abundant gene fragments, the shotgun procedure is preferred. The obtained sequences were analyzed against the UniGene and Expressed Gene Anatomy Database (EGAD) databases and the results were visualized and analyzed with the ExProView software enabling rapid pair-wise comparison and identification of individual genes or functional groups of genes with altered expression levels. The identified differentially expressed gene sequences were comprised of both genes with known involvement in atherosclerosis or cholesterol biosynthesis and genes previously not implicated in these processes. The applicability of a solid-phase shotgun RDA protocol, combined with virtual chip monitoring, results in new starting points for characterization of novel candidate drugs.

Nasal symptoms and pathophysiology in farmers.

OBJECTIVES: Increased morbidity and mortality in lower airway diseases have been reported among farmers. The aim of this study was to assess upper airway problems in farmers. SUBJECTS AND METHODS: Twenty-five dairy farmers, 20 pig farmers, 21 grain farmers and 19 control subjects were studied, by use of questionnaire, skin-prick test, dynamic spirometry, nasal inspection, acoustic rhinometry (before and after a decongestant) as well as by determinations of the olfactory threshold and nasal lavage (NAL) concentrations of eosinophil cationic protein (ECP), myeloperoxidase (MPO) and albumin. RESULTS: Compared with the control group, farmers had more complaints of work-related symptoms from the lower airways, and symptoms of smell impairment, and more often had nasal polyps and hyperaemia of the nasal mucosa. They also had higher levels of MPO in NAL (especially dairy farmers and pig farmers), and a tendency to more swollen nasal mucosa and lower olfactory threshold (especially grain farmers). CONCLUSIONS: The farmers had more pathological findings in their nasal mucosa, possibly indicating effects of allergens and irritants in their work environment. More studies are needed to evaluate work environment factors causing these pathological findings in farmers.

Molecular analysis of commensal host-microbial relationships in the intestine.

Human beings contain complex societies of indigenous microbes, yet little is known about how resident bacteria shape our physiology. We colonized germ-free mice with Bacteroides thetaiotaomicron, a prominent component of the normal mouse and human intestinal microflora. Global intestinal transcriptional responses to colonization were observed with DNA microarrays, and the cellular origins of selected responses were established by laser-capture microdissection. The results reveal that this commensal bacterium modulates expression of genes involved in several important intestinal functions, including nutrient absorption, mucosal barrier fortification, xenobiotic metabolism, angiogenesis, and postnatal intestinal maturation. These findings provide perspectives about the essential nature of the interactions between resident microorganisms and their hosts.

A prospective study of morbidity and mortality rates among farmers and rural and urban nonfarmers.

Farmers are known to have lower morbidity and mortality rates than the mean for other occupational groups in the general population. Whether this is due to the urban-rural health gradient or to occupational factors related to farming is not clear. To explore this issue, we conducted a prospective study of farmers and matched rural and urban referents. Official hospital admission and mortality data for the years 1989-1996 were obtained. The relative risk of being admitted to hospital were 10% higher among rural and urban referents than among the farmers. The biggest differences were seen for mental and cardiovascular disorders. The odds of dying during follow-up did not differ between the two rural groups but were doubled among urban referents. In conclusion, the lower morbidity and mortality rates among farmers are partly due to the urban-rural health gradient but in addition salutogenic factors linked to farming seem to be active.

Psychosocial conditions and access to an occupational health service among farmers.

To determine whether membership in an occupational health service program varies with correlation with psychosocial risk factors, this study was carried out among farmers in connection with a larger investigation of salutogenic factors. The study was based on information collected via questionnaires (answered on location) and standardized interviews. The material consists of 364 farmers or persons engaged in agriculture who had occupational health care and 548 without it. There were clear differences in psychosocial patterns between the groups. Those with occupational health care were less often single and had more education and more social contacts than did those without such care. Eating times were more regular and meals were better in those with occupational health care. Karasek-Theorell's indices for psychological demands and decision latitude at work were also higher in this group. Better-educated farmers and those with larger farms were more often members of an occupational health care program. In addition, this group had fewer psychosocial risk factors.

