Chemoimmunotherapy for cutaneous melanoma with dacarbazine and epifocal contact sensitizers: results of a nationwide survey of the German Dermatologic Co-operative Oncology Group

Purpose To scrutinize published data from small mono-centric studies and case reports which implicated high response rates and promising survival times for a combination therapy consisting of epifocal dinitrochlorobenzene (DNCB) and dacarbazine (DTIC) for metastasized melanoma. This therapy merges the effects of an allergic contact dermatitis elicited at the site of a cutaneous metastasis, and systemic chemotherapy. Methods We performed a retrospective survey with nine German centers and evaluated 72 patients treated from 1993 to 2005. Results The objective response rate in stage III melanoma (n = 39) was 62%. In contrast, only 9% objective responses were observed in 33 stage IV patients. Interestingly, more than half of patients with objective remissions remained progression-free for more than 1 year irrespective of the stage of disease. Conclusions Epifocal DNCB combined with DTIC is effective in patients with regionally metastasized melanoma not amenable to surgery or isolated limb perfusion, whereas in stage IV disease in spite of few durable remissions the addition of DNCB does not improve the therapeutic efficacy of DTIC.     

Structure-activity relationship of antiestrogens: a study using triarylbutenone, benzofuran, and triarylfuran analogues as models for triarylethylenes and triarylpropenones

In a study of the structure-activity relationship (SAR) of antiestrogens use has been made of certain 1,2,3-triarylbutenones, of 2-arylbenzofurans carrying aryl or aroyl substituents at C3, and of 2,3,4-triarylfurans as conformationally constrained models for triarylethylene (TAE) and triarylpropenone (TAP) prototypes. The position-specific contributions of substituents to receptor affinity and to agonist-antagonist profiles were used as aids in characterizing the relative binding orientation of the prototypes. Although most compounds were found to be weak receptor ligands and poorly active in vivo, the following conclusions could be drawn about their SAR: (i) (Z)-TAPs and TAEs interact with the receptor in an analogous manner using the trans-stilbene core, with their agonist-antagonist profiles depending on the nature of other substructures. (ii) Incorporation into the benzofuran framework introduces a stereoelectronic constraint that compromises the normal binding interactions of TAE, as well as TAP, prototypes, resulting in their poor affinities and weak biological activities. (iii) (E)-TAPs can interact with the receptor through their S-cis conformation, but such a binding mode is unlikely to account for their behavior as antagonists.     

Myocarditis and pericarditis in children

Myocarditis and pericarditis are rare but important causes of pediatric chest pain. The diagnostic criteria, clinical course, causes, and treatment of myocarditis is reviewed. There is particular attention to the relationship of myocarditis with dilated cardiomyopathy. Supportive therapy remains the standard of care for pump dysfunction. The identification and treatment of pericarditis with associated large pericardial effusion can be lifesaving. This article reviews the important clinical features that might lead the clinician to diagnose either myocarditis or pericarditis and thus separate the few patients with either of these conditions from the legions of children with noncardiac chest pain.