SEVENTY-TWO HOUR COMPARISON OF METHYLPREDNISOLONE SULEPTANATE AND METHYLPREDNISOLONE SODIUM SUCCINATE IN PATIENTS WITH ACUTE ASTHMA

SUMMARY The efficacy and safety of the methylprednisolone prodrugs methylprednisolone suleptanate and methylprednisolone sodium succinate were evaluated in a multicentre, randomised, double-blind, double-dummy parallel study of 88 patients hospitalised with acute asthma. Each study drug was administered as a bolus intravenous injection of 40mg methylprednisolone equivalents every 6 hours for 48 hours. Methylprednisolone 32mg was administered orally 6 hours after the last dose. Pulmonary function, medical events, and clinical laboratory values were assessed at predefined intervals before and during the 72-hour study. The primary response measure of pulmonary function was per cent predicted forced expiratory volume in one second (FEV₁) at 48 hours. Secondary response measures were peak expiratory flow rate (PEFR) and FEV₁/forced vital capacity (FVC) ratio. Although both drugs demonstrated within-group mean changes from baseline (starting at 6 hours) that were statistically significant for each response, there were no statistically significant differences between the two groups. The mean percent predicted FEV₁ at 48 hours and mean per cent change from baseline were 64% and 13% (p<0.0001) for the methylprednisolone suleptanate group and 67% and 17% (p<0.0001) for the methylprednisolone sodium succinate group, respectively. The mean PEFR and FEV₁/FVC ratio at 48 hours were 5.77 l/s and 73% for the methylprednisolone suleptanate group and 5.78 l/s and 76% for the methylprednisolone sodium succinate group, respectively. There were no clinically or statistically significant between-group differences in any of the safety parameters. In this study, methylprednisolone suleptanate and methylprednisolone sodium succinate have been shown to be therapeutically equivalent in the treatment of patients hospitalized with acute asthma.     

人白细胞介素24mRNA在瘢痕疙瘩中的表达及意义

目的:从基因水平测量瘢痕疙瘩组织中白细胞介素24的表达水平,探讨白细胞介素24在瘢痕疙瘩发生、发展过程中的作用和意义。方法:实验于2005-10/2006-09在广东医学院整形外科研究所完成。①选取2004-06/2005-10广东医学院附属医院整形外科收治的患者,瘢痕疙瘩标本12例,正常瘢痕标本10例,行巨乳缩小、除皱术、植皮等患者正常皮肤标本12例,患者均知情同意且自愿捐献标本,实验经医学伦理委员会批准。标本取材部位为颜面、前胸、四肢等,切取后液氮保存。②低温条件下切取秤量组织,采用Trizol法提取总RNA。电泳鉴定总RNA完整性,并统一调整总RNA含量为10g/L,-70℃储存。RT-PCR二步法合成cDNA。③以正常皮肤、正常瘢痕为对照,以GAPDH作为扩增内参照基因,将正常皮肤、正常瘢痕和瘢痕疙瘩各类标本总RNA反转录的cDNA模板浓度调整相对一致进行扩增反应。以白细胞介素24mRNA与GAPDHmRNA的光密度积分值之比作为各类组织标本中白细胞介素24的相对含量,比较白细胞介素24mRNA在正常皮肤、正常瘢痕及瘢痕疙瘩组织中的表达情况。结果:①各类组织标本中总RNA抽提结果:正常皮肤、正常瘢痕和瘢痕疙瘩组织中抽提总RNA经甲醛变性凝胶电泳后显示较清晰的18s和28s条带,经紫外分光光度计测定A260/A280≈2.0。②各类组织标本中白细胞介素24mRNA的表达:白细胞介素24和GAPDH基因表达产物通过RT-PCR方法得到的特异性DNA片段长度分别为173bp和577bp。瘢痕疙瘩的白细胞介素24mRNA与GAPDHmRNA的吸光度比值明显低于正常皮肤、正常瘢痕(0.577±0.113,1.070±0.185,1.139±0.195;t=7.436×10-8～4.745×10-8,P均<0.01),正常皮肤与正常瘢痕白细胞介素24mRNA的相对表达量基本一致(t=0.405,P>0.05)。结论:瘢痕疙瘩的形成可能与白细胞介素24在组织中的表达降低有关。提示采用基因疗法提高早期瘢痕疙瘩中白细胞介素24的含量与活性,可能为瘢痕疙瘩的康复治疗提供有效途径。     

Comparison of the cumulative irritation potential of adapalene gel and cream with that of erythromycin/tretinoin solution and gel and erythromycin/isotretinoin gel

