Skin manifestations and clinical features of drug reaction with eosinophilia and systemic symptoms: a retrospective multicentre study of 125 patients.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction generally accompanied by skin manifestations as the first and most frequent symptoms. However, skin manifestations and associated clinical features of DRESS have not been fully explored and evaluated. OBJECTIVES: This study aimed to describe the skin manifestations of DRESS in detail and analyse their association with demographic characteristics and extra-cutaneous clinical features. METHODS: We conducted this retrospective study on patients with DRESS diagnosed between September 2009 and August 2021 at three medical institutes and validated using the RegiSCAR score. Data regarding demographics, skin manifestations and clinical characteristics were retrieved through thorough chart reviews. RESULTS: Among 182 potential cases of DRESS, the validated 125 cases were analysed. A widespread rash extending over more than 50% of the body surface area was observed in 122 patients (97.6%) and typical facial oedema was experienced by 67 patients (53.6%). Polymorphous maculopapules were the most common rash morphology (106, 84.8%): specifically, exfoliative (59, 47.2%), urticarial (57, 45.6%) and purpuric forms (39, 31.2%) were common. Mucosal involvement was observed in 41 patients (32.8%). Patients with carboxamide antiepileptics (carbamazepine and oxcarbazepine) experienced more oedema (P = 0.014) and typical facial oedema than those with allopurinol (P = 0.021). The RegiSCAR score was higher in patients with purpura (P < 0.01). CONCLUSIONS: Skin manifestations of DRESS exhibit a wide range of skin lesions and can vary according to the culprit drugs. Early suspicion and prompt intervention are needed to improve prognosis.

Evaluation of exposure risk for healthcare personnel performing the open technique HIPEC procedure using cisplatin.

OBJECTIVE: To perform an evaluation of the risk to healthcare personnel of exposure to cisplatin during a Hyperthermic Intraperitoneal Chemotherapy (HIPEC) procedure in an operating room environment. METHODS: Breathing zone air samples were taken from the operating room (OR) before, during and after the procedure of HIPEC filter membrane adsorption and the liquid impact method was applied to collect air samples. The samples of surface wipe from the floor of the OR were taken after the procedure. Inductively coupled plasma mass spectrometry(ICP-MS) was used to detect the content of cisplatin in all the samples. RESULTS: Thirty-six air samples and three surface wipes were collected from three different locations of healthcare personnel breathing zones. All the breathing zone air samples were negative for cisplatin; however, cisplatin contamination was detected on three surface wipes from the floor, but in a lowconcentration(≤ 2.25 ng). CONCLUSION: The results suggest that the risk of inhalation of cisplatin was extremely low for the healthcare personnel during the procedure of HIPEC, but the contamination of the OR floor should be taken into consideration.

The Process of Developing a Unit-Based Army Resilience Program.

PURPOSE OF REVIEW: We review military doctrine, military public health data, medical literature, and educational literature with the intent of condensing key precepts into a succinct, pragmatic description of the essential steps for leaders looking to build a resilience program to provide secondary prevention services. RECENT FINDINGS: Although there continues to be a shortage of high-level evidence in support of specific preventive programs, there are numerous large-scale reviews of prevention and health promotion efforts. When combined with population-specific analyses, several essential concepts emerge as most relevant for smaller-scale prevention programs. The key tenets that program leaders should embrace to optimize program effectiveness include utilization of an instructional design approach, focus on evidence-based practices, and teaching resilience skills in order to decrease risk factors and increase protective factors for improved mental health outcomes.

[Clinical outcomes of opening coronary chronic total occlusion lesions with the assistance of BridgePoint devices].

