Treatment of knee osteoarthritis: relationship of clinical features of joint inflammation to the response to a nonsteroidal antiinflammatory drug or pure analgesic.

Our randomized double blinded comparison of acetaminophen versus analgesic and antiinflammatory doses of ibuprofen in the treatment of 182 subjects with knee osteoarthritis (OA) systematically evaluated soft tissue tenderness and joint swelling. Improvement in these signs of joint inflammation was associated with lessening of disability (p = 0.02), and reduction in rest pain (p = 0.07), but not with the drug treatment regimen. Thus, joint tenderness and swelling, presumptive evidence of synovitis, may not be a priori indications for use of an antiinflammatory drug, or predict greater responsiveness to treatment with an antiinflammatory drug than to a pure analgesic, in symptomatic treatment of patients with knee OA.     

Frontotemporal dementia and parkinsonism linked to chromosome 17 with the N279K tau mutation

We present a case of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) harboring the N279K mutation in the MAPT gene from the family known as pallido‐ponto‐nigral degeneration (PPND). This 49‐year‐old man was followed for 17 years. He presented at age 41 years with left leg stiffness and en‐bloc turning. During the course of his illness he developed a constellation of symptoms including parkinsonism, pyramidal signs, vertical gaze palsy, dysphagia, dystonia, personality and cognitive dysfunction, weight loss and mutism. Gross neuropathological examination showed mild atrophy of the cerebral cortex, hippocampal formation, amygdala, thalamus, subthalamic nucleus and depigmentation of the substantia nigra. Microscopy revealed neuronal loss and gliosis in the same regions. Tau immunohistochemistry showed pretangles, numerous threads, grain‐like structures and oligodendroglial tau‐positive inclusions (“coiled bodies”). In the spinal cord the tau pathology was more abundant in gray than white matter. Pretangles and threads were present in the anterior and, to a lesser extent, in the posterior horns. FTDP‐17 should be suspected in patients with a history of familial parkinsonism combined with behavioral and cognitive changes, onset before age 65 years and an aggressive clinical course.     

Learning and memory function in men with untreated blood pressure elevation

Learning and memory processes were compared in 20 men with untreated blood pressure elevation and 20 normotensive control subjects matched for age, education, and average alcohol consumption. Subjects were identified from a larger sample of 469 factory workers who had participated in an epidemiologic investigation. Three measures (e.g., Symbol-Digit Learning Test [Ryan & Butters, 1980] and Visual Reproductions-Immediate and Delayed Recall [Wechsler, 1945] ) from a previously administered test battery were chosen for comparison on the basis of statistical power calculations. Results indicate that relative to normotensive control subjects, men with elevated blood pressure performed more poorly on all three tests. These results are independent of other known influences on neuropsychological performance and are likely a consequence of elevated blood pressure.     

Cerebral vascular effects of angiotensin II: new insights from genetic models.

Very little is known regarding the mechanisms of action of angiotensin II (Ang II) or the consequences of Ang II-dependent hypertension in the cerebral circulation. We tested the hypothesis that Ang II produces constriction of cerebral arteries that is mediated by activation of AT1A receptors and Rho-kinase. Basilar arteries (baseline diameter approximately 130 microm) from mice were isolated, cannulated and pressurized to measure the vessel diameter. Angiotensin II was a potent constrictor in arteries from male, but not female, mice. Vasoconstriction in response to Ang II was prevented by an inhibitor of Rho-kinase (Y-27632) in control mice, and was reduced by approximately 85% in mice deficient in expression of AT1A receptors. We also examined the chronic effects of Ang II using a model of Ang II-dependent hypertension, mice which overexpress human renin (R+) and angiotensinogen (A+). Responses to the endothelium-dependent agonist acetylcholine were markedly impaired in R+A+ mice (P<0.01) compared with controls, but were restored to normal by a superoxide scavenger (PEG-SOD). A-23187 (another endothelium-dependent agonist) produced vasodilation in control mice, but no response or vasoconstriction in R+A+ mice. In contrast, dilation of the basilar artery in response to a NO donor (NONOate) was similar in R+A+ mice and controls. Thus, Ang II produces potent constriction of cerebral arteries via activation of AT1A receptors and Rho-kinase. There are marked gender differences in cerebral vascular responses to Ang II. Endothelial function is greatly impaired in a genetic model of Ang II-dependent hypertension via a mechanism that involves superoxide.     

Pathogenesis of postoperative hyponatraemia following correction of scoliosis in children

Eight paediatric patients undergoing major surgery for correction of scoliosis who were treated postoperatively with hypotonic saline and 5% dextrose have been studied. Plasma sodium, renin and aldosterone, and urine volume, sodium and osmolality were measured. These patients had an impaired ability to excrete a sodium-free water load. In the first 60 h urine volume remained reduced, while in the first 36 h urine sodium remained concurrently high. If the first 36 h postoperation are considered, the sodium-free water given was quantitatively retained and the serum sodium at 36 h was significantly correlated with the amount of free water given (P less than 0.01). To minimize postoperative hyponatraemia and the associated shift of water into the brain causing cerebral oedema, it is recommended that no more than 50 ml/kg sodium-free water be given until urine sodium falls and volume increases.     

Building bridges between neural models and complex decision making behaviour.

Diffusion processes, and their discrete time counterparts, random walk models, have demonstrated an ability to account for a wide range of findings from behavioural decision making for which the purely algebraic and deterministic models often used in economics and psychology cannot account. Recent studies that record neural activations in non-human primates during perceptual decision making tasks have revealed that neural firing rates closely mimic the accumulation of preference theorized by behaviourally-derived diffusion models of decision making. This article bridges the expanse between the neurophysiological and behavioural decision making literatures specifically, decision field theory [Busemeyer, J. R. & Townsend, J. T. (1993). Decision field theory: A dynamic-cognitive approach to decision making in an uncertain environment. Psychological Review, 100, 432-459], a dynamic and stochastic random walk theory of decision making, is presented as a model positioned between lower-level neural activation patterns and more complex notions of decision making found in psychology and economics. Potential neural correlates of this model are proposed, and relevant competing models are also addressed.     

A sports medicine clinic in the community.

We report the attempt to set up a mini sports medicine clinic in a health centre resourced by a Department of Community Medicine. The type of problems seen are similar to those reported by other clinics. On the results of this pilot project, we believe it would be possible to establish similar clinics in health centres elsewhere in the United Kingdom. The National Health Service resources required are minimal, but the benefits to local communities are considerable.     

High tech home care: a look at a success story.

The expansion of technology has allowed patients to receive intravenous therapy at home. This case study discusses the problems of a patient with diabetes mellitus and malignant otitis externa. This patient received intravenous therapy for the last 3 years of his life. In spite of several hospitalizations, he was able to return and remain home until his death. Management of the patient's discharge and home care seemed to be a major factor in his ability to remain in the community.