BACKGROUND: Adapalene is a naphthoic acid derivative with retinoid activity that is effective in the treatment of mild to moderate acne vulgaris. OBJECTIVE: This study assessed the cumulative irritation potential of adapalene gel (0.1%) and adapalene cream (0.1%) compared with that of erythromycin (4%)/tretinoin (0.025%) solution, erythromycin (4%)/tretinoin (0.025%) gel, erythromycin (2%)/isotretinoin (0.05%) gel, and white petrolatum (negative control). METHODS: This was a single-center, randomized, controlled, investigator-blinded, intraindividual comparison study in healthy subjects with normal skin. The cumulative irritation assay (patch test) was used to assess the potential for irritation (including erythema) of the treatments. Each subject received all study treatments, randomly applied under occlusion (patch), to sites on either side of the midline on the mid-thoracic area of the back. All patches were applied to the same sites throughout the study, unless the degree of reaction to the treatment or adhesive necessitated removal. For 3 weeks, each test material was applied daily, Monday through Friday, for approximately 24 hours; the Friday patches were left in place over the weekend for approximately 72 hours. RESULTS: All 36 subjects (26 men, 10 women; age, 18-49 years [mean, 30 years]) completed the study. In the course of the study, all subjects had > or =1 application discontinued prematurely on > or =1 site due to intolerance. There were no discontinuations with white petrolatum. All erythromycin/tretinoin gel patches were discontinued at day 10; 35 of 36 erythromycin/isotretinoin gel patches were discontinued at day 9; and 35 of 36 erythromycin/tretinoin solution patches were discontinued at day 11 or day 17. The adapalene products, although slightly more irritating (mean cumulative irritation index, 0.25-1) than white petrolatum, were significantly less irritating than the erythromycin/tretinoin and erythromycin/isotretinoin products (P < 0.01). CONCLUSIONS: Adapalene gel and cream were well tolerated, with possible benefits for compliance. Their low irritation potential should be considered when prescribing a topical retinoid for the treatment of acne vulgaris.     

Development and validation of the Humanitarian Aid Difficulty Scale for Japanese healthcare workers

Few studies have investigated deployment‐related experiences of healthcare workers dispatched for medical humanitarian aid or attempted to assess their difficult living and working environments. This is the first study to develop and validate a scale to measure these kinds of difficulties, in 264 Japanese healthcare workers. The Humanitarian Aid Difficulty Scale was developed in three stages. First, an item pool was generated based on literature and expert reviews. The scale was then tested in a pilot study. Reliability and validity were identified through exploratory and confirmatory factor analysis and Cronbach's alpha. The scale consisted of 23 items across five factors based on exploratory factor analysis (cooperation, health status, infrastructure, culture and customs, and supplies and equipment). The total variance explained was 60.7%. Reliability of the five factors was acceptable and validity was supported by confirmatory factor analysis. Cronbach's alpha for the scale was 0.87. The scale may enable evaluation of the level of difficulty of the living and working environments of Japanese healthcare workers in medical humanitarian aid who are at a greater risk of distress.     

DDD Pacing: An Effective Treatment Modality for Recurrent Atrial Arrhythmias

We performed atrial EP studies (atrial substrate evaluation) on 10 patients. These patients had evidence of paroxysmal, sustained, recurrent atrial arrhythmias (7 men and 3 women with a mean age of 64 ± 15 years). All patients combined a brady-tachy syndrome; 7 patients had a sick sinus syndrome (SSS) and 3 patients a typical vagally induced atrial arrhythmia. No anti-arrhythmic drug was allowed in 3 patients with SSS, 1 drug failed in 4 patients and the combination of 2 drugs failed in 3 patients during the first to eighth years prior to pacemaker implantation. Atrial substrate evaluation was feasible in all these patients off anti-arrhythmic therapy and showed important abnormalities of atrial loco-regional conduction parameters and long refractory periods (RP). The remarkable point was, in 7 patients, a paradoxical improvement in intra-atrial conduction delay at rapid pacing rate. The DDD pacing mode was chosen in all patients. No technical problem occurred during implantation. Atrial pacing rate was programmed to be slightly higher than the mean diurnal heart rate calculated on Holter monitoring. After implantation, the mean follow-up period was 18 ± 25 months with an average of one Holter every 4 months during the first 2 years. The 7 patients who improved intra-atrial conduction at rapid pacing rate were controlled without drugs, 2 patients were controlled with 1 drug, and 1 patient with 2 drugs. Atrial pacing in the DDD mode in a selected group of patients prevents paroxysmal and drug-resistant atrial arrhythmias. Atrial substrate evaluation is a sensitive tool for assuring the long-term benefit of atrial pacing. In this subset of patients, maintenance of AV synchrony by DDD pacing is preferable to catheter ablation of the His bundle.     

