Effects of balance training with visual feedback during mechanically unperturbed standing on postural corrective responses

Evidence of a non-specific effect of balance training on postural control mechanisms suggests that balance training during mechanically unperturbed standing may improve postural corrective responses following external perturbations. The purpose of the present study was to examine kinematics of the trunk as well as muscular activity of the lower leg and paraspinal muscles during postural responses to support-surface rotations after short-term balance training. Experiments were performed in control (n=10) and experimental (n=11) groups. The experimental group participated in the 3-day balance training program. During the training, participants stood on a force platform and were instructed to voluntarily shift their center of pressure in indicated directions as represented by a cursor on a monitor. Postural perturbation tests were executed before and after the training period: the slow and fast 10° dorsiflexions were induced at angular velocities of approximately 50°s(-1) and 200°s(-1), respectively. In the experimental group, the amplitude of the trunk displacements during slow and fast perturbations was up to 33.4% and 26.7% lower, respectively, following the training. The magnitude of the muscular activity was reduced in both the early and late components of the response. The kinematic parameters and muscular responses did not change in the control group. The results suggest that balance training during unperturbed standing has the potential to improve postural corrective responses to unexpected balance perturbation through (1) improved neuromuscular coordination of the involved muscles and (2) adaptive neural modifications on the spinal and cortical levels facilitated by voluntary activity.     

Accumulation of Amphotericin B in Human Macrophages Enhances Activity against Aspergillus fumigatus Conidia: Quantification of Conidial Kill at the Single-Cell Level

A cytofluorometric assay that allowed assessment of damage to phagocytosed Aspergillus fumigatus conidia at the single-cell level was developed. After ingestion by monocyte-derived macrophages (MDMs), conidia were reisolated by treatment of the cells with streptolysin O, a pore-forming toxin with lytic properties on mammalian cells but not on fungi. The counts obtained by staining of damaged conidia with propidium iodide and quantification by cytofluorometry correlated with colony counts. By the use of this method, we demonstrate that MDMs differentiated in vitro by low-dose granulocyte-macrophage colony-stimulating factor and gamma interferon have only a limited capacity to damage Aspergillus conidia in vitro. The killing rate 12 h after phagocytosis was found to be only 10 to 15%. However, intracellular loading of the phagocytes with amphotericin B (AmB) dose dependently enhanced the anticonidial activity. Preincubation of macrophages with only 1 μg of AmB per ml resulted in an uptake of 18 fg of AmB/cell, leading to killing rates of 50 to 60%. The experimental protocol provides a new tool for the rapid quantification of anticonidial activity against A. fumigatus in vitro. Intracellular accumulation of AmB may represent an important factor underlying the efficacy of this antifungal drug in the prophylaxis and treatment of Aspergillus infections.     

Enhancing the Effectiveness of Abortive Therapy: A Controlled Evaluation of Self-Management Training

Research suggests that approximately one half of recurrent headache sufferers fail to adhere properly to drug treatment regimens with as many as two thirds of patients failing to make optimal use of abortive medications such as ergotamine. In spite of these findings there are no controlled studies that have attempted to evaluate methods for improving adherence to drug regimens for the treatment of chronic headache disorders. In an initial effort to address this adherence problem thirty-four recurrent migraine sufferers were randomized to abortive therapy with ergotamine tartrate plus caffeine (standard abortive therapy) or to standard abortive therapy accompanied by a brief educational intervention designed to facilitate the migraine sufferer's effective use of ergotamine. Patients who received the adjunctive educational intervention attempted to abort a greater percentage of their migraine attacks (70% vs 40%) and showed larger reduction in headache activity (e.g., 40% vs 26% reduction in month two of treatment). However, patients in both treatment groups used similar amounts of abortive medication when attempting to abort a migraine attack and showed similar reductions in analgesic medication use with abortive therapy. There results suggest that brief educational interventions designed to address the problem of patient adherence may yield significant improvements in standard therapies. We argue that such educational interventions deserve more attention in the headache treatment literature than they have received to date.     

