Altered suppressor function of regulatoryT cells in type 1 diabetes

Background: Type 1 diabetes [T1D] is a T cell mediated autoimmune disease targetingthe insulin-producing beta cells within pancreatic islets. Autoimmune diseases maydevelop as a consequence of altered balance between regulatory [Tregs] andautoreactive T cells

Objectives: To evaluate Treg cells frequency and suppressivefunction in the peripheral blood of newly diagnosed T1D patients in comparison withhealthy controls

Methods: Fifteen new cases of T1D patients and 15 age- and sexmatchedhealthy controls were recruited to this study. Their peripheral bloodmononuclear cells [PBMCs] were isolated and CD4[+]CD25[+]FoxP3[+]CD127[-/low] Treg cellswere studied by flowcytometry technique. Thereafter, Tregs were isolated by Magnetic-Activated Cell Separation [MACS] technology and by using CFSE [carboxyfluoresceinsuccinimidyl ester] dilution assay, their suppressive activity was evaluated in thecoculture of CD4[+]CD25[-] T responder cells with Treg cells

Results: The percentage ofCD4[+]CD25[+]FoxP3[+]CD127[-/low] Tregs did not differ between T1D patients and healthycontrols but the MFI [mean fluorescence intensity] of transcription factor FoxP3[forkhead box protein P3] was significantly decreased in T1D patients [20.03 +/- 1.4 vs.31.33 +/- 2.95, p=0.0017]. Moreover, the suppressive function of CD4[+]CD25[+]CD127[-/low]Treg cells was significantly diminished in T1D patients in comparison with controlgroup [35.16 +/- 4.93% vs. 60.45 +/- 5.26%, respectively, p=0.0015]

Conclusion: Presentstudy indicates an impaired immune regulation among T1D patients, characterized bydefects in suppressive function and expression of FoxP3 in Treg cells without anysignificant decrease in their frequency in peripheral blood

Evaluation of physicians' awareness of pediatric diseases in Iran

Physicians' awareness about pediatric health problems is very important in health system. This has not been investigated in Iran as yet. Therefore this study was conducted to characterize the knowledge of the Iranian physicians which has direct association with health status of children. One hundred and four physicians, mainly pediatric specialists [58.6%] working in the state hospitals [45.1%] were enrolled. They filled a valid and reliable questionnaire, containing 26 questions about basic and important pediatric issues before and after an educational pediatric program [EPP]. Thirty nine [37.5%] physicians answered correctly more than 2/3 of all questions [passed the examination] before EPP, which increased to 42.3% after EEP. Subgroup analysis showed that the total scores of general practitioners [P=0.007] was significantly increased after the EPP. Moreover, physicians with shorter practicing time [P=0.006] and those with shorter time past graduation [P=0.01] had a significant improvement in their total scores after the program. The best scores of educational issues were documented in growth and development [16.0%; P=0.04], followed by dermatology [9.2%, P=0.04], urology [9.1%; P=0.04], and asthma and allergy [9.0%, P=0.04]. This study revealed that there are gaps in the knowledge of professionals about the pediatric issues

Hypocalcemic seizure and related factors after neonatal period; A single-center, retrospective study

Seizures are the most common disorder of the central nervous system in childhood and constitute a significant number of admissions to the pediatric emergency departments. The aim of this study is evaluate the etiology of hypocalcemic seizures in pediatrics. A single-center, hospital based descriptive study was done in the academic referral center for hypocalcemic seizure of Tehran University of Medical Sciences, Iran. Data was evaluated based on the medical records of each patient. Case files of these children's were analyzed for age at presentation, sex, weight, clinical features, biochemical parameters [serum calcium, magnesium, phosphorus and alkaline phosphatase] ,type of seizure, history of previous seizure and history of drug intake. A total 38 children with hypocalcemic seizure, consisting of 19 boys and 19 girls, with ages ranging from one month to 14 years, were enrolled in this study. The most common patterns of seizures were generalized seizures [83.8%]. the mean levels of serum alkaline phosphatase was significantly greater in patients under the age of 2 years [1234 +/- 541.03] rather above than 7 years of age [922.75 +/- 147.45] [p = .021]. Rickets was the commonest cause of seizures rickets were diagnosis in 80.8% subjects under 2 years of age, whereas none of those over 7 years old had not rickets , these results were statistically significant [p = .015]. Current observational study indicates that rickets could be a major cause of hypocalcemic convulsion in infants and children. Screening children presenting with hypocalcemic convulsions for rickets and/or other cause of hypocalcemia can help in early diagnosis and institution of specific therapy

randomized clinical trial of insulin Glargine and Aspart, compared to NPH and regular insulin in children with type 1 diabetes mellitus

