Toxic epidermal necrolysis; 15 years'' experience in a Dutch burns centre

BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe and potentially fatal drug reaction characterized by an extensive skin rash with blisters and exfoliation, frequently accompanied by mucositis. The wounds caused by TEN are similar to second-degree burns and severe cases may involve large areas of skin loss. OBJECTIVES: Analysis of our results in patients with TEN and evaluation of the variety of therapeutic interventions that has been studied and suggested in TEN. PATIENTS/METHODS: Retrospective analysis of 19 consecutive patients with TEN treated in our burns centre between 1989 and 2004. RESULTS: Immediate withdrawal of any potentially fatal drug, maximum supportive care, and a restricted and tailored antibiotic, medical and surgical treatment regimen confined mortality to 21%, whereas prognosis scores like APACHE II and SCORTEN predicted mortality of 22 and 30%, respectively. A positive contribution of selective digestive decontamination is suggested but has yet to be established. CONCLUSIONS: Because of a potentially fatal outcome, fast referral of a patient suspected of TEN to a specialized centre (mostly a burns unit or specialized dermatology centre) for expert wound management and tailored comprehensive care is strongly advised and contributes to survival.     

女性慢性下腹痛的干预性治疗

1背景 育龄妇女常见慢性下腹痛，可造成身体损害、情绪忧伤及导致巨大的健康服务费用。美国在这方面的花费超过8亿8千万美元（Mathias 1996）。英国全国数据库的一般性诊治资料显示，慢性下腹痛发病率及流行率与偏头痛、背部痛、哮喘发病率相似（Zondervan 1999）。     

Type 1 and 2 isoenzymes of cAMP-dependent protein kinase in Leydig cell steroidogenesis.

This study examined the functional significance of the type 1 (T1) and type 2 (T2) cAMP-dependent protein kinase (PK-A) isoenzymes in androgen production by mouse Leydig cells. Leydig cells were exposed to cAMP analogues selective for either of the two cAMP binding sites on the regulatory subunits of each PK-A isoenzyme. As the two binding sites have been shown to exhibit positive cooperativity, coexposure to the appropriate combination of analogues will synergistically increase androgen production if either T1 or T2 PK-A is present and functional in the cell. We found that both PK-A isoenzymes are present and functionally active, though the T1 kinase predominates. Coexposure to the cAMP analogues and cAMP or luteinizing hormone also synergistically increased androgen production via both isoenzymes while forskolin acted only via the T1 isoenzyme, suggesting that forskolin may instigate cellular events in addition to cAMP synthesis.     

Interaction between cyclic nucleotide second messenger systems in murine Leydig cells.

Mouse Leydig cell androgen production can be acutely stimulated by atrial natriuretic factor (ANF) via cyclic guanosine 3',5'-monophosphate (cGMP). This stimulation can approach that seen with high concentrations of luteinizing hormone (LH) acting via cyclic adenosine 3',5'-monophosphate (cAMP). To assess the potential for synergistic interaction between LH/cAMP and ANF/cGMP Leydig cells were co-exposed to ANF and LH or ANF/cGMP and site/type-selective cAMP analogues. Co-exposure to 1 nM ANF and 1 ng/ml LH elicited a synergistic increase in androgen production. Both 500 microM 8-bromo-cGMP and ANF (1.0-2.5 nM) synergized with cAMP analogues selective for either of the two major isoenzymes of protein kinase A. Phosphodiesterase (PDE) inhibition was not involved as inclusion of a PDE inhibitor only augmented the response. It appears that ANF/cGMP may interact cooperatively with LH/cAMP in the stimulatory control of androgen production in the mouse Leydig cell and that the site of synergistic interaction may be the activation of the cAMP-dependent protein kinase.