Disability and not osteoarthritis predicts cardiovascular disease: a prospective population-based cohort study.

BACKGROUND: Previous studies found an association between osteoarthritis (OA) and risk of cardiovascular disease (CVD) and therefore suggested intensive treatment of cardiovascular risk factors in OA patients. However, prospective population-based data is lacking. OBJECTIVES: To investigate the association between OA and CVD longitudinally in a general population and examine the role of disability in this association. METHODS: This study was embedded in the Rotterdam Study, a prospective population-based cohort study in Rotterdam, the Netherlands that started in 1989. At baseline 4648 persons aged ≥55, free of CVD were classified into those with and those without radiographic or clinical OA. HRs adjusted for traditional cardiovascular risk factors for developing CVD (a composite of fatal and non-fatal coronary heart disease and stroke) were calculated. RESULTS: During a median follow-up of 14.4 years, 1230 cardiovascular events occurred, of which 101 were in participants with clinical OA. Presence of radiographic OA at baseline was not related to future CVD (HR 0.99, 95% CI 0.86 to 1.15), neither was presence of clinical OA (HR 1.09, 95% CI 0.88 to 1.34). However, persons with increasing disability were more likely to suffer a cardiovascular event compared with non-disabled persons (HR 1.26, 95% CI 1.12 to 1.42); this was independent of the presence of OA. CONCLUSIONS: In this large population-based study, participants with OA were not at increased risk of CVD. The close relation between disability and osteoarthritis may explain previous findings. Further studies are required in order to clarify whether OA patients need more intensive treatment of their cardiovascular risk factors.

Social distance and spatial distance are not the same, observations on the use of GIS in leprosy epidemiology.

Contacts of leprosy patients have a higher risk of developing clinical leprosy. Being a contact is defined socially, but with the introduction of geographical information systems (GIS) in infectious disease epidemiology, it is necessary to relate spatial distance to social distance. We measured the distances between patients and their socially defined contacts in northwest Bangladesh. Contact categories differ in mean distance to the index patients. Sixty-seven per cent of the high-risk contacts lived within 10 metres (m), while all low-risk contacts lived >10 m from the index patient. Classification based on intervals of spatial distance creates categories that contain contacts of different socially defined categories, illustrated by a category of people living between 10 m and 20 m consisting of 47% of high-risk contacts and 52% low-risk contacts. Classification of contacts based on the spatial distance, as performed with GIS techniques, produces other groups than with social definitions.

Position-specific oxygenation of benzo(a)pyrene by different forms of purified cytochrome P-450 from rabbit liver.

High-pressure liquid chromatography was used to detect oxygenated products of benzo[a]pyrene formed in a reconstituted microsomal mixed-function oxidase system containing cytochrome P-450 (P-450LM), phospholipid, and NADPH-cytochrome P-450 reductase (NADPH: ferricytochrome oxidoreductase, EC 1.6.2.4). Three cytochrome fractions purified from a single source, hepatic microsomes from phenobarbital-treated rabbits, were studied; the various forms of the cytochrome are designated by their relative electrophoretic mobilities. The total benzo[a]pyrene oxygenation rate was greatest for P-450LM1,7, intermediate for P-450LM2, and least for P-450LM4. The phenolic products were eluted in two peaks, A and B, that contained primarily 9-hydroxy- and 3-hydroxybenzo[a]pyrene, respectively. The ratio of peak A to peak B phenols was 0.11 for P-450LM2 and 0.45 for P-450LM4. Thus, the relative amounts of the various phenols formed by these two cytochrome fractions differ markedly. The positional specificity of the hydroxylation is also indicated by large differences in the fluorescence spectra of the phenolic products formed by the two cytochromes. P-450LM2 and P-450LM4 did not form benzo[a]pyrene dihydrodiols, thereby showing that benzo[a]pyrene oxide hydratase activity was absent from these purified preparations. Ninety percent of the phenols formed by P-450LM1,7 were eluted in peak B; the metabolites produced by this preparation also included dihydrodiols, thus indicating the presence of hydratase activity. The positional specificities of different forms of cytochrome P-450 may channel polycyclic aromatic hydrocarbon metabolism into the various activation and detoxification pathways and thereby help determine the cytotoxic and carcinogenic activity of these compounds.

Purified liver microsomal cytochrome P-450. Separation and characterization of multiple forms.

During the purification of rabbit liver microsomal cytochrome P-450 (P-450LM), evidence was obtained for the occurrence of at least four distinct forms. These were distinguished by polyacrylamide gel electrophoresis after treatment with sodium dodecyl sulfate in the presence or absence of mercaptoethanol and were shown to have characteristic spectra as the reduced carbon monoxide complexes. They are designated by their relative electrophoretic mobilities. P-450LM2, which was purified to apparent homogeneity, is induced by phenobarbital and has a subunit molecular weight of 50,000. P-450LM4, which was also extensively purified, is induced by beta-naphthoflavone and has a molecular weight of 54,000. P-450LM1,7, which is induced neither by phenobarbital nor beta-naphthoflavone, is a mixtureMIXTURE OF ABOUT EQUAL AMOUNTS OF TWO FORMS WITH MOLECULAR WEIGHTS OF 47,000 AND 60,000 RESPECTIVELY. Some preparations were obtained containing primarily P-450LM1 or P-450LM7. Benzphetamine, ethylmorphine, and p-nitroanisole are hydroxylated preferentially by P-450LM2, and benzpyrene by P-450LM1,7. Biphenyl is hydroxylated in both positions 2 and 4 by all of the preparations, but the latter position is strongly favored by the action of P-450LM2. Testosterone is hydroxylated primarily in position 16alpha by P-450LM2 and in position 6beta by P-450LM1,7. Although the occurrence of additional forms of the cytochrome with highly similar electrophoretic behavior is not ruled out, it appears that the presence of these forms differing in subunit molecular weight may account for the variety of catalytic activities attributed to this pigment of liver microsomes.