Objective: Appropriate treatment of patients with Type 1 diabetes mellitus [T1DM] is necessary to avoid further complications. This study was performed to compare the efficacy of insulin Glargine and Aspart with NPH insulin and regular insulin regimen in a group of children with T1DM

Methods: Forty patients with T1DM were enrolled in this study. During run-in, all subjects were treated with conventional therapy consisting of twice-daily NPH and thrice-daily regular. Following randomization, 20 subjects received Glargine and Aspart and 20 subjects received NPH and Regular insulin

Findings: Mean HbA1c was 8.8% and 8.6% at first and 8.4% and 8.2% at the end of study for subjects randomized initially to Glargine and Aspart and for those randomized to NPH and Regular, respectively [P>0.05]. Mean fasting blood glucose [FBS] of the subjects randomized initially to Glargine and Aspart was 217+/-101 mg/dL, with no significant difference to 196+/-75 mg/dL for those randomized to NPH and Regular [P=0.48]. This was also true at the end of the study. The difference in total cholesterol and triglyceride between the two groups in the beginning of study and at the end did not show any significance

Conclusion: The current study showed no significant difference in glycemic control [Glycated hemoglobin [HbA1c] and FBS] and lipid profile [total cholesterol and triglyceride] between two regimes

Serum zinc level in children presenting with febrile seizures

To determine the frequency of low serum zinc level in children presenting with febrile seizures at The Children's Hospital and the Institute of Child Health [CH/ICH] Multan. This is an observational cross sectional study conducted at the Department of Pediatric Medicine, The Children's Hospital and the Institute of Child Health, Multan from September 2010 to March 2011. Children [6 months to 6 years of age] presenting with febrile seizures who satisfied inclusion and exclusion criteria were enrolled for the study. Cause of fever was determined after detailed history, physical examination and relevant investigations. Four milliliters centrifuged blood sample was preserved in acid washed test tube. Separated serum was used to measure serum zinc level by employing Randox kit on auto-analyzer in all cases. The outcome variable [serum zinc level] was recorded on a predesigned proforma. Out of 100 enrolled children, there were 66 [66%] male with male to female ratio of 1:0.52. Mean age of the children was 23.97 +/- 14.45 months. Upper respiratory tract infection was the most frequent cause of fever apparent in 24 children [24%] followed by tonsillitis 17 [17%], pneumonia 16 [16%], urinary tract infection 16 [16%], otitis media 15 [15%], and bronchiolitis 12 [12%]. Frequency of low serum zinc level was 26% in children with febrile seizures. Zinc deficiency could be a potential risk factor for febrile seizure in children

Reliability of pubertal self assessment method: an Iranian study

This investigation aims to evaluate the validity of a Persian Tanner Stages Self-Assessment ? Questionnaire. In this cross sectional study, 190 male students aged 8-16 years selected from three layers of different regions of Tehran [North, Central and South] were enrolled. A Persian questionnaire illustrated with Tanner stages of puberty [genital development and pubic hair distribution] was prepared. Children were asked to select the illustration that best described their pubertal development. Tanner status of the children was also estimated by an independent physician using physical examination. The degree of agreement between subjects' judgments with assessments made by the rater was compared through the calculation of the weighted kappa statistic coefficient. We found a substantial agreement between self-assessment of pubertal development made by the children and doctor's assessment of genital development [kappa=0.63, P<0.0001] and also the pubic hair distribution [kappa= 0.74, P<0.0001]. Although a large proportion of subjects in G4 [89.2%] and G5 [85.7%] were capable of accurately or almost accurately identifying their own Tanner sexual stages, some degree of disagreement was observed in G3 Tanner stage [%46.9]. Self-assessment of puberty should be used very cautiously and may not be a substitute method for routine evaluation of pubertal state especially for early and mid pubertal groups

Acanthosis nigricans. abnormal facial appearance and dentition in an insulin resistance syndrome

