Neurofilament M and calbindin D28k are present in mutually exclusive subpopulations of enteric neurons in the rat submucous plexus

Immunocytochemical methods have been used to examine the localisation of 3 neurofilament proteins and the calcium binding protein, calbindin D_28k, in whole mount preparations of the submucous plexus in the Wistar rat. Neurofilament-M (160 kDA protein) was present in 40% of the submucosal neurons, staining fine filaments in the soma and the axonal processes. Calbindin D_28k was present in 40% of the submucosal neurons staining both the soma and nerves within the plexus. The neurofilament proteins and calbindin D_28k were never observed within the same neurons. Neurofilament-M was co-localised with substance P and calcitonin gene-related peptide but not somatostatin or the other neuropeptides investigated. Calbindib D_28k was co-localised with vasoactive intestinal polypeptide and neuropeptide Y. Galanin- and somatostatin-immunoreactive neurons did not contain either the neurofilament proteins or calbindin D_28k. The results demonstrate the presence of subsets of submucosal neurons that can be distinguished by the presence of neurofilament-M or calbinsin D_28k.     

Comparison of assays for determination of peptide content for lyophilized thymalfasin*

Abstract: Precise determination of the peptide content in drug substance samples depends highly upon the particular peptide compound and methodology used. Four independent methods were evaluated and compared to determine which would produce the best experimental precision for analysis of thymalfasin (thymosin α‐1). Four different methods were evaluated including elemental analysis (CHN), quantitative amino acid analysis (AAA), high‐performance liquid chromatography (HPLC), and Kjeldahl. This study demonstrates that the AAA method is highly variable in one laboratory while quite precise in another laboratory. Similarly, HPLC results depended on the laboratory conducting the study with more precise values obtained under cGMP. On the contrary, the CHN method yielded highly precise [i.e. <2% coefficient of variation (CV)] values. As precise knowledge of protein content is fundamental for the compounding of final pharmaceutical product of a specific potency, the CHN analysis is recommended for peptide content determination of the drug substance thymalfasin.     

Detection of Atrial Fibrillation by Implanted Devices with Wireless Data Transmission Capability

Remote telemetry may facilitate the management of implantable devices. We tested the reliability of a new automatic, wireless home monitoring (HM) system that archives data every 24 hours. We retrospectively analyzed archival data from 276 consecutive pacing system implants to define temporal atrial fibrillation (AF) patterns and associated ventricular rate. An "AF day" was defined by a >20%/24 hour mode switch (MS) duration, irrespective of the MS number. Management decisions resulting from transmissions were noted. A pilot study confirmed that 89% of 22,356 transmissions were successful, of which >90% were received in <5 minutes. Data integrity was 100% preserved. Overall, AF developed in 29 patients (10.5%), representing a total of 645 AF days (mean = 22.2 ± 29.6 AF, median = 9 days), over 12 ± 2 months of monitoring. AF was infrequent (50% of 24 hours. Ventricular rates during 645 AF days in 29 patients averaged 95.1 ± 9.9 beats/min (median = 94 beats/min). Ventricular rates were >80 beats/min in 25 ± 30 AF days (median = 11 days). HM enabled rapid anticoagulation decisions. In recipients of implantable devices, automatic wireless telemetry with HM was efficient and reliable. Its application may overcome some current challenges in AF management by early notification and precise measurement of both AF burden and ventricular rate during AF.     

应用动力髁螺钉联合骨肽注射液治疗股骨髁上骨不连疗效观察

目的观察应用动力髁螺钉联合骨肽注射液治疗股骨髁上骨不连的疗效。方法53例股骨髁上骨不连患者随机分为两组：对照组（26例）和治疗组（27例）,两组均应用动力髁螺钉治疗,治疗组加用骨肽注射液治疗。随访,进行疗效评价,记录骨愈合时间和测定疼痛指数。结果治疗组疗效优于对照组。结论应用动力髁螺钉联合骨肽注射液治疗股骨髁上骨不连可提高疗效。     

BIOCHEMICAL CORRECTION IN THE SYNDROME OF HYPERTENSION AND HYPERKALAEMIA BY SEVERE DIETARY SALT RESTRICTION SUGGESTS RENIN-ALDOSTERONE SUPPRESSION CRITICAL IN PATHOPHYSIOLOGY

1. Plasma potassium and chloride concentrations were raised and plasma renin activity, aldosterone, bicarbonate and arterial pH were reduced in two brothers with the syndrome of hypertension and hyperkalaemia with normal glomerular filtration rate (Gordon's syndrome), on unrestricted or moderately restricted sodium diets. 2. These abnormalities were corrected in both patients within 10 days of severe sodium restriction. 3. Pressor sensitivity to cold and angiotensin II decreased on low sodium diet, associated with a fall in blood pressure. 4. Increasing distal tubular sodium delivery by infusion of normal saline increased fractional excretion of potassium when aldosterone had been stimulated by severely restricted sodium diet, but not when aldosterone levels were low on unrestricted sodium diet. 5. These findings are consistent with excessive sodium reabsorption as the primary renal lesion in Gordon's syndrome, leading to volume expansion and suppression of renin and aldosterone. Severe dietary sodium restriction leading to volume contraction, by stimulating renin and aldosterone and promoting kaliuresis, corrects the abnormalities.     

