Ultrasonographic measurement of the median nerve in patients with rheumatoid arthritis without symptoms or signs of carpal tunnel syndrome

OBJECTIVES: Ultrasonography (US) has shown increased cross-sectional area of the median nerve in carpal tunnel syndrome (CTS). Knowledge of the normal distribution of the areas is a prerequisite to evaluate pathology. Presently, the distribution of cross-sectional areas of the median nerve was explored in patients with rheumatoid arthritis (RA). METHODS: The median nerves of patients with RA having no symptoms or signs of CTS were examined with bilateral US at the entrance of the carpal tunnel. RESULTS: A total of 154 patients with RA were included. The median nerve was divided in 11.7% of the hands. The mean (SD) cross-sectional areas of the undivided median nerves were not significantly different on either sides (8.3 (1.5) mm(2) on the right side and 8.3 (1.4) mm(2) on the left side). The areas of the examined 308 median nerves ranged from 5.0 to 12.8 mm(2), with the 97.5 centile being 11.1 mm(2). Areas >10.0 mm(2) were found in 10% of the patients. CONCLUSIONS: The mean cross-sectional areas of the median nerve in patients with RA were similar to those reported in healthy controls. However, 10% of the patients had values that overlap with areas commonly reported in patients with mild idiopathic CTS.     

Activation of a presynaptic glutamate transporter regulates synaptic transmission through electrical signaling

Whereas glutamate transporters in glial cells and postsynaptic neurons contribute significantly to re-uptake of synaptically released transmitter, the functional role of presynaptic glutamate transporters is poorly understood. Here, we used electrophysiological recording to examine the functional properties of a presynaptic glutamate transporter in rat retinal rod bipolar cells and its role in regulating glutamatergic synaptic transmission between rod bipolar cells and amacrine cells. Release of glutamate activated the presynaptic transporter with a time course that suggested a perisynaptic localization. The transporter was also activated by spillover of glutamate from neighboring rod bipolar cells. By recording from pairs of rod bipolar cells and AII amacrine cells, we demonstrate that activation of the transporter-associated anion current hyperpolarizes the presynaptic terminal and thereby inhibits synaptic transmission by suppressing transmitter release. Given the evidence for presynaptic glutamate transporters, similar mechanisms could be of general importance for transmission in the nervous system.     

Physical therapy interventions for patients with osteoarthritis of the knee: an overview of systematic reviews

Patients with osteoarthritis of the knee are commonly treated by physical therapists. Practice should be informed by updated evidence from systematic reviews. The purpose of this article is to summarize the evidence from systematic reviews on the effectiveness of physical therapy for patients with knee osteoarthritis. Systematic reviews published between 2000 and 2007 were identified by a comprehensive literature search. We graded the quality of evidence across reviews for each comparison and outcome. Twenty-three systematic reviews on physical therapy interventions for patients with knee osteoarthritis were included. There is high-quality evidence that exercise and weight reduction reduce pain and improve physical function in patients with osteoarthritis of the knee. There is moderate-quality evidence that acupuncture, transcutaneous electrical nerve stimulation, and low-level laser therapy reduce pain and that psychoeducational interventions improve psychological outcomes. For other interventions and outcomes, the quality of evidence is low or there is no evidence from systematic reviews.     

Risk and protective factors for psychological distress among adolescents: a family study in the Nord-Trøndelag Health Study

Purpose  

The study aimed to investigate potential adolescent and parental psychosocial risk and protective factors for psychological distress among adolescents and, in addition, to examine potential gender and age differences in the effects of risk factors on adolescent psychological distress.     

Good long-term efficacy of pallidal stimulation in cervical dystonia: a prospective, observer-blinded study

Background and purpose: Deep brain stimulation of the internal globus pallidus (GPi‐DBS) is established as an effective treatment of primary generalised dystonia in controlled studies. In cervical dystonia (CD), only one previous study has reported observer‐blinded outcome assessment of long‐term GPi‐DBS, with 1‐year follow‐up. Methods: In this prospective, single‐centre study, eight patients with CD (7 women:1 man, 4 focal:4 segmental) treated with bilateral GPi‐DBS for median (range) 30 (12–48) months, were evaluated by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS; Severity, Disability and Pain scores), the Short‐Form Health Survey‐36 (SF‐36), and the Becks Depression Index in an open design. In addition, a blinded rater assessed the TWSTRS Severity score from videos obtained preoperatively and at the last follow‐up. Results: In the blinded evaluation, median (range) TWSTRS Severity score improved from 25 (19–30) to 8 (4–23) (P = 0.028), thus a 70% (23–82) score reduction. In the open evaluation, median Severity score improvement at the last follow‐up was 73%, representing a significant further improvement from 50% at 6 months. The Disability and Pain scores improved by median 91% and 92%, respectively, and the SF‐36 subdomain scores improved significantly. A reversible right hemiparesis and aphasia occured in one patient 4 days postoperatively, because of reversible oedema around the left electrode. No other serious adverse effects and no permanent morbidity were observed. Conclusions: This single‐blinded study shows good long‐term efficacy of GPi‐DBS in CD patients and supports using this treatment in those who have insufficient response to medical treatment.     

