Phenotypical heterogeneity in RAG-deficient patients from a highly consanguineous population

Mutations affecting recombination activation genes RAG1 and RAG2 are associated with variable phenotypes, depending on the residual recombinase activity. The aim of this study is to describe a variety of clinical phenotypes in RAG-deficient patients from the highly consanguineous Egyptian population. Thirty-one patients with RAG mutations (from 28 families) were included from 2013 to 2017. On the basis of clinical, immunological and genetic data, patients were subdivided into three groups; classical T^–B^– severe combined immunodeficiency (SCID), Omenn syndrome (OS) and atypical SCID. Nineteen patients presented with typical T^–B^–SCID; among these, five patients carried a homozygous RAG2 mutation G35V and five others carried two homozygous RAG2 mutations (T215I and R229Q) that were detected together. Four novel mutations were reported in the T^–B^–SCID group; three in RAG1 (A565P, N591Pfs*14 and K621E) and one in RAG2 (F29S). Seven patients presented with OS and a novel RAG2 mutation (C419W) was documented in one patient. The atypical SCID group comprised five patients. Two had normal B cell counts; one had a previously undescribed RAG2 mutation (V327D). The other three patients presented with autoimmune cytopaenias and features of combined immunodeficiency and were diagnosed at a relatively late age and with a substantial diagnostic delay; one patient had a novel RAG1 mutation (C335R). PID disorders are frequent among Egyptian children because of the high consanguinity. RAG mutations stand behind several variable phenotypes, including classical SCID, OS, atypical SCID with autoimmunity and T^–B⁺ CID.     

Cross sectional quality of life assessment in patients with androgenetic alopecia

Assessment of quality of life (QOL) of patients with androgenetic alopecia (AGA) has become increasingly important, both in order to evaluate the influence of the disease on patients and the therapy they require. We aimed to assess QOL in subjects complaining from AGA and evaluated the effects of various sociodemographic factors affecting their QOL. QOL was assessed in 400 patients with AGA and 100 controls using the World Health Organization Quality of life (WHOQOL‐BREF) questionnaire. Four domains (physical, psychological, social, and environmental) and two items (overall perception of QOL and health) of the WHOQOL‐BREF were the primary end points of this study. Patients had a lower QoL and less general satisfaction in all four domains of assessment than controls. The social impact was significantly higher in patients < 30 years of age (P = .003). Patients with severer form of AGA significantly had higher scores in all domains compared to those with less severe forms. Disease severity negatively impacted all the four domains significantly (P = .021). AGA harmfully affected the patient's QOL which warns the physicians to pay more attention to QOL impairment in patients of AGA for the better understanding of the disease burden on individual patients.     

Clinical characteristics and outcome of children stung by scorpion

Scorpion envenomation is a health problem in children in tropical and subtropical regions. The aim of this study was to evaluate demographic and clinical characteristics as well as outcomes in referred children to Assiut University Children Hospital during the year 2012 with a history of scorpion sting. The medical files of these patients were reviewed retrospectively for demographic data, time and site of biting, and clinical manifestations. Laboratory investigations of the patients were reviewed for complete blood count (CBC), liver function tests, creatinine phosphokinase (CPK), lactate dehydrogenase (LDH), arterial blood gases, and serum electrolytes. Results showed 111 children with a history of scorpion sting; 69 males and 42 females with a median age of 5 years. Out of the studied patients, 53.2 % were classified as class III of clinical severity with recorded pulmonary edema in 33.3 %, cardiogenic shock in 46.8 %, and severe neurological manifestations in 22.8 %. Twelve patients (10.8 %) were classified as class II with mild systemic manifestations, and 36 % of the patients were classified as class I with only local reaction. Outcomes of these patients were discharge without sequelae in 55.8 %, discharge with sequelae in 26.1 %, and death in 18.1 %. Conclusion: more than half of stung children had a severe clinical presentation and about one fifth died. Aggressive treatment regimens are recommended for such patients to improve the outcome.     

Hypocretin/orexin modulates body weight and the metabolism of glucose and insulin

The hypocretin/orexin (Hcrt/orexin) unit affects the functions of the nervous, cardiovascular, gastrointestinal, and reproductive systems. Hcrt/orexin ligands and receptors have been localized to different parts of the central and peripheral nervous systems, cerebrospinal fluid and blood, exocrine (pancreas, salivary, lacrimal) as well as endocrine (pancreatic islets, pituitary, adrenal) glands. Several factors including stress, glucagon‐like peptide‐1 agonists, glutamate, nicotine, glucose, and hypoglycaemia stimulate the expression of Hcrt/orexin system, but it is inhibited by ageing, bone morphogenetic protein, hypoxia/hypercapnia, melanocortin receptor accessory protein 2, and glucagon. Literature reports show that Hcrt/orexin can significantly increase insulin secretion from normal and diabetic rat pancreata. Hcrt/orexin decreases blood glucose concentration and reduces insulin resistance partly via increased tissue expression of glucose transporter type 4. It reduces obesity by increasing browning of fat cells and energy expenditure. Taken together, Hcrt/orexin modulates obesity and the metabolism of glucose and insulin. The Hcrt/orexin system may thus be a target in the development of new therapies for the treatment of diabetes mellitus.     

