A New Contact Probe for Intraoperative Laser Ablation

Several clinical factors decrease the accuracy of intraoperative laser ablation. The distance to the target, the irradiation angle, and the media are reported among these factors. We developed a new laser probe to resolve these problems. This probe has a hollow conical tube with a tip covered by a thin film. Zero-degree centigrade saline was fed into this probe. Results from using the new probe were compared with those from the conventional noncontact irradiation method with cooling by sprinkled cooling water. In beating canine hearts, ventricles were irradiated with neodymium-yttrium aluminum garnet (Nd:YAG) lasers at 50–200 //mm². There was no difference in the mean volume of irradiated tissue between the new and the noncontact method. However, the distribution of volume values in the new method was smaller than that in the noncontact method (P < 0.05). In conclusion, results obtained indicate that this new probe could perform more accurate intraoperative ablation than the conventional method. Problems of stabilizing the distance to the target, the irradiation angle, and the media were resolved.     

Dural afferents express acid-sensing ion channels: a role for decreased meningeal pH in migraine headache

Migraine headache is one of the most common neurological disorders. The pathological conditions that directly initiate afferent pain signaling are poorly understood. In trigeminal neurons retrogradely labeled from the cranial meninges, we have recorded pH-evoked currents using whole-cell patch-clamp electrophysiology. Approximately 80% of dural-afferent neurons responded to a pH 6.0 application with a rapidly activating and rapidly desensitizing ASIC-like current that often exceeded 20 nA in amplitude. Inward currents were observed in response to a wide range of pH values and 30% of the neurons exhibited inward currents at pH 7.1. These currents led to action potentials in 53%, 30% and 7% of the dural afferents at pH 6.8, 6.9 and 7.0, respectively. Small decreases in extracellular pH were also able to generate sustained window currents and sustained membrane depolarizations. Amiloride, a non-specific blocker of ASIC channels, inhibited the peak currents evoked upon application of decreased pH while no inhibition was observed upon application of TRPV1 antagonists. The desensitization time constant of pH 6.0-evoked currents in the majority of dural afferents was less than 500 ms which is consistent with that reported for ASIC3 homomeric or heteromeric channels. Finally, application of pH 5.0 synthetic-interstitial fluid to the dura produced significant decreases in facial and hind-paw withdrawal threshold, an effect blocked by amiloride but not TRPV1 antagonists, suggesting that ASIC activation produces migraine-related behavior in vivo. These data provide a cellular mechanism by which decreased pH in the meninges following ischemic or inflammatory events directly excites afferent pain-sensing neurons potentially contributing to migraine headache.     

TRPM8 and Migraine

Migraine is among the most common diseases on earth and one of the most disabling, the latter due in large part to poor treatment efficacy. Development of new therapeutics is dependent on the identification of mechanisms contributing to migraine and discovery of targets for new drugs. Numerous genome‐wide association studies (GWAS) have implicated the transient receptor‐potential M8 (TRPM8) channel in migraine. This channel is predominantly expressed on peripheral sensory neurons and is known as the sensor for cold temperature in cutaneous tissue but is also expressed on deep visceral afferents where cold is not likely a stimulus. Consequently, a number of alternative endogenous agonists have been proposed. Apart from its role in cold sensation, TRPM8 also contributes to cold allodynia after nerve injury or inflammation, and it is necessary for cooling/menthol‐based analgesia. How it might contribute to migraine is less clear. The purpose of this review is to discuss the anatomical and physiological mechanisms by which meningeal TRPM8 may play a role in migraine as well as the potential of TRPM8 as a therapeutic target. TRPM8 is expressed on sensory afferents innervating the meninges, and these neurons are subject to developmental changes that may influence their contribution to migraine. As in viscera, meningeal TRPM8 channels are unlikely to be activated by temperature fluctuations and their endogenous ligands remain unknown. Preclinical migraine studies show that activation of meningeal TRPM8 by exogenous agonists can both cause and alleviate headache behaviors, depending on whether other meningeal afferents concurrently receive noxious stimuli. This is reminiscent of the fact that cold can trigger migraine in humans but menthol can also alleviate headache. We propose that both TRPM8 agonists and antagonists may be potential therapeutics, depending on how migraine is triggered in individual patients. In this regard, TRPM8 may be a novel target for personalized medicine in migraine treatment.     

美国国家骨髓库20年回顾:成人无关供者造血干细胞移植

自1987年起,美国国家骨髓库(NMDP)提供了>30 000份URD-HCT,其中70%以上的受者是患有恶性血液病或获得性血液疾病的成人.在此期间发生很大变化,包括无偿捐献队伍的扩大、PBSCs采集、脐血库(UCB)的加入、HLA分型技术的进步、新药物的使用、低强度预处理(RIC)以及移植后免疫调节等.本文就过去20年NMDP成人受者HCT的数据及分析作一介绍.     

A Major Antigenic Domain of Hantaviruses is Located on the Aminoproximal Site of the Viral Nucleocapsid Protein

Hantavirus nucleocapsid protein has recently been shown to be an immunodominant antigen in hemorrhagic with renal syndrome (HFRS) inducing an early and long-lasting immune response. Recombinant proteins representing various regions of the nucleocapsid proteins as well as segments of the G1 and the G2 glycoproteins of hantavirus strains CG18-20 (Puumala serotype) and Hantaan 76-118 have been expressed in E. coli. The antigenicity of these proteins was tested in enzyme immunoassays and immunoblots. These studies revealed that human IgG immune response is primarily directed against epitopes located within the amino acid residues 1 to 119 of the amino terminus of viral nucleocapsid proteins. This fragment was recognized by all HFRS patient sera tested (n=128). The corresponding enzyme immunoassays proved to be more sensitive than the indirect immunofluorescence assays. Furthermore, the majority of bank vole monoclonal antibodies raised against Puumala virus reacted specifically with this site. A recombinant G1 protein (aa 59 to 401) derived from the CG 18-20 strain was recognized by 19 out of 20 sera from HFRS patients.     

Intermittent Ventricular Bigeminy as an Expression of Two-Level Wenckebach Periodicity in the Reentrant Pathway of Extrasystoles

A patient with intermittent ventricular bigeminy is reported in whom the presence of two-level Wenckebach periodicity in the reentrant pathway of extra-systoles is suggested. When sinus arrest was caused by vagal stimulation, no ectopic QRS complex occurred. This indicated that ventricular bigeminy was not parasystolic bigeminy but ordinary extrasystolic bigeminy. Observations of the electrocardiogram suggested that Wenckebach block occurred at two different levels in the reentrant pathway of ventricular extrasystoles. When extrasystoles were noninterpolated, Wenckebach block occurred at the distal level of the pathway and caused termination of ventricular bigeminy. On the other hand, when extrasystoles were interpolated, Wenckebach block occurred at the proximal level of the pathway. This is the first report to suggest the presence of two-level Wenckebach periodicity in a reentrant pathway of extrasystoles.     

美国国家骨髓库20年回顾:成人无关供者造血干细胞移植

自1987年起,美国国家骨髓库(NMDP)提供了>30 000份URD-HCT,其中70%以上的受者是患有恶性血液病或获得性血液疾病的成人.在此期间发生很大变化,包括无偿捐献队伍的扩大、PBSCs采集、脐血库(UCB)的加入、HLA分型技术的进步、新药物的使用、低强度预处理(RIC)以及移植后免疫调节等.本文就过去20年NMDP成人受者HCT的数据及分析作一介绍.