Clinical measurement of swallowing in health and in neurogenic dysphagia

We studied clinical features potentially related to dysphagia and three indices from a timed test of swallowing--average volume per swallow (ml), average time (s) per swallow and swallowing capacity (ml/s)--in 181 screened healthy adults and 30 patients with motor neurone disease (MND). In healthy adults, age, sex and height accounted for 44.3% and 55.6% of the variance of log average volume per swallow and log swallowing capacity, respectively. Symptoms and signs were more prevalent in the MND group and were associated with reduced swallowing capacity and reduced average volume per swallow; repeatability studies on these two indices in both groups showed that the median difference between the mean of two recordings on successive days and the mean of all recordings (6-15 over 3 days) was < 5% (maximum third quartile 12.8%, indices expressed as percent predicted according to age and sex). Using this simple bedside test, swallowing function can be quantified on a ratio scale and expressed as percent of that predicted by age and sex; such information may improve the predictive value of clinical assessment and provides a practical way of monitoring change in patients with dysphagia.      

Structural basis of protein kinase C activation by tumor promoters

Protein kinase C (PKC) is an important enzyme that helps govern cell metabolism and growth. The enzyme is physiologically activated when an (S)-diglyceride binds to its own regulatory domain. The saturable binding site of the regulatory domain can also be bound by any of a group of structurally diverse tumor promoters, including debromoaplysiatoxins (DATs), phorbol esters, ingenols, teleocidins, and bryostatins. The question of how the same binding site can be the target of these structurally diverse molecules is of considerable importance and is addressed in this article. The relatively rigid structure of DAT and the fact that it possesses a diglyceride moiety renders it an ideal starting template. Structure-activity studies with PKC reveal that the C29 but not the C30 stereocenter of DAT is critical for activity. Furthermore, 3-deoxy-DAT and DAT are equipotent as PKC activators, hence the C3 hydroxyl group of DAT is not critical for activity. Straightforward structural considerations show that the C30 hydroxyl group of DAT matches the C3 hydroxyl group of diglyceride, the C29 stereocenter of DAT matches the C2 stereocenter of (S)-diglyceride, and the C1 ester moiety of DAT matches the C2 ester moiety of diglyceride. Based on these studies and on published structure-activity observations on other tumor promoters, a structural hypothesis is developed to account for the chemical mechanism of tumor promoter action. Experimentally testable predictions are made concerning the interactions with PKC of several classes of tumor PKC activators.     

Gender Differences in the Clinical Characteristics and Atrioventricular Nodal Conduction Properties in Patients With Atrioventricular Nodal Reentrant Tachycardia

Gender Differences in Patients With AVNRT. Introduction: The detailed electrophysiological characteristics of the gender differences associated with atrioventricular nodal reentrant tachycardia (AVNRT) have not been clarified. This study investigated the gender‐related electrophysiological differences in a large series of patients undergoing radiofrequency catheter ablation. Methods and Results: A total of 2,088 consecutive AVNRT patients (men/women 869/1,219) who underwent catheter ablation were enrolled in this study. We evaluated the gender differences in their electrophysiological characteristics. Women had a significantly younger age of onset, higher incidence of multiple jumps, shorter AH interval, atrial effective refractory period (ERP), anterograde fast pathway ERP, anterograde slow pathway ERP, and retrograde slow pathway ERP, and longer ventricular ERP than men. The incidence of baseline ventriculoatrial dissociation was lower in women than in men. Women needed less isoproterenol/atropine to induce AVNRT. No gender differences in the radiation exposure time, procedure time, complication rate, acute success rate, or second procedure rate were noted. Both typical and atypical AVNRT were more predominant in women. In the patients with atypical AVNRT, there was no significant gender difference in incidence of baseline ventriculoatrial dissociation; however, the retrograde slow pathway ERP was significantly shorter in women than in men. Women of premenopausal age (≤50 years old) had a significantly higher incidence of anterograde multiple jumps and a retrograde jump phenomenon, and a shorter anterograde slow pathway ERP and retrograde slow pathway ERP than those of women over 50 years old. Conclusion: Gender differences in the anterograde and retrograde AV nodal electrophysiology were noted in the patients with AVNRT. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1114‐1119)     

The Novel Electrophysiology of Complex Fractionated Atrial Electrograms: Insight from Noncontact Unipolar Electrograms

