Molecular genetic diagnosis of Glanzmann syndrome in Iranian population; reporting novel and recurrent mutations.

BACKGROUND: Glanzmann thrombasthenia (GT) is a rare autosomal recessive abnormality of platelet aggregation with quantitative and/or qualitative abnormality of αIIbß3 integrin. The αIIbß3 is a platelet fibrinogen receptor, which is required for platelet aggregation, firm adhesion, and also spreading. The disease is more prevalent in the populations with a higher rate of consanguineous marriages as in some Middle Eastern populations including Iraq, Jordan, and Iran. Different types of mutations in ITGA2B and ITGB3 genes have been previously reported to cause the disease. RESULT: In this study, 16 patients with the clinical diagnosis of GT were studied. Direct sequencing of the exons and exon-intron boundaries of the above genes revealed mutations in 14 patients (detection rate: 87.5%). Briefly, out of fifteen types of identified mutations, 14 were novel. Seven mutations in the ITGB3 gene included 4 missense [c.2T > C, c.155 G > T, c. 538 G > A, c.1990 G > T], one nonsense mutation [c.1303 G > T], a small deletion [c.1656_1658delCTC] and a deletion of one nucleotide [c.401delA]. Mutations in the ITGA2B were 8 different mutations consisting 2 missense [c.286 T > A, c.842 C > T], 2 deletions [c.1899 del T, c.189-319_236del], an insertion [c.1071_1072insG] and one splice site mutations [c.409-3 C > G], one synonymous mutation that might alter the normal splicing process [c.1392 A > G] and a nonsense mutation [c.1555 C > T]. The causative mutation in 2 patients remained unknown. Using long-range PCR and sequencing, we found a rather large deletion. The break point of this deletion covers 319 nt from the last part of the first intron and 48 nt from the beginning of the second exon of ITGA2B gene. The deletion was also detected in two unrelated patients with the same ethnicity. In addition, in silico analyses of novel mutations were performed. CONCLUSION: There was no recurrent mutation in the studied population. This may be due to either small sample size or the heterogeneity of the studied population.

Job satisfaction and its relationship to Radiation Protection Knowledge, Attitude and Practice (RPKAP) of Iranian radiation workers.

This study aimed to find the association between job satisfaction and radiation protection knowledge, attitude and practice of medical radiation workers occupationally exposed to ionizing radiation. In this crosssectional study, 530 radiation workers affiliated to Tehran University of Medical Sciences completed a knowledge, attitude and practice questionnaire on protecting themselves against radiation and Job Descriptive Index as a job satisfaction measure during May to November 2014. Opportunities for promotion (84.2%) and payment (91.5%) were the most important factors for dissatisfaction. Radiation workers who were married, had more positive attitudes toward protecting themselves against radiation, and had higher level of education accounted for 15.8% of the total variance in predicting job satisfaction. In conclusion, medical radiation workers with a more positive attitude toward self-protection against radiation were more satisfied with their jobs. In radiation environments, improving staff attitudes toward their safety may be considered as a key strategy to increase job satisfaction.

Job satisfaction and its relationship to radiation protection knowledge, attitude and practice [RP-KAP] of Iranian radiation workers

This study aimed to find the association between job satisfaction and radiation protection knowledge, attitude and practice of medical radiation workers occupationally exposed to ionizing radiation. In this cross-sectional study, 530 radiation workers affiliated to Tehran University of Medical Sciences completed a knowledge, attitude and practice questionnaire on protecting themselves against radiation and Job Descriptive Index as a job satisfaction measure during May to November 2014. Opportunities for promotion [84.2%] and payment [91.5%] were the most important factors for dissatisfaction. Radiation workers who were married, had more positive attitudes toward protecting themselves against radiation, and had higher level of education accounted for 15.8% of the total variance in predicting job satisfaction. In conclusion, medical radiation workers with a more positive attitude toward self-protection against radiation were more satisfied with their jobs. In radiation environments, improving staff attitudes toward their safety may be considered as a key strategy to increase job satisfaction