Objective: To investigate the safety, efficacy and prognosis of antegrade dissection re-entry (ADR) with the assistance of BridgePoint devices in opening coronary chronic total occlusion (CTO). Methods: A total of 87 consecutive patients, who underwent percutaneous coronary intervention using BridgePoint devices from April 2016 to December 2018 in Xijing Hospital, were included in this study. General information of the selected patients, features of CTO lesions and intraoperative parameters were recorded. Short-term outcomes including technical success rate (defined as achieving TIMI 3 blood flow with residual stenosis<30%), surgical success rate (defined as no major adverse cardiovascular events (MACE) occured while hospitalized), complications, and MACE during hospitalization were observed. MACE included death, recurrent myocardial infarction, target vascular reconstruction (TVR) and cardiac tamponade. Patients were followed up by outpatient or telephone visits at 30 days and 6, 12, 24 and 36 months after discharge. Results: Eighty-seven patients, aged (61±10) years with J-CTO scores (2.49±0.52) were included, and 75(86%) were male. Six patients underwent direct ADR with BridgePoint system, and all were successful. Eighty-one patients underwent rescue ADR using BridgePoint devices, and 62 of them were successful. The success rate of ADR with BridgePoint devices was 78.2% (68/87). Nine out of the 19 failed cases succeeded after the application of rescue antegrade/retrograde technique. The technical success rate was 88.5% (77/87). Coronary perforation occurred in 2 cases (2.3%), one case was treated with covered stent and the other case with tamponade was treated with pericardiocentesis. One patient developed periprocedural myocardial infarction, and one patient suffered from sudden death, and one patient had cardiac tamponade. In-hospital MACE occurred in 3 (3.4%) patients. The surgical success rate was 85.1% (74/87).The procedure time was (175±72)minutes and the amount of contrast used was (449±155)ml. During a follow-up of 17(11, 26) months, the incidence of MACE within 30 days was 4.7% (4/86), while 10.5% (9/86) within 6 months, 17.4% (15/86) within 17 months. Conclusion: Opening CTO with the assistance of BridgePoint devices is feasible and safe, with high success rate and satisfactory outcome.

Incidence of cephalosporin-induced anaphylaxis and clinical efficacy of screening intradermal tests with cephalosporins: A large multicenter retrospective cohort study.

BACKGROUND: Few studies have investigated the incidence of anaphylaxis induced by individual or structurally similar cephalosporins. The aims of the study were to assess the incidence of cephalosporin-induced anaphylaxis and evaluate the clinical efficacy of screening skin tests. METHODS: In this retrospective cohort study, we obtained information on total cephalosporin use and cephalosporin-induced anaphylaxis in intravenous cephalosporin recipients in 12 general hospitals between 2013 and 2015. Cephalosporins were divided into 4 groups according to similar side-chain structures. The incidence of cephalosporin-induced anaphylaxis was assessed for each cephalosporin, cephalosporin generation, and side-chain group. To verify the efficacy of screening intradermal tests (IDT) with cephalosporin, the 12 hospitals were assigned to the intervention or control group depending on whether they performed screening IDT before the administration of cephalosporins. RESULTS: We identified 76 cases of cephalosporin-induced anaphylaxis with 1 123 345 exposures to intravenous cephalosporins (6.8 per 100 000 exposures), and the incidence of fatal anaphylaxis by cephalosporin was 0.1 cases per 100 000 exposures. The highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100 000 exposures) and side-chain group 1 (cefepime, cefotaxime, ceftizoxime, ceftriaxone, and cefuroxime; 9.3 per 100 000). There was no case of anaphylaxis induced by cefoxitin, cefmetazole, cefminox, and cefotiam. The clinical effectiveness of routine screening IDT was not significant (P = .06). CONCLUSIONS: The incidence of cephalosporin-induced anaphylaxis differed according to individual drugs and side-chain structure. Screening IDT showed no clinical efficacy at a population level.

[Magnetic resonance imaging characteristics of encephalopathy of prematurity].