Chemical shift differences between free and Fab-bound peptide correlate with a two-stage selection of peptide sequences from a random phage display library to delineate critical and non-critical residues for antibody recognition

Epitope libraries provide a method to identify peptide ligands for antibodies, receptors or other binding proteins. As such, they provide a powerful tool to rapidly identify lead ligands in the drug discovery process. In an attempt to correlate structural information with the results from peptide screening, we have used NMR spectroscopy of peptide/antibody complexes to demonstrate that core residues identified through a two-stage selection process undergo a larger structural change upon binding antibody than do positions in the peptide amenable to a variety of side chains. The model system used was the M2 monoclonal antibody/Flag? octapeptide epitope system. We have analyzed two peptides: Ac-Asp-Tyr-Lys-Leu-Gly-Asp-Asp-Leu-NH₂ (peptide l), which contains several non-core positions randomized, and Ac-Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Leu-NH₂ (peptide 2), which closely corresponds to the original Flag? sequence. Enrichment of the peptides with ¹⁵N facilitated the investigation by permitting spectral editing of the peptide resonances in the presence of antibody. For peptide 1 the absolute shifts for the free vs. Fab-bound peptide were found to be largest for the amide groups of Asp-1 and Asp-6, in agreement with classification of these residues as critical by the phage display library selection process. For peptide 2 the largest absolute shifts were observed for Asp-1 and Asp-4, with the other aspartic acid residues also showing significant but smaller changes. © Munksgaard 1995.     

Atrial Synchronous Ventricular Pacing with a Single Lead: Reliability of Atrial Sensing During Physical Activities, and Long-term Stability of Atrial Sensing

A VDD pacing system with bipolar single-pass leads, were implanted in 36 consecutive patients (average age 72 ± 2years) with high degree atrioventricular block and normal sinus node function. At implant the atrial signal amplitude was 2.6 ± 0.2mV measured by a pacing system analyser (PSA), 1.8 ± 0.1mV measured peak-to-peak from the telemetered calibrated electrogram, and 1.3 ± 0.1mV measured from the sensing threshold. At one month follow-up the peak-to-peak amplitudes (mV) of the telemetered atrial electrograms were not significantly different measured continuously during resting supine with quiet breathing (1.4 ± 0.1), sitting (1.6 ± 0.2). standing (1.5 ± 0.1), arm swinging (1.4 ± 0.2), hyperventilation (1.3 ± 0.1), Vaisalva manoeuvre (1.4 ± 0.1), and treadmill exercise (1.9 ± 0.6). The telemetered atrial electrogram amplitude and the atrial sensing threshold varied between 1.2 ± 0.09mV and 1.8 ± 0.1mV, and between 0.95 ± 0.07mV and 1.3 ± 0.01mV, respectively at 0.5, 1, 3, 6 and 12 months follow-up, but the changes were statistically nonsignificant. The Event Summary showed sensing of 98% to 99% of the atrial events at the different follow-up periods.     

非瓣膜病房颤患者左心耳血流动力学的TEE研究

应用多平面经食管超声心动图技术（Ｍ－ＴＥＥ），对３０例健康人和３０例非瓣病房颤患者（ＮＶＡＦ）心底短轴切面测量了左心耳最大直径，同一心动周期内左心耳最大及最小面积及左心耳最大空速度，产将ＮＶＡＦ患者按照自发显影及血栓的有无分为２组。发现ＮＶＡＦ组左心耳增大，收缩力及血流速度均减低，且这种变化在有血栓和有血栓形成倾向的患者中更为明显。     

Atypical Form of the Fourth Criterion for Transient Entrainment

The typical fourth criterion for transient entrainment is defined when both a sudden shortening in conduction interval to and a distinct change in electrogram morphology at a bipolar recording site are demonstrated while performing overdrive pacing of a reentrant tachycardia from a single pacing site at two different constant rates. The purpose of this article was to test the hypothesis that if an intracardiac recording site showing both orthodromic and antidromic capture with entrainment pacing is located suitably distant from the circuit, sudden shortening in conduction interval to that site may occur without any significant change in the bipolar electrogram morphology (i.e., atypical form of the fourth criterion). Atrial overdrive pacing of orthodromic tachycardia was performed in 20 patients with either left anterior (12 patients) or left posterior (8 patients) accessory pathways. We investigated the effects of overdrive pacing from the proximal or distal coronary sinus, specifically effects on the electrogram interval and the electrogram morphology at the right atrial appendage. Overdrive pacing of orthodromic tachycardia from the proximal coronary sinus was performed in 10 of the 12 patients with left anterior accessory pathways; those 10 patients demonstrated the first entrainment criterion at the right atrial appendage site. Overdrive pacing of orthodromic tachycardia at still shorter cycle lengths demonstrated a sudden shortening in conduction interval to the right atrial appendage site. Despite shortening in conduction interval the morphology of the right atrial appendage electrogram was completely or almost identical to that during orthodromic tachycardia, indicating an atypical form of the fourth criterion. This criterion was not demonstrated in patients with left posterior accessory pathways. Thus, atypical fourth entrainment criterion was demonstrated during overdrive pacing of orthodromic tachycardia from the proximal coronary sinus only in patients with left anterior accessory path ways. Demonstration of atypical fourth criterion seems largely dependent on the location of the accessory pathway, the pacing, and the recording sites.