西藏自治区1976-2010年甲、乙类传染病流行趋势分析

目的 了解西藏自治区1976-2010年甲、乙类传染病的流行趋势,为该地区的传染病防治工作提供参考依据。方法 收集西藏自治区1976年1月-2010年12月甲、乙类传染病的疫情报告数据,根据各年的人口数计算相关传染病的发病率、死亡率和病死率,分析其流行趋势。结果 西藏自治区甲、乙类传染病的总发病率、死亡率和病死率分别从1976年的2 572.20/10万、10.49/10万和0.41%下降到2010年的530.19/10万、1.67/10万和0.31%,发病率、死亡率和病死率总体均呈下降趋势（均P<0.05）;1976-2010年西藏自治区发病率居于前5位的甲、乙类传染病依次为细菌性痢疾（909.01/10万）、麻疹（194.06/10万）、百日咳（92.49/10万）、肺结核（76.83/10万）、病毒性肝炎（60.81/10万）,占甲、乙类传染病报告数的82.31%;死亡率居于前5位的甲、乙类传染病依次为病毒性肝炎（7.78/10万）、细菌性痢疾（3.32/10万）、麻疹（2.26/10万）、百日咳（0.89/10万）和流行性乙型脑炎（0.67/10万）,占甲乙类传染病报告数的95.86%;病死率居于前5位的甲、乙类传染病依次为鼠疫（56.32%）、艾滋病（27.27%）、炭疽（13.92%）、病毒性肝炎（12.79%）和流行性乙型脑炎（10.84%）。结论 西藏自治区甲、乙类传染病的发病率、死亡率和病死率总体上均呈下降趋势,但细菌性痢疾、麻疹、百日咳、肺结核、病毒性肝炎、流行性乙型脑炎、鼠疫、艾滋病、炭疽仍为西藏自治区应重点防治的甲、乙类传染病。     

Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population

Sertraline is a commonly used SSRI antidepressant drug, metabolized by CYP2C19 and CYP2B6, that exhibits a substantial interindividual variation in clinical response, of which only a part can be attributed to known genetic variants. In the current study we have examined the role of a newly discovered ultrarapid CYP2C:TG haplotype and CYP2B6 variants in order to identify the possible missing heritability for such variation in sertraline response in a large patient population (n = 840). Compared to the reference group (CYP2C19*1/*1, n = 160), sertraline exposure was increased by 128% in CYP2C19 PMs (n = 29, p < 0.001) but decreased by about 20% in CYP2C19 ultrarapid metabolizers (Ums) (homozygous carriers of CYP2C19*17 and/or CYP2C:TG haplotype) with the diplotypes CYP2C19*17/*17, CYP2C:TG/TG, or CYP2C19*17/CYP2C:TG (n = 135, p < 0.003, p = 0.022, p < 0.003, respectively). Interestingly, in patients carrying the increased function CYP2B6*4 allele, and also carrying the CYP2C19*17 and CYP2C:TG alleles (n = 10), sertraline exposure was 35.4% lower compared to the reference group, whereas in subjects being poor metabolizers (PM) in both the CYP2C19 and CYP2B6 gene, the sertraline concentrations were raised by 189%. In summary, the CYP2C19 variants including the CYP2C:TG haplotype had a significant impact on sertraline metabolism, as well as the CYP2B6*4, *6, and *9 alleles. Knowing the CYP2B6 and CYP2C19 genotype, including the CYP2C:TG haplotype status, can prospectively be useful to clinicians in making more appropriate sertraline dosing decisions

Study highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Sertraline is a commonly used antidepressant subjected to metabolism by multiple enzymes with CYP2C19 playing a key role along with CYP2B6 and CYP3A4. Previous pharmacogenetic studies have reported significant effects of CYP2C19 and CYP2B6 genotypes on sertraline concentration, but with inconsistent findings probably reflecting that the concurrent effects of the genotypes have not been investigated in a large patient population. Furthermore, the studies have not accounted for the recently discovered CYP2C:TG haplotype associated with increased CYP2C19‐mediated metabolism.

• WHAT QUESTION DID THIS STUDY ADDRESS?

Our study investigated the impact of the novel CYP2C:TG haplotype on sertraline serum concentration in a large population genotyped for CYP2C19 (variants *2, *3, *4, and *17) and CYP2B6 (variants *4, *6, and *9).

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study demonstrates that the novel CYP2C haplotype (CYP2C:TG) is associated with increased rate of CYP2C19 metabolism of sertraline, as previously shown for escitalopram. In addition, patients carrying both the CYP2B6*4 variant and CYP2C19 genotypes encoding ultrarapid CYP2C19 metabolism are at increased risk of underexposure and therapeutic failure when treated with standard recommended doses of sertraline, whereas patients with only inactive or decreased function alleles of both CYP2C19 and CYP2B6 have a lower capacity for sertraline metabolism than CYP2C19 poor metabolizers carrying functional CYP2B6 alleles.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Preemptive genotyping of sertraline patients would include CYP2C:TG, CYP2C19, and CYP2B6 variants to increase the dose precision of the drug in patients suffering from depression and/or anxiety.