Surgical treatment for cervical myelopathy in patients aged > 80 years

The surgical outcomes of 13 patients who were diagnosed with cervical spondylotic myelopathy were reviewed retrospectively. Mean patient age at surgery was 83 years. The severity of cervical spondylotic myelopathy was evaluated using the Japanese Orthopaedic Association score. Daily activities were evaluated using the Barthel index. The preoperative JOA score and Barthel index were 7.8 and 63.5, respectively. The mean JOA score and Barthel index maximum recovery rate were 35% and 24%, respectively. The results of this study imply that surgery for patients with cervical spondylotic myelopathy aged > 80 years is warranted.     

Postural reaction during maximum grasping maneuvers using a hand dynamometer in healthy subjects

The purpose of this study was to quantitatively evaluate spontaneous body sway during maximum grasping maneuver with a hand dynamometer, which we sometimes encounter in clinical practice. The postural reaction of the whole body during maximum grasping maneuver was analyzed in 26 right-handed healthy male volunteers using a three-dimensional motion analysis system (VICON system, Oxford Metrics, UK) and force plates. We found that the gravity center of the body moved toward the grasping side. Also, voluntary rotation of the trunk and flexion of the neck was observed during grasping on each side.     

Twice-daily administration of a long-acting angiotensin-converting enzyme inhibitor has greater effects on neurohumoral factors than a once-daily regimen in patients with chronic congestive heart failure

Although many clinical trials have evaluated the use of long-acting angiotensin-converting enzyme (ACE) inhibitors in patients with chronic congestive heart failure (CHF), there are no data regarding whether a once-daily or twice-daily regimen is preferable with respect to effects on the neuroendocrine system. To address this issue, the authors evaluated the comparative effects of the administration schedule on neurohumoral factors and autonomic nervous activity in patients with CHF. Thirty-two patients with mild compensated CHF received lisinopril (5-20 mg/d) orally either once a day (n = 17) or twice a day (n = 15) for more than 3 months. After this initial therapy, patients receiving a once-daily regimen switched to a twice-daily regimen and vice-versa, and patients were followed for an additional 3 months. Neurohumoral factors and the coefficient of variance in the electrocardiographic R-R interval (CVRR) were measured. Hemodynamic parameters, renal function, plasma concentrations of brain natriuretic peptide and aldosterone, and CVRR did not differ between the two regimens. However, the plasma concentration of norepinephrine was significantly lower, and plasma renin activity tended to be lower with the twice-daily regimen. These findings suggest that twice-daily administration of long-acting ACE inhibitors may have better effects on the neuroendocrine system than a once-daily regimen in patients with mild CHF.     

Effects of lithium and valproate on agonist-induced platelet intracellular calcium mobilization: relevance to myosin light chain kinase

Serotonin (5-HT)- or thrombin-stimulated platelet intracellular calcium (Ca) mobilization has been reported to be enhanced in patients with bipolar disorders. However, the mechanism of this enhancement is unknown. As a preliminary study, the authors examined the effects of a myosin light chain kinase (MLCK) inhibitor, 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9), and two drugs that are mainstays of treatment for bipolar disorder, lithium and valproate, on 5-HT- or thrombin-induced Ca increase in the platelets of normal subjects. When preincubated with 30 microM ML-9, Ca responses to both agonists were enhanced. Valproate showed a dose-dependent attenuation of agonist-induced intracellular Ca rise, both in the absence and presence of ML-9. Although lithium alone had no significant effect on the Ca increase, a high concentration of lithium significantly decreased Ca mobilization only in the presence of ML-9. These results suggest that the enhanced Ca response observed in bipolar disorder might be relevant to decreased function of MLCK and that the mechanism of action of lithium may include a compensatory effect on MLCK modulation.     

Regional analysis of differently phosphorylated tau proteins in brains from patients with Alzheimer's disease

Neurofibrillary tangles (NFT) in Alzheimer's disease (AD) are composed of abnormally phosphorylated tau proteins. Many phosphorylation sites have been reported in the AD brain, and NFT distribution was now roughly classified into 3 stages by Braak stage; this classification is based on pathological studies using the specific silver impregnation technique. The aim of our study was to examine the regional distribution of differently phosphorylated tau proteins with 5 site-specific monoclonal antibodies against the tau proteins, AT8, AT180, HT7, Tau2 and Tau5. We then compared our findings with those obtained from silver-stained NFT in an attempt to clarify the relationship between abnormal phosphorylation sites of the tau protein and NFT development. AT180 and AT8 labeled the highest and Tau2 the lowest density of NFT in any regions, while Tau5 and HT7 showed inconsistent distribution. In the limbic cortex, cornu ammonis, entorhinal cortex and cingulate cortex, silver-stained NFT density significantly correlated with density of NFT labeled with the 5 anti-tau antibodies, but cerebral isocortices showed heterogenous patterns of tau-positive NFT. Quantification of tau-positive regional NFT density showed that the AD-associated phosphorylation process progresses from the C-terminal to the N-terminal of the amino acid sequence, and correlation of Gallyas-stained NFT density with tau-labeled NFT density was more significant in the limbic cortices than the cerebral isocortices, which implies that stereotypical phosphorylation occurs in the limbic structures.     

Initiation of therapy: when and what to start with?

Introduction of HAART (highly active antiretroviral therapy) has resulted in dramatic reductions in AIDS-related opportunistic complications and death. We have faced, however, severe complications due to HAART such as lactic acidosis and lipodystrophy syndrome. Regimens currently employed in the treatment may be complex, require multiple drugs to take, difficult to tolerate owing to adverse effects, and decrease level of quality of life in some patients. Decisions about when and with what to initiate HAART must take into account the risk-benefit ratio associated with the therapy. In this article, issues that must be considered in determining timing of initiation and choice of anti-retroviral drugs are discussed.     

Salivary cystatins induce interleukin-6 expression via cell surface molecules in human gingival fibroblasts

Recently, family 2 cystatins have been demonstrated to upregulate interleukin-6 (IL-6) production by human gingival fibroblasts [Biol. Chem. 381 (2000) 1143]. To elucidate the mechanism of the IL-6 inducing activity of cystatins, we tested NF-kappa B activation with salivary cystatins SA1 and SA2-stimulated human gingival fibroblast whole cell lysates. The IL-6 production by human fibroblasts in response to these cystatins was inhibited by tyrosine kinase inhibitors and an inhibitor of NF-kappa B activation. The IL-6 inducing activity of the cystatins was depressed by the anti-CD58 monoclonal antibody. These findings supply evidence that cystatins SA1 and SA2 adhere to human fibroblasts and that the event results in tyrosine phosphorylation and upregulation of the release of IL-6 mediated enhancement of NF-kappa B activity.