Objective: To explore the MRI manifestation of encephalopathy of prematurity (EOP), so as to find an access to the early prevention, early diagnosis, effective treatment and prognosis. Methods: A total of 2 718 premature infants were collected, MRI and clinical data were analyzed who were admitted to NICU of Children's Hospital of Fudan University between January 1, 2009 and December 31, 2014. The manifestation and lesions distribution in MRI were analyzed. Results: All the 2 718 preterm infants underwent MRI. 58.8% (1 599/2 718) of which had normal MRI apperance, whereas 24.9% (678/2 718) showed manifestations of EOP.78.8% (534/678) EOP were non-cystic EOP. 21.2% (144/678) EOP were cystic EOP. Periventricular and cerebral lobe white matter were primary distributions of these lesions. Cystic lesions were primarily distributed in the body of periventricular whiter matter (49.3%). However, more non-cystic EOP were found in cerebral parietal lobe whiter matter (25.1%). Non-cystic EOP were also distributed in the body of periventricular whiter matter, frontal lobe and basal ganglia(20.8%, 20.2% and 18.9%, respectively ). Conclusions: The morbidity rate of EOP in preterm infants was 24.9%. 21.2% (144/678) EOP were cystic EOP. 78.8% (534/678) EOP were non-cystic EOP. Cystic lesions were primarily distributed in the body of periventricular whiter matter. Non-cystic EOP were also distributed in the body of periventricular whiter matter, frontal lobe and basal ganglia.

Staphylococcal enterotoxin IgE sensitization in late-onset severe eosinophilic asthma in the elderly.

BACKGROUND: Asthma in the elderly (aged ≥ 65 years old) is a significant concern with high morbidity, but the pathophysiology remains unclear particularly in late-onset asthma. Recent studies suggest staphylococcal enterotoxin IgE (SE-IgE) sensitization to be a risk factor for asthma in general populations; however, the associations have not been examined in late-onset elderly asthma. OBJECTIVE: We aimed to examine the associations of SE-IgE sensitization with late-onset asthma in the elderly, using a database of elderly asthma cohort study. METHODS: A total of 249 elderly patients with asthma and 98 controls were analysed. At baseline, patients were assessed for demographics, atopy, induced sputum profiles and comorbidities including chronic rhinosinusitis (CRS). Serum total IgE and SE-IgE levels were measured. Asthma severity was assessed on the basis of asthma outcomes during a 12-month follow-up period. RESULTS: At baseline, serum SE-IgE concentrations were significantly higher in patients with asthma than in controls [median 0.16 (interquartile range 0.04-0.53) vs. 0.10 (0.01-0.19), P < 0.001]. Elderly asthma patients with high SE-IgE levels had specific characteristics of having more severe asthma, sputum eosinophilia and CRS, compared to those with lower SE-IgE levels. In multivariate logistic regression analyses, the associations between serum SE-IgE concentrations and severe asthma were significant, independently of covariables [SE-IgE-high (≥ 0.35 kU/L) vs. negative (< 0.10 kU/L) group: odds ratio 7.47, 95% confidence interval 1.86-30.03, P = 0.005]. Multiple correspondence analyses also showed that high serum SE-IgE level had close relationships with severe asthma, CRS and sputum eosinophilia together. CONCLUSIONS AND CLINICAL RELEVANCE: This is the first report on the significant associations of SE-IgE sensitization with late-onset asthma in the elderly, particularly severe eosinophilic asthma with CRS comorbidity. Our findings indicate a potential implication of SE in the high morbidity burden of elderly asthma and suggest clues to the pathogenesis of severe late-onset eosinophilic asthma in the elderly.

Effect of dual Bt-expression transformation vectors on transgene expression in tobacco.

This study aimed to determine the influence of vector structure on dual Bt gene expression and establish an efficient expression vector using Cry1Ac and Cry3A genes. Four vectors (N4, N5, N10, and S23) were developed and used for genetic transformation of tobacco to obtain insect-resistant transgenic lines. The vectors were constructed using the MAR structure, applying different promoter and enhancer sequences, and changing the transgene open-reading frame sequence. The average Cry1Ac toxalbumin expression quantity was 67 times higher in N5 than in N4 transgenic lines (8.77 and 0.13 µg/g, respectively). In contrast, the average Cry3A toxalbumin expression quantity was 1.5 times higher in N4 than in N5 lines (12.70 and 8.21 µg/g, respectively). The sequences of both Bt genes significantly influenced toxalbumin expression, although upstream Bt genes presented lower expression levels. The average Cry1Ac toxalbumin content was 13 times higher in the transgenic lines of AtADH 5'-non-translated sequence N5 (8.77 mg/g) than in the omega N10 lines (0.67 mg/g). Furthermore, the average Cry1Ac toxalbumin content was 5 times higher in MAR N5 than in non-MAR S23 lines (8.77 and 1.63 mg/g, respectively). The average Cry3A toxalbumin content was 1.3 times higher in N5 than in S23 lines (8.21 and 6.48 mg/g, respectively). Moreover, toxalbumin expression levels differed significantly among the S23-transformed lines. The MAR structure applied on both ends of the genes increased both the level and stability of exogenous gene expression. In conclusion, N5 was the most optimal of the four tested vectors.