Potent and selective inhibition of human cytomegalovirus replication by 1263W94, a benzimidazole L-riboside with a unique mode of action

Benzimidazole nucleosides have been shown to be potent inhibitors of human cytomegalovirus (HCMV) replication in vitro. As part of the exploration of structure-activity relationships within this series, we synthesized the 2-isopropylamino derivative (3322W93) of 1H-beta-D-ribofuranoside-2-bromo-5,6-dichlorobenzimidazole (BDCRB) and the biologically unnatural L-sugars corresponding to both compounds. One of the L derivatives, 1H-beta-L-ribofuranoside-2-isopropylamino-5,6-dichlorobenzimidazole (1263W94), showed significant antiviral potency in vitro against both laboratory HCMV strains and clinical HCMV isolates, including those resistant to ganciclovir (GCV), foscarnet, and BDCRB. 1263W94 inhibited viral replication in a dose-dependent manner, with a mean 50% inhibitory concentration (IC(50)) of 0.12 +/- 0.01 microM compared to a mean IC(50) for GCV of 0.53 +/- 0.04 microM, as measured by a multicycle DNA hybridization assay. In a single replication cycle, 1263W94 treatment reduced viral DNA synthesis, as well as overall virus yield. HCMV mutants resistant to 1263W94 were isolated, establishing that the target of 1263W94 was a viral gene product. The resistance mutation was mapped to the UL97 open reading frame. The pUL97 protein kinase was strongly inhibited by 1263W94, with 50% inhibition occurring at 3 nM. Although HCMV DNA synthesis was inhibited by 1263W94, the inhibition was not mediated by the inhibition of viral DNA polymerase. The parent benzimidazole D-riboside BDCRB inhibits viral DNA maturation and processing, whereas 1263W94 does not. The mechanism of the antiviral effect of L-riboside 1263W94 is thus distinct from those of GCV and of BDCRB. In summary, 1263W94 inhibits viral replication by a novel mechanism that is not yet completely understood.     

An open-label, uncontrolled, prospective study of the effects of atorvastatin 10 mg on low-density lipoprotein cholesterol levels in chinese adults with coronary artery disease and hypercholesterolemia

Background: A high level of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for coronary artery disease (CAD). Evidence shows that lowering LDL-C improves the outcomes of patients with CAD. Atorvastatin is an established drug for the treatment of hypercholesterolemia.Objective: The purpose of this open-label, uncontrolled, prospective study was to assess the effectiveness of treatment with atorvastatin 10 mg/d for 18 weeks in achieving the target level of LDL-C (<2.6 mmol/L [<100 mg/dL]) established by the National Cholesterol Education Program (NCEP) (United States) for patients with established CAD and hypercholesterolemia.Methods: Chinese patients with CAD, hypercholesterolemia (defined as a baseline LDL-C level between 3.4 and 5.2 mmol/L [131-201 mg/dL]), and body mass index <30 kg/m² were eligible. Atorvastatin 10 mg/d was given to each patient for 18 weeks. Lipid profiles were checked at 6, 12, and 18 weeks. To assess the extent of the achievement of NCEP LDL-C target levels, patients were categorized into 3 groups retrospectively according to baseline LDL-C level: group 1, 3.4 to 4.0 mmol/L (131-154 mg/dL); group 2, 4.01 to 4.6 mmol/L (155-178 mg/dL); and group 3, 4.61 to 5.2 mmol/L (179-201 mg/dL).Results: A total of 63 patients (50 men, 13 women; mean age, 64.3 years) were enrolled. Significant decreases in total cholesterol (31.3% at week 18), LDL-C (42.9% at week 18), and triglycerides (21.8% at week 18) from baseline levels were found at 6, 12, and 18 weeks of treatment (P < 0.001 for all). The changes in high-density lipoprotein cholesterol levels were nonsignificant. In group 1, 83.3% of patients met the target level of LDL-C; group 2, 87.5%; group 3, 37.5%; groups 1 and 2 combined, 85.2%. Atorvastatin 10 mg/d was well tolerated. Clinical adverse events were mild and transient; no severe adverse events were reported. One patient (1.6%) developed an elevated alanine aminotransferase level and withdrew. Sixty-two of 63 patients (98.4%) completed the study.Conclusions: In this group of Chinese patients with CAD and hypercholesterolemia treated with atorvastatin 10 mg/d for 18 weeks, 85.2% of patients with a baseline LDL-C level of 3.4 to 4.6 mmol/L achieved the NCEP target LDL-C level of <2.6 mmol/L, suggesting that atorvastatin 10 mg/d is efficacious in preventing secondary CAD.     

A training course for psychiatric nurses in Russia

This article describes the impact on mental health services in Russia of a training course for psychiatric nurses in the management of aggression. This project, which is part of a seven-year international partnership between mental health professionals in the UK and Russia, demonstrates the importance of nurse training to effect change in healthcare organisations.