A Monogenic Disease with a Variety of Phenotypes: Deficiency of Adenosine Deaminase 2

2019 ◽  
Vol 47 (1) ◽  
pp. 117-125 ◽  
Author(s):  
Seza Özen ◽  
Ezgi Deniz Batu ◽  
Ekim Z. Taşkıran ◽  
Hatice Asuman Özkara ◽  
Şule Ünal ◽  
...  

Objective.Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disorder associated with ADA2 mutations. We aimed to investigate the characteristics and ADA2 enzyme activities of patients with DADA2 compared to non-DADA2 patients.Methods.This is a descriptive study of 24 patients with DADA2 who were admitted to the Adult and Pediatric Rheumatology, Pediatric Haematology, and Pediatric Immunology Departments of Hacettepe University. All ADA2 exons were screened by Sanger sequencing. Serum ADA2 enzyme activity was measured by modified spectrophotometric method.Results.Twenty-four patients with DADA2 were included: 14 with polyarteritis nodosa (PAN)-like phenotype (Group 1); 9 with Diamond-Blackfan anemia (DBA)-like features, and 1 with immunodeficiency (Group 2). Fourteen PAN-like DADA2 patients did not have the typical thrombocytosis seen in classic PAN. Inflammatory attacks were evident only in Group 1 patients. Serum ADA2 activity was low in all patients with DADA2 except one, who was tested after hematopoietic stem cell transplantation. There was no significant difference in ADA2 activities between PAN-like and DBA-like patients. In DADA2 patients with one ADA2 mutation, serum ADA2 activities were as low as those of patients with homozygote DADA2. ADA2 activities were normal in non-DADA2 patients. ADA2 mutations were affecting the dimerization domain in Group 1 patients and the catalytic domain in Group 2 patients.Conclusion.We suggest assessing ADA2 activity along with genetic analysis because there are patients with one ADA2 mutation and absent enzyme activity. Our data suggest a possible genotype–phenotype correlation in which dimerization domain mutations are associated with PAN-like phenotype, and catalytic domain mutations are associated with hematological manifestations.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 833.1-833
Author(s):  
W. Wang ◽  
T. Zhang ◽  
L. Wang ◽  
H. Song

Background:Adenosine deaminase 2 deficiency (DADA2) is a rare antoinflammatory disease caused by mutations in ADA2 gene, few Chinese cases have been reported.Objectives:To describe and compare the clinical features, genotypes, and treatments of Chinese DADA2 patients and foreign cases.Methods:Primary immunodeficiency disease Panel or Whole Exome Sequencing was performed to suspected subjects, and assays for adenosine deaminase 2(ADA2) enzyme activity were also carried out to them and their parents. Case reports of Chinese and foreign patients with DADA2 were searched from PubMed and Chinese domestic databases.Results:Seven unrelated DADA2 children from China were included in our study, 5 were identified at Peking union medical college hospital and 2 had been reported previously (1 on PubMed and 1 in Chinese literatures). 14 mutations in ADA2 were identified, and 9 of which have not been found in other countries. Four children receiving enzymatic analysis had lower ADA2 enzyme activity compared to their parents. Phenotypic manifestations included fever, skin symptoms, vasculitis, neurologic involvement, et al. The treatments varying from steroids, immunosuppressants, and tocilizumab, anti-TNF therapy and hematopoietic stem cell transplantation (HSCT) were effective depending on different phenotype and severity.Conclusion:This study includes the biggest number of Chinese DADA2 patients at present. We recommend combination of enzymatic analysis with gene screening to confirm the diagnosis. Genotypes of patients from China were some different, the clinical manifestations were similar. We suggest anti-TNF therapy may not be necessary for mild case and HSCT should be considered even without hematological phenotype.References:[1]Zhou Q, Yang D, Ombrello AK, Zavialov AV, Toro C, Zavialov AV, et al. Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med. 2014;370:911-920.[2]Meyts I, Aksentijevich I. Deficiency of Adenosine Deaminase 2 (DADA2): Updates on the Phenotype, Genetics, Pathogenesis, and Treatment. J Clin Immunol. 2018;38:569-578.[3]Wang XN, Zhou ZX, Li SN, Lai JM, Su GX, Kang M, et al. A case report of DADA2. Chin J Rheumatol. 2019;23:476-478.[4]Liu L, Wang W, Wang Y, Hou J, Ying W, Hui X, et al. A Chinese DADA2 patient: report of two novel mutations and successful HSCT. Immunogenetics. 2019;71:299-305.Disclosure of Interests:None declared


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2344-2344
Author(s):  
Jianyun Liao ◽  
Xiaoting Liu ◽  
Yuelin He ◽  
Zhiyong Peng ◽  
Huaying Liu ◽  
...  

