Activities of various quinolone antibiotics against Mycobacterium leprae in infected mice.

Previously, pefloxacin and ofloxacin were found to be active against Mycobacterium leprae in vitro, in experimental animals, and in clinical trials of lepromatous leprosy patients. In this study, we compared certain more recently developed fluoroquinolones (lomefloxacin, PD 124816, WIN 57273, temafloxacin, and sparfloxacin) with pefloxacin and ofloxacin in M. leprae-infected mice at doses of 50, 150, and 300 mg/kg given five times weekly. All seven of the fluoroquinolones studies were active against M. leprae; temafloxacin and sparfloxacin were the most active, being fully bactericidal at all three dosage schedules. Additionally, sparfloxacin was found to be fully bactericidal at 15 and 30 mg/kg given five times weekly.     

The art of gene therapy for glioma： a review of the challenging road to the bedside

Glioblastoma muhiforme （GBM） is a highly invasive brain tumour that is unvaryingly fatal in humans clesplte even aggres- sive therapeutic approaches such as surgical resection followed by chemotherapy and radiotherapy. Unconventional treatment options such as gene therapy provide an intriguing option for curbing glioma related deaths. To date, gene therapy has yielded encouraging results in preclinical animal models as well as promising safety profiles in phase I clinical trials, but has failed to demonstrate significant therapeutic efficacy in phase III clinical trials. The most widely studied antiglioma gene therapy strategies are suicide gene therapy, genetic immuno- therapy and oncolytic virotherapy, and we have attributed the challenging transition of these modalities into the clinic to four major road- blocks ： （ 1 ） anatomical features of the central nervous system, （2） the host immune system, （3） heterogeneity and invasiveness of GBM and （4） limitations in current GBM animal models. In this review, we discuss possible ways to jump these hurdles and develop new gene therapies that may be used alone or in synergy with other modalities to provide a powerful treatment option for patients with GBM.     

Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells

During the innate response to many inflammatory and infectious stimuli, dendritic cells (DCs) undergo a differentiation process termed maturation. Mature DCs activate antigen-specific naive T cells. Here we show that both immature and mature DCs activate resting human natural killer (NK) cells. Within 1 wk the NK cells increase two-- to fourfold in numbers, start secreting interferon (IFN)-gamma, and acquire cytolytic activity against the classical NK target LCL721.221. The DC-activated NK cells then kill immature DCs efficiently, even though the latter express substantial levels of major histocompatibility complex (MHC) class I. Similar results are seen with interleukin (IL)-2--activated NK cell lines and clones, i.e., these NK cells kill and secrete IFN-gamma in response to immature DCs. Mature DCs are protected from activated NK lysis, but lysis takes place if the NK inhibitory signal is blocked by a human histocompatibility leukocyte antigen (HLA)-A,B,C--specific antibody. The NK activating signal mainly involves the NKp30 natural cytotoxicity receptor, and not the NKp46 or NKp44 receptor. However, both immature and mature DCs seem to use a NKp30 independent mechanism to act as potent stimulators for resting NK cells. We suggest that DCs are able to control directly the expansion of NK cells and that the lysis of immature DCs can regulate the afferent limb of innate and adaptive immunity.     

Effects of sensory cueing on voluntary arm use for patients with chronic stroke: a preliminary study

Fong KN, Lo PC, Yu YS, Cheuk CK, Tsang TH, Po AS, Chan CC. Effects of sensory cueing on voluntary arm use for patients with chronic stroke: a preliminary study.

Objective

To investigate the effect of a 2-week program of sensory cueing in which vibration induces the use of the paretic upper extremity in participants with chronic stroke in the community.

Design

A single-group longitudinal study.

Setting

Self-help organizations.

Participants

A convenience sample of 16 community residents (N=16) with chronic unilateral stroke and mild to moderate upper-extremity impairment stratified by the severity of their paretic arm function, measured by using the Functional Test for the Hemiplegic Upper Extremity (FTHUE).

Interventions

Participants engaged in repetitive upper-extremity task practice for 2 weeks while wearing an ambulatory sensory cueing device on their affected hand for 3 hours a day.

Main Outcome Measures

Evaluations were conducted on the 3 occasions of pretest (1 day before training), posttest (immediately after training), and follow-up test (2 weeks after training) by using the following behavioral measures of paretic upper-extremity performance: the Action Research Arm Test (ARAT), the Box and Block Test, the Fugl-Meyer Assessment (FMA), the FTHUE, power and pinch grips, the Motor Activity Log assessment of arm use, and kinematic data obtained from the device.

