A multicentre prospective feasibility study of carbon dye tattooing of biopsied axillary node and surgical localisation in breast cancer patients.

BACKGROUND: The primary aim of this prospective, multicentre feasibility study was to determine whether the biopsied axillary node can be marked using black carbon dye and successfully identified at the time of surgery. METHODS: We included breast cancer patients undergoing needle biopsy of the axillary node. The biopsied node was tattooed at the time of needle biopsy (fine needle aspiration or core biopsy) or at a separate visit with black carbon dye (Spot® or Black Eye™). Participants underwent primary surgery or neoadjuvant chemotherapy (NACT) and axillary surgery (SNB or ALND) as per routine care. RESULTS: 110 patients were included. Median age of the women was 59 (range 31-88) years. 48 (44%) underwent SNB and 62 (56%) ALND. Median volume of dye injected was 2.0 ml (range 0.2-4.2). Tattooed node was identified intra-operatively in 90 (82%) patients. The identification rate was higher (76 of 88, 86%) in the primary surgery group compared with NACT (14 of 22, 64%) (p = 0.03). Of those undergoing NACT, the identification rate was better in the patients undergoing SNB (3 of 4, 75%) compared with ALND (11 of 18, 61%) (p > 0.99). The tattooed node was the sentinel node in 78% (28 of 36) patients in the primary surgery group and 100% (3 of 3) in the NACT group. There was no learning curve for surgeons or radiologists. The identification rate did not vary with timing between dye injection and surgery (p = 0.56), body mass index (p = 0.62) or volume of dye injected (p = 0.25). CONCLUSION: It is feasible to mark the axillary node with carbon dye and identify it intra-operatively. ClinicalTrials.gov: NCT03640819.

Emergency Department Presentation After Total Hip and Knee Arthroplasty: A Systematic Review.

BACKGROUND: Recent changes to payment models for elective total joint arthroplasty (TJA) have led to increased interest in postdischarge health care utilization. Although readmission has historically been of primary interest, emergency department (ED) presentation is increasingly a point of focus. The purpose of this review was to summarize the available literature pertaining to ED visits after total hip arthroplasty and total knee arthroplasty. METHODS: PubMed, MEDLINE, and Embase were searched. Clinical studies reporting rate, reasons, and/or risk factors associated with ED presentation after TJA were included. Pooled return to ED rates were calculated using weighted means. RESULTS: Twenty-seven studies (n = 1,484,043) were included. After TJA, the mean 30-day and 90-day rates of ED presentation were 8.1% and 10.3%, respectively. Rates were slightly higher in total knee arthroplasty vs total hip arthroplasty patients at 30 days (11.5% vs 6.5%) and 90 days (10.8% vs 9.7%). The most common reasons for ED presentation after TJA were pain (4.6%-35%), medical concerns (5.6%-24.5%), and swelling (1.4%-17.5%). Studies analyzing the timing of ED visits found that most occurred within the first 2 weeks postdischarge. Black race and Medicaid/Medicare insurance coverage were identified as risk factors associated with ED visits. CONCLUSION: ED visits present a high burden for the health care system, as upward of 1 in 10 patients will return to the ED within 90 days of TJA. Future efforts should be made to develop cost-effective and patient-centered interventions that reduce preventable ED visits after TJA. As well, these rates should be taken into consideration when allocating resources for the care of TJA patients.

Target of rapamycin, a master regulator of multiple signalling pathways and a potential candidate gene for crop improvement.