Insulin resistance syndromes are a heterogeneous group of disorders with variable clinical phenotypes, associated with increased blood glucose and insulin levels. Herein, a 10-year old girl with abnormal face and dentition is presented. She has suffered from diabetes mellitus type 1 since she was 6 years old. Hyperglycemia did not respond to age appropriate insulin dosage; therefore, insulin dosage was increased, but did not lead to appropriate glycemic control. Twenty two exons of insulin receptor gene [INSR], on short arm of chromosome 19, were sequenced, but no identifiable disease causing mutation was detected. Although a rare mutation within the intronic or promoter region has not been exduded in this case, further molecular studies on patients with insulin resistance syndromes associated with certain features are needed

Transient neonatal diabetes as a presentation of fanconi- bickel syndrome

Fanconi- Bickel Syndrome [FBS] is a rare type of glycogen storage disease [GSD] Characterized by hepatomegaly, proximal renal tubular acidosis [RTA] and marked growth retardation. We report a case of FBS presenting with diabetic ketoacidosis and transient neonatal diabetes. A female infant, product of consanguineous marriage presented with diabetic ketoacidosis at age 33 days, and was treated as neonatal diabetes with insulin. At age 14 months, insulin was discontinued. She presented with short stature, hepatomegaly, RTA and hypophosphatemic rickets at age 4 and [FBS] was diagnosed. Diagnosis was confirmed by mutation analysis, showing mutation in SLC2 A2 gene. In conclusion,: neonatal diabetes or diabetic ketoacidosis may be the first presentation of infants with FBS

Mental health problems of Iranian female adolescents and its association with pubertal development: a nationwide study

Mental health problems including emotional and behavioral problems during puberty may be under influence of different risk factors including cultures, living in urban or rural areas and ethnic factors which may vary between different countries. The main aim of this study is to investigate the profile of emotional and behavioral problems and the role of factors such as age, stage of puberty, ethnicity, rurality and living in urban area, as risk factors in Iranian girls. As a part of a large national study we evaluated the emotional and behavioral problems in different stages of puberty in a community sample of Iranian adolescent girls from public schools that were selected by clustered random sampling method. In all subjects, demographic characteristics, and pubertal stages were measured. Emotional and behavioral problems were evaluated using Strength and Difficulties Questionnaire [SDQ]. The associations of age, pubertal development indices, socioeconomic and demographic factors with the behavioral problems were assessed. A total number of 4576 students enrolled the study and responded to the questions. The mean age of participants was 13.83 +/- 2.19 years. The mean total score of difficulties in participants was 14.34 +/- 5.81. According to these results 813 [17.8%] adolescents had total problem scores higher than Goodman's cutoff points and the most frequent problem domain was conduct problems [20.5%]. According to the results the most related variable with the total difficulty score of SDQ were ethnicity, residency in urban areas and development of menstrual cycle respectively. The results of this study showed that the most correlated factors with mental health problems in Iranian girls during puberty are ethnicity, urbanity and development of menstrual cycle

Dental problems in hypophosphatemic rickets, a cross sectional study

Hypophosphatemic rickets is an uncommon metabolic bone disorder which affects all ages and both sexes. It is characterized by low concentration of serum phosphate levels, impairment of mineralization of bone matrix and teeth with variable etiology. Dental problems in this disorder have not been described well in previous studies. All hypophosphatemic rickets patients who came to a referral clinic during 2008-2010 enrolled in this study. All patients had low phosphorous and high ALP, normal PTH and 25-hydroxy-vitamin D and normal or low level of serum calcium. After diagnosis all patients were examined by a dentist for enamel hypoplasia, taurodontism, dental abscess, gingivitis, dental caries, and dentition delay. Nineteen patients were enrolled in this study. The average age of the patients was 10 [ +/- 4.23] years [range 3-17]. Seventy-nine percent of patients had regular follow-up after diagnosis of background disease. Dental caries and delay in the dentition were most prevalent [each one 47.7%] followed by enamel hypoplasia in 42.1% of the patients. Other problems were taurodontism in 15.8% patients, dental abscess and gingivitis in 10.9%. Hypophosphatemic rickets is a disease with different clinical features; one of them is dental problem, dental caries is the most common problem

Molecular diagnosis of congenital adrenal hyperplasia in Iran: focusing on CYP21A2 gene

