Hemodynamics and annuloplasty in isolated mitral regurgitation in children.

Isolated mitral insufficiency in children is quantitated angiographically by comparing the stroke volumes of the right ventricle and left ventricle. The disease results in greater enlargement of the left atrium than of the left ventricle and is accompanied by a significant increase in left atrial "distensibility." Right and left heart pressures may be normal or may be increased; they tend to be elevated in the group with regurgitant fractions of over 50%. Annuloplasty results in marked clinical and hemodynamic improvement and may even be corrective.     

结核病中断治疗的危险因素分析:赞比亚301例结核病患者前瞻性队列研究

背景:赞比亚一家城市结核病门诊部。目的:确认与中断治疗增加有关的患者特征,尤其是关于接受治疗的相关知识及费用因素。设计:对15岁以上、开始治疗的结核病患者进行前瞻性队列研究,采用半结构式调查表调查及对其后一周三次直接观察下治疗(DOT)就诊情况的观察。结果:301例患者中,共有76例(25.2%)中断了治疗,25例未恢复治疗。中断治疗率较高者为对治疗成功信心不足者(HR3.64;95%CI:1.42-9.31,P=0.007)及因接受治疗有明显的时间和费用限制者(HR2.67;95%CI:1.05-6.81;P=0.04)。在不同治疗阶段这些因素的影响不同,在开始治疗的90天,对治疗成功信心不足的因素影响明显,而因到门诊部接受治疗而增加交通费用的因素则多发生于治疗90天后。结论:在赞比亚,在开始治疗及治疗期间的不同阶段均可发现中断治疗的高危人群。在治疗3个月后,患者对治疗成功信心增强后,可考虑采用以家庭为基础的自我服药,这样可减少患者去门诊部接受治疗的费用。     

Certification in Medical Physics Imaging,The Workforce and Training Models

The pathway to becoming a qualified medical physicist (QMP) in the imaging physics disciplines includes several certification organizations. Imaging QMPs play an essential role in the safe practice of the diagnostic disciplines, and their qualifications are necessary for compliance with federal bodies and professional accreditation organizations. The future demand for imaging QMPs is largely unknown, but professional organizations that represent these groups agree that efforts should be made to increase the number of matriculating trainees. The number of imaging residency programs that provide the necessary professional experience to enter the certification pathway has increased substantially in recent years. Most of these programs follow a traditional academic hospital-based training model, but guidance on program construction from the accrediting body permits flexibility. Existing training models for medical physics imaging also include consortiums of affiliate partners and private consulting service groups. In this article, the authors briefly review the certification pathways for imaging QMPs, workforce estimates, and training models.     

Differential slow inactivation and use-dependent inhibition of Nav1.8 channels contribute to distinct firing properties in IB4+ and IB4- DRG neurons

Nociceptive dorsal root ganglion (DRG) neurons can be classified into nonpeptidergic IB(4)(+) and peptidergic IB(4)(-) subtypes, which terminate in different layers in dorsal horn and transmit pain along different ascending pathways, and display different firing properties. Voltage-gated, tetrodotoxin-resistant (TTX-R) Na(v)1.8 channels are expressed in both IB(4)(+) and IB(4)(-) cells and produce most of the current underlying the depolarizing phase of action potential (AP). Slow inactivation of TTX-R channels has been shown to regulate repetitive DRG neuron firing behavior. We show in this study that use-dependent reduction of Na(v)1.8 current in IB(4)(+) neurons is significantly stronger than that in IB(4)(-) neurons, although voltage dependency of activation and steady-state inactivation are not different. The time constant for entry of Na(v)1.8 into slow inactivation in IB(4)(+) neurons is significantly faster and more Na(v)1.8 enter the slow inactivation state than in IB(4)(-) neurons. In addition, recovery from slow inactivation of Na(v)1.8 in IB(4)(+) neurons is slower than that in IB(4)(-) neurons. Using current-clamp recording, we demonstrate a significantly higher current threshold for generation of APs and a longer latency to onset of firing in IB(4)(+), compared with those of IB(4)(-) neurons. In response to a ramp stimulus, IB(4)(+) neurons produce fewer APs and display stronger adaptation, with a faster decline of AP peak than IB(4)(-) neurons. Our data suggest that differential use-dependent reduction of Na(v)1.8 current in these two DRG subpopulations, which results from their different rate of entry into and recovery from the slow inactivation state, contributes to functional differences between these two neuronal populations.     

A new Nav1.7 sodium channel mutation I234T in a child with severe pain

Dominant gain‐of‐function mutations that hyperpolarize activation of the Na_v1.7 sodium channel have been linked to inherited erythromelalgia (IEM), a disorder characterized by severe pain and redness in the feet and hands in response to mild warmth. Pharmacotherapy remains largely ineffective for IEM patients with cooling and avoidance of triggers being the most reliable methods to relieve pain. We now report a 5 year old patient with pain precipitated by warmth, together with redness in her hands and feet. Her pain episodes were first reported at 12 months, and by the age of 15–16 months were triggered by sitting as well as heat. Pain has been severe, inducing self‐mutilation, with limited relief from drug treatment. Our analysis of the patient's genomic DNA identified a novel Na_v1.7 mutation which replaces isoleucine 234 by threonine (I234T) within domain I/S4–S5 linker. Whole‐cell voltage‐clamp analysis shows a I234T‐induced shift of −18 mV in the voltage‐dependence of activation, accelerated time‐to‐peak, slowed deactivation and enhanced responses to slow ramp depolarizations, together with a −21 mV shift in the voltage‐dependence of slow‐inactivation. Our data show that I234T induces the largest activation shift for Na_v1.7 mutations reported thus far. Although enhanced slow‐inactivation may attenuate the gain‐of‐function of the I234T mutation, the shift in activation appears to be dominant, and is consistent with the severe pain symptoms reported in this patient.     

Common problems with antiretroviral therapy among three Swedish groups of HIV infected individuals

Objective The main objective of this study was to identify and compare the common problems and difficulties associated with combination antiretroviral therapy (CART) as experienced by three major groups of HIV infected individuals (homo- or bisexuals, former injecting drug users and origins of Sub-Saharan Africa) in Sweden. Methods Based on the results from in-depth interviews with 15 representatives from the three major groups, a questionnaire was designed for use in a problem detection study (PDS). The study was conducted with 195 HIV-positive patients residing in the major cities of Sweden. Results The overall response rate was 79%. The problems identified in all three groups were negative attitudes from the public, worries about disease progression or therapy failure, medication or drug-related problems and problems in connection to pharmacy visits. A specific problem in the homo- or bisexual group was drug-related problems such as adverse effects, drug interactions and pill burden. For former injecting drug users, the specific problem was disease-related conflicts with relatives and the problem of coping with the social and psychological burden caused by the HIV infection. The African group termed the risk of exposing their medication at the pharmacy as a specific problem, as this could reveal their HIV status. Conclusions Our findings regarding problems with CART in three patient groups in Sweden may be of use to tailor pharmacy care to HIV infected individuals. General strategies to improve adherence need to be complemented with approaches that will address the specific needs for the different patient groups affected by HIV. Further studies on group-specific interventions that promote concordance and adherence to CART will be necessary to minimize therapy failure and viral resistance.