Monogenic lupus due to DNASE1L3 deficiency in a pediatric patient with urticarial rash,hypocomplementemia, pulmonary hemorrhage,and immune-complex glomerulonephritis

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease and usually involves the skin, musculoskeletal system, and kidneys. More than 30 genes have been to monogenic lupus, so far. Monogenic lupus is often characterized by an early-onset, similar family history, and syndromic appearance. Herein we present a pediatric patient with DNASE1L3 deficiency, suffering from both urticarial skin lesions, recurrent hemoptysis, and renal involvement, eventually diagnosed as this rare monogenic lupus.The patient suffered from recurrent urticarial rash and hemoptysis since the age of 15 months of age. He had microscopic hematuria, mild proteinuria, hypocomplementemia, and positive antinuclear antibody, anti-dsDNA, and antineutrophil cytoplasmic antibodies. Renal biopsy yielded immunocomplex glomerulonephritis. Due to early-onset, similar sibling history and consanguineous parents, we suspected monogenic lupus and performed whole-exome sequencing, which further revealed a homozygous T97Ifs*2 mutation (NM_004944.4: c.290_291delCA/p.Thr97Ilefs*2) in DNASE1L3 gene.In conclusion, DNASE1L3 deficiency should be thought when juvenile SLE occurs with early disease-onset, pulmonary hemorrhage, glomerulonephritis, and recurrent urticarial rash along with ANCA positivity.     

Paratracheal air cysts: prevalence and relevance to pulmonary emphysema and bronchiectasis using thoracic multidetector CT

PURPOSE

We aimed to determine the prevalence of paratracheal air cysts (PTACs) and the relationship of PTACs with emphysema and bronchiectasis through retrospective analysis of multidetector computed tomography (MDCT) findings.

METHODS

MDCT findings of 1027 consecutive patients who underwent routine thorax examination between January 2012 and January 2013 were evaluated retrospectively for the presence of PTACs. Localization of the PTACs, as well as their size, shape, and relationship with the trachea were examined. Presence of emphysema and bronchiectasis was recorded, and bronchiectasis severity index was calculated when present. We randomly selected 80 patients who had no visible PTACs as the control group. The findings of patients with and without PTACs were compared.

RESULTS

PTACs were determined in 82 of 1027 patients (8%), in 8.8% of females and 7.3% of males. The presence of PTACs was determined to be independent of gender (P = 0.361). Eighty-one PTACs (98.8%) were located in the right side of the trachea and 56.1% had a tracheal connection. The presence of PTACs significantly correlated with the presence and severity of bronchiectasis (P = 0.001 and P = 0.005 respectively). There was no significant relationship between the presence of PTACs and the presence of emphysema on CT images (P = 0.125).

CONCLUSION

The prevalence of PTACs was determined as 8% in this study. There was significant association between PTACs and bronchiectasis.Paratracheal air cysts (PTACs) are small collections of air adjacent to the trachea at the level of the thoracic inlet (1). Pathological diagnosis of PTACs in surgically confirmed cases includes tracheal diverticulum, lymphoepithelial cyst, and bronchogenic cyst (1–3). These cysts are covered with ciliary columnar epithelium and connected with the trachea (4). The majority of PTACs are reported as tracheal diverticula in the literature, due to their connection with the trachea (2). The thoracic inlet between the cartilage and muscle layers in right posterolateral wall of the trachea is the most common location for PTACs. A relationship may be seen between an isolated PTAC and the trachea l lumen (5). These lesions may cause recurrent infections by acting as a reservoir for secretions.Occasionally, PTACs can be confused with other causes of extraluminal air collections as laryngocele, pharyngocele, Zenker’s diverticulum, apical hernia of the lung, mediastinal air, apical paraseptal blebs, or bullae. To distinguish PTACs from other pathologies, its typical location in the right posterior paratracheal region at the thoracic inlet can be helpful: PTACs locate away from the lung pleura, communicate with the trachea and have rounded margins that can be differentiated from emphysematous changes (6).PTACs are usually discovered incidentally on thorax computed tomography (CT). They may be associated with a chronic cough or chronic obstructive pulmonary diseases (COPD). The reported prevalence of PTACs ranges from 0.75% to 8.1% (4, 6–8). There have been a limited number of studies reporting the incidence of PTACs related to COPD or emphysema as detected by CT, and the reported results are variable (4, 6, 8–11). The relationship between PTACs and pulmonary emphysema or bronchiectasis is still unclear. To our knowledge, no published study has evaluated the relationship between PTACs and bronchiectasis, using a bronchiectasis severity index and objective measures to determine the extent of bronchiectasis on CT images.The purpose of our study was to evaluate the prevalence and characteristics of PTACs, as well as their relationship with bronchiectasis and emphysema, on thorax CT scans.     