Genetic transformation and expression of transgenic lines of Populus x euramericana with insect-resistance and salt-tolerance genes.

We characterized new transgenic varieties of poplar with multiple insect-resistant and salt stress tolerant genes. Two insect-resistant Bacillus thuringiensis (Bt) genes, Cry1Ac and Cry3A, and a salt-tolerant gene, Betaine aldehyde dehydrogenase (BADH) were inserted into a vector, p209-Cry1Ac-Cry3A-BADH. The clone of Populus x euramericana was transformed by the vector using the Agrobacterium-mediated method. Three transgenic lines were assessed using genetic detection and resistance expression analysis. PCR revealed that exogenous genes Cry1Ac, Cry3A, BADH and selective marker gene NPTII were present in three transgenic lines. Quantitative real-time PCR (qPCR) showed significant differences in the transcriptional abundance of three exogenous genes in different lines. Results of assays for Bt toxic proteins showed that the Cry1Ac and Cry3A toxic protein content of each line was 12.83-26.32 and 2108.91-2724.79 ng/g, respectively. The Cry1Ac toxic protein content of different lines was significantly different; the Cry3A toxic protein content was about 100 times higher than that of the Cry1Ac toxic protein. The insect-resistance test revealed the mortality rate of transgenic lines to Hyphantria cunea L1 larvae varied by 42.2-66.7%, which was significantly higher than non-transgenic lines. The mortality rate of L1 and L2 Plagiodera versicolora larvae was 100%. The insecticidal effect of transgenic lines to P. versicolora larvae was higher than that to H. cunea larvae. NaCl stress tolerance of three transgenic lines under 3-6% NaCl concentration was significantly higher than that of non-transgenic lines.

Diversity of arthropod community in transgenic poplar-cotton ecosystems.

Poplar-cotton agro-ecosystems are the main agricultural planting modes of plain cotton fields in China. Here, we performed a systematic survey of the diversity and population of arthropod communities in four different combination of poplar-cotton eco-systems, including I) non-transgenic poplar and non-transgenic cotton fields; II) non-transgenic poplar and transgenic cotton fields [Bacillus thuringiensis (Bt) cotton]; III) Bt transgenic poplar (high insect resistant strain Pb29) and non-transgenic cotton; and IV) transgenic poplar and transgenic cotton fields, over a period of 3 years. Based on the statistical methods used to investigate community ecology, the effects of transgenic ecosystems on the whole structure of the arthropod community, on the structure of arthropods in the nutritive layer, and on the similarity of arthropod communities were evaluated. The main results were as follows: the transgenic poplar-cotton ecosystem has a stronger inhibitory effect on insect pests and has no impact on the structure of the arthropod community, and therefore, maintains the diversity of the arthropod community. The character index of the community indicated that the structure of the arthropod community of the transgenic poplar-cotton ecosystem was better than that of the poplar-cotton ecosystem, and that system IV had the best structure. As for the abundance of nutritional classes, the transgenic poplar-cotton ecosystem was also better than that of the non-transgenic poplar-cotton ecosystem. The cluster analysis and similarity of arthropod communities between the four different transgenic poplar-cotton ecosystems illustrated that the structure of the arthropod community excelled in the small sample of the transgenic poplar-cotton ecosystems.

Impacts of transgenic poplar-cotton agro-ecosystems upon target pests and non-target insects under field conditions.

