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）。     

Assessment of genetic and nongenetic influences on pulmonary function. A twin study

To better understand the extent to which familial similarities in pulmonary function (PF) are attributable to genetic rather than to shared environmental influences, we studied the twinship aggregation of PF in 256 monozygotic (MZ) and 158 dizygotic (DZ) adult twin members of the Greater Boston Twin Registry. Genetic influences on various spirometric measures were estimated with twinship intrapair correlations adjusted using a regression model to control for similarities in the anthropomorphic characteristics of twins, and for the effects of a number of environmental factors that included childhood respiratory illness, occupational dust exposure, and smoking history. A significant influence of smoking on all air-flow measures was observed in this population for whom genetic similarities were adjusted. However, highly significant adjusted intrapair correlations for all spirometric measures, ranging from 0.52 to 0.76, were observed for the MZ twins. The intrapair correlations for the DZ twins were approximately one-half the magnitude of those for the MZ twins. These data suggest that a large proportion of the measured variability in PF may be accounted for by genetic influences other than those associated with body size.     

Development and validation of school-based asthma and allergy screening instruments for parents and students.

BACKGROUND: The increasing morbidity attributable to asthma among school-aged children suggests the potential utility of school-based asthma screening programs. OBJECTIVE: We report our efforts to develop and validate culturally sensitive and clinically useful screening questionnaires (parent and child versions) for asthma and allergies among urban US school children. METHODS: Instrument development was accomplished through literature review, expert medical and child developmental input, focus group feedback, and a rigorous trial of the instruments in a public school setting. Questionnaires were distributed to 2,800 children and their families in an urban public school system (grades kindergarten through 6). Validity was evaluated by blinded comparison of results against a standardized clinical evaluation in 107 children, with final designations determined by an expert panel. RESULTS: Questionnaires pertaining to 2,083 children were returned (participation rate of 74%). A moderate level of agreement was observed between parent and student questionnaire responses (r values = 0.36 to 0.50; P values < 0.001). The highest frequency of asthma-like symptoms was reported for African-American boys and the lowest for Caucasian girls. The items from the parent questionnaire that best predicted asthma were "breathing problems" (occurring rarely or more; odds ratio 12.8; 95% confidence interval, 4.5 to 36.1) and "problems coughing" (sometimes or more; odds ratio 9.7; 95% confidence interval, 3.6 to 26.5). Considering the presence of cough (sometimes or more) and/or breathing problem (rarely or more) yielded a sensitivity of 80%; a specificity of 75%, a positive predictive value of 50%, and a negative predictive value of 92%. Similar levels of prediction were observed for the items "trouble breathing" and "noisy breathing" as directly reported by the students. Allergic rhinitis was best predicted by report of a runny/stuffy no se (sometimes or more; sensitivity of 83%, specificity of 61%).Allergic conjunctivitis was best predicted by "itchy eyes." CONCLUSIONS: Administration of a school-based questionnaire is feasible, with a high response rate and excellent internal consistency. A high sensitivity and acceptable specificity was achieved by using one to two questions for asthma, allergic rhinitis, and allergic conjunctivitis. Among the children in grades 2 or above, comparable levels of prediction could be achieved with the student or parent version.     

Localization of fetal major histocompatibility complex antigens and maternal leukocytes in murine placenta. Implications for maternal-fetal immunological relationship

An immunohistochemical study of the days 14-19 murine placenta and uterus using a panel of antibodies specific for maternal and paternal class I major histocompatibility complex (MHC) antigens, specific leukocyte subsets, and other lineage-specific markers was performed to elucidate the nature of the maternal tolerance of the fetal implant in the uterus. Fetally derived trophoblast lining maternal blood spaces lacked MHC antigens, but other interstitial trophoblasts expressed fetally derived polymorphic class I MHC determinants. The latter class I MHC-bearing trophoblasts were most prominent in the maternal decidua basalis where they were mixed with maternal cells. Our results identify two factors that may be relevant for understanding why these alloantigen-bearing fetal cells are not rejected by the mother: a paucity of la-bearing antigen presenting cells, macrophages, and mature T and B lymphocytes and the presence of large numbers of Thy-1+ asialo-GM-1+ CD4- CD8- bone marrow-derived (CLA/Ly5+) cells of maternal origin in the decidua basalis. These latter cells correspond to previously described granulated metrial gland cells that may be involved in local immunoregulation.     

Role of the host in pathogenesis of Helicobacter-associated gastritis: H. felis infection of inbred and congenic mouse strains.

In humans, Helicobacter pylori establishes a chronic infection which can result in various degrees of gastric inflammation, peptic ulcer disease, and a predisposition to gastric cancer. It has been suggested that bacterial virulence factors such as the vacuolating toxin (VacA) and the cytotoxin-associated gene product (CagA) may play a major role in determining the clinical outcome of Helicobacter infections. The role of host responses in these varied outcomes has received little attention. Helicobacter felis, which does not express CagA or VacA, causes chronic infection and inflammation in a well-characterized mouse model. We have used this model to evaluate the role of host responses in Helicobacter infections. BALB/c, C3H, and C57BL/6 mice were orally infected with a single strain of H. felis, and 2 and 11 weeks after infection, the mice were sacrificed and evaluated histologically for magnitude of H. felis infection. Intensity and extent of inflammation, and cellular composition of the inflammatory infiltrate. All three strains of mice demonstrated comparable levels of infection at 11 weeks, but the pattern and intensity of inflammation varied from minimal in BALB/c mice to severe in C57BL/6 mice. Gastric epithelial erosions were noted in C3H mice, and mucous cell hyperplasia was observed in C3H and C57BL/6 mice. Abundant mucosal mast cells were observed in the gastric tissues of all three mouse strains. Studies using major histocompatibility complex (MHC)-congenic mice revealed probable contributions by both MHC and non-MHC genes to Helicobacter-induced inflammation. Thus, large variations in the severity of disease were observed after infection of different inbred strains and congenic mice with a single isolate of H. felis. These results demonstrate the importance of the host response in disease outcome following gastric Helicobacter infection.     

CD25+ T cells induce Helicobacter pylori‐specific CD25− T‐cell anergy but are not required to maintain persistent hyporesponsiveness

The gastric pathogen Helicobacter pylori infects over half the world's population. The lifelong infection induces gastric inflammation but the host fails to generate protective immunity. To study the lack of protective H. pylori immunity, CD4⁺CD25⁺ T_reg cells were investigated for their ability to down‐regulate H. pylori‐specific CD4⁺CD25⁻ cells in a murine model. CD25⁻ lymphocytes from infected mice were hyporesponsive to antigenic stimulation in vitro even in the absence of CD25⁺ T_reg cells unless treated with high‐dose IL‐2. Transfer of CD45RB^hi naïve CD25⁻ cells from infected mice into rag1^−/− mice challenged with H. pylori resulted in severe gastritis and reduced bacterial loads, whereas transfer of CD45RB^lo memory CD25⁻ cells from H. pylori‐infected mice resulted in only mild gastritis and persistent infection. CD25⁻ cells stimulated in the absence of CD25⁺ cells in rag1^−/− mice promoted bacterial clearance, but lost this ability when subsequently transferred to WT mice harboring CD25⁺ cells. These results demonstrate that CD25⁺ cells induce anergy in CD25⁻ cells in response to H. pylori infection but are not required to maintain hyporesponsiveness. In addition, CD25⁺ cells are able to suppress previously activated CD25⁻ cells when responding to H. pylori challenge in vivo.