Evaluation of salivary total oxidant-antioxidant status and DNA damage of children undergoing fixed orthodontic therapy

Objective:To determine the total oxidant status (TOS), total antioxidant status (TAS), and the 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels and their interrelationship in the saliva of children undergoing fixed orthodontic therapy.Materials and Methods:Thirty children were randomly divided into three groups. The attachments were bonded to all of the teeth using three different orthodontic composites: Transbond XT, Kurasper F, and GrenGloo. The salivary levels of TOS, TAS, and 8-OHdG were determined three times, as follows: before treatment (T₁) and at 1 month (T₂) and 3 months (T₃) following appliance placement. All data were statistically analyzed.Results:There were no significant differences in TOS, TAS, and 8-OHdG within the same time periods among the three different orthodontic composites (P > .05). TAS in all composite groups decreased over time. These decreases were found to be significant for Kurasper F and GrenGloo at the T₁–T₃ and T₂–T₃ time periods (P < .05). In all composite groups 8-OHdG decreased between T₁ and T₂ (P < .05). However, 8-OHdG in all composite groups increased from T₂ to T₃. These differences in 8-OHdG were significant in Kurasper F and GrenGloo (P < .05).Conclusions:Fixed orthodontic appliances bonded with the tested composites did not increase the cytotoxicity markers in saliva.     

The effects of aquatic,isometric strength-stretching and aerobic exercise on physical and psychological parameters of female patients with fibromyalgia syndrome

[Purpose] There are various treatment modalities for fibromyalgia syndrome (FMS), which is characterized by widespread pain and fatigue. The aim of this study was to investigate the effects of aquatic, aerobic and isometric strength-stretching exercises on the physical and psychological parameters of patients with FMS. [Subjects and Methods] Seventy five female patients with FMS were randomly selected and divided into three groups. Patients (18–50 years) were treated for 3 months using one of three methods: a home-based isometric strength and stretching exercise program (ISSEP), a gym-based aerobic exercise program (AEP), and a pool-based aquatic aerobic exercise program (AAEP). Items evaluated were: the number of tender points, Visual Analog Scale (VAS), Fibromyalgia Impact Questionnaire (FIQ), the Six-Minute Walk Test (6MWT), SF-36 physical and mental health scores, and the Beck Depression Inventory (BDI). [Results] The results revealed that AAEP was the most effective treatment of the three. All of the groups showed significant improvements in all variables between pre-and post-test, except the mean values of VAS and BDI in ISSEP. [Conclusion] The results suggest that aquatic aerobic exercise program is more effective than AEP and ISSEP in the treatment of FMS.Key words: Fibromyalgia, Exercise, Treatment     

A new silent germline mutation of the TSH receptor: coexpression in a hyperthyroid family member with a second activating somatic mutation.

BACKGROUND: Up to date, three thyroid-stimulating hormone receptor (TSHR) germline variants have been reported for which no functional consequences have been detected by in vitro characterizations. However, familial nonautoimmune hyperthyroidism and hot nodules are clearly associated with constitutively activating TSHR germline mutations. We describe a family with a new TSHR germline mutation that is associated with euthyroidism in 13 family members and hyperthyroidism in 1 family member. METHODS: Mutation analysis of the TSHR gene was performed by denaturing gradient gel electrophoresis. TSHR constructs were characterized by determination of cell surface expression, 3'-5'-cyclic adenosine monophosphate (cAMP) accumulation, and constitutive cAMP activity. RESULTS: A novel TSHR germline mutation (N372T) was found in a man who presented with thyrotoxicosis. The mutation was also detected in 13 family members, all of whom were euthyroid. Interestingly, an additional constitutively active somatic mutation (S281N) was identified on the second parental TSHR allele of the hyperthyroid index patient. Linear regression analysis showed a lack of constitutive activity for N372T. Moreover, coexpression studies of N372T with S281N did not reveal any evidence for a functional influence of N372T on the constitutively active mutation (CAM). CONCLUSIONS: N372T is unlikely to cause altered thyroid function. This is consistent with the finding that only the index patient with the additional somatic mutation S281N was hyperthyroid.     