Abstract OBJECTIVE:To investigate the role of donor lymphocyte infusions (DLI) in preventing post-transplant graft rejection (GR) in hematopoietic stem cell transplantation (HSCT) for patients with β-thalassemia major (TM); METHODS: A total of 50 patients with TM who had mixed chimerism (MC) after HSCT from June 2011 to June 2016 was divided into 4 groups. The group 1 included the patients with grade I MC ratio of 90%-95% (n=20) but not DLI; Group 2 patients had same grade I MC ratio as Group 1 and received DLI (n=11); Group 3 had grade II MC ratio of 75%-90% (n=13); Group 4 had grade III MC of <75% (n=6). Group 1 received gradually reduced immunosuppressive agents; Groups 2 to 4 received DLIs of gradually increasing dose after reduction of immunosuppressive agents; RESULTS: (1) Full donor chimerism (FDC) conversion rates in the groups 1 to 4 were 100%, 100%, 85%, and 66.7%, respectively; The incidence of graft versus host disease (GVHD) in groups 1 to 4 was 15%, 27.3%, 46.2%, and 33.3%, respectively; (2) There was no significant differeces as comparing incidence of GVHD in group 1 and in group 2 (15% vs. 27.3%, P = 0.638); (3) A significant difference was found in comparing patients receiving initial DLI at ≤180 and > 180 days and the incidence of GVHD was 50% vs 10% (P=0.049); (4) Comparing the accumulated doses of DLI >1×107/kg with ≤1×107/kg, the incidence of GVHD was 50% vs. 27.3% (P=0.142); CONCLUSION: 1. The optimal choice for post-transplant MC grade 1 patient is only observation and decreasing the immunosuppressive drugs; 2. For grade 2-3 patients with high risk of rejection, the fractional increasing dose DLI can effectively reverse the unstable chimera to FDC; 3. Post-DLI GVHD was associated with DLI timing, and the incidence of GVHD was higher in patients who received DLI at ≤180 days after transplantation. Disclosures No relevant conflicts of interest to declare.


VASA ◽  
2020 ◽  
Vol 49 (4) ◽  
pp. 281-284
Author(s):  
Atıf Yolgosteren ◽  
Gencehan Kumtepe ◽  
Melda Payaslioglu ◽  
Cuneyt Ozakin

Summary. Background: Prosthetic vascular graft infection (PVGI) is a complication with high mortality. Cyanoacrylate (CA) is an adhesive which has been used in a number of surgical procedures. In this in-vivo study, we aimed to evaluate the relationship between PVGI and CA. Materials and methods: Thirty-two rats were equally divided into four groups. Pouch was formed on back of rats until deep fascia. In group 1, vascular graft with polyethyleneterephthalate (PET) was placed into pouch. In group 2, MRSA strain with a density of 1 ml 0.5 MacFarland was injected into pouch. In group 3, 1 cm 2 vascular graft with PET piece was placed into pouch and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. In group 4, 1 cm 2 vascular graft with PET piece impregnated with N-butyl cyanoacrylate-based adhesive was placed and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. All rats were scarified in 96th hour, culture samples were taken where intervention was performed and were evaluated microbiologically. Bacteria reproducing in each group were numerically evaluated based on colony-forming unit (CFU/ml) and compared by taking their average. Results: MRSA reproduction of 0 CFU/ml in group 1, of 1410 CFU/ml in group 2, of 180 200 CFU/ml in group 3 and of 625 300 CFU/ml in group 4 was present. A statistically significant difference was present between group 1 and group 4 (p < 0.01), between group 2 and group 4 (p < 0.01), between group 3 and group 4 (p < 0.05). In terms of reproduction, no statistically significant difference was found in group 1, group 2, group 3 in themselves. Conclusions: We observed that the rate of infection increased in the cyanoacyrylate group where cyanoacrylate was used. We think that surgeon should be more careful in using CA in vascular surgery.