Poplar-cotton agro-ecosystems are the main agricultural planting modes of cotton fields in China. With increasing acres devoted to transgenic insect-resistant poplar and transgenic insect-resistant cotton, studies examining the effects of transgenic plants on target and non-target insects become increasingly important. We systematically surveyed populations of both target pests and non-target insects for 4 different combinations of poplar-cotton eco-systems over 3 years. Transgenic Bt cotton strongly resisted the target insects Fall webworm moth [Hyphantria cunea (Drury)], Sylepta derogata Fabrieius, and American bollworm (Heliothis armigera), but no clear impact on non-target insect cotton aphids (Aphis gossypii). Importantly, intercrops containing transgenic Pb29 poplar significantly increased the inhibitory effects of Bt cotton on Fall webworm moth in ecosystem IV. Highly resistant Pb29 poplar reduced populations of the target pests Grnsonoma minutara Hubner and non-target insect poplar leaf aphid (Chaitophorus po-pulialbae), while Fall webworm moth populations were unaffected. We determined the effects of Bt toxin from transgenic poplar and cotton on target and non-target pests in different ecosystems of cotton-poplar intercrops and identified the synergistic effects of such combinations toward both target and non-target insects.

[A prospective study on association between sleep duration and the risk of chronic obstructive pulmonary disease in adults in Suzhou].

Objective: To investigate the prospective association of sleep duration with the development of chronic obstructive pulmonary disease (COPD) in adults in Suzhou. Methods: The study used the data of 53 269 participants aged 30-79 years recruited in the baseline survey from 2004 to 2008 and the follow-up until December 31, 2017 of China Kadoorie Biobank (CKB) conducted in Wuzhong District, Suzhou. After excluding participants with airflow limitation, self-reported chronic bronchitis/emphysema/coronary heart disease history at the baseline survey and abnormal or incomplete data, a total of 45 336 participants were included in the final analysis. The association between daily sleep duration and the risk for developing COPD was analyzed by using a Cox proportional hazard regression model, and the hazard ratio (HR) values and their 95%CI were calculated. The analysis was stratified by age, gender and lifestyle factors, and cross-analysis was conducted according to smoking status and daily sleep duration. Results: The median follow-up time was 11.12 years, with a total of 515 COPD diagnoses in the follow-up. After adjusting for potential confounders, multifactorial Cox proportional hazard regression analysis showed that daily sleep duration ≥10 hours was associated with higher risk for developing COPD (HR=1.42, 95%CI: 1.03-1.97). The cross analysis showed that excessive daily sleep duration increased the risk for COPD in smokers (HR=2.49, 95%CI: 1.35-4.59, interaction P<0.001). Conclusion: Longer daily sleep duration (≥10 hours) might increase the risk for COPD in adults in Suzhou, especially in smokers.

[Incidence of chronic obstructive pulmonary disease and risk factors in the Suzhou cohort].

Objective: To understand the incidence of chronic obstructive pulmonary disease (COPD) in the Suzhou cohort, and explore the risk factors for the development of COPD in Suzhou, and provide a scientific basis for COPD prevention. Methods: This study was based on the China Kadoorie Biobank project in Wuzhong District, Suzhou. After excluding individuals with airflow obstruction and self-reported chronic bronchitis, emphysema, or pulmonary heart disease at baseline, 45 484 individuals were finally included in the analysis. Cox proportional risk models were used to analyze risk factors of COPD and calculate hazard ratios and 95% confidence interval (CI) in the Suzhou cohort. The effect modifications of smoking on the association between other risk factors and COPD were evaluated. Results: Complete follow-up was available through December 31, 2017. Participants were followed up for a median of 11.12 years, and 524 individuals were diagnosed with COPD during the follow-up period; the incidence was 105.54 per 100 000 person-years. Multivariate Cox proportional risk regression models showed that age (HR=3.78, 95%CI:3.32-4.30), former smoking (HR=2.00, 95%CI:1.24-3.22), current smoking (<10 cigarettes/day, HR=2.14, 95%CI:1.36-3.35;≥10 cigarettes/day, HR=2.69, 95%CI:1.60-4.54), history of respiratory disease (HR=2.08, 95%CI:1.33-3.26), daily sleep duration ≥10 hours (HR=1.41, 95%CI:1.02-1.95) were associated with increased risk of COPD. However, education level of primary school and above (primary or junior high school, HR=0.65, 95%CI:0.52-0.81; high school and above, HR=0.54, 95%CI:0.33-0.87), consuming fresh fruit daily (HR=0.59, 95%CI:0.42-0.83) and consuming spicy food weekly (HR=0.71, 95%CI:0.53-0.94) were associated with reduced risk of COPD. Conclusions: The incidence of COPD is low in Suzhou. Older age, smoking, history of respiratory disease, and long sleep duration were risk factors for the development of COPD in the Suzhou cohort.

