A modality-specific somatosensory evoked potential test protocol for clinical evaluation: A feasibility study

ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system.MethodsIn order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference.ResultsWe found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings.ConclusionIn this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application.SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials.     

Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CL_R) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CL_R (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CL_R of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates.     

哮喘患儿血清嗜酸性粒细胞阳离子蛋白改变及其意义

目的：评价变应性哮喘患儿血清嗜酸性粒细胞阳离子蛋白（S-ECP）水平改变及其意义。方法：测定25例哮喘发作期患儿糖皮质激素吸入治疗12周前后，及20例未予糖皮质激素吸入治疗的哮喘缓解期患儿S-ECP水平，并对发作期患儿S-ECP水平变化与血嗜酸性粒细胞计数（B-EOS）、肺功能一秒用力呼气量（FEV1）、一秒用力呼气量比用力肺活量（FEV1/FVC）及症状评分的关系作相关性分析。结果：哮喘发作组治疗后S-ECP水平较治疗前显著降低，与对照组（健康儿童10名）比较差异无显著性；哮喘缓解组S-ECP水平明显高于发作组治疗后，但明显低于发作组治疗前。哮喘发作组治疗前S-ECP水平变化与B-EOS无相关性，与FEV1、FEV1/FVC呈负相关，与症状评分呈正相关。结论：监测S-ECP水平可作为评价哮喘气道炎症程度、病情预后和指导抗炎治疗的有效指标。     

Characteristics of the Nonselective Cation Current （NSCCs） in Rabbit Left Ventricular Epicardial, Midmyocardial and Endocardial Myocytes

Objectives Recent studies have described regional differences in the electrophysiology and pharmacology of ventricular myocardium in canine, feline, rat, guinea pig, and human hearts. This has been shown to be due to a smaller IKs and a lager sodium-calcium exchange current (INa-Ca) and late INa in M region (deep subepicardial to midmyocardial). Studies from our laboratory have found a new repolarization current-nonselective cation current (NSCCs) existing in rabbit right ventricular myocytes. Methods We examined the characteristics of NSCCs in epicardial, M region, and endocardial cells isolated from the rabbit left ventricle with standard microelectrode and whole-cell patch-clamp techniques. The permeability to Na , K , Li , Cs but not to Cl- indicating that it was a nonselective cation current. Gd3 (0.1 mmol/l) and La3 (0.1 mmol/l) can block the current markedly. Results Further characterization of NSCCs was significantly smaller in M cells than in epicardial and endocardial cells. NSCCs current density was significantly smaller in M cells than in epicardial and endocardial cells. With repolarization to -80 mV, INs current density was (-0.44±0.05) PA/PF in endocardial cells, (-0.12±0.05) PA/PF in M cells and (-0.28±0.07) PA/PF in epicardial cells; and with repolarization to 30 mV, INs current density was (1.09±0.29) PA/PF in endocardial cells, (0.38±0.09) PA/PF in M cells and (0.91±0.32) PA/PF in epicardial cells. Conclusions Transmural dispersion of repolarization was due to the heterogeneity of NSCCs in rabbit left ventricle epicardial, endocardial myocytes and M cells. These findings may advance our understanding of the ionic basis for our understanding of factors contributing to the development of cardiac arrhythmias.     

酸性成纤维细胞生长因子的分离纯化及活性鉴定

目的：从牛脑中分离纯化酸性成纤维细胞生长因子（aFGF)并鉴定生物活性，方法：根据DenisGOSPODAROW-ICZ的方法，新鲜牛脑匀浆，三步硫酸铵盐析。最后沉淀物溶解透析后予离子交换层析及琼脂糖胶亲和层析，促3T3细胞DNA合成率鉴定生物活性。结果：用1.0mol/LNaCl的缓冲液洗脱得到分子量为13600的多肽，得率为610μg/kg牛脑，氨基酸组成分析与已知的aFGF相同，促3T3细胞DNA合成的最低浓度为0.5ng/ml，最大效应浓度50ng/ml，ED50值为8ng/ml。结论：aFGF具有强烈的促细胞增殖作用。     

Cobalt-dependent potentiation of net inward current density in Helix aspersa neurons.