MedAlliance ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 14-24

The clinic and diagnostics of tuberculosis meningitis (TM) in 926 patients treated in St. Petersburg hospitals in 1965–1994 (group 1) and in 1995–2018 (group 2) is presented. The TM clinic is demonstrated to be determined by the form of tuberculosis and its characteristic generalization nature in the presence of repeated waves of bacteremia and allergic vasculitis of greater or lesser severity. There is clinical peculiarity of TM in primary pulmonary tuberculosis and its early large-focal and late miliar generalization, as well as in hematogenous tuberculosis. In patients of the 1st and 2nd groups the TM clinic shows in some respects a noticeable similarity, in others — a significant difference. Despite the typical symptoms, early diagnosis of TM took place in less than 20% of patients. Clinical examples illustrating the unusual development of TM, contrasting with its usual course, are given. A number of objective and subjective factors contributing to the adverse evolution of TM and its lethal outcome are discussed. These include the peculiarity of modern tuberculosis, especially when associated with HIV infection, as well as medical errors associated with ignorance of the pathogenesis of tuberculosis and failure to comply with the minimum examination for tuberculosis.


2019 ◽  
Vol 70 (7) ◽  
pp. 2608-2613
Author(s):  
Larisa Simona Deac ◽  
Kamel Earar ◽  
Adela Loredana Colceriu Burtea ◽  
Alexandra Stefania Berghe ◽  
Aurora Antoniac ◽  
...  

This study evaluates and compares by dye penetration method and SEM photomicrographs the sealing obtained using two different classes of adhesive systems (etch-and-rinse and self-etch with selective etching) with SDR (Dentsply) bulk fill composite. 84 class V cavities were prepared on oral and vestibular face of 42 intact, freshly extracted wisdom teeth. The cavities were randomly divided in two groups and restored: Group 1 with prime &bond one select (Dentsply) and SDR (Dentsply) and Group 2 with prime&bond one Etch&Rinse (Dentsply) and SDR (Dentsply). Prime&bond one Select (Dentsply) is a single component adhesive and can be used in self etch mode, in selective enamel etch mode, or in etch-and-rinse mode. We chosen for this study the selective etch of the enamel mode. Prime&bond one Etch Rinse (Dentsply) is a universal etch-and-rinse one-bottle dental adhesive, designed to be used in two steps. The bulk fill composites are commonly used in modern dentistry due to their properties of low polymerization shrinkage and curing in layer of 4 mm depth, offering the practitioner a fast clinical procedure with good results. The results showed a good sealing at enamel and dentin margins with no statistically significant difference between adhesives, even though the mean of enamel infiltration was smaller for Group1. Furthermore the results show that there were differences between the two groups, for the infiltrations at the enamel, the values of microleakage being arithmetically higher for Group 1, but with no statistically difference between the two groups.SEM images showed for both groups a good adhesion surface with the tooth, but the hybrid layer of the total-etch adhesives is different from the hybrid layer formed by self etch adhesives, in terms of thickness, uniformity. In conclusion both adhesive systems have equivalent sealing qualities and can be successfully used with SDR.


2020 ◽  
Author(s):  
Guy Tobias ◽  
Assaf B Spanier

BACKGROUND Gingivitis is a non-painful, inflammatory condition that can be treated with home remedies. Left untreated gingivitis can lead to tooth loss. Periodic dental examinations are important for early diagnosis and treatment of gum diseases. In order to contain the spread of the corona virus, governments, including in Israel, have restricted movements of their citizens which has caused routine dental checkups to be postponed. OBJECTIVE This study aimed to examine the ability of an mHealth app- iGAM to reduce gingivitis. METHODS A prospective observational cohort study was performed, 160 unpaid participants were divided into 2 equal groups and downloaded the iGAM app. Group 1 photographed their gums weekly for eight weeks. Group 2 photographed their gums at the time of recruitment and 8 weeks later. After photo submission, the participants received the message "It is recommended to read the information contained within the app regarding maintaining oral hygiene habits". A single blinded researcher examined the images and scored them according to the Modified Gingival Index (MGI). RESULTS The average age of group 1 was 26.77 (S.D. ± 7.43), and 28.53 (S.D. ± 10.44) for group 2. The majority were male (74.7% in group 1 vs. 66.7% in group 2), most participants described themselves as "secular", most were "single", non-smokers (74.7% vs. 78.4%) and did not take medications (85.3% vs. 78.4%). 126 subjects completed the study. A statistically significant difference (P <.001) was found in the dependent variable (MGI) in a linearly negative manner. As time passed, the gum condition improved, there were significantly lower gingivitis scores in group 1 (M = 1.16, S.D. ± 1.18) compared to group 2 (M = 2.16, S.D. ± 1.49), after eight weeks. Those with more recent dental visits had a lower MGI (p = .037). No association was found between knowledge and behavior, most participants were familiar with the recommendations for maintaining oral health, yet they only performed some. CONCLUSIONS A dental selfie taken once a week using an mHealth app (iGAM) reduced the signs of gingivitis and promoted oral health. During the current pandemic where social distancing recommendations may be causing people to avoid dental clinics, this app can remotely promote gum health. CLINICALTRIAL The protocol was approved by Hadassah research ethics committee (IRB, 0212-18-HMO)