Differences in the use of health care facilities and patterns of general risk factors in farmers with and without occupational health care programs.

To investigate whether differences in the use of health care facilities and the distribution of risk factors were related to the accessibility of occupational health services, 912 farmers in a large research project were studied. Information was collected from nine different localities in rural areas, using questionnaires, standardized interviews, physical examinations, and blood tests. The results showed that there was hardly any difference in the use of general health care facilities between the groups. Those with occupational health services generally had more medical visits, but also had fewer diagnoses of cardiac disease. Known risk factors were present more often in the group without occupational health services. The work of the occupational health care service and the individual's interest in health questions appeared to be of significance in the way the risk factors were distributed.

Working environment conditions in rural areas according to psychosocial indices.

The aim of this work was to study psychosocial working environment factors among farmers and other people living in rural areas. The study was carried out as a cross-section investigation. All persons visiting local occupational health service centres for a health check up have been asked to answer an inquiry which was based on the Karasek-Theorell questionnaire on job strain. Five extra items on worry about the future were added. The questionnaire was completed by over 3,800 persons. Three of four indices showed significant difference with respect to sex. Women experienced less stimulance at work, authority over work and had a greater fear of the future. Farmers had a significantly higher index for psychological demands, stimulance at work as well as authority over work than other occupational groups. The index for authority over work was very high in comparison with presented results for different occupations in other studies. With respect to worry about the future, the farmers had a significantly higher index than nearly all the other occupational groups. The low risk of coronary heart disease (CHD) among farmers reported in other studies can probably be related to good psychosocial working environment as measured by the indices in this study as well as other known life style factors.

Reported health status among farmers and nonfarmers in nine rural districts.

Farmers appear to have a lower morbidity and mortality rate than other occupational groups. Whether this better health is due to exposure to farming or to the well-known fact that rural populations have better health than urban ones, irrespective of occupation, is not clear. To explore this problem, all male farmers in nine administrative areas and age-matched nonfarmers from the same rural areas were sampled and invited to participate in a survey. 1782 (76%) men responded. We found that farmers had somewhat lower rates of outpatient health care utilization for causes other than trauma and fewer hospital admissions. These differences were independent of the urban-rural factor and could not be explained by traditional determinants of health and health care utilization. Other factors, linked to farming or to farmers' lifestyles, are probably involved.

Prevalence of antibodies specific to Puumala virus among farmers in Sweden.

OBJECTIVES: The Puumala virus is the causative agent of nephropathia epidemica, a European form of hemorrhagic fever with a renal syndrome. From its reservoir in bank voles, the virus is spread by airborne transmission to humans. Occupational risks for the acquisition of nephropathia epidemica are not well defined. The prevalence of serum antibodies to Puumala virus was determined for Swedish farmers. From a comparison of the prevalence among farmers from various parts of the country, the assumption that Puumala virus occurs endemically only in the northern and central parts of Sweden was also tested. METHODS: Serum samples from 910 farmers and 663 referents living in various rural parts of Sweden were tested with an enzyme-linked immunosorbent assay, using a recombinant nucleocapsid protein of Puumala virus as the antigen. RESULTS: North of a latitude of 59 degrees N, the prevalence of Puumala virus antibodies was significantly higher among farmers (12.9%) than among referents (6.8%). In the southern areas, antibodies to Puumala virus were rare, and altogether only 2 of 459 persons had antibodies. Seropositive persons did not differ from seronegative ones with regard to blood pressure, and they did not comprise cases of chronic renal disease. CONCLUSIONS: Serological evidence confirmed that the exposure of humans to Puumala virus is firmly restricted to the northern and central parts of Sweden. In addition the evidence indicated that, in this region, farming is associated with an increased risk of contracting hantavirus infection.

Energy expenditure of Chinese infants in Guangdong Province, south China, determined with use of the doubly labeled water method.