La présente étude avait pour objectif de déterminer l'association entre la satisfaction au travail et les connaissances, attitudes et pratiques en matière de radioprotection des travailleurs exposés aux rayonnements médicaux ionisants dans le cadre de leur activité professionnelle. Au cours de cette étude transversale, 530 travailleurs exposés aux rayonnements rattachés à l'université de Sciences médicales de Téhéran ont rempli, entre mai et novembre 2014, un questionnaire portant sur les connaissances, attitudes et pratiques pour se protéger contre les rayonnements, ainsi que sur l'indice de satisfaction professionnelle Job Descriptive Index dans le but d'évaluer leur satisfaction au travail. Les possibilités de promotion [84,2%] et les salaires [91,5%] étaient les facteurs les plus importants d'insatisfaction. Les travailleurs exposés aux rayonnements qui étaient mariés étaient davantage disposés à se protéger des rayonnements, et avaient un niveau d'éducation plus élevé représentant 15,8% de la variance totale relative à l'évaluation de la satisfaction au travail. En conclusion, les travailleurs exposés aux rayonnements médicaux ayant une attitude plus positive vis-à-vis du fait de se protéger étaient plus satisfaits de leur travail. Dans des environnements à rayonnement, améliorer la disposition du personnel à se protéger peut être considéré comme une stratégie clé pour augmenter la satisfaction au travail

Health education and peer leaders' role in improving low vaccination coverage in Akre district, Kurdistan Region, Iraq.

The role of religious leaders in improving vaccination coverage has not been well researched. This intervention study investigated the role of a health education campaign and peer spiritual leaders in improving vaccination coverage rates in Akre district in Kurdistan region, Iraq. An information campaign was conducted in 30 villages with low vaccination coverage. The participation of peer spiritual leaders was sought in 15 villages of the Sorchi tribe known to have persistent low coverage rates. The vaccination coverage rates of DPT1, DPT2, DPT3 and measles vaccines during the post-intervention period (January to June 2007) were significantly improved (95.5%, 90.0%, 84.4% and 80.3% respectively) compared with the pre-intervention period (January to June 2006) (55.9%, 42.7%, 21.5% and 27.6% respectively). The dropout rates of those vaccines were also significantly decreased. Vaccination in villages where spiritual leaders were involved improved significantly more than other villages.

Health education and peer leaders-role in improving low vaccination coverage in Akre district, Kurdistan region, Iraq

The role of religious leaders in improving vaccination coverage has not been well researched. This intervention study investigated the role of a health education campaign and peer spiritual leaders in improving vaccination coverage rates in Akre district in Kurdistan region, Iraq. An information campaign was conducted in 30 villages with low vaccination coverage. The participation of peer spiritual leaders was sought in 15 villages of the Sorchi tribe known to have persistent low coverage rates.The vaccination coverage rates of DPTT, DPT2, DPT3 and measles vaccines during the post-intervention period [January to June 2007] were significantly improved [95.5%, 90.0%, 84.4% and 80.3% respectively] compared with the pre-intervention period [January to June 2006] [55.9%, 42.7%, 21.5% and 27.6% respectively]. The dropout rates of those vaccines were also significantly decreased. Vaccination in villages where spiritual leaders were involved improved significantly more than other villages

Level of physical activity among teaching and support staff in the education sector in Dohuk, Iraq.

Sedentary lifestyle is a major underlying cause of death, disease, and disability worldwide. This survey in 2006 aimed to estimate the current level of physical activity among 293 school and university teaching staff and 246 support staff working in the education sector in Dohuk city, Iraq. The short form of the international physical activity questionnaire (IPAQ) was used to estimate physical activity. Using the higher IPAQ cutoff point (i.e. high, not moderate, level of activity) the prevalence of physical activity beneficial to health among all participants was 39.5%. Small but nonsignificant differences in physical activity were found among sex, age and BMI categories. Teachers reported significantly higher physical activity levels than support staff, and individuals with longer average sitting times per day reported significantly lower levels of physical activity.