2018 ◽  
Vol 46 (1) ◽  
Author(s):  
Ricardo Christ ◽  
Aleksandro Schafer Da Silva ◽  
Mateus Eloir Grabriel ◽  
Luan Cleber Henker ◽  
Renan Augusto Cechin ◽  
...  

  Background: Nitrate and nitrite poisoning is associated with pasture intake that has high nitrate levels and leads to acute methemoglobinemia. Pasture may accumulate nitrate under certain conditions, such as excessively fertilized soil or en­vironmental conditions that enhance the N absorption (rain preceded by a period of drought). After ingestion of plants, this substrate reaches the rumen and, in physiological conditions, is reduced to nitrite and afterward to ammonia. The aim of this study was to evaluate changes in cholinesterase activities and oxidative stress caused by subclinical poisoning for nitrate and nitrite in cattle fed with Pennisetum glaucum in three different fertilization schemes. Materials, Methods & Results: In order to perform the experimental poisoning, the pasture was cultivated in three dif­ferent paddocks: with nitrogen topdressing (urea; group 1), organic fertilizer (group 2) or without fertilizer (group 3; control). Nitrate accumulation in forage was evaluated by the diphenylamine test. After food fasting of 12 h, nine bovine were randomly allocated to one of the experimental groups and fed with fresh forage (ad libitum) from respective pad­dock. In different time points from beginning of pasture intake (0, 2, 4, 6 and 9 h) heart rate and respiratory frequency were assessed, as well as mucous membrane color and behavioral changes. Blood samples from jugular vein into vials with and without anticoagulant were collected. From blood samples, serum nitrite levels, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme activity were evaluated, as well as oxidative stress through the following param­eters: levels of nitrate/nitrite (NOx), thiobarbituric acid reactive substances (TBARS) and reactive oxygen species (ROS), beyond the antioxidant system by enzyme activity measurement of catalase (CAT) and superoxide dismutase (SOD). The diphenylamine test was positive to group 1 and 2, so that the pasture presented 3.16 mg/kg, 2.98 mg/kg and 1.67 mg/kg of nitrate for group 1, 2 and 3, respectively. In addition, cows from group 1 demonstrated increased (P < 0.05) nitrite levels in serum, compared to other groups, and greater heart rate after 9 h (P < 0.05). The AChE and BChE activity in group 1 showed significant increase (P < 0.05) at 4 and 6 h (AChE), and 4 and 9 h (BChE) compared to group 3. Also, NOx levels were lower at 6 and 9 h (P < 0.05) and at 9 h (P < 0.05) for animals of group 1 and 2, respectively, when compared to group 3. Furthermore, in the group 1 levels of ROS and TBARS were significantly higher (P < 0.05) after 2 and 4 h, and 6 and 9 h compared to other groups, respectively. The CAT activity increased significantly (P < 0.05) with 2 and 4 h of the experiment, but on the other hand, decreased at 6 and 9 h in group 1. Nevertheless, the animals from group 2 presented only a significant reduction in this enzyme activity at 9 h. Furthermore, SOD activity was reduced in animals of groups 1 (P < 0.05) at 4, 6 and 9 h, compared to other groups. Discussion: It was concluded that the nitrate and nitrite poisoning by pasture intake cultivated and fertilized with urea leads to increased levels of serum nitrite, as well as the cholinesterase activity and causes oxidative stress in cattle. It is conjectured that the cholinesterase activity and oxidative stress may assist in understanding the pathophysiology of changes caused by poisoning.Keywords: plant toxicology, poisoning, methemoglobin, cholinergic system, oxidative stress.


2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Daniele Tognetto ◽  
Chiara De Giacinto ◽  
Alberto Armando Perrotta ◽  
Tommaso Candian ◽  
Alessandro Bova ◽  
...  