The doubly labeled water method was used to measure the energy expenditure of a group of 41, 4- or 6-mo-old infants with a cross-sectional design. The infants were divided into two groups according to whether they were breast-fed (11 at 4 mo, 9 at 6 mo) or formula fed (11 at 4 mo, 10 at 6 mo). Anthropometric measurements were recorded at birth and at the beginning and end of the 8-d study. Anthropometric data, which were supported by the food intake and energy expenditure results, indicated that the infants were within the norms for European and American infants of the same age. Mean energy intakes of 352 kJ (84 kcal) kg(-1) x d(-1) at 4 and 6 mo were lower than the FAO/WHO/UNU recommended value of 452 kJ (108 kcal) x kg(-1) x d(-1)) and Chinese recommendations of 502 kJ (120 kcal) kg(-1) x d(-1). However, some authors believe that values of 398 kJ (95 kcal) kg(-1) x d(-1) at 4 mo and 356 kJ (85 kcal) kg(-1) x d(-1) at 6 mo are more appropriate. At 6 mo the infants' length-for-age and weight-for-age were at the National Center for Health Statistics 55th and 47th percentiles, respectively, whereas 58% were below the 50th percentile for weight-for-length. We conclude that at 4 mo infants receive sufficient energy for their requirements. However, at 6 mo energy requirements might well be greater than the revised recommendations, when infants are being weaned to alternative foods and are more prone to the influence of diet on their growth and development.

PIP: This cross-sectional study uses the doubly labeled water method to measure energy intake, energy expenditure, and energy used for growth in groups of 4- and 6-month old Chinese infants who were predominantly either breast-fed or formula fed. Anthropometric measurements were recorded at birth and at the beginning and end of the 8-day study. Anthropometric data, which were supported by the food intake and energy expenditure results, indicated that the infants were within the norms for European and American infants of the same age. Mean energy intakes were lower than the WHO recommended value. However, some authors believe that values of 398 kilojoule (kJ) at 4 months and 356 kJ at 6 months were more appropriate. At 6 months old, the infants¿ length-for-age and weight-for-age were at the National Center for Health Statistics 55% and 47%, respectively, whereas 58% were below the 50% for weight-for-length. Therefore, infants at 4 months were able to receive sufficient energy for their requirements. However, at 6 months energy requirements might be greater than the revised recommendations, when infants were being weaned to alternative foods and were more prone to the influence of diet on their growth and development.

Coxarthrosis and farm work: a case-referent study.

The purpose of this case-referent study was to analyze the association between coxarthrosis and occupation. The study was performed in a Swedish agricultural county and comprised 269 cases of radiologically verified arthrosis of osteoarthritis (< 3 mm joint space) that were compared to 538 randomly selected controls in the same region, matched for age, sex, and place of residence. Farmers and agricultural workers showed an increased risk of coxarthrosis and the observed risk increased with increasing number of years of farming. Tractor driving and milking were associated with coxarthrosis, whereas no association with other types of machine work could be demonstrated. An association between coxarthrosis and heavy physical work before the age of 16 years was also observed. The results give only limited information on the external causes of coxarthrosis, however. More detailed studies of groups of individuals with coxarthrosis in order to obtain more information about contributing and underlying factors would therefore be valuable.

Distribution of branch point prenyltransferases in regions of bovine brain.

Bovine brains contain large amounts of isoprenoid compounds and the enzymes involved in their biosynthesis were investigated. Ten different regions were dissected from fresh bovine brains and, in addition, fractions from cerebellum, spinal cord, and hypophysis were obtained. The cholesterol concentration was found to be approximately 8 mg/g in the cortex regions and three times higher in the pons, medulla oblongata, and white matter. Dolichol concentration varied between 8 and 40 micrograms/g in the different tissues, and ubiquinone was found at a lower level, which varied between 3 and 25 micrograms/g. Farnesylpyrophosphate synthase activity in cytosolic fractions from various regions exhibited only a twofold variation, whereas geranylgeranyl pyrophosphate synthase displayed larger differences, being particularly rich in the pons, medulla oblongata, white matter, and spinal cord. Squalene synthase activity was lowest in the thalamus and threefold higher in the pons. Determination of specific activity based on cholesterol content revealed that enzyme activities in various regions are not related to the actual lipid amount present. Both cis- and trans-prenyltransferases exhibited similarities in their regional distribution showing up to 20-fold differences in activity. Thus, it appears that the mevalonate pathway lipids and the various branch point enzymes involved in their syntheses vary greatly in different brain regions and are subjected to separate regulation.