Assessment of genetic diversity and variation of Robinia pseudoacacia seeds induced by short-term spaceflight based on two molecular marker systems and morphological traits.

The black locust (Robinia pseudoacacia) is a forest legume that is highly valued as a honey plant and for its wood. We explored the effect of short-term spaceflight on development of R. pseudoacacia seedlings derived from seeds that endured a 15-day flight; the genetic diversity and variation of plants sampled from space-mutagenized seeds were compared to plants from parallel ground-based control seeds using molecular markers and morphological traits. In the morphology analysis, the space-mutagenized group had apparent variation compared with the control group in morphological traits, including plant height, basal diameter, number of branches, branch stipular thorn length, branch stipular thorn middle width, leaflet vertex angle, and tippy leaf vertex angle. Simple sequence repeat (SSR) and sequence-related amplified polymorphism (SRAP) molecular marker analyses showed a slightly higher levels of genetic diversity in the space-mutagenized group compared to the control group. In the SRAP analysis, the space-mutagenized group had 115 polymorphic bands vs 98 in the controls; 91.27% polymorphic loci vs 77.78% in the controls; 1.9127 ± 0.2834 alleles vs 1.7778 ± 0.4174 in the controls; Nei's genetic diversity (h) was 0.2930 ± 0.1631 vs 0.2688 ± 0.1862 in the controls, and the Shannon's information index (I) was 0.4452 ± 0.2177 vs 0.4031 ± 0.2596 in the controls. The number of alleles was significantly higher in the space-mutagenized group. In the SSR analysis, the space-mutagenized group also had more polymorphic bands (51 vs 46), a greater percentage of polymorphic loci (89.47% vs 80.70%); h was also higher (0.2534 ± 0.1533 vs 0.2240 ± 0.1743), as was I (0.3980 ± 0.2069 vs 0.3501 ± 0.2412). These results demonstrated that the range of genetic variation in the populations of R. pseudoacacia increased after spaceflight. It also suggested that the SSR and SRAP markers are effective markers for studying mutations and genetic diversity in R. pseudoacacia. The data provide valuable molecular evidence for the effects of the space environment on R. pseudoacacia and may contribute to future space-breeding programs involving forest trees.

The use of the kurtosis metric in the evaluation of occupational hearing loss in workers in China: implications for hearing risk assessment.

This study examined: (1) the value of using the statistical metric, kurtosis [ß(t)], along with an energy metric to determine the hazard to hearing from high level industrial noise environments, and (2) the accuracy of the International Standard Organization (ISO-1999:1990) model for median noise-induced permanent threshold shift (NIPTS) estimates with actual recent epidemiological data obtained on 240 highly screened workers exposed to high-level industrial noise in China. A cross-sectional approach was used in this study. Shift-long temporal waveforms of the noise that workers were exposed to for evaluation of noise exposures and audiometric threshold measures were obtained on all selected subjects. The subjects were exposed to only one occupational noise exposure without the use of hearing protection devices. The results suggest that: (1) the kurtosis metric is an important variable in determining the hazards to hearing posed by a high-level industrial noise environment for hearing conservation purposes, i.e., the kurtosis differentiated between the hazardous effects produced by Gaussian and non-Gaussian noise environments, (2) the ISO-1999 predictive model does not accurately estimate the degree of median NIPTS incurred to high level kurtosis industrial noise, and (3) the inherent large variability in NIPTS among subjects emphasize the need to develop and analyze a larger database of workers with well-documented exposures to better understand the effect of kurtosis on NIPTS incurred from high level industrial noise exposures. A better understanding of the role of the kurtosis metric may lead to its incorporation into a new generation of more predictive hearing risk assessment for occupational noise exposure.

Major arterial aneurysms and pseudoaneurysms in Behçet's disease: results from a single centre.