Prevalence of microalbuminuria in children with sickle cell disease.

Renal involvement is common in homozygous sickle cell disease (HbSS), including glomerular hypertension and hypertrophy similar to that seen in rodent models of ablative nephrectomy and stage I diabetic nephropathy (DN). The proteinuria in the rodent models is attenuated by angiotensin converting enzyme inhibition (ACEI). Microalbuminuria (MA) is a sensitive marker for renal involvement in DN prior to the development of proteinuria, and is also attenuated with ACEI. Elevated urinary microalbumin/creatinine ratios (U Alb/Cr) >20 mg/g Cr are reported in 39%-43% of adults with HbSS, and studies are ongoing in this age group to assess the effect of attenuated proteinuria by ACEI on long-term renal function. The purpose of this study was to prospectively investigate the prevalence of MA in children with HbSS and determine factors which affect its expression. U Alb/Cr values were measured on spot urine samples in 102 children (aged 2-18 years, mean 9.47+/-4.62, M:F=53:49) by rate nephelometry. Children with prior known proteinuria, hypertension, or fever/pain episode in the last 15 days were excluded. MA was present in 26.5% of all children with HbSS. However, in children between the ages of 10 and 18 years, the prevalence was 46% (similar to the prevalence in adults). There was a strong correlation between patient age and prevalence of MA (P<0.0001) by both univariate and multivariate analysis. However, pain frequency, hospitalization, transfusion program, ferritin levels, and Cr clearance (C(Cr)) did not correlate with prevalence, although C(Cr) (as estimated by Schwartz formula) was elevated in all. We conclude that the prevalence of MA in the 2nd decade of life is similar to that in adults.

Renal osteodystrophy.

Secondary hyperparathyroidism develops in most patients with chronic renal failure, and is associated with the histologic finding of osteitis fibrosa cystica. The disease is characterized by growth failure and severe bone deformities in children, especially the very young. The pathogenesis of renal osteodystrophy is related to phosphate retention, and its effect on calcium and calcitriol metabolism, in addition to roles played by metabolic acidosis, cytokines, and degradation of parathyroid hormone. Treatment includes restriction of dietary phosphorous intake, phosphate binders, and use of active metabolites of vitamin D.

Mineral content of infant formula after treatment with sodium polystyrene sulfonate or calcium polystyrene sulfonate.

Options for the management of infants with hyperkalemia secondary to renal insufficiency are limited for infants not maintained on dialysis. Precipitation of potassium (K+) from infant formula with sodium polystyrene sulfonate (KX) prior to feeding has been reported. However, its effect on calcium (Ca2+) and sodium (Na+) has not been quantitatively defined. The purpose of this study was to examine the effects of two K+ exchange resins: KX and calcium polystyrene sulfonate (RC) on Na+, K+, and Ca2+. Infant formula powder (Similac PM 60/40, Ross Laboratories, Columbus, OH, USA) was prepared with deionized water (DW) and KX or RC (1 g/mEq of K+) was added. The formula was decanted after 50 minutes and Na+, K+, and Ca2+ were assayed in the supernatant. Na+ and K+ were also assayed in ready-to-feed PM 60/40 (RTF). KX decreased the K+ concentration by 4.5 fold (P < 0.001) and increased the Na+ content by 3.8 fold (P < 0.001). In RC there was a 1.6-fold increase in Ca2+ content (P < 0.001), and a 13% decrease in K+ concentrations (P < 0.05). Preparation of the formula with DW reduced the K+ concentration by 30% compared to ready-to-feed formula (P < 0.001). We conclude that, although KX significantly reduces the K+ content of formulas, DW may be a more practical and convenient method of preparing formula for the hyperkalemic infant.

