Background-Endothelial function is known to be impaired in subjects with chronic heart failure(CHF), but the association between endothelial function and subsequent mortality risk in CHF has not been previously report...Background-Endothelial function is known to be impaired in subjects with chronic heart failure(CHF), but the association between endothelial function and subsequent mortality risk in CHF has not been previously reported. Methods and Results-Biomarkers of endothelial function in the systemic arterial circulation(flow-mediated dilation [FMD] in the brachial artery) and the pulmonary circulation(exhaled nitric oxide [NO] production during submaximal exercise) were prospectively assessed in 259 subjects with New York Heart Association class II-III CHF. In subjects with FMD measurements(n=149), there were 12 deaths and 5 urgent transplantations over a median follow-up period of 841 days. In subjects with exhaled NO production measurements(n=110), there were 18 deaths and 1 urgent transplantation over a median follow-up period of 396 days. Both decreased FMD and decreased exhaled NO production were associated with increased risk of death or urgent transplantation after adjustment for other known CHF prognostic factors(age, etiology of CHF, functional class, left ventricular ejection fraction) in Cox multivariate proportional hazards models(adjusted hazard ratio [HR] estimate for a 1%decrease in FMD=1.20; 95%confidence interval [CI], 1.03 to 1.45; P=0.027; adjusted HR estimate for a 1-ppb/min decrease in exhaledNOproduction=1.31,95%CI, 1.01 to 1.69,P=0.04)-. Conclusions-Endothelial dysfunction in CHF, as assessed by FMD in the brachial artery and exhaled NO production during submaximal exercise, is associated with an increased mortality risk in subjects with both ischemic and nonischemic CHF.展开更多
An adverse cutaneous reaction to a systemically administered drug may rarely manifest as acute generalized exanthematous pustulosis (AGEP). Several recent reports have documented positive patch test results in patient...An adverse cutaneous reaction to a systemically administered drug may rarely manifest as acute generalized exanthematous pustulosis (AGEP). Several recent reports have documented positive patch test results in patients with a history of AGEP, while two have demonstrated drug- specific in vitro lymphocyte proliferative responses. These findings suggest that drug- specific T cells mediate AGEP. We describe two patients with a history of AGEP who each demonstrated positive patch test results specific for the inciting drug: Patient # 1 to the antibiotic metronidazole, and Patient # 2 to the calcium channel- blocker diltiazem. Histologic examination of biopsy specimens taken from the patch test sites of these patients revealed spongiotic dermatitis and perivascular lymphocytes consistent with a delayed- type hypersensitivity reaction, rather than demonstrating subcorneal neutrophilic pustules more typical of AGEP. In vitro testing by measuring peripheral T cell proliferative responses to chemically purified drug correlated with the clinical response. In a direct cross- comparison, patch test results were shown to correlate with in vitro lymphocyte proliferative responses in two patients with a history of AGEP to different drugs. These findings provide additional evidence that the pathogenesis of AGEP involves a T cell- mediated immune response.展开更多
Background: Nevi on certain areas of the body such as the acral, genital, and flexural regions may exhibit uncommon but characteristic histopathologic features. The purpose of this study was to characterize the distin...Background: Nevi on certain areas of the body such as the acral, genital, and flexural regions may exhibit uncommon but characteristic histopathologic features. The purpose of this study was to characterize the distinctive features of nevi with a junctional component located on and around the ear. Materials and methods: A total of 101 compound and junctional nevi of the ear received at the Yale Dermatopathology Laboratory during a 10- year period were examined in this study. The most characteristic feature of the majority of these nevi was irregularity of nesting pattern, with nests, which varied in size and shape and which were sometimes located between rete ridges. Results: Forty- two (42% ) of nevi on and around the ear showed poor circumscription, lateral extension of the junctional component beyond the dermal component, and elongation of rete ridges with bridging between them. A subset of these nevi (26 cases)showed uniformly large melanocytes with large vesicular nuclei without prominent nucleoli, and abundant pale, finely granular cytoplasm. These lesions did not show a tendency to recur. Conclusions: This study supports the existence of a subset of nevi on or near the ear that, like certain nevi located on other special sites, exhibit unusual but characteristic features, which may be misinterpreted as atypical or malignant.展开更多