Adaptive differentiation of murine lymphocytes. IV. (Responder × Nonresponder) F(1) T cells can be taught to preferentially help nonresponder,rather than responder, B cells

Responses to the synthetic terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT) in the mouse are controlled by H-2-1inked Ir-GLTgenes. (Responder × nonresponder) F(1) hybrid mice, themselves phenotypic responders, can be primed with GLT to develop specific helper cells capable of interacting with 2,4-dinitrophenyl hapten (DNP)-primed F(1) B cells in response to DNP-GLT. Unlike the indiscriminant ability of F(1) helper T cells for conventional antigens (i.e. not Ir gene-controlled), which can help B cells of either parental type (as well as F(1)) equally well, GLT-primed F(1) T cells can only provide help under normal circumstances for B lymphocytes of responder parent origin; they are unable to communicate effectively with nonresponder parental B cells (1, and the present studies). The present studies reveal, however, that the induction of a parental cell-induced allogeneic effect during priming of F(1) mice to GLT actually dictates the direction of cooperating preference that will be displayed by such F(1) helper cells for B cells of one parental type or the other. Thus, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by parental BALB/c cells, develop into effective helpers for nonresponder A/J B cells, but fail to develop effective helpers for responder BALB/c B cells, and vice-versa. In contrast, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by either parental type, display significantly enhanced levels of helper activity for B cells derived from F(1) donors. These results are interpreted to reflect the existence of two interdependent events provoked by the allogeneic effect: one event augments the differentiation of GLT-specific helper T cells belonging to the subset corresponding to the opposite parental type; this would explain the development of increased helper activity provided to partner B cells of opposite parental type (as well as of F(1) origin). The second event, we postulate, involves the production of responses against the receptors which normally self-recognize native cell interaction determinants; this form of anti-idiotype response is restricted against self- recognizing receptors of the same parental type used for induction of the allogeneic effect, hence explaining diminished helper activity of such F(1) cells for partner B lymphocytes of corresponding parental type.     

Moderate Ingestion of Alcohol Is Associated With Acute Ethanol‐Induced Suppression of Circulating CTX in a PTH‐Independent Fashion

The “J shape” curve linking the risk of poor bone health to alcohol intake is now well recognized from epidemiological studies. Ethanol and nonethanol components of alcoholic beverages could influence bone remodeling. However, in the absence of a solid underlying mechanism, the positive association between moderate alcoholic intake and BMD remains questionable because of confounding associated social factors. The objective of this work was to characterize the short‐term effects of moderate alcohol consumption on circulating bone markers, especially those involved in bone resorption. Two sequential blood‐sampling studies were undertaken in fasted healthy volunteers (age, 20–47 yr) over a 6‐h period using beer of different alcohol levels (<0.05–4.6%), solutions of ethanol or orthosilicic acid (two major components of beer), and water ± calcium chloride (positive and negative controls, respectively). Study 1 (24 subjects) assessed the effects of the different solutions, whereas study 2 (26 subjects) focused on ethanol/beer dose. Using all data in a “mixed effect model,” we identified the contributions of the individual components of beer, namely ethanol, energy, low‐dose calcium, and high‐dose orthosilicic acid, on acute bone resorption. Markers of bone formation were unchanged throughout the study for all solutions investigated. In contrast, the bone resorption marker, serum carboxy terminal telopeptide of type I collagen (CTX), was significantly reduced after ingestion of a 0.6 liters of ethanol solution (>2% ethanol; p ≤ 0.01, RM‐ANOVA), 0.6 liters of beer (<0.05–4.6% ethanol; p < 0.02), or a solution of calcium (180 mg calcium; p < 0.001), but only after calcium ingestion was the reduction in CTX preceded by a significant fall in serum PTH (p < 0.001). Orthosilicic acid had no acute effect. Similar reductions in CTX, from baseline, were measured in urine after ingestion of the test solutions; however, the biological variability in urine CTX was greater compared with serum CTX. Modeling indicated that the major, acute suppressive effects of moderate beer ingestion (0.6 liters) on CTX were caused by energy intake in the early phase (～0–3 h) and a “nonenergy” ethanol component in the later phase (～3 to >6 h). The early effect on bone resorption is well described after the intake of energy, mediated by glucagon‐like peptide‐2, but the late effect of moderate alcohol ingestion is novel, seems to be ethanol specific, and is mediated in a non–calcitonin‐ and a non–PTH‐dependent fashion, thus providing a mechanism for the positive association between moderate alcohol ingestion and BMD.