Cyclic adenosine monophosphate modulation of contractility via slow Ca2+ channels in chick heart

The catecholamines exert a positive inotropic effect associated with elevated tissue cyclic AMP levels and possibly with increase in the number of membrane slow cationic channels available for voltage activation. In the present study, catecholamines (isoproterenol, dopamine and dobutamine) were tested for their ability to affect the maximum upstroke velocity (+ V_max) of the slow action potentials, the first derivative ($\text{d}\text{T}\text{d}\text{t}$) of developed tension accompanying the slow responses, and the tissue cyclic AMP levels in the ventricular myocardium of isolated perfused chick hearts. To study the slow channels exclusively, the fast Na⁺ channels were voltage inactivated by elevated (25 mm) K⁺. In this condition of functional removal of the fast channels, the heart could not be excited by intense electrical stimulation. It was found that these catecholamines induced slow action potentials accompanied by contractions. Elevation of the concentration of these agents produced increases in + V_max, $\text{d}\text{T}\text{d}\text{t}$, and cyclic AMP in a dose-dependent fashion; a close correlation was obtained between the cyclic AMP level, + V_max and $\text{d}\text{T}\text{d}\text{t}$. These results support the hypothesis that the increases in + V_max of the slow action potentials and in contraction are explained by increase in the number of available slow channels mediated by intracellular cyclic AMP levels, and the resulting increase in the Ca²⁺ influx.     

行动学习法在妇产科护生带教中的应用效果评价

目的 探讨行动学习法在妇产科护生带教中的应用效果.方法 选取在妇产科实习的护生192名,实验组（96名）采用行动学习法带教,对照组（96名）采用常规带教法.通过理论考试、操作考核评价两组护生学习情况,通过自行设计的问卷评价教学效果.结果 实验组理论考试和操作考核成绩、住院患者对护生评价、护生对带教方式评价均优于对照组,差异均具有统计学意义（P＜0.01或P＜0.05）.结论 行动学习法带教可提高妇产科护生教学效果和护生综合能力,宜在护生临床带教工作中推广应用.     

Role of cyclic AMP in glucagon-induced stimulation of hepatic glucose output in man

The interrelationship between glucagon action on splanchnic glucose output and cyclic AMP production was studied in healthy volunteers after hepatic venous catheterization. Glucagon was infused according to four different protocols to achieve arterial levels ranging from 300 to 9000 ng/I. Infusion of glucagon which resulted in arterial levels of the hormone of 4000-9000 ng/1 was associated with a marked increase in net splanchnic cyclic AMP production and in the arterial levels of the cyclic nucleotide. The rise in cyclic AMP efflux from the splanchnic area was transient but an augmented splanchnic production was still evident after 30 min of glucagon infusion. Splanchnic glucose output rose 3-5 fold. Infusion of glucagon at lower rates, resulting in arterial levels of 300-900 ng/I, did not measureably stimulate the efflux of cyclic AMP from the splanchnic area. In spite of this, splanchnic glucose output rose 2-3 fold and the blood glucose level increased 20-50% during glucagon infusion at these lower rates.

It is concluded that (1) factors other than cyclic AMP are rate limiting in the stimulation of hepatic glucose production, and (2) although cyclic AMP is an established 'second messenger' of glucagon action, other factors may also be of importance in mediating the physiological response of this hormone.     

Onset of action of a lozenge containing flurbiprofen 8.75 mg: A randomized,double-blind,placebo-controlled trial with a new method for measuring onset of analgesic activity

A new onset-of-action model was utilized to distinguish the pharmacologic activity of flurbiprofen 8.75 mg delivered in a lozenge from the demulcent effect of the lozenge base. In a randomized, double-blind, placebo-controlled trial, patients with sore throat rated pain on a Sore Throat Pain Intensity Scale before taking one flurbiprofen or placebo lozenge and at frequent (2-minute) intervals over the first hour after treatment. Further ratings of the Sore Throat Pain Intensity Scale and other patient-reported outcomes (difficulty swallowing, swollen throat, pain relief) were obtained at varying intervals over 6 hours. Onset of pharmacologic activity was defined as the median time of first perceived pain reduction if a patient reported clinically meaningful (at least moderate) relief. The conventional method of comparing mean treatment responses at each time point was also implemented. Demulcent action was detected at the first 2-minute assessment. By the new method, 102 flurbiprofen-treated patients were identified as first perceiving pain relief at 12 minutes, compared with >120 minutes by 102 patients using placebo (P < 0.001). By the conventional method, mean percentage pain reduction for flurbiprofen 8.75 mg was first significantly differentiated from placebo at 26 minutes (P < 0.05). Efficacy of flurbiprofen lozenge was demonstrated for 3.5-4 hours on the 4 patient-reported outcomes (all P < 0.05 compared with placebo). There were no serious adverse events. This patient-centered onset-of-action model identifies the initiation of pain relief in patients who are definite drug responders, here demonstrating that a flurbiprofen 8.75-mg lozenge provides early relief of sore throat.     