Evaluation of renal function during childhood.

There are several methods to evaluate renal function during childhood. The use of serum creatinine, either alone or in combination with the Schwartz formula, is reliable and quick, but requires knowledge of conceptual age. A plasma creatinine concentration of 88.4 mumol/L (1.0 mg/dL), for example, represents normal renal function in an adolescent but more than 50% loss of renal function in a 5-year-old child. A timed urine collection for creatinine clearance is another evaluative method, but the adequacy of the urine collection always should be determined first. Urea clearance rarely is used to measure GFR because of the complex factors that influence urea excretion. Measurement of the disappearance of radioactive-labeled substances in plasma can be used to determine GFR. Radionuclide renal scans also can be used and offer the advantage of estimating the GFR of each kidney. Although infants and newborns have an intact urine diluting ability, their concentrating ability is impaired. The maximal urinary concentration in the neonatal period is less than 700 mOsm/kg, but reaches adult values of 1200 mOsm/kg by 6 to 12 months of life. Similarly, the infant kidney has a limited capacity for salt regulation, predisposing the infant to salt disturbances.

Alterations in plasma phosphorus, red cell 2,3-diphosphoglycerate and P50 following open heart surgery.

OBJECTIVES: To evaluate changes in and the correlation between plasma phosphorus, red cell 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP), and P50 in children following heart surgery. EXPERIMENTAL DESIGN: Prospective, observational study with factorial design. SETTING: A pediatric intensive care unit in a university hospital. PATIENTS: Twenty children undergoing open heart surgery for congenital heart defects. INTERVENTIONS: None. MEASURES: Red cell 2,3-DPG and ATP, P50, plasma phosphorus, and arterial lactate were obtained before and at 1, 8, 16, 24, 48, and 72 hours after surgery. The amount of intravenous fluid and glucose administered, and age of blood utilized were documented. Variables were analyzed by repeated measure analysis of variance followed by paired t-tests. To investigate the relationship between variables at each time point, scatterplot matrices and correlation coefficients were obtained. RESULTS: There was a reduction in plasma phosphorus, red cell 2,3-DPG, and P50 and an increase in arterial lactate at 1, 8, 16, 24, 48, and 72 hours after surgery. Red cell 2,3-DPG correlated with P50 at 1, 8 and 16 hours. The decrease in the plasma phosphorus correlated with the amounts of intravenous fluid and glucose administered on the day of surgery and on the first and second postoperative days. The age of the blood utilized correlated with the decrease in red cell 2,3-DPG on the day of surgery. CONCLUSIONS: Reduction in red cell 2,3-DPG, P50, and plasma phosphorus occurs after open heart surgery in children. These changes can potentially contribute to impaired oxygen utilization in the postoperative period, when adequacy of tissue oxygenation is critical.

Application since 1980 of antihypertensive agents to treat pediatric disease.

Strategies for using antihypertensive agents have changed significantly since 1980. This paper reviews clinical studies devoted to the use of antihypertensive agents in children beyond the newborn period. The availability of converting enzyme inhibitors and calcium channel blockers has significantly improved BP control in children with secondary forms of hypertension. The role of antihypertensive agents to chronically treat primary hypertension in children remains unclear. Additionally, some treatment protocols used in adults that apply to the treatment of hypertensive children and that have been used in the treatment of nonhypertensive disease are discussed. Preliminary studies suggest that the rate of decline of renal function in some forms of progressive renal disease may be retarded by the use of converting enzyme inhibitors.

Acute changes in endothelin-1 after hemodialysis for chronic renal failure.