Relationship of Helicobacter pylori to Bcl-2 family expression, DNA content, and pathological characteristics of gastric cancer

Background. Despite the fact that the association of Helicobacter pylori with an increased risk of gastric cancer has been well documented, the exact mechanisms of this association have not been fully elucidated. Scarce data on H. pylori infection and its relationship with the different pathological characteristics are available in Egypt. Aim of the Study. The rationale of the present study was to determine the prevalence of H. pylori in a group of gastric cancer patients and to analyze the relationship between H. pylori infection with the different pathological characteristics including the types of gastric cancer and tumor location within the stomach, in addition, to investigate the Bcl-2 and Bax expressions along with DNA flow cytometric analysis in the gastric cancer patients with and without H. pylori infection. Methods. Samples were obtained from 66 consecutive patients with gastric cancer (46 males and 20 females). The youngest patient was 20 yr old, the oldest 76 yr with mean age of 52.8 yr. The samples were subjected for histopathological characterization, H. pylori detection, DNA flow cytometric analysis, and Bcl-2 and Bax expressions detection, in addition to apoptosis analysis. Results. The obtained results showed that the H. pylori infection was found in 38/66 (57.6%) [Odds ratio=1.357 with 95% confidence interval (CI) 0.84–2.2]. There was a statistical significance for Bcl-2, Bax, and apoptosis with H. pylori status (p=0.009, 0.008, 0.032, respectively). On the other hand, There was a statistical significance for H. pylori infection with the disease grade (p=0.015) and lymph node metastasis (p=0.05). No statistical significance was found between H. pylori status with the patients’ age, gender, tumor site, tumor type, depth of invasion, and stromal reaction. Conclusions. These data may indicate that the H. pylori infection not only contributes in the disease formation through the apoptosis dysregulation but also takes a part in the disease dissemination and progression. In addition, it may reflect a biologic, pathogenic, and ethnic background affecting the relationship of H. pylori infection to gastric cancer in the Egyptian patients. A high rate of smoking in Egypt and the diet are important factors that may affect such background. Further studies are warranted.     

Significance of matrix metalloproteinase 9 and CD34 expressions in esophageal carcinoma: correlation with DNA content

BACKGROUND: Esophageal carcinoma is common in many countries, and it is characterized by poor prognosis and rapid clinical progression with a high frequency of lymph node metastasis and recurrence. The present study was carried out to evaluate the correlation between vascular endothelial cell marker (CD34), matrix metalloproteinase type 9 (MMP9), and DNA content in esophageal carcinoma. METHODS: A total of 38 patients were classified with histopathologic examination as 8 cases with adenocarcinoma, 24 cases with squamous cell carcinoma, and the last 6 cases with undifferentiated carcinoma. The obtained results of the patient group were compared with the results of 6 cases with proven normal esophageal mucosa as a control group. The samples of patients and controls were subjected to immunohistochemical evaluation of CD34 and MMP9 expression along with DNA index determination using flow cytometry. RESULTS: There was a significant difference between patients and normal cases in DNA index, CD34, and MMP9 pattern (P = 0.003, <0.001, and 0.002, respectively). DNA index was positively correlated with MMP9 (r = 0.574, P < 0.001) and with CD34 (r = 0.562, P < 0.001). MMP9 was correlated with CD34 (r = 0.55, P < 0.001). A significant difference was found in both microvessel density and MMP9 expression with respect to tumor grade and stage. The microvessel density in patients with highly positive staining for MMP9 was higher than in those with negative and weak staining for MMP9 (P = 0.002). CONCLUSION: The analysis of DNA content along with detection of CD34 and MMP9 in esophageal cancer can successfully differentiate the different pathologic lesions and hence can be used powerfully in disease prognosis reflecting valuable information about the aggressiveness and activity of those lesions.     