OBJECTIVE: Behçet's disease (BD) with arterial involvement is closely correlated with mortality and morbidity due to life-threatening complications such as arterial occlusion and aneurysm rupture. We aimed to determine the clinical characteristics of BD patients with aneurysms and pseudoaneurysms in the major arterial systems. METHODS: Medical records of 30 BD patients diagnosed with aneurysms or pseudoaneurysms in the major arterial systems were reviewed to determine the clinical characteristics of BD, the sites and types of arterial aneurysms or pseudoaneurysms, laboratory test results, and response to treatment. RESULTS: A total of 47 aneurysms and pseudoaneurysms (32 saccular aneurysms, eight fusiform aneurysms, and seven pseudoaneurysms) were detected in 30 patients. Most aneurysms and pseudoaneurysms (27 patients, 90%) had not ruptured. Symptomatic lesions presented in 21 patients (70%), and asymptomatic lesions were incidentally detected in nine (30%). Ten of the 30 patients (33.3%) presented two or more aneurysmal lesions. Recurrence was observed in five patients (16.7%) after treatment with stent graft (n = 3), graft interposition (n = 1), or graft embolization (n = 1). CONCLUSION: We suggest that BD patients diagnosed with major arterial aneurysms should be further evaluated to detect possible associated venous or arterial thrombosis formations or aneurysmal lesions at other sites.

Additive role of tiotropium in severe asthmatics and Arg16Gly in ADRB2 as a potential marker to predict response.

BACKGROUND: Recent findings have raised new interests about the use of anticholinergics, especially tiotropium, for the treatment of asthma. This study was performed to determine whether an additional improvement in lung function is obtained when tiotropium is administrated in addition to conventional therapies in severe asthmatics, and to identify factors capable of predicting the response to tiotropium, using a pharmacogenetic approach. METHODS: A total of 138 severe asthmatics on conventional medications and with decreased lung function were randomly recruited. Tiotropium 18 microg was added once a day and lung functions were measured every 4 weeks. Responders were defined as those with an improvement of > or = 15% (or 200 ml) in the forced expiratory volume in 1 s (FEV1) that was maintained for at least 8 successive weeks. Eleven single nucleotide polymorphisms (SNPs) in CHRM1-3 (coding muscarinic receptors one to three) which were identified by re-sequencing, and Arg16Gly and Gln27Glu in ADRB2 (coding beta(2) adrenoreceptor) were scored in 80 of the 138 asthmatics. RESULTS: Forty-six of the 138 asthmatics (33.3%) responded to tiotropium treatment. Logistic regression analyses (controlled for age, gender, and smoking status) showed that Arg16Gly in ADRB2 [P = 0.003, OR (95% CI) = 0.21 (0.07-0.59) in a minor allele-dominant model] was significantly associated with response to tiotropium. CONCLUSIONS: As many as 30% of severe asthmatics on conventional medications with reduced lung function were found to respond to adjuvant tiotropium. The presence of Arg16Gly in ADRB2 may predict response to tiotropium.

Benzo[a]pyrene-induced necrosis in the HepG(2) cells via PARP-1 activation and NAD(+) depletion.

Benzo[a]pyrene (BaP), a member of polycyclic aromatic hydrocarbons (PAH), has been reported to induce cell death in various cell types. However, the underlying mechanisms are controversial. In the present study, we report that BaP induces necrotic cell death in human hepatoma (HepG(2)) cells. The process is dependent on the activation of poly(ADP-ribose)polymerase-1 (PARP-1), a nuclear enzyme responsible for repairing DNA damage. Once activated, PARP-1 catalyzes the formation of ADP-ribose polymers on acceptor proteins at the expense of NAD(+). Incubation of cells with high extracellular concentration of NAD(+) (5mM) after BaP treatment caused an elevation in intracellular NAD(+) level and blocked cell death. Inhibitor of PARP-1 suppressed both overactivation of PARP-1 activity and NAD(+) depletion. Moreover, addition of pyruvate (5mM), but not glutamate (5mM) or glutamine (5mM), could restore ATP production and prevent cell death. These results elucidated a sequence of events linking cellular metabolism to the progression of cell death induced by this organic toxicant.