Endothelin is a recently described, potent renal vascular and systemic vasoconstrictor peptide. To evaluate the response of this peptide to volume contraction, we measured eight baseline and posthemodialysis samples from seven children, aged 14.5 +/- 3 years, with chronic renal failure. Plasma was extracted and endothelin-1 was measured by radioimmunoassay. Dialysis was performed for a 3- to 3 1/2-hour period, and body weight decreased from 38.0 +/- 14.3 to 36.2 +/- 13.8 kg (p < 0.01) during this time. There were no significant changes in heart rate or respiratory rate after dialysis, but blood pressure fell from 127/80 +/- 22/16 to 114/72 +/- 20/21 mm Hg (p = 0.05 for the systolic pressure). Plasma endothelin-1 concentration increased from 1.5 +/- 1.2 pg/ml at baseline to 7.3 +/- 8.9 pg/ml (p = 0.06) after dialysis; the fall in body weight from dialysis correlated with the increase in endothelin (r = -0.75; p = 0.05). Thus volume contraction from hemodialysis is associated with a rise in plasma endothelin-1, which is related to the acute change in body weight.

Antagonism of medetomidine-induced ataxia in rats by yohimbine, aminophylline and caffeine.

The actions of the alpha 2-antagonist yohimbine and methylxanthines aminophylline and caffeine were evaluated in reversing ataxia, increase in landing foot splay (LFS), produced by the alpha 2-agonist medetomidine in male rats. Medetomidine at 0.1 and 0.15 mg/kg, i.p. increased LFS by 42.9 and 69.6%, respectively. The peripherally acting alpha 2-agonist ST91 (0.125 to 0.5 mg/kg, i.p.) did not significantly affect the LFS. Intraperitoneal injection of yohimbine at 0.5 and 1 mg/kg, aminophylline at 25, 50 and 100 mg/kg, and caffeine at 25 and 50 mg/kg significantly antagonized medetomidine (0.15 mg/kg, i.p.)-induced ataxia. Yohimbine was more effective (100 and 111%) than the methylxanthines (28 to 72%) in reversing medetomidine ataxia. Aminophylline and caffeine, but not yohimbine, significantly reduced LFS in non-medetomidine treated rats. The data suggested that medetomidine ataxia in rats could be specifically antagonized by yohimbine and to a lesser extent by aminophylline and caffeine.

Adaptation to taurine deprivation in the phosphate-depleted rat.

The nonessential amino acid taurine, which is inert in renal tissue, was used to study renal adaptation in the presence of phosphate (P) depletion in the rat. Weanling rats were placed on the control diet (0.7% P, normal taurine) for 4 wk, then fed one of the experimental diets or continued on the control diet for 1 wk. The diets used were 1) P+T- (0.7% P, low taurine), 2) P-T+ (0.1% P, normal taurine); and 3) P-T- (0.1% P, low taurine). Taurine deficiency was associated with avid tubular reabsorption of taurine, irrespective of P status. This was associated with a 4- to 5-fold increase in the Vmax of uptake (p less than 0.001). On the other hand, P depletion increased the Km of taurine uptake by 6.6- to 9.5-fold, suggesting a decrease in the affinity of the taurine symport (p less than 0.001). This was independent of the taurine status of the animals. Although there was no effect of diet on the urinary excretion of beta-alanine, P depletion, irrespective of taurine status, resulted in a 2-fold increase in the Km of beta-alanine uptake. We conclude that the taurinuria of P depletion is reversed in taurine deprivation. The adaptive response involves an increase in the Vmax of uptake. However, the increase in Km of taurine uptake observed in P depletion does not reverse with taurine depletion.

The effect of aggressive nutrition on infection rates in patients maintained on peritoneal dialysis.