Reliability of the Mangled Extremity Severity Score in the Management of Peripheral Vascular Injuries in Children: A Retrospective Review

This study was aimed to evaluate different management modalities for peripheral vascular trauma in children, with the aid of the Mangled Extremity Severity Score (MESS). A single-center retrospective analysis took place between 2010 and 2017 at University Hospitals, having emergencies and critical care centers. Different types of vascular repair were adopted by skillful vascular experts and highly trained pediatric surgeons. Patients were divided into three different age groups. Group I included those children between 5 and 10 years; group II involved pediatrics between 11 and 15 years; while children between 16 and 21 years participated in group III. We recruited 183 children with peripheral vascular injuries. They were 87% males and 13% females, with the mean age of 14.72 ± 04. Arteriorrhaphy was performed in 32%; end-to-end anastomosis and natural vein graft were adopted in 18% and 29% respectively. On the other hand, 20% underwent bypass surgery. The age groups I and II are highly susceptible to penetrating trauma ( p  = 0.001), while patients with an extreme age (i.e., group III) are more susceptible to blunt injury ( p  = 0.001). The MESS has a significant correlation to both age groups I and II ( p  = 0.001). Vein patch angioplasty and end-to-end primary repair should be adopted as the main treatment options for the repair of extremity vascular injuries in children. Moreover, other treatment modalities, such as repair with autologous vein graft/bypass surgery, may be adopted whenever possible. They are cost-effective, reliable, and simple techniques with fewer postoperative complication, especially in poor/limited resources.     

Anatomical closure of trocar site by using tip hole needle and redirecting suture hook

Background  

The incidence of trocar site incisional hernia following laparoscopic surgery is reported to be relatively high. The main reasons are trocar diameter and design, pre-existing fascial defects, and some operation- and patient-related factors. The goal of this article is to present a new procedure for anatomical closure of the trocar site to prevent its herniation.     

A comparative study of validated spectrophotometric and TLC- spectrodensitometric methods for the determination of sodium cromoglicate and fluorometholone in ophthalmic solution

The determination of sodium cromoglicate (SCG) and fluorometholone (FLU) in ophthalmic solution was developed by simple, sensitive and precise methods. Three spectrophotometric methods were applied: absorptivity factor (a-Factor method), absorption factor (AFM) and mean centering of ratio spectra (MCR). The linearity ranges of SCG were found to be (2.5–35 μg/mL) for (a-Factor method) and (MCR); while for (AFM), it was found to be (7.5–50 μg/mL). The linearity ranges of FLU were found to be (4–16 μg/mL) for (a-Factor method) and (AFM); while for (MCR), it was found to be (2–16 μg/mL). The mean percentage recoveries/RSD for SCG were found to be 100.31/0.90, 100.23/0.57 and 100.43/1.21; while for FLU, they were found to be 100.11/0.56, 99.97/0.35 and 99.94/0.88 using (a-Factor method), (AFM) and (MCR), respectively. A TLC-spectrodensitometric method was developed by separation of SCG and FLU on silica gel 60 F₂₅₄ using chloroform:methanol:toluene:triethylamine in the ratio of (5:2:4:1 v/v/v/v) as developing system, followed by spectrodensitometric measurement of the bands at 241 nm. The linearity ranges and the mean percentage recoveries/RSD were found to be (0.4–4.4 μg/band), 100.24/1.44 and (0.2–1.6 μg/band), 99.95/1.50 for SCG and FLU, respectively. A comparative study was conducted between the proposed methods to discuss the advantage of each method. The suggested methods were validated in compliance with the ICH guidelines and were successfully applied for the determination of SCG and FLU in their laboratory prepared mixtures and commercial ophthalmic solution in the presence of benzalkonium chloride as a preservative. These methods could be an alternative to different HPLC techniques in quality control laboratories lacking the required facilities for those expensive techniques.     

Serum levels of bcl-2 and cellular oxidative stress in patients with viral hepatitis

PURPOSE: This study was conducted to investigate the presence of bcl-2 protein in the serum of patients with viral hepatitis and to find out if there is any correlation between bcl-2 protein levels and cellular oxidative stress in the pathogenesis of viral hepatitis. METHODS: This study was carried out on 130 patients with viral hepatitis, 70 with chronic hepatitis, 30 with liver cirrhosis and 30 with hepatocellular carcinoma (HCC) in addition to 20 healthy persons as the control. Serum bcl-2 protein was estimated by enzyme-linked immunosorbent assay, serum malondialdehyde (MDA), nitric oxide (NO) and antioxidant enzymes (GSH, GSH-px, GR and SOD) were measured using spectrophotometric analysis. RESULTS: bcl-2 protein level was significantly elevated in the serum of HCC, cirrhosis and chronic hepatitis groups as compared to control group. There were significant positive correlations between higher bcl-2 protein level and viral hepatitis markers (HBsAg, anti-HCV antibodies) in HCC and cirrhotic patients as compared to chronic hepatitis group. An increase in oxidative stress markers (MDA, NO) and a decrease in antioxidant enzyme activities (SOD, GSH and GSH-px) were observed. However, there was a negative correlation between bcl-2 levels and GR in all studied patient groups. CONCLUSIONS: The release of oxidative free radicals, deficiency in antioxidant enzymes and the expression of bcl-2 protein might play a role in the pathogenesis of viral hepatitis. The ability to measure bcl-2 protein in the serum could be useful as a prognostic marker of cancer patients.