Unipolar Characteristics of CFAEs. Background: The noncontact mapping (NCM) system possesses the merit of global endocardial recording for unipolar and activation mapping. Objective: We aimed to evaluate the unipolar electrogram characteristics and activation pattern over the bipolar complex fractionated atrial electrogram (CFAE) sites during atrial fibrillation (AF). Methods: Twenty patients (age 55 ± 11 years old, 15 males) who underwent NCM and ablation of AF (paroxysmal/persistent = 13/7) were included. Both contact bipolar (32–300 Hz) and NCM virtual unipolar electrograms (0.5–300 Hz) were simultaneously recorded along with the activation pattern (total 223 sites, 11 ± 4 sites/patient). A CFAE was defined as a mean bipolar cycle length of ≤ 120 ms with an intervening isoelectric interval of more than 50 ms (Group 1A, n = 63, rapid repetitive CFAEs) or continuous fractionated activity (Group 1B, n = 59, continuous fractionated CFAEs), measured over a 7.2‐second duration. Group 2 consisted of those with a bipolar cycle length of more than 120 ms (n = 101). Results: The Group 1A CFAE sites exhibited a shorter unipolar electrogram cycle length (129 ± 11 vs 164 ± 20 ms, P < 0.001), and higher percentage of an S‐wave predominant pattern (QS or rS wave, 63 ± 13% vs 35 ± 13%, P < 0.001) than the Group 2 non‐CFAE sites. There was a linear correlation between the bipolar and unipolar cycle lengths (P < 0.001, R = 0.87). Most of the Group 1A CFAEs were located over arrhythmogenic pulmonary vein ostia or nonpulmonary vein ectopy with repetitive activations from those ectopies (62%) or the pivot points of the turning wavefronts (21%), whereas the Group 1B CFAEs exhibited a passive activation (44%) or slow conduction (31%). Conclusions: The bipolar repetitive and continuous fractionated CFAEs represented different activation patterns. The former was associated with an S wave predominant unipolar morphology which may represent an important focus for maintaining AF. (J Cardiovasc Electrophysiol, Vol. 21, pp. 640‐648, June 2010)     

药学专业物理化学实验教学改革思路

针对药学专业物理化学实验教学中存在的问题,从优化实验项目与内容、改进数据处理方法、探索新的教学模式、贯彻绿色环保理念等方面探讨改革思路。     

生活方式改善对预防糖尿病的重要作用

营养过剩、肥胖．缺少运动是糖尿病发病的重要原因。本文针对这些原因阐述了防止肥胖、控制饮食和增加运动等生活方式的改善对预防糖尿病的重要作用。     

Technology insight: therapy for Duchenne muscular dystrophy-an opportunity for personalized medicine?

Since the identification of dystrophin as the protein product of the Duchenne and Becker muscular dystrophy locus, many different mutations, encompassing the entire spectrum of gene mutations ranging from point mutations to large deletions, have been found. These discoveries have led to the investigation of a variety of methods aimed at the treatment of muscular dystrophy, including strategies for gene replacement, gene correction, and modification of the gene product. The preferred approach in each case depends on the nature of the gene defect. In this Review, we focus on methods that have been developed for gene correction and for the modification of gene products. This mutation-focused approach offers the opportunity for 'personalized' gene therapy for muscular dystrophy and might also be a logical strategy for the treatment of other genetic disorders.     

Variability of influenza AH1N1 infections in a neonatal unit in Spain

We describe three positive influenza AH1N1 cases in a neonatal unit during the influenza pandemic in Spain. One term baby presented with an upper respiratory tract infection, another preterm infant with an apnea episode following nosocomial infection, and thirdly, a term infant of a mother with influenza AH1N1 had severe respiratory distress and pneumothoraces needing high-frequency ventilation.     

Management of resistant halo nevi

Background: Halo nevus (HN) is a rare dermatologic disorder characterized by typical whitish rim surrounding an existing melanocytic nevus resembling halo. It is a cosmetic problem that may be linked to vitiligo, and it is advised to remove these nevi in order to avoid development of vitiligo.

Objectives: The aim of the present study is to evaluate the cosmetic outcome after nevus removal and leukoderma dermabrasion with epithelial graft followed by narrow-band ultraviolet B (NB-UVB) phototherapy as management of resistant halo nevi and avoidance of development of vitiligo.

Patients and Methods: Ten patients with persisting halo nevi were selected as candidates in this study. Superficial dermabrasion was carried out using proper diamond fraises on depigmented rim and then punch biopsy probes with suitable size were used to harvest the nevus. Thiersch graft was prepared and applied on the dermabraded depigmented area. After 1 week of the procedure, patients were exposed to NB-UVB twice weekly and were followed up for 3 months.

Results: Repigmentation was noticed in 2 weeks and was nearly fully accomplished in all 10 patients within the 3-month period. No other vitiligo lesions developed during this period in all patients except for one case.

Conclusion: Excision of Sutton’s nevus with combined dermabrasion and Thiersch grafting followed by phototherapy is a good aesthetic maneuver in treating halo nevi and helps in avoiding further vitiligo depigmentation.