Results

Significant differences were found in ARAT and FMA scores among the pretest, posttest, and follow-up evaluations. The lower functioning group achieved a more significant increase in overall upper-extremity score than in the hand score for the FMA.

Conclusion

A combination of sensory cueing and movement-based strategies is useful and feasible in improving paretic upper-extremity performance in participants with chronic stroke; however, additional studies with a larger sample size and longer treatment period in a randomized controlled trial would be beneficial.     

Analysis of multilocus sequence typing schemes for 35 different bacteria revealed that gene loci of 10 bacteria could be replaced to improve cost-effectiveness

Although multilocus sequence typing (MLST) has been widely used for bacterial typing, the contribution of the gene loci to the discriminatory power of each MLST scheme is unknown. We analyzed the discriminatory powers of 36 MLST schemes using all combinations of the 7 loci and contributions of each locus to the schemes. In 10 schemes, sequencing 6 loci can achieve the discriminatory powers of 7 loci. For the other 26 schemes, the median marginal increase in discriminatory power when 7 instead of 6 loci were used is 0.0004. Sequencing the 7 loci of 50 strains each of Pseudomonas aeruginosa and Acinetobacter baumannii revealed that the discriminatory power for P. aeruginosa was 0.9861 when either 6 (without trp) or 7 loci were used and that for A. baumannii was 0.9363 when 5, 6, or 7 loci were used. Genes that have no additional or minimal contribution to the overall discriminatory powers should be replaced.     

Stabilization and regression of albuminuria in Chinese patients with type 2 diabetes: A one-year randomized study of valsartan versus enalapril

This study was designed to compare the short-term (1-y) tolerability and antiproteinuric efficacy of enalapril and valsartan in patients with type 2 diabetes. Fortytwo patients with normal renal function or early-stage nephropathy were recruited in Hong Kong and randomized to valsartan 80 mg/day or enalapril 5 mg/day; the doses were increased to 160 mg and 10 mg daily, respectively, as tolerated. Early-morning urine was analyzed for albumin and creatinine and 24-hour urinary albumin excretion at baseline and 1 year after therapy began. Twenty-two patients were randomized to valsartan and 20 to enalapril. The 2 treatment groups were similar in terms of age, sex distribution, and duration of diabetes or hypertension. Blood pressure decreased to a similar extent (−2.5% to −5.0%) with each drug. Similarly, the 24-hour urinary albumin excretion decreased by 5% to 6% with each drug. The albumin-creatinine ratio in early-morning urine samples and plasma creatinine levels decreased in the valsartan group and increased in the enalapril group, but the difference was not significant. Plasma potassium levels were stable in both groups at the end of study. Cough was reported by 7 (35%) patients receiving enalapril and none of those receiving valsartan (P=.003). In conclusion, enalapril and valsartan both reduced blood pressure and albuminuria to a similar extent with 1 year of therapy in Chinese patients with type 2 diabetes and normal renal function or early-stage nephropathy. Fewer adverse events were reported with valsartan, but both drugs appear to be relatively safe.     

Reliability and validity study of Silver's test for Hong Kong-Chinese with dementia

There has been great concern regarding the functional and cognitive abilities of elderly people in performing activities of daily living. 'Silver's test' has been widely used to assess the abilities and mental functions of the aging population in Hong Kong. The purpose of this study was to establish the validity and reliability of a Chinese version of Silver's test (CVST) for Hong Kong-Chinese with dementia. A sample of 78 (21 male and 57 female) elderly subjects was recruited through two-stage cluster sampling. They were administered both the CVST and the Chinese Mini-Mental Status Examination (MMSE). Spearman rank-order correlation coefficient (rs) and intra-class correlation coefficient (ICC) showed that the CVST had a very good inter-rater reliability (rs=0.9573, P=0.000; ICC=0.9966) and test-retest reliability (rs=0.9693, P<0.001; ICC=0.9769). The internal consistency of the test was satisfactory (Cronbach's alpha=0.8396). The Mann-Whitney U-test showed that the CVST could discriminate the demented elderly subjects from the non-demented subjects, suggesting the best cut-off score to be 34, yielding a high sensitivity of 96.4% and equally good specificity of 96.7%. There was also a high positive correlation (rs=0.9218, P<0.001) between the total scores of the CVST and the MMSE. Suggestions for the modification of Silver's test were also made. In conclusion, the initial reliability and validity of the CVST has been established for Hong Kong-Chinese with dementia. It appears to be a sensitive and practical cognitive assessment acceptable to this population.