文摘Background-Endothelial function is known to be impaired in subjects with chronic heart failure(CHF), but the association between endothelial function and subsequent mortality risk in CHF has not been previously reported. Methods and Results-Biomarkers of endothelial function in the systemic arterial circulation(flow-mediated dilation [FMD] in the brachial artery) and the pulmonary circulation(exhaled nitric oxide [NO] production during submaximal exercise) were prospectively assessed in 259 subjects with New York Heart Association class II-III CHF. In subjects with FMD measurements(n=149), there were 12 deaths and 5 urgent transplantations over a median follow-up period of 841 days. In subjects with exhaled NO production measurements(n=110), there were 18 deaths and 1 urgent transplantation over a median follow-up period of 396 days. Both decreased FMD and decreased exhaled NO production were associated with increased risk of death or urgent transplantation after adjustment for other known CHF prognostic factors(age, etiology of CHF, functional class, left ventricular ejection fraction) in Cox multivariate proportional hazards models(adjusted hazard ratio [HR] estimate for a 1%decrease in FMD=1.20; 95%confidence interval [CI], 1.03 to 1.45; P=0.027; adjusted HR estimate for a 1-ppb/min decrease in exhaledNOproduction=1.31,95%CI, 1.01 to 1.69,P=0.04)-. Conclusions-Endothelial dysfunction in CHF, as assessed by FMD in the brachial artery and exhaled NO production during submaximal exercise, is associated with an increased mortality risk in subjects with both ischemic and nonischemic CHF.
文摘An adverse cutaneous reaction to a systemically administered drug may rarely manifest as acute generalized exanthematous pustulosis (AGEP). Several recent reports have documented positive patch test results in patients with a history of AGEP, while two have demonstrated drug- specific in vitro lymphocyte proliferative responses. These findings suggest that drug- specific T cells mediate AGEP. We describe two patients with a history of AGEP who each demonstrated positive patch test results specific for the inciting drug: Patient # 1 to the antibiotic metronidazole, and Patient # 2 to the calcium channel- blocker diltiazem. Histologic examination of biopsy specimens taken from the patch test sites of these patients revealed spongiotic dermatitis and perivascular lymphocytes consistent with a delayed- type hypersensitivity reaction, rather than demonstrating subcorneal neutrophilic pustules more typical of AGEP. In vitro testing by measuring peripheral T cell proliferative responses to chemically purified drug correlated with the clinical response. In a direct cross- comparison, patch test results were shown to correlate with in vitro lymphocyte proliferative responses in two patients with a history of AGEP to different drugs. These findings provide additional evidence that the pathogenesis of AGEP involves a T cell- mediated immune response.
文摘Background: Nevi on certain areas of the body such as the acral, genital, and flexural regions may exhibit uncommon but characteristic histopathologic features. The purpose of this study was to characterize the distinctive features of nevi with a junctional component located on and around the ear. Materials and methods: A total of 101 compound and junctional nevi of the ear received at the Yale Dermatopathology Laboratory during a 10- year period were examined in this study. The most characteristic feature of the majority of these nevi was irregularity of nesting pattern, with nests, which varied in size and shape and which were sometimes located between rete ridges. Results: Forty- two (42% ) of nevi on and around the ear showed poor circumscription, lateral extension of the junctional component beyond the dermal component, and elongation of rete ridges with bridging between them. A subset of these nevi (26 cases)showed uniformly large melanocytes with large vesicular nuclei without prominent nucleoli, and abundant pale, finely granular cytoplasm. These lesions did not show a tendency to recur. Conclusions: This study supports the existence of a subset of nevi on or near the ear that, like certain nevi located on other special sites, exhibit unusual but characteristic features, which may be misinterpreted as atypical or malignant.
