Serum metabolism of bradykinin and des-Arg9-bradykinin in patients with angiotensin-converting enzyme inhibitor-associated angioedema

Angioedema (AE) associated with angiotensin-converting enzyme inhibitors (ACEi) is a rare, but potentially life-threatening adverse reaction. Several studies have suggested that bradykinin (BK) is responsible for ACEi-induced AE, but the mechanism remains unclear. We investigated the metabolism of BK and des-Arg9-BK in the serum of 20 patients with a history of ACEi-associated AE and 21 control (C) subjects. Synthetic BK was incubated with the sera for various periods of time and residual BK and generated des-Arg9-BK were quantified by specific and sensitive enzyme immunoassays. No significant difference of half-life (t1/2) of both BK and des-Arg9-BK could be measured between C subjects and patients with AE (AE) in absence of ACEi. However, an analysis according to the prolonged (+) or not (-) t1/2 of des-Arg9-BK allowed a new stratification of C subjects and AE patients in four subgroups. The preincubation of sera with enalaprilat at a concentration inhibiting ACE significantly prevented the rapid degradation of BK and des-Arg9-BK in these four subgroups. In presence of ACEi, a subgroup (50%) of AE patients (AE + ) had a particularly significant rise of the t1/2 of des-Arg9-BK. Once ACE was inhibited, the concentration or the nature of the ACEi had no significant effect on the t1/2 of des-Arg9-BK. However, a test dilution of AE + sera with a control (C) serum showed that an enzyme defect rather than a circulating inhibitor could be responsible for the abnormal metabolism of des-Arg9-BK when ACE is inhibited. In conclusion, half of the patients with ACEi-associated AE present in serum had an enzyme defect involved in the des-Arg9-BK metabolism leading to its accumulation. The B1 agonist could be responsible, at least in part, for the local inflammatory reaction associated with the AE.     

BCG vaccination and risk of atopy

Context  It has been suggested that BCG vaccination may protect against development of allergic diseases, particularly when given just after birth. BCG vaccination was given routinely to all infants in Greenland until 1990, when it was withdrawn from the vaccination program. Whether this resulted in an increased prevalence of atopy in children born after the stop of BCG vaccination is unknown. Objective  To determine whether BCG vaccination and age at BCG vaccination are associated with development of atopy. Design, Setting, and Participants  Cross-sectional study among schoolchildren aged 8 to 16 years in 4 towns on the northwest coast of Greenland. Participants had a blood sample drawn and information on BCG vaccination was obtained during 2 periods, November 1998 and November 2001. A total of 1686 children (79% of available children) participated, 1575 of whom had complete information on vaccination status. Atopy was defined as a positive test result in an assay that tests for IgE specific against the most common inhalant allergens in serum. Main Outcome Measures  Odds ratio (OR) of atopy in BCG-vaccinated compared with unvaccinated children and OR according to age at vaccination. Results  The risk of atopy was the same in BCG-vaccinated compared with unvaccinated children after adjustment for confounders (OR, 1.03; 95% confidence interval, 0.72-1.48). The risk of atopy in BCG-vaccinated children was not associated with age at vaccination (P = .17). Conclusions  BCG vaccination administered to infants is not associated with reduced risk of development of atopy.      

Homogeneous deuteriodeiodination of iodinated tyrosine in angiotensin‐I using synthesized triethyl[2H]silane and Pd(0)

In our efforts to develop new reactions for the efficient labelling of peptides and proteins with tritium, we now report the use of silane hydrides together with homogenous Pd(0) catalysis for the protio‐ and deuteriodeiodination of an o‐iodo‐tyrosine containing peptide (angiotensin‐I) performed at room temperature. Copyright © 2010 John Wiley & Sons, Ltd.     

Malignancies associated with renal transplant: first case report of a nephroblastoma occurring in an adult host kidney

The increased incidence of malignancies after renal transplantation has been well documented. We describe the first reported case of a nephroblastoma (Wilms tumor) occurring in the host kidney of an adult after renal transplantation.     