A low concentration of transition metal ions Co2+ and Ni2+ increases the inward current density in neurons from the land snail Helix aspersa. The currents were measured using a single electrode voltage-clamp/internal perfusion method under conditions in which the external Na+ was replaced by Tris+, the predominant external current carrying cation was Ca2+, and the internal perfusate contained 120 mM Cs+/0 K+; 30 mM tetraethylammonium (TEA) was added externally to block K+ current. In the presence of Co2+ (3 mM) or Ni2+ (0.5 mM) inward Ca2+ currents were stimulated normally by voltage-dependent activation of Ca2+ channels. There was a 5-10% decrease in the rate of rise of the inward current. The principal effect of Co2+ and Ni2+ in increasing the current density seems to be a decrease in the rate at which the inward currents decline during a depolarizing voltage pulse. The results may be due to a decrease in a voltage-dependent or Ca(2+)-dependent outward current and/or an inhibition of Ca2+ channel inactivation. Outward current under these conditions (zero internal K+) was significant and most likely due to Cs+ efflux through the voltage-activated or Ca(2+)-activated nonspecific cation channels. Co2+ is an extremely effective blocker of this outward current. These results are not an artifact of internal perfusion or the special ionic conditions. Intracellular recording of unperfused neurons in normal Helix Ringer's solution showed that the Ca(2+)-dependent action potential duration was increased significantly by low concentrations of Co2+. This result is consistant with the Co(2+)-dependent increase in inward (depolarizing) current seen in voltage-clamp experiments.     

Compartment syndrome. Exclusively the result of increased pressure in the muscular compartment?

Summary The compartment syndrome (cs) is characterized by an increased tissue pressure in a limited space. Pathophysiologically, it is a multifactorial disease that is potentially induced by an initial trauma and develops according to the existence of cofactors. Cofactors are, for instance, the circulation of the patient and the initial treatment of the impending cs. In particular, the microcirculation is altered with endothelial destruction, development of a capillary leak, protein loss from intravasal space and the development of an interstitial and intracellular third space. An impaired drainage of the lymphatic and venous system causes a venous infarction. An arterial infarction results if the tissue pressure exceeds the arteriolar pressure. An accompanying ischemia reperfusion mechanism increases the trauma load. In disadvantageous cases, the patients are in danger of developing a multi-organ deficiency syndrome (MODS) by an uncontrolled inflammatory reaction, by intravasal volume loss and by a myonephropathic systemic reaction. Clinically, the patients suffer a disproportionate amount of pain, followed by neurological signs. Especially in noncompliant patients, tissue pressure measurement is useful. Resuscitation of the circulation as well as splitting of casts is important. In case of a manifest cs, dermatofasciotomy has to be performed as an emergency operation. Even if cs is diagnosed early and fasciotomy is carried out early, the development of sequellae cannot be avoided in every single case.      

Without Parental Consent: Conducting Research With Homeless Adolescents

ISSUES AND PURPOSE. To identify the ethical and legal implications of conducting research with homeless adolescents and to discuss guidelines for conducting research without parental consent.
CONCLUSIONS. Ethical principles of capacity, risk, postponement, and truthful disclosure within the context of the rights of minors to consent to healthcare treatment form the basis of the argument for allowing adolescents to consent to participate in research without parental consent when there is minimal risk or when such consent could place them at increased risk for harm.
PRACTICE IMPLICATIONS. Adolescents who are the target population for clinical research or who are intended recipients of nursing care should be involved in setting priorities, purposes, and protocols. Parents and other adults from their communities should be included in developing strategies to protect their confidentiality and privacy while helping them achieve autonomy in making informed health-related decisions.     

中医辨证在航天医学中应用的可能性分析

为探讨中医在载人航天中的应用,用中医学辨证论治方法,分析了航天环境(包括微重力、辐射.狭小隔离环境、昼夜节律变化等)对机体的生理影响,认为在航天初期是实证,辨证为:经气厥道,升降失常,治则为升清降浊止呕,活血行气开窍;航天时间较长期时,由于航天环境长期的综合作用,损伤人体正气,使人体呈现虚实夹杂的症状,辨证为肝肾阴虚合并血瘀气滞,治则:滋阴补肾柔肝,健脾益气活血.     

The Development and Teaching of the Ethical Principles and Guidelines for Family Scientists*

This article describes the development of the Ethical Principles and Guidelines for Family Scientists that the National Council on Family Relations Board of Directors unanimously approved. Furthermore, it discusses the importance of ethics education for family professionals and provides suggestions for educators. Finally, the ethical principles and guidelines are delineated. We argue that the development of a scholarship on ethics education is important for current and future family scientists.