Organizational and structural reform in aged care organizations: empowerment towards a change process

Aims The aims were first to explore strategies for both structural and organizational reform by the process of action research, and second to use collective self-inquiry by all study participants as a way of examining problems and deciding on actions to bring about change. Rationale It was hoped that this process would empower the staff, aged residents and family members to own and therefore be meaningfully involved in improving practice and care standards. Background/introduction Three aged care centres expressed a desire to enhance the quality of care provided in order to meet the criteria for accreditation. They wanted to participate in a process that would assist them in critically examining their resource allocation, service delivery patterns and outcomes for residents. Research methods Original data were collected in three different aged care facilities over a three-year period from 1996 to 1998 in order to seek answers to the usefulness of action research in the change process. The methodology included participant observation, interviews and focus group discussions with all participants. Results/findings Organizational change occurred across the three centres with subsequent changes in the outcomes for both residents and staff. The themes which emerged from the data analysis process and which enhanced the participatory process included the need for flattened organizational structures and management's willingness to fully support the process and to be more transparent. The factors that inhibited the process included the organizational culture and tokenistic support by management. Discussion/conclusion Participatory action research was found to be a successful process for identifying and acting on the enhancers and inhibitors to structural and organizational reform.     

Change in process: bringing about change in health care through action research

• ? A 2-year action-research project aiming to facilitate the management of change was carried out in a district general hospital.
• ? Hospital managers and senior ward nurses had very different views concerning the source of challenges and problems within the hospital organization.
• ? A case-study of nurses' experience of change at ward level was produced as part of the diagnostic phase of the action research.
• ? The results of the case-study indicated that general managers and professionals had different agendas for change hut that there is common ground between them.

     

Effects of successful cardioversion of persistent atrial fibrillation on right ventricular refractoriness and repolarization.

AIM: Changes in ventricular refractoriness and repolarization after successful electrical cardioversion to sinus rhythm in persistent atrial fibrillation (AF) patients were studied. METHODS AND RESULTS: In 33 AF patients with controlled ventricular response, right ventricular ERP (VERP) at three basic cycle lengths (600, 500, 400 ms), as well as monophasic action potential duration (MAPd(90)) at a drive cycle length of 500 ms, were measured just before, 20 min and 24 h after cardioversion. VERP at 600 ms changed from 241+/-19 ms to 249+/-21 ms to 253+/-24 ms (P<0.001), VERP at 500 ms changed from 234+/-19 ms to 242+/-22 ms to 246+/-23 ms (P<0.001) and VERP at 400 ms changed from 224+/-20 ms to 232+/-23 ms to 236+/-24 ms (P<0.001). MAPd(90) changed from 247+/-16 ms preconversion to 252+/-17 ms 20 min postconversion to 253+/-19 ms after 24 h (P<0.05). Change in refractoriness at 500 ms was well correlated with change of mean RR interval before and 20 min after conversion (R=0.616, P<0.001). There was no correlation between RR variability and VERP before cardioversion. CONCLUSION: Restoration of sinus rhythm in persistent AF patients is followed by significant effects on ventricular refractoriness and repolarization related to cycle length change. No AF related ventricular electrophysiological alterations were found.     

食管癌组织KAI1/CD82的表达与其生物学行为的关系

目的　探讨食管癌组织和正常食管组织中KAI1/CD82 表达的临床意义及其与生物学行为的关系。方法　应用免疫组化SABC法 ,检测 5 2例食管癌及 3 3例食管正常组织中KAI1/CD82 的表达 ,并进行比较分析。结果　食管正常组织、无淋巴结转移食管癌组织和有淋巴结转移食管癌组织KAI1/CD82 的表达率分别为 48 5 % ( 16/3 3 )、 73 7% ( 2 8/3 8)、 2 8 6% ( 4 /14 ) ,食管正常组织、无淋巴结转移食管癌组织、有淋巴结转移食管癌组织KAI1/CD82 的表达有显著差异 (P <0 0 5 )。结论　KAI1/CD82 在食管癌早期高水平表达对肿瘤的恶性进程起抑制作用 ,一旦无法保持KAI1/CD82 的高水平表达则促使肿瘤进入发展期 ,进而发生转移。     

2型糖尿病的循证治疗

以Meta-分析和随机对照试验文献为基础,回顾近年来用于2型糖尿病血糖控制的药物治疗及与衰老相关的糖尿病问题的循证证据.结果发现,胰岛素联合口服降糖药的治疗方案更能改善2型糖尿病患者的胰岛素抵抗和胰岛β细胞功能缺陷;应警惕老年2型糖尿病患者合并的认知功能障碍和抑郁症.