The target of rapamycin (TOR) protein regulates growth and development in photosynthetic and non-photosynthetic eukaryotes. Although the TOR regulatory networks are involved in nutrient and energy signalling, and transcriptional and translational control of multiple signalling pathways, the molecular mechanism of TOR regulation of plant abiotic stress responses is still unclear. The TOR-mediated transcriptional regulation of genes encoding ribosomal proteins (RP) is a necessity under stress conditions for balanced growth and productivity in plants. The activation of SnRKs (sucrose non-fermenting-related kinases) and the inactivation of TOR signalling in abiotic stresses is in line with the accumulation of ABA and transcriptional activation of stress responsive genes. Autophagy is induced under abiotic stress conditions, which results in degradation of proteins and the release of amino acids, which might possibly induce phosphorylation of TOR and, hence, its activation. TOR signalling also has a role in regulating ABA biosynthesis for transcriptional regulation of stress-related genes. The switch between activation and inactivation of TOR by its phosphorylation and de-phosphorylation maintains balanced growth in response to stresses. In the present review, we discuss the important signalling pathways that are regulated by TOR and try to assess the relationship between TOR signalling and tolerance to abiotic stresses in plants. The review also discusses possible cross-talk between TOR and RP genes in response to abiotic stresses.

Clinical, Laboratory, and Molecular Findings for 63 Patients With Severe Combined Immunodeficiency: A Decade´s Experience.

BACKGROUND: Severe combined immunodeficiency (SCID) is a life-threatening pediatric disease. We report on the clinical evaluation, immunological assessment, molecular analysis, and outcomes of SCID patients in a tertiary referral center in Iran. METHODS: From January 2006 to December 2015, we performed a prospective cohort study in which initial screening and advanced immunological tests were carried out on patients suspected of having SCID. Genetic analysis was also performed to confirm the diagnosis. RESULTS: A total of 63 patients were diagnosed with SCID (43 male [68.3%]). The median age at onset and diagnosis and diagnostic delay were 40 and 110 and 60 days respectively. A total of 49 patients (77.8%) had a history of BCG vaccination, and of these, one-third experienced BCG-associated complications. The most common clinical manifestations were pneumonia, recurrent oral candidiasis, chronic diarrhea, and failure to thrive. Of the thirteen patients who underwent hematopoietic stem cell transplantation, 8 survived and 5 died before they could receive the transplant. Most patients (34.9%) were classified as having T-B-NK+ SCID and had a mutation in the RAG2 or RAG1 gene. CONCLUSIONS: Autosomal recessive SCID is the most common type in Iranian patients. Providing high-quality training to physicians and patients' families to reduce the diagnostic delay should be prioritized. It is also important to raise awareness of live vaccination and to expand stem cell donor registries to speed up the transplantation process.

Long-term outcomes of fludarabine, melphalan and antithymocyte globulin as reduced-intensity conditioning regimen for allogeneic hematopoietic stem cell transplantation in children with primary immunodeficiency disorders: a prospective single center study.

Reduced-intensity conditioning (RIC) has offered many primary immunodeficiency disorder (PID) patients who are ineligible for myeloablative regimens a chance of cure. However, the beneficial role of RIC was questioned following reports suggesting higher chance of rejection and lower symptom resolution rate in mixed chimerism settings. Forty-five children affected by PIDs with a median age of 21 months underwent allogeneic hematopoietic stem cell transplantation in our institute from 2007 to 2013. All patients received an identical RIC regimen. Forty-one patients had successful primary engraftment (91%). Of the successful engraftments, 80% (n=33) had stable full donor chimerism at last contact. Overall, eleven transplant-related mortalities were reported including five patients due to sepsis, three children due to grade IV acute GvHD, two due to chronic GvHD and one patient due to sepsis after primary graft failure. The median post-transplantation follow-up of deceased patients was 55 days. Five-year overall survival and disease-free survival was 75.6% and 68.89%, respectively. All surviving patients with successful engraftment became disease free, regardless of having full or mixed chimerism. Our study suggests that RIC regimen provides satisfactory rates of successful engraftment and full chimerism. Furthermore, patients with mixed chimerism were stable in long-term follow-up and this chimerism status offered the potential to resolve symptoms of immunodeficiency.

MR imaging of the urinary bladder.

MR imaging is the modality of choice for accurate local staging of bladder cancer. In addition, bladder MR imaging helps detect lymph node involvement, and in conjunction with computed tomography, provides complete staging. Familiarity with optimal imaging protocols, normal urinary bladder anatomy, and pathologic MR imaging appearances is essential for the radiologist. Evolving techniques, such as use of diffusion-weighted imaging and lymphotropic nanoparticle-enhanced MR imaging, may further enhance the ability of MR imaging in local and nodal staging.