Purpose. To compare the capsule edges ultrastructure obtained by two femtosecond laser-assisted cataract surgery (FLACS) platforms and manual continuous curvilinear capsulorhexis (CCC) using scanning electron microscopy (SEM). Setting. Eye Clinic, University of Trieste, Italy. Design. Experimental comparative study. Methods. 150 anterior capsules were collected and divided into three groups as follows: Group 1 (50 capsules) obtained with manual CCC, Groups 2 and 3 (each with 50 capsules) obtained with the Catalys Laser and the LenSx Laser, respectively. All samples were imaged by means of SEM and regularity of the cut surface, and thickness of the capsule edge were evaluated and compared. Results. All femtosecond laser (FSL) capsules were perfectly circular, whereas some alteration of the circular shape was observed in the manual ones. Group 1 showed a smooth and regular capsule edge without any surface irregularity, conversely Groups 2 and 3 showed postage-stamp perforations on the capsule edge. The cut surface irregularity value in Group 2 was 1.4 ± 0.63, while it was 0.7 ± 0.49 in Group 3 (p<0.05). Group 1 had a significantly lower thickness of the capsule edge than the FSL groups (p<0.05). No statistically significant difference in the capsule edge thickness between the FSL groups was found (p=0.244). Conclusions. Despite the presence of slight cut surface irregularities, both FSL capsulotomies showed a better geometry and circularity than the manual ones. Capsulotomy specimens obtained using both FSL capsulotomies showed laser-induced alterations of the capsule edge when compared with smooth and regular edges obtained using manual CCC.


2021 ◽  
Vol 28 (3) ◽  
pp. 328-338
Author(s):  
Ogbutor Udoji Godsday ◽  
Nwangwa Eze Kingsley ◽  
Nwogueze Bartholomew Chukwuebuka ◽  
Chukwuemeka Ephraim ◽  
Ezunu Emmanuel ◽  
...  

Decline in normal physiological pulmonary function has been attributed to premorbid conditions such as prehypertension. Research evidence suggests that physical activity reduces age-related decline in pulmonary function and improves the efficiency of the lungs in prehypertensive patients. However, there is a scarcity of data evidence relating to isometric exercise and pulmonary function. Furthermore, the interrelationship between the intensity and duration of isometric exercise and pulmonary function in these patients is still uncertain. Therefore, this study was undertaken to investigate the effect of isometric handgrip exercise on pulmonary function capacity in adults with prehypertension. To determine the effectiveness of isometric handgrip exercise on pulmonary function capacity in adults with prehypertension. A quasi experiment using a pre- and post-exercise method was carried out in two out-patients hospital settings. The sample comprised 192 sedentary pre-hypertensive subjects, aged between 30–50 years, that were randomly distributed into three groups of 64 participants each. The subjects performed, for 24 consecutive days, an isometric handgrip exercise at 30% Maximum Voluntary Contraction (M.V.C.). At the end of the 24 days, group one (GP1) discontinued, while group two (GP2) continued the exercise protocol for another 24 consecutive days and group three (GP3) continued with the exercise protocol for another 24 consecutive days but at 50% M.V.C. Determinants of lung function (outcomes) were Forced Expiratory Volume in 1 s (FEV1), Forced Vital Capacity (FVC), FEV1/FVC Ratio and Peak Expiratory Flow Rate (PEFR). The study shows that there was no statistically significant difference in the pre- and post-exercise outcomes for FEV1, FVC, FEV1/FVC Ratio and PEFR after 24 days for group 1. In group 2, there was a statistically significant difference in the FVC [(mean = 0.12 ± 0.12), (p = 0.002)], FEV1 [(mean = 0.15 ± 0.17), (p = 0.003)] and PEF [(mean = 0.85 ± 0.35), (p = 0.001)] after 48 days. In group 3, there was a statistically significant difference (p = 0.001) in all the outcomes assessed after 48 days. There was a between groups difference in favour of group 2 compared with group 1 for outcomes of FEV1 [(mean = 0.142 ± 0.68), (p = 0.005)] and PEF [(mean = 0.83 ± 0.19), (p = 0.0031)]. There was statistically significant difference in favour of group 3 compared to group 2, by increasing the exercise intensity from 30% to 50% M.V.C., for outcomes of FVC [mean change = 0.10 ± 0.052), (p = 0.005)], FEV1/FVC [mean change = 3.18 ± 0.75), (p = 0.017)] and PEF [(mean change = 0.86 ± 0.35), (p = 0.001)] after 48 days. Isometric handgrip exercise (after 48 days at 30% to 50% M.V.C.) improves outcomes of pulmonary function capacity in adults with prehypertension. Meanwhile, duration and/or increase in intensity of the isometric effort significantly contributed to the affects attained.


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