György Temesszentandrási

Short-term prophylaxis in hereditary angioedema due to deficiency of the C1-inhibitor – a long-term survey

Hereditary angioedema is a potentially life‐threatening disorder, because edema occurring in the mucosa of the upper airways can lead to suffocation. The management of HAE consists of avoiding the triggering factors, prophylaxis, and the acute treatment of edematous episodes. Medical procedures can also provoke edematous attacks, and therefore, short‐term prophylaxis (STP) is recommended before such interventions. Our aim was to evaluate the efficacy and safety of STP administered before medical procedures.

The influence of trigger factors on hereditary angioedema due to C1-inhibitor deficiency

BackgroundHereditary angioedema (HAE) resulting from C1-inhibitor deficiency is characterized by attacks of subcutaneous and submucosal edema. Many factors have been presumed to induce edema. Our study analyzed these factors in a fairly large patient population.MethodsIn the first stage of our study, we analyzed the data recorded by 92 subjects in their patient diaries over seven years. The second phase included 27 HAE patients, who had been completing the diary entry ‘Trigger factors’ every day for seven months whether or not they had experienced an attack.ResultsDuring the initial stage, 91% of the subjects described some factor possibly related to the onset of an attack. They could identify a trigger factor – most commonly (21%) mental stress – in 30% of the 3176 attacks. We found a significant (p < 0.001) difference in the distribution of the trigger factors of the edematous attacks of different locations. The 27 participants of the second phase identified 882 potential trigger factors and recorded 365 attacks. Of these, 246 (67%) occurred on days when the patients identified a potential trigger factor. The likelihood of edema-formation associated with the latter was as follows: menstruation – 63%, infection – 38%, mental stress – 26%, physical exertion – 25%, meteorological changes – 21%, fatigue – 17%.ConclusionThis analysis of the trigger factors explored, for the first time, their potential role in inducing HAE attacks. Our findings might open new perspectives in extending the indications for edema-prophylaxis, and could contribute to a better understanding of the pathomechanism of HAE attacks.

Association of human fetuin-A rs4917 polymorphism with obesity in 2 cohorts.

Background Previous studies have shown association of the multifunctional hepatic protein α2HS-glycoprotein/human fetuin A with insulin resistance, type 2 diabetes mellitus, metabolic syndrome, obesity, and atherosclerosis. Reports of contribution of α2HS-glycoprotein/human fetuin A rs4917 single-nucleotide polymorphism to the development of these pathologic processes are inconsistent. We aimed to investigate the association between variants of rs4917 and parameters of obesity, lipid status, the proinflammatory cytokine tumor necrosis factor α (TNF-α), adipokines (adiponectin, resistin), and insulin resistance in 2 cohorts. Methods Eighty-one healthy persons (cohort 1) and 157 patients with previous myocardial infarction (cohort 2) were included in this cross-sectional study. rs4917 Polymorphism was determined by the allele-specific KASP by design genotyping assays. Results In cohort 1, T-nucleotide carriers had lower low-density lipoprotein cholesterol levels compared with non-T carriers. The serum concentration of TNF-α was found to be higher carrying the non-T allele in cohort 1; however, this difference was not observed in cohort 2. In cohort 2, T carriers had lower body mass index and abdominal and waist circumferences than did non-T carriers. The T nucleotide was more frequent in nonobese than in obese patients (χ2 = 5.217, P = 0.022). Nonobese, nondiabetic T carriers still had lower body mass index and waist circumference than did non-T carriers. Conclusions Our data suggest that the T nucleotide in rs4917 is associated with more favorable lipid status among healthy persons (i.e., lower low-density lipoprotein cholesterol) and anthropologic parameters of obesity in cohort 2. The protective role of the T allele may also be associated with lower TNF-α levels found in healthy individuals.