Fatty liver-induced changes in stereotypic behavior in rats and effects of glucagon-like peptide-1 analog on stereotypy

Although understanding the relation between psychotic behavior and immune abnormalities has been the focus of research for many years, it remains to be elucidated whether the changes in cytokine levels are part of etiology or a result of the stress associated with the disorder. In accordance with previous studies on changes in cytokine levels due to metabolic changes and psychosis, we hypothesized that fatty liver may potentiate apomorphine-induced stereotypy in a rodent model and that a synthetic glucagon-like peptide-1 analog exenatide would ameliorate this effect. In this study, 18 male Sprague Dawley albino mature rats were used. We induced hepatosteatosis in these rats by feeding them with 30% fructose dissolved in drinking water for 8 weeks. The animals were divided into three groups, namely, the normal group, the intracerebroventricular (ICV) exenatide group, and the ICV NaCl group. Apomorphine-induced stereotypic behavior test was performed in all groups and the liver was removed for histopathological examination after all the rats were euthanized. In the nonalcoholic fatty liver (NAFL) group, stereotypy scores were significantly increased compared with the control group rats (p < 0.00001). A significant decrease in stereotypy scores were observed in the ICV exenatide group with NAFL when compared with the ICV saline group with NAFL (p < 0.005). In addition, brain malondialdehyde and tumor necrosis factor-α levels decreased in the ICV exenatide group. The results of this study showed that fatty liver enhances the effect of apomorphine on stereotypy, which was reversed by exenatide possibly by antioxidant and anti-inflammatory effects.     

Successful Hypothermia Treatment of Hypoxic-Ischemic Encephalopathy in a Neonate with Epidermolysis Bullosa

Despite advances in the neonatal care, hypoxic ischemic encephalopathy in late preterm and term infants remains an important cause of morbidity and mortality. There is lack of data on the application of therapeutic hypothermia in the existence of severe skin lesions. Epidermolysis bullosa is a rare group of inherited conditions which causes blisters in skin and mucosal membranes. In this report, the authors describe a successful whole-body hypothermia treatment of severe hypoxic ischemic encephalopathy in a term newborn with dystrophic epidermolysis bullosa. They observed that therapeutic hypothermia may also be given in newborns with dystrophic epidermolysis bullosa without any complications.     

Quantitation of escitalopram and its metabolites by liquid chromatography‐tandem mass spectrometry in psychiatric patients: New metabolic ratio establishment

Therapeutic drug monitoring (TDM) is used to determine the concentration of drug in plasma/serum to adjust the dose of the therapeutic drug. Selective and sensitive analytical methods are used to determine drug and metabolite levels for the successful application of TDM. The aim of the study was to develop and validate using LC‐MS/MS to analyse quantitative assay of escitalopram (S‐CT) and metabolites in human plasma samples. In order to provide a convenient and safe treatment dose, it was aimed to determine the levels of S‐CT and its metabolites in the patients’ plasma. A new method with short sample preparation and analysis time was developed and validated using LC‐MS/MS to analyse quantitative assay of S‐CT and its metabolites in plasma. Also, plasma samples of 30 patients using 20 mg S‐CT between the ages of 18 and 65 years were analysed by the validated method. The mean values of S‐CT, demethyl escitalopram and didemethyl escitalopram in plasma of patients were 27.59, 85.52 and 44.30 ng/mL, respectively. At the end of the analysis, the metabolic ratio of S‐CT and metabolites was calculated. It is considered that the method for the quantitative analysis of S‐CT and its metabolites in human plasma samples may contribute to the literature on account of its sensitive and easy application. Additionally, the use of our data by physicians will contribute to the effective drug treatment for their patients who take S‐CT.