Reference Intervals for Serum Immunoglobulins IgG, IgA, IgM and Complements C3 and C4 in Iranian Healthy Children.

BACKGROUND: Determination of reference ranges of each serum protein in normal population of each country is required for studies and clinical interpretation. The aim of this study was defining reference range values of immunoglobulins and complement components in Iranian healthy children. METHODS: This study was conducted from June 2003 to June 2006 in Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences. Serum levels of IgG, IgM, IgA, C3 and C4 in 800 Iranian healthy children from newborn to 18 years of age in four population were measured by nephelometry. Kolmogrov-Smirnov tests and Pearson correlation tests were used for analysis. RESULTS: Our results mainly agree with previous reports, except for some discrepancy that might be due to the ethnic and geographic variety. There was a significant difference between two sexes only with IgA in the group of 1-3 months old, which was higher in male group and IgM in groups of 3-5, 6-8 and 9-11 years old that were higher in female groups. Mean of other serum immunoglobulins and complements was not significantly different between male and female groups. CONCLUSION: These results can be considered as a local reference for use in laboratories, clinical interpretations, and research for Iranian children.

Reduced-intensity conditioning hematopoietic SCT for pediatric patients with LAD-1: clinical efficacy and importance of chimerism.

Pediatric patients with leukocyte adhesion deficiency type-I (LAD-I) experience severe and recurrent life-threatening bacterial infections with failure of pus formation and delayed wound healing. LAD-I is a rare inherited disease caused by mutation in the leukocyte CD18 integrin expression, resulting in defective adherence and migration of leukocytes, in particular neutrophilic granulocytes through the intravascular space. Hematopoietic SCT is the only curative treatment option available to patients with LAD-I. Since 2007, in a prospective trial, reduced-intensity conditioning regimen have been developed for 10 consecutive patients with LAD-I who were referred to our center. Based upon available data, it is the first time that such a number of patients affected by LAD-I have been treated with this regimen. This study attempts to show that reduced-intensity regimen leads to a favorable result in LAD-I patients even in those who have experienced comorbid complications. Following transplantation, some patients develop mixed chimerism, however, in our study mixed chimerism was not followed by transplant rejection.

Effect of Ramadan fasting on serum heat shock protein 70 and serum lipid profile.

INTRODUCTION: Ramadan, the holy month for the Islamic world, is a period every year when food and fluid intake is restricted to the pre-sunrise and post-sunset hours. The aim of this study was to evaluate the effect of Ramadan fasting on the serum concentration of heat shock protein 70 (HSP70) and serum lipid profile in healthy men. METHODS: A total of 32 male volunteers with a mean age of 28.5 (range 23-37) years were selected for the study. Blood samples were obtained one day prior to Ramadan and on the 3rd and 25th days of fasting. Serum HSP70, triglyceride (TG), cholesterol (Chol), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), LDL/HDL and Chol/HDL ratios were investigated. RESULTS: It was observed that the mean concentrations of serum HSP70 and HDL on the 25th day of Ramadan were significantly higher than those recorded one day before Ramadan and on the 3rd day of Ramadan, and the levels on the 3rd day of Ramadan was significantly higher than those recorded one day before Ramadan. Mean concentrations of serum TG, Chol, LDL, and LDL/HDL and Chol/HDL ratios on the 25th day of Ramadan were significantly lower than those recorded one day before Ramadan and on the 3rd day of Ramadan, and the levels found on the 3rd day of Ramadan were also significantly lower than those recorded one day before Ramadan. CONCLUSION: Ramadan fasting increases serum HSP70 and improves serum lipid profile.

The Study of Total IgE Reference Range in Healthy Adults in Tehran, Iran.