Effect of squalestatin 1 on the biosynthesis of the mevalonate pathway lipids.

The effects of squalestatin 1 on rat brain and liver homogenates and on Chinese hamster ovary tissue culture cells have been investigated. This compound effectively inhibits squalene biosynthesis in a highly selective manner. Cytoplasmic farnesyl pyrophosphate and geranylgeranyl pyrophosphate synthases are not affected, which is also the case for microsomal cis-prenyltransferase. In tissue culture cells, squalestatin 1 inhibits cholesterol biosynthesis completely, but does not alter dolichol synthesis or protein isoprenylation to a great extent. Incorporation of [3H]mevalonate into ubiquinone-9 and -10 increases 3-4-fold, probably as a result of increased synthesis of this lipid. Squalestatin 1 appears not only to be an effective inhibitor of cholesterol biosynthesis, but also to be more specific than other inhibitors used earlier in various in vitro and in vivo systems.

Age-dependent changes in rat liver prenyltransferases.

Mevalonate pathway lipids including cholesterol, ubiquinone and dolichol, are of great importance for cellular function. Many of the enzymes of this pathway are thus strictly regulated. During development of the rat, the cellular levels of certain of these lipids vary. Prenyltransferases have been investigated and it is reported here that farnesyl pyrophosphate synthase activity in rat liver cytosol decreases after birth to a lower, steady level. This decrease is not paralleled by the level of synthase protein, which shows two maxima, one immediately after birth and the other 30 days later. cis-Prenyltransferase activity is low after birth, increases continuously up to day-54 and then decreases to a low level which was maintained throughout the remainder of the study (365 days). Squalene synthase exhibits high activity after birth, but decreases during the first 100 days thereafter, and subsequently remains at the low level thus reached. In contrast to these changes in the activities of the prenyltransferases, the level of cholesterol is constant and the dolichol concentration increases continuously throughout the entire period studied.

Isoprenoid biosynthesis in rat liver mitochondria. Studies on farnesyl pyrophosphate synthase and trans-prenyltransferase.

Mevalonate pathway enzyme activities in rat liver mitochondria were investigated, and it was found that isopentenyl pyrophosphate can be utilized for the synthesis of all-trans-polyprenyl pyrophosphates in vitro. In this reaction sequence intermediate formation of farnesyl pyrophosphate (FPP) predominates, and the FPP synthase activity was studied in more detail. The mitochondrial activity constitutes 13% of the total hepatic capacity for FPP synthesis, exceeding the corresponding microsomal, nuclear, and peroxisomal activities by 10-fold. Mitochondrial FPP synthase exhibits trypsin sensitivity only after sonication of intact mitochondria and upon subfractionation the activity is found localized in the matrix. FPP synthase activities at different locations responded distinctly when rats were treated with a diet enriched in cholesterol or containing mevinolin or cholestyramine. With the high cholesterol diet, mitochondrial FPP synthase activity increased 2-fold, while the cytosolic activity was slightly decreased. Both mevinolin and cholestyramine treatment resulted in 3-fold increases in cytosolic FPP synthase activities, without altering the mitochondrial activity. FPP was utilized as substrate for trans-prenyltransferase activity in the inner mitochondrial membrane. The products formed in this reaction were identified as nona- and decaprenyl-PP, and the reaction was influenced by changes in both substrate and Mg2+ concentration, giving more decaprenyl-PP when the concentrations of these substances were increased. These results demonstrate that mitochondria utilize endogenously produced FPP for isoprenoid biosynthesis and that the biosynthetic steps in mitochondria are regulated independently from those occurring in other subcellular compartments.