An investigation of risk factors for symptomatic osteoarthritis of the knee in women using a life course approach.

STUDY OBJECTIVE: To explore risk factors for symptomatic knee osteoarthritis (OAK) in women, which included wearing high heeled shoes. DESIGN: Matched case-control study. Exposure information obtained by interview, included details about past footwear. Self reported weight and height data obtained representing when women left school, were aged 36-40 and were aged 51-55. Regular work activities (including periods when homemaker or carer), smoking, and hormone related data gathered using a life-grid. SETTING: Interviews in participants' homes. Cases identified from orthopaedic hospital surgical waiting list, controls identified by general practitioners (GPs) PARTICIPANTS: Women aged 50 to 70 years. Cases awaiting knee replacement surgery. Controls, who had no past knee surgery and no knee pain in the past three years, were matched for age and GP. Altogether 111 eligible women were interviewed (29 cases, 82 controls). MAIN RESULTS: Univariate analyses identified several significant associations with OAK including past knee injury, arthritis of the feet, heavy smoking, being overweight (BMI 25 or above) and various occupational activities. Virtually all measures of high heeled shoes use were associated with reduced risk of OAK, although none of these findings were statistically significant. In multivariate analysis only BMI 25 or above at age 36-40 remained significantly associated with OAK (OR 36.4, 95% CI 3.07 to 432, p=0.004), although weak evidence suggested certain occupational activities might increase risk. Weight gain in early adult life was particularly pronounced among cases. CONCLUSIONS: Being overweight before the age of 40 considerably increased the risk of subsequent symptomatic OAK in women. Wearing high heeled shoes did not.

Effect on cardiac sympathetic nerve activity of phenylephrine microinjected into the cat intermediolateral cell column.

1. In anaesthetized cats the effect of the alpha 1-adrenoceptor agonist phenylephrine, microinjected into the left intermediolateral cell column of the spinal cord at the third thoracic level, was studied on left inferior cardiac nerve activity. 2. Microinjection of 100 nl of 10 or 40 mM-phenylephrine caused increases in inferior cardiac nerve activity in fifteen out of seventeen experiments. 3. The microinjection of the alpha 1-adrenoceptor antagonist alfuzosin (100 nl of 10 mM) into the intermediolateral cell column antagonized the excitatory response elicited by phenylephrine. 4. Increases in inferior cardiac nerve activity produced by glutamate and 5-hydroxytryptamine microinjected into the intermediolateral cell column were not antagonized by alfuzosin. 5. It is concluded that activation of alpha 1-adrenoceptors in the region of the intermediolateral cell column can cause an increase in the firing rate of sympathetic preganglionic neurones which innervate postganglionic neurones projecting into the inferior cardiac nerve.

[3H]prazosin binding in the intermediolateral cell column and the effects of iontophoresed methoxamine on sympathetic preganglionic neuronal activity in the anaesthetized cat and rat.

The autoradiographic localization of [3H]prazosin (alpha 1-adrenoceptor ligand) binding sites was determined in cat spinal cord sections. High levels of [3H]prazosin binding were found in the intermediolateral cell column (IML) at thoracic and lumbar levels. The iontophoresis of the alpha 1-adrenoceptor agonist methoxamine onto sympathetic preganglionic neurones (SPNs) in anaesthetized cats and rats caused excitation of 8 cat SPNs and 13 rat SPNs. These results suggest an excitatory role for some of the catecholaminergic innervation of the IML.