BACKGROUND: IgE is an antibody class that regarded as an important factor in the pathogenesis of allergic diseases, asthma, immune responses to parasitic infection and it could be responsible for the late- phase allergic response. The objective of this study was to evaluate total IgE in healthy Iranian adults, establishment of reference range of total IgE and assess helpfulness of this value in clinical diagnosis atopic and allergic diseases. METHOD: Three hundred sixty six healthy adults from blood transfusion volunteers (18 to 60 years) were selected in this study. A specific questionnaire (including demographic factors, smoking status and …) was filled out for each person. Also, we evaluated effect of race and education on total IgE. These adults had no history of allergic disease. The total serum IgE level using a commercial enzyme immunoassay and CBC (Eosinophil count) was determined in them. RESULTS: Mean of age was 37.32± 10.93 yrs and 219 cases were males and 147 females. The geometric mean of total IgE was 20.84 IU/ml (2-373 IU/ml) (95% percentile= 250) (95% confidence interval=46.27-62.70). No differences was observed between mean of IgE log in males and females (P= NS) but mean of total IgE log in females is more than males. CONCLUSION: Normal range of serum total IgE obtained in this study could be helpful for diagnosis of IgE-dependent allergic disease, as reference ranges in Iranian healthy adults.

Instability of the structure and allergenic protein content in Arizona cypress pollen.

BACKGROUND: The allergenic characteristics of pollen and their levels of expression may vary depending on the plant species, the degree of maturation and the influence of environmental factors such as climate and atmospheric pollution. The objective of this survey was the comparison of the structure and allergenic protein content in Arizona cypress (Cupressus arizonica, CA) pollen collected just after microsporangia dehiscence and 2 weeks later in urban areas. METHODS: The morphology and structure of pollen were examined by scanning electron microscopy. Pollen protein content was quantitatively and qualitatively investigated by Bradford protein assay, SDS-PAGE and densitometric analysis respectively. Fifteen allergic subjects, according to their clinical history of seasonal rhino-conjunctivitis and bronchial asthma have been selected for skin prick testing and ImmunoCap using CA standard allergen and for immunoblotting using extracts of CA mature pollen collected from Tehran. RESULTS: After 2 weeks, numerous cracks and collapses appeared in pollen surfaces. Western blotting performed by using extracts of pollen collected from Tehran, revealed that sera-specific immunoglobulin E of all allergic subjects reacted to a 35 kDa protein. The presence of this new major allergen and the decrease of Cup a 1 provide reliable explications about the low efficiency of standard commercial allergens in the diagnosis of the CA pollen allergy in Tehran. CONCLUSION: The instability of the pollen structure and protein content affects CA pollen allergenic properties. This study also suggests that to optimize CA standard allergen preparations, the eventual variability of pollen allergenic components have to be considered for each region.

A systematic review of recent asthma symptom surveys in Iranian children.

Asthma is the most prevalent chronic disease in children. To quantify the national prevalence of asthma symptoms in Iranian children, we conducted a systematic review and meta-analysis. After internet and hand searching for population-based prevalence estimates published from 1998 to 2003 from 142 articles, dissertations and reports of research projects, 19 of them were selected. All the selected studies on children had been performed by the International Study of Asthma and Allergies in Childhood (ISAAC) protocol. We analyzed the data using NCSS software. In the included 19 studies, 61,067 children in different age groups had been examined by the ISAAC protocol. The lowest prevalence of asthma symptoms was 2.7% in Kerman and the highest was 35.4% in Tehran (capital of Iran). Overall prevalence of asthma symptoms at a national level was estimated as 13.14% (95% CI: 9.97-16.30%). Based on this study, the prevalence of asthma symptoms in Iran is higher than that estimated in the international reports. This information can be used to help prioritize asthma prevention and control within the range of Iranian public health concerns.

Asthma in patients with atopic dermatitis.