Aggressive nutrition has been reported to improve growth parameters in children undergoing peritoneal dialysis. The current study reports the effect of a program of aggressive nutrition, started in 1/1988, on catheter-related infection rates in children undergoing chronic peritoneal dialysis. A combination of high calorie foods, supplements, "candy bar diets", and, when necessary, modular gastrostomy feedings, to provide 3-4 gm/kg/d and 100-120 kcal/kg/d was used. Peritonitis and catheter infection rates were assessed. A total of 37 pediatric patients underwent peritoneal dialysis from 1/1986-7/1990, with a total cumulative experience of 596 patient months. The peritonitis rate decreased from 1 episode/5.53 patient-month in 1987 to 1 episode per 46 patient-month in 1990. There was no significant effect on the catheter infections or the number of admissions/patient month. However, there was a 55% decline in the number of hospitalization days/patient month (p less than 0.01). The decrease in the peritonitis rate was independent of the modality of peritoneal dialysis or the usage of ultraviolet connecting devices. In 10 patients followed sequentially, the peritonitis rate was less (1 episode/23.5 patient months) after gastrostomy tube placement and feedings than before gastrostomy tube placement (1 episode/8.28 patient months) (p less than 0.01). There were no significant differences in serum albumin or total protein levels between the two observation periods. We conclude that adequate nutrition may play a role in decreasing the peritonitis rate in children maintained on peritoneal dialysis and speculate improved white cell function as a possible underlying mechanism.

Perturbation of renal amino acid transport by brush border membrane vesicles in the vitamin D-deficient rat.

Vitamin D deficiency is characterized by secondary hyperparathyroidism, phosphaturia, bicarbonaturia, and generalized amino aciduria. While the site at which the phosphaturia ensues has been described to occur at the apical membrane of the renal proximal tubule, no studies are available for amino aciduria. Thus, weanling rats were fed five vitamin D-deficient diets for 4-6 weeks: (i) VLC, 0.02% Ca, 0.3% P; (ii) VLC + 1,25[OH]2D, same + 500 pmole ip for 2 days; (iii) LC, 0.45% Ca, 0.3% P; (iv) HC, 2.5% Ca, 0.3% P; and (v) VLP, 1.2% cA, 0.1% P. The normal diet contained 1.2% Ca, 0.7% P, and 2.5 micrograms% vitamin D. Amino acids, serum 25[OH]D, 1,25[OH]2D, and PTH, using a specific anti-rat PTH antibody, were measured. There were 4.65 +/- 1.1- and 10 +/- 1.39-fold increases in the urinary excretion of taurine and proline, respectively, irrespective of diet. Hypocalcemia, secondary hyperparathyroidism, and increased concentrations of urinary cAMP were demonstrated in all diets, except VLP. Taurinuria and prolinuria manifested at the renal brush border membrane. There was 21-25% and 26-39% attenuation in the peak of the overshoot of Na(+)-dependent uptake of taurine and proline, respectively, that was statistically significant as compared to that of normal diets (P less than 0.01). VLC resulted in a reduction in the Vmax of taurine (VLC, 78.26 +/- 6.88 vs normal, 115.4 +/- 6.26 pmole/mg protein/min, P less than 0.01) and proline (VLC, 402.06 +/- 31.26 vs normal, 589.49 +/- 37.42 pmole/mg protein/15 sec, P less than 0.01) uptake. Acute supplementation with pharmacological doses of 1,25[OH]2D normalized the Vmax of taurine and proline uptake, without affecting their renal excretion. The VLP diet induced and increase in the Km of taurine (VLP, 58.95 +/- 1.88 microM vs normal, 39.75 +/- 2.75 microM P less than 0.01) and proline (VLP, 116.75 +/- 8.87 microM vs normal, 76.82 +/- 7.27 microM P less than 0.01) uptake, without an associated perturbation in the Vmax of uptake. We conclude that the amino aciduria of vitamin D deficiency manifests at the apical membrane of the proximal tubule by an attenuation in the Na(+)-dependent uptake of amino acids. This is associated with a reduction in the initial rate of uptake or number of active transporters in the presence of secondary hyperparathyroidism and hypocalcemia, or a decrease in the affinity of the symport in the presence of P depletion. The data suggest the interplay of multiple factors in the causation of amino aciduria.