Early Mortality after Radical Radiotherapy in Head and Neck Cancer – A Nationwide Analysis from the Danish Head and Neck Cancer Group (DAHANCA) Database

AimsCurative-intent radiotherapy (RT) or chemoradiation (CRT) of squamous cell carcinoma of the head and neck (HNSCC) produces high survival rates, but is associated with substantial toxicity. However, there are no commonly accepted quality metrics for early mortality in radiation oncology. To assess the applicability of early mortality as a clinical quality indicator, this study investigated the temporal distribution, risk factors and trends of 90- and 180-day overall and non-cancer mortality in a nationwide cohort of HNSCC patients treated with RT/CRT.Materials and methodsInformation on all HNSCC patients treated with curative-intent RT/CRT in Denmark between 2000 and 2017 was obtained from the national Danish Head and Neck Cancer Group clinical database. Deaths in patients with residual or recurrent disease after RT/CRT were classified as cancer-related. Possible risk factors were investigated using logistic regression analysis.ResultsData from 11 419 patients were extracted. In total, 90- and 180-day mortality risks were 3.1% and 7.1%, respectively. There was a uniform temporal distribution of 180-day mortality. In multivariable analysis, increasing age, stage, performance status, earlier treatment year and hypopharyngeal cancer were significantly associated with an increased risk (P < 0.05). Risk factor estimates were comparable for 90- versus 180-day mortality as well as for overall versus non-cancer mortality. Between 2000 and 2017 there was a significant decrease in 180-day mortality, which was driven by a reduction in cancer-related events.ConclusionThe distribution of 180-day overall and non-cancer mortality did not indicate a well-defined early high-risk period. Moreover, risk factor estimates were highly similar across risk periods and groups. Taken together, our findings question the applicability of early mortality as a standard metric for treatment-associated toxicity.     

Epstein-Barr virus-associated gastric carcinoma among patients with pernicious anemia

Approximately 9% of gastric carcinomas worldwide are associated with Epstein-Barr virus (EBV), making it the most frequent EBV-associated malignancy. Pernicious anemia, a condition with chronic gastritis and achlorhydria, is strongly associated with gastric carcinoma. Both chronic inflammation and the lack of stomach acid may influence the likelihood of EBV infection of the neoplastic gastric epithelium, but the prevalence of EBV-associated gastric carcinoma among patients with pernicious anemia is unknown. Therefore, we conducted a Danish nationwide case-control study comparing gastric carcinoma patients with pernicious anemia (PA-GC) with those without pernicious anemia (nonPA-GC), frequency matched 1:2. Tumor tissues were reclassified by expert histopathologists blinded to pernicious anemia and EBV status. In total, 186 samples (55 PA-GC and 131 nonPA-GC) were identified. EBV-associated gastric carcinoma (EBV-GC) was more common among PA-GC compared with nonPA-GC, adjusted odds ratio (OR) = 2.53 (CI: 0.88; 7.14), p = 0.08, with further adjustment for lymphocytic infiltrate OR = 2.94 (0.99-8.67), p = 0.05. Gastric carcinomas with signet-ring cell morphology were significantly less common in patients with PA-GC compared with nonPA-GC (OR = 0.05, CI 0.01; 0.24). Although these conditions are rare, we found suggestive evidence that EBV-associated gastric carcinomas are more common among gastric carcinoma patients with pernicious anemia compared with those without.     

EBV-associated gastric carcinoma in high- and low-incidence areas for nasopharyngeal carcinoma

Background:

Approximately 10% of gastric carcinomas are associated with Epstein–Barr virus (EBV). The Inuit in Greenland have a high incidence of EBV-associated nasopharyngeal carcinoma.

Methods:

We conducted a population-based case–control study comparing gastric carcinomas in Greenland and in Denmark.

Results:

The prevalence rate of EBV-associated gastric carcinomas was 8.5% in both populations.

Conclusion:

The findings of this study argue against a general susceptibility to EBV-associated carcinomas among the Inuit.