OBJECTIVE: This cross-sectional study was designed to estimate the frequency of asthma in patients with atopic dermatitis (AD), and its related factors. METHODS: The study population consisted of 236 patients with AD who were referred to Children Medical Center in 1997-2002 and their diagnosis was based on Hanifin & Rajka criteria. Severity of AD was categorized based on Severity Scoring of Atopic Dermatitis (SCORAD) index. Asthma was diagnosed with medical history and clinical examination (three or more episodes of wheezing and/or dyspnea and/or cough after 1 year old). The patients were divided in two groups according to having or not having asthma. RESULTS: The mean age of patients with AD was 38.67+/-2.68 month and the mean age at onset of asthma was 20+/-2.5 month. The frequency of asthma in AD patients was 27.5%. The mean of SCORAD in nonasthmatic patients was 52.27 +/- 2.52 and in asthmatic patients was 56.2+/- 4.2 (P= 0.4). The mean of duration of breastfeeding in asthmatic patients was 12.2+/-1.6 month and in non-asthmatic patients was 11.16+/-6.3 month (P = 0.87). There was no significant difference between asthmatic patients and others in serum IgE levels (P = 0.65) and blood eosinophil count. (P = 0.49). CONCLUSION: These results confirmed that development of asthma in patients with AD is more than normal population and AD can be a significant predisposing factor to developing asthma but the causative factors are not clear.

Molecular diagnosis of X-linked chronic granulomatous disease in Iran.

Chronic granulomatous disease (CGD) is an inherited disorder of pathogen killing by phagocytic leukocytes caused by mutations in NADPH oxidase subunits. Patients with CGD have life-threatening bacterial and fungal infections. Children's Medical Center at Tehran University is the referral center for immunodeficiency in Iran. During 2 years of study, 11 non-consanguineous families with clinically diagnosed CGD were referred to this center. In functional assays performed on neutrophils from affected children and their mothers; no activity or strongly decreased oxidase activity was detected in the patients' cells. In oxidase tests that scored this activity on a per-cell basis, a mosaic pattern was detected in the neutrophils from all 11 mothers. Western blot analysis revealed an X91 degrees phenotype in all patients. Mutation screening in the CYBB gene encoding gp91(phox) by SSCP analysis followed by sequencing showed nine different mutations, including two novel mutations. The present survey is the first study aimed to analyze the clinical features and the molecular diagnosis of X-CGD in Iranian patients.

ENT manifestations in Iranian patients with primary antibody deficiencies.

OBJECTIVE: One hundred and nine patients with primary antibody deficiencies were selected in order to determine the frequency of ENT complications. METHOD: Demographic information and ENT medical histories were collected for each patient. Duration of study for each patient was divided into two periods of before diagnosis and after diagnosis and the initiation of treatment. RESULTS: Eighty-two of 109 patients (75.2 per cent) experienced ENT infections during the course of the disease (63: otitis media, 75: sinusitis and nine: mastoiditis). At the time of diagnosis, 52 (47.7 per cent) out of 109 patients presented with an ENT symptom. The frequencies of episodes were 27 for sinusitis and 25 for otitis media (one complicated with mastoiditis). After immunoglobulin replacement therapy the incidence of otitis media was reduced from 1.75 before treatment to 0.39 after treatment per patient per year (p = 0.008). The incidence of sinusitis also significantly decreased from 2.38 to 0.78 (p value = 0.011). CONCLUSION: ENT infections are common medical problems in primary antibody deficiency patients. Persistent and recurrent ENT infections should be suspected as originating from a possible underlying immunodeficiency.

Analysis of class-switched memory B cells in patients with common variable immunodeficiency and its clinical implications.