Complete kinetic follow-up of symptoms and complement parameters during a hereditary angioedema attack

We studied the kinetics of C1‐inhibitor (C1‐INH) and other complement parameters in a self‐limited edematous attack (EA) in a patient with hereditary angioedema due to C1‐INH deficiency to better understand the pathomechanism of the evolution, course, and complete resolution of EAs. C1‐INH concentration and functional activity (C1‐INHc+f), C1(q,r,s), C3, C4, C3a, C4a, C5a, and SC5b‐9 levels were measured in blood samples obtained during the 96‐hour observation period. The highest C1‐INHc+f, C4, and C1(q,r,s) levels were measured at baseline, and their continuous decrease was observed during the entire observation period. C4 depletion started at prodromal phase, and C4 was lowest after the maximum severity peak. Compared to baseline, C4a level was four times higher 7 hours before the onset of the attack. C1‐INH did not increase after resolution of the attack suggesting that factors other than C1‐INH may be important in this process. C4a may be a useful biomarker for the prediction of EAs.

Human fetuin-A Rs4918 polymorphism and its association with obesity in healthy persons and in patients with myocardial infarction in two Hungarian cohorts

Background Human fetuin A (AHSG) has been associated with the development of obesity, insulin resistance, type 2 diabetes mellitus, and atherosclerosis. Observations on the role of AHSG rs4918 single-nucleotide polymorphism are contradictory. We investigated the association between variants of rs4918 and parameters of obesity, lipid status, tumor necrosis factor-α (TNFα), adipokines (adiponectin, resistin, leptin), and insulin resistance in healthy persons and in patients with previous myocardial infarction. Material/Methods This was a cross-sectional study comprising cohort 1 (81 healthy individuals) and cohort 2 (157 patients with previous myocardial infarction). We used the allele-specific KASP genotyping assay to detect rs4918 polymorphism. Results In cohort 1, G-nucleotide carriers had significantly lower serum TNFα, adiponectin, and higher leptin concentrations than in non-G carriers. These differences, however, were not observed in cohort 2. In cohort 2, G-carriers had lower BMI and waist circumferences than in non-G carriers. The G allele was more frequent among lean than obese patients (RR=1.067, 95%CI=1.053–2.651, p=0.015). An association between BMI and rs4918 polymorphism was observed among patients without diabetes (CC/CG/GG genotypes: p=0.003, G vs. non-G allele: p=0.008) but not in diabetics. In addition, a strong linearity between BMI and the CC/CG/GG genotypes (association value: 4.416, p=0.036) and the frequency of the G allele (7.420, p=0.006) could be identified. In cohort 2, non-obese, non-diabetic G-carriers still had lower BMI and waist circumferences than in non-G carriers. Conclusions The rs4918 minor variant is associated with lower TNFα and adiponectin, higher leptin levels in healthy persons, and more favorable anthropomorphic parameters of obesity in cohort 2.

Management of pregnancies in a hereditary angioedema patient after treatment with attenuated androgens since childhood

but did not fi nd nerves associated with spiral arterioles in eight abnormal placental beds in the 3rd trimester of pregnancy (Khong et al. 1997). Uterine nerves are sparse in the second half of pregnancy, owing to marked increases in uterine size associated with hyperplasia and hypertrophy; muscle cells proliferate and enlarge, whereas the nerves are relatively fi xed (Wikland et al. 1984). It may not be possible to identify abnormal nerves near uterine spiral arterioles in the 3rd trimester of pregnancy, owing to the enlargement of the uterus and lengthening of injured blood vessels. Th e level of the section in the placental bed and the original source of the neural injury may also be signifi cant in this context. In contrast to recent theories of pre-eclampsia, the ‘ uterine reinnervation ’ view imputes a pre-pregnancy injury to the uterus (Quinn 2014). Neural signals from the uterus to the kidneys result in vasoconstriction in the renal cortex, hypertension and proteinuria, and varying phenotypes of the hypertensive disorders of pregnancy. Further studies to identify neural cytokines in thickened, uterine spiral arterioles in the fi rst half of pregnancy may be helpful.