Congenital adrenal hyperplasia [CAH] is characterized by impaired biosynthesis of cortisol. 21-hydroxylase deficiency is the most common cause of CAH affecting 1 in 10000-15000 live births over the world. The frequency of the disorder is very high in Iran due to frequent consanguineous marriages. Although biochemical tests are used to confirm the clinical diagnosis, molecular methods could help to define accurate diagnosis of the genetic defect. Recent molecular approaches such as polymerase chain reaction based methods could be used to detect carriers and identify different genotypes of the affected individuals in Iran which may cause variable degrees of clinical expression of the condition. Molecular tests are also applied for prenatal diagnosis, and genetic counseling of the affected families. Here, we are willing to delineate mechanisms underlying the disease, genetic causes of CAH, genetic approaches being used in the country and recommendations for health care improvement on the basis of the molecular and clinical genetics to control and diminish such a high prevalent disorder in Iran. Also, the previous studies on CAH in Iran are gathered and a diagnostic algorithm for the genetic causes is proposed

effect of long-term steroid therapy on linear growth of nephrotic children

Steroids are still the mainstay of management of nephrotic syndrome [NS]. It was shown that steroids could impair growth and development of children. However, other clinical studies have shown conflicting results. Hospital records of 147 children with diagnosis of NS who were followed during 1988-2008 are reviewed relating to height measurements. All patients were treated with prednisolone and had been followed for at least five years. Height measures were transformed into standard deviation score [SDS]. Information on dose and duration of prednisolone therapy, histological findings of biopsy as well as concomitant use of steroid-sparing agents [SSA] were also analyzed. Mean age at onset of NS was 5.94 years and at last follow-up visit 15.08 years. All patients had normal renal function during entire duration of the study. Analysis of the whole population did not show any significant alterations in the height SDS [Ht[SDS]] between the first and the last follow-up visit [P=0.5; -0.76 +/- 2.0 vs. -0.89 +/- 2.05 respectively]. The patients were divided into two subgroups. Subgroup A, which achieved growth improvement, was composed of 62 children [initial [Ht[SDS]] -1.63; final [Ht[SDS]] -0.08; P<0.001] and subgroup B, that showed growth retardation, included 85 children [initial [Ht[SDS]] -0.13; final [Ht[SDS]] -1.59; P<0.001]. No statistically significant retardation of linear growth was observed in the study population as a group following treatment with prednisolone according to the guidelines of ISKDC. Although about 62 subjects had growth retardation, children treated with prednisolone were not different from those who had increased growth

[Dental problems in children with calcium metabolism disorders]

Calcium metabolism disorders can be acute or chronic and chronic disorders can cause different disease states such as dental problems. In this descriptive cross-sectional study done in Children's Medical Center affiliated to Tehran University of Medical Sciences during 2005-2009, all [93] patients with hypoparathyroidism, nutritional rickets, hypophosphatemic rickets and renal osteodysthrophy from the endocrinology and nephrology departments of the Center were referred to a dentist there for orodental examination. Subsequently, the frequency of dental problems including taurodontism, enamel hypoplasia, dental abscess, dental caries and gingivitis were recorded and analyzed. Nutritional rickets was the most common disorder in this study and delay in dentition was the most frequent dental problem in the patients [61.9%]. Most cases of taurdontism and enamel hypoplasia were seen in patients with hypoparathyroidism [33% and 50%, respectively]. Dental abscess, dental caries and gingivitis were more common in patients with renal osteodysthrophia [50%, 90% and 20%, respectively]. In addition, dental caries and delay in dentition were the most prevalent disorders in this study [69.8% and 49.5%, respectively]. According to the above findings, it seems that effective screening, regular periodic examinations, proper diagnosis and timely treatment of dental diseases are the main principles of prevention of orodental problems. Moreover, dentists as well as pediatricians should be aware of the features of the aforesaid disorders which lead to dental problems so that early intervention could prevent subsequent serious and more invasive dental problems

Female sex as a risk factor for glycemic control and complications in Iranian patients with type one diabetes mellitus

The aim of this study was to evaluate the influence of sex on glycemic control, diabetes complications and associated abnormalities in patients with type one diabetes mellitus. In a cross-sectional study in 309 patients [156 females and 153 males within the age range of 3-16 years] with type one diabetes mellitus referred to endocrinology clinic in Children's Medical Center in Tehran from March 2005 to March 2007 gender differences in diabetes control were analyzed. Mean glycosylated hemoglobin [HbA1c], was significantly higher in females [9.25 vs. 8.01]. Insulin dose per kilogram of body weight was significantly more in girls [0.91 +/- 0.31 vs. 0.74 +/- 0.37, P<0.001] self monitoring of blood glucose was performed significantly more in boys. Frequency of Diabetic ketoacidosis, height growth problems and dyslipidemia were significantly higher in girls. 1.20 +/- 0.86 vs. 0.93 +/- 0.55, P=0.004], [-0.05 +/- 1.20 vs. -0.41 +/- 1.17, P=0.015], [134.60 +/- 44.43 vs. 110.56 +/- 20.72, P=<0.001] respectively. Female sex is a risk factor in glycemic control and complications of diabetes type I and females should be managed more seriously regarding self monitoring of blood glucose, nutritional and psychological factors and puberty issues