BACKGROUND: Common variable immunodeficiency (CVID) comprises a heterogeneous group of primary immunodeficiency disorders characterized by hypogammaglobulinemia leading to recurrent infections. Some patients with CVID are more susceptible to earlier onset of respiratory disease and bronchiectasis. It has been suggested that memory B cells, characterized by CD27 expression, can be used as a means to classify subsets of CVID patients. OBJECTIVE: The aim of this study was to classify a sample of Iranian patients with CVID by quantification of peripheral blood memory B cells and immature B cells and to assess the relationship between this classification and the clinical characteristics of the patients. METHODS: The study included 29 patients with CVID and 20 healthy controls. Patients were grouped as follows, according to the quantification of peripheral memory B cells: group I had less than 0.4% switched memory B cells (CD27+, immunoglobulin [Ig] M-, IgD-) in peripheral blood lymphocytes (PBL), while in group II switched memory B cells represented more than 0.4% of PBL. Group I patients were further subdivided into groups Ia and Ib according to the proportion of CD21- peripheral B cells. The clinical and laboratory findings for the patients were then compared among the 3 groups. RESULTS: The percentage of switched memory B cells (CD27+IgM-IgD- cells in peripheral B lymphocytes) was markedly reduced in CVID patients compared with controls (P < .001). This percentage was less than 0.4% (group I) in 20 patients (69%) (P < .05). In the remaining 9 patients (group II) and all healthy controls, the percentage was greater than 0.4%. Bronchiectasis was more frequent in group I than group II (P < .05). Following subdivision of group I patients into groups Ia and Ib based on CD21 peripheral B cells, the rate of autoimmunity was found to be much higher in group Ia than group Ib. CONCLUSIONS: CVID patients with reduced numbers of switched memory B cells are more prone to recurrent respiratory infections and development of bronchiectasis, and as such, need more special care than other CVID patients. Thus, classification of CVID patients by assessment of switched memory B cells could help physicians to predict clinical prognosis of these patients.

Pulmonary complications in primary hypogammaglobulinemia: a survey by high resolution CT scan.

BACKGROUND: Primary hypogammaglobulinemia disorders are a group of heterogeneous immunodeficiency syndromes with an increased susceptibility to pulmonary complications. METHODS: The aim of this study was to evaluate the extent of lung abnormalities in primary hypogammaglobulinaemic patients by high resolution computed tomography (HRCT) scan and pulmonary function test (PFT). HRCT and PFT were performed in 22 Iranian patients with primary hypogammaglobulinemia. RESULTS: Pathological bronchial findings were observed in thirteen patients: three patients showed only peribronchial thickening and the remaining ten patients suffered from both bronchiectasis and peribronchial wall thickening. Mild type of bronchiectasis and peribronchial wall thickening were the most common type, predominantly observed in the right middle and both right and left lower lobe segments of lungs. Although bullae were not found, emphysema, air-trapping, and collapse/consolidation were observed in two patients. Bronchial involvement was mostly limited to 1 up to 5 bronchopulmonary segments; only one HRCT indicated bronchial involvement in more than nine bronchopulmonary segments. Pathological bronchial findings mostly observed in the proximal bronchi; meanwhile the involvement of the distal bronchi was less common. Decreasing FEVI and FVC were observed in 65% and 55% of patients, respectively. There was a significant correlation between the HRCT score and the predicted values by PFT. The delay of diagnosis in patients with bronchiectasis was significantly higher than those without bronchiectasis. CONCLUSIONS: It seems that the majority of hypogammaglobulinaemic patients suffer from the mild type of bronchiectasis, which is mostly observed in the proximal bronchi of the lower lobe segments. The delay of diagnosis plays an important role in the occurrence of this complication in these patients.

Serum concentration of selenium in healthy individuals living in Tehran.

OBJECTIVE: To investigate whether daily diet provides adequate selenium intake in healthy men and women living in Tehran, Iran. METHOD: Serum level of selenium was determined in 184 healthy individuals of both genders. The samples were divided into two age groups, adults and children, for analysis. The serum level of selenium was determined using hydride generation and flame atomic absorption spectroscopy. RESULTS: The mean and standard deviation of serum selenium levels in children (1-16 years) was 84.3 +/- 11 microg/l and there was no significant difference between genders in this group. In adults (older than 16 years) the mean serum selenium level was 100.6 +/- 13 SD microg/l; among women the mean was 93.9 +/- 14 SD microg/l and among men it was 102.2 +/- 12 SD microg/l. The mean selenium level in men was higher than in women and data analysis showed a significant difference between them (p < 0.005). There was also a positive correlation between higher selenium serum concentration and age in men (P < 0.001). Daily intake of selenium in men and women was calculated to be 67 microg and 62.1 microg respectively. CONCLUSION: Our results show that the serum concentration of selenium in an Iranian population is similar to other nationalities in the Middle East, particularly Saudi Arabia.