Recognition and management of phaeochromocytoma

Phaeochromocytomas and paragangliomas (PPGL) are catecholamine-secreting neuroendocrine tumours. These tumours may be identified incidentally, as part of a work-up for multiple endocrine neoplasia or following haemodynamic surges during unrelated procedures. Advances in preoperative management and improved management of intraoperative haemodynamic instability have significantly reduced surgical mortality from around 40% to less than 3%. Surgery is the definitive treatment in most cases and laparoscopic resection where possible is associated with improved outcomes. Anaesthetic management of PPGL cases represents a unique haemodynamic challenge both before, during and after tumour resection. In this article we describe the physiology of these tumours, their diagnosis, preoperative optimization methods, intraoperative anaesthetic management and management of postoperative complications.     

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.     

Recent advances in preclinical in vitro approaches towards quantitative prediction of hepatic clearance and drug-drug interactions involving organic anion transporting polypeptide (OATP) 1B transporters

Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CL_h) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CL_h involving OATP1B-mediated hepatic uptake. CL_h can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CL_h and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction.     

改良大骨瓣联合软通道微创介入逐渐减压术治疗重型颅脑损伤的疗效分析

目的：探讨改良大骨瓣联合软通道微创介入逐渐减压术治疗重型颅脑损伤的疗效。方法方便选择自2009年12月—2014年11月该院收治的重型颅脑损伤病例70例,随机分为改良组和对照组2组,每组35例,改良组施行改良大骨瓣联合软通道微创介入逐渐减压术,对照组按标准大骨瓣开颅、硬脑膜一次性全切开,对比分析两组的并发症发生率及预后。结果改良组发生迟发性颅内血肿、大面积脑梗塞及弥漫性脑肿胀等并发症9例(25.7％,9/35),预后良好者23例(65.7％,23/35),对照组发生并发症19例(54.3％,19/35),预后良好者14例(40.0％,14/35),两组并发症发生率和预后差异具有统计学意义(P<0.05)。结论改良大骨瓣联合软通道微创介入逐渐减压术治疗重型颅脑损伤,效果良好,显著降低死亡率。     

Cerebrovascular and neurological perspectives on adrenoceptor and calcium channel modulating pharmacotherapies

Adrenoceptor and calcium channel modulating medications are widely used in clinical practice for acute neurological and systemic conditions. It is generally assumed that the cerebrovascular effects of these drugs mirror that of their systemic effects – and this is reflected in how these medications are currently used in clinical practice. However, recent research suggests that there are distinct cerebrovascular-specific effects of these medications that are related to the unique characteristics of the cerebrovascular anatomy including the regional heterogeneity in density and distribution of adrenoceptor subtypes and calcium channels along the cerebrovasculature. In this review, we critically evaluate existing basic science and clinical research to discuss known and putative interactions between adrenoceptor and calcium channel modulating pharmacotherapies, the neurovascular unit, and cerebrovascular anatomy. In doing so, we provide a rationale for selecting vasoactive medications based on lesion location and lay a foundation for future investigations that will define neuroprotective paradigms of adrenoceptor and calcium channel modulating therapies to improve neurological outcomes in acute neurological and systemic disorders.     

Ligustrazine inhibits high voltage-gated Ca~(2+) and TTX-resistant Na~+ channels of primary sensory neuron and thermal nociception in the rat:a study on peripheral mechanism

Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the antinoci-ceptive effect of ligustrazine and, if any, the peripheral ionic mechanism involved. Methods Paw withdrawal Latency ( PWL) to noxious heating was measured in vivo and whole-cell patch recording was performed on small dorsal root ganglion (DRG) neurons. Results Intraplantar injection of ligustrazine (0.5 mg in 25μl) significantly prolonged the withdrawal latency of ipsilateral hindpaw to noxious heating in the rat. Ligustrazine not only reversibly inhibited high-voltage gated calcium current of dorsal root ganglion (DRG) neuron in dose-dependent manner with IC50 of 1.89 mmol/L, but also decreased tetrodotoxin (TTX) -resistant sodium current in relatively selective and dose-dependent manner with IC50 of 2.49 mmol/L. Conclusion The results suggested that ligustrazine could elevate the threshold of thermal nociception through inhibiting the high-voltage gated calcium current and TTX-resistant sodium current of DRG neuron in the rat.     

A Clinical Study of Reversing Left Ventricular Hypertrophy in Hypertensive Patients by Adalat

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Ineffectiveness of organic calcium channel blockers in antagonizing long-term potentiation

Evidence has accumulated suggesting that the presence of calcium is critical for development of hippocampal long-term potentiation (LTP). However, there is a paucity of information about whether calcium's role in LTP is pre- or postsynaptic. In the present study, we examined the effectiveness of nitrendipine, verapamil, flunarizine and the benzodiazepine diazepam in: blocking voltage-dependent calcium channels; blocking synaptic transmission; and preventing development of LTP. Using the in vitro slice preparation, we obtained intracellular and extracellular recordings from guinea pig hippocampal CA1 pyramidal cells. At the cellular level, all 4 drugs were ineffective in blocking voltage-dependent calcium spikes (TTX resistant) and the calcium-dependent afterhyperpolarization. Verapamil and diazepam appeared to antagonize synaptic transmission, as reflected in smaller population spike amplitudes. Development of long-term potentiation was not affected by the presence of verapamil, flunarizine and diazepam. Nitrendipine appeared to reduce the percentage of slices exhibiting LTP; however, ethanol, the vehicle used to dissolve nitrendipine, was shown in separate experiments to reduce the percentage of slices exhibiting LTP. These results suggest that neither the organic calcium channel blockers--nitrendipine, verapamil, and flunarizine--nor micromolar concentrations of diazepam are potent blockers of extrasynaptic voltage-sensitive calcium channels in hippocampus. They thus cannot be used to demonstrate a specific pre- or postsynaptic calcium role in LTP.