Assessment of pubertal development in Iranian girls

We estimated pubertal development of 7,493 normal Iranian girls aged 6 to 20 years in a cross-sectional study. Pubertal stages were assessed according to Tanner. The mean ages to achieve secondary sexual characteristics as well as the mean age at menarche were estimated. Weight and height were measured and body mass index [BMI] was calculated. Reference curves for different breast stages and menarche were constructed. The percentiles for attaining each stage were compared to data proposed by Tanner. The mean age at breast bud stage [B2] was 10.10, pubic hair stage [P2] was 9.83, and menarche age was 12.55 years. The anthropometric variables were interpreted in different maturity stages. The mean age at attainment of puberty was compared with those of other populations. Not only the onset of puberty in Iranian girls but also the duration of puberty is similar to data from most other countries. A lower age limit for the definition of precocious puberty than the traditional 8 years is documented for Iranian girls. However, it should be noted that considering the rate of evolution of pubertal findings is more important than the age of their appearance

Wolfram syndrome: endocrinological features in a case series study and review of the literature

Wolfram syndrome [WFS] is a rare and complex genetic disorder referred to as DIDMOAD [diabetes insipidus, diabetes mellitus, optic atrophy and deafness]. All insulin dependent diabetic patients presented over a period of 10 years, who had optic atrophy or a positive family history of WFS, were enrolled in the study. Criteria for the diagnosis of WFS were the presence of insulin dependent diabetes mellitus [IDDM] along with optic atrophy unexplained by any other disease and/or some other abnormalities associated with WFS. WFS has been diagnosed in sixteen patients, 9 males and 7 females aged 5.5 to 22yr [median age of 13.4 yr]. Nine patients [more than half] came from consanguineous marriages. The earliest manifestation of WFS was IDDM [at a median age of 5.4yrs]. All patients developed non-autoimmune IDDM before the age of 8 years old. Only two cases were ketoacidotic. Common diabetic complications of proliferative retinopathy, glomerulosclerosis and neuropathy were remarkably absent in our patients even with long-lasting diabetes mellitus. Antidiuretic hormone [ADH]-responsive diabetes insipidus was confirmed by water deprivation test in 8 patients [50%]. The incidence of diabetes insipidus in our patients was lower compared to other studies. Growth retardation, as short stature and a weight below the 5th percentile for age and gender, was found in 13 [81%] and 5 [31%] patients respectively. Early diagnosis and proper treatment aimed at relieving the symptoms and preventing the future complications are of paramount value and importance

Exercise and diabetes type 1 recommendations, safety

Type 1 diabetic subjects without any complications and with a good control could participate in all levels of sports activities, both recreational and professional. But, there are some limitations for subjects who have chronic side effects of diabetes. A detail pre-participation physical examination is needed to find out these complications. All diabetics should be encouraged to perform suitable exercise and sports. To prevent acute diabetic side effects of exercise, hypo and hyperglycemia, diabetic athletes may need to adjust their nutrition and insulin dosage. Depending on the characteristics of the exercise, the ambient environment and the level of blood glucose before exercise, diabetic athletes need to consume some carbohydrate before, during and after exercise. Also, if the exercise takes more than 30 minutes, insulin should be reduced by 14-50%. Every athlete on the base of scientific recommendations, should find his or her own approach in the management of nutrition and insulin adjustment and integrity of them with exercise and sport. This could be achieved by trial and error

Treatment of precocious puberty by a long-acting gonadotropin-releasing hormone analogue in children

The GnRH analogue has been shown to be effective in the treatment of precocious puberty when given as a daily subcutaneous injection. We studied the effectiveness of a long-acting GnRH analogue, Triptoreline, for the treatment of central precocity, by suppressing gonadotropin and estradiol secretion in three children with true precocious puberty. One month after single dose intramuscular injection of depot GnRH analog Triptoreline, our patients showed significant decreases in serum estradiol and blunting of the responses of LH and FSH to GnRH test. No adverse effects were noted during the first six to eight months of treatment