Prevalence of transient congenital hypothyroidism in central part of Iran.

BACKGROUND: Congenital hypothyroidism (CH) considered a common endocrine disorder in Iran. We report the epidemiologic findings of CH screening program in Isfahan, seven years after its development, regarding the prevalence of transient CH (TCH) and its screening properties comparing with permanent CH (PCH). MATERIALS AND METHODS: In this cross-sectional study, children with primary diagnosis of CH were studied. Considering screening and follow-up lab data and the decision of pediatric endocrinologists, the final diagnosis of TCH was determined. RESULTS: A total of 464,648 neonates were screened. The coverage percent of the CH screening and recall rate was 98.9 and 2.1%, respectively. Out of which, 1,990 neonates were diagnosed with primary CH. TCH was diagnosed in 1,580 neonates. The prevalence of TCH was 1 in 294 live births. 79.4% of patients with primary CH had TCH. Mean of screening (54.7 ± 59.0 in PCH vs 21.8 ± 28.9 in TCH), recall (56.5 ± 58.8 in PCH vs 36.6 ± 45.0 in TCH), and thyroid stimulating hormone (TSH) and mean of TSH before (2.0 ± 2.9 in PCH vs 1.6 ± 1.6 in TCH) and after (37.7 ± 29.5 in PCH vs 4.3 ± 1.9 in TCH) discontinuing treatment at 3 years of age was significantly higher in PCH than TCH (P < 0.0000). CONCLUSION: The higher rate of CH in Isfahan is mainly due to the transient form of the disease. Further studies for evaluating the role of other environmental, autoimmune and/or genetic factors in the pathophysiology of the disease is warranted.

Thyroid function abnormalities among first-degree relatives of Iranian congenital hypothyroidism neonates.

BACKGROUND: Congenital hypothyroidism (CH) is a relatively common metabolic disease in neonates. Until recent years the disorder was usually regarded as occurring in a sporadic manner. Over the past few years, however, a considerable proportion of familial cases have been identified, and possible roles of autoimmune factors suggested. The aim of the present study was to evaluate abnormality of thyroid function tests in first-degree relatives of CH neonates and compared this to the normal population. METHODS: From 2002 until 2007 thyroid function tests (T4 and thyroid-stimulating hormone [TSH]) were done in randomly selected CH and normal neonates (n= 194 and n= 350, respectively) and their first-degree relatives. Most mothers of the CH neonates and control groups were also evaluated for thyroid peroxidase antibody (TPOAb). RESULTS: Thyroid function test in first-degree relative of neonates with CH (361 parents, 136 siblings) were compared with those in control groups (665 parents, 478 siblings). Abnormal thyroid function tests were found in 85 patients in the CH group versus 96 patients in the control group; hypothyroidism was found in 75 (15.1%) and 57 subjects (5%) person in the CH and control groups, respectively (P < 0.05). Positive TPO antibody was found in 22 mothers (17.3%) of CH neonates in comparison with 65 mothers (32.5%) of control groups (P < 0.05). Frequency of hyperthyroidism in parents of control group had trend to be higher than parents of CH neonates (P= 0.05) CONCLUSION: Familial and genetic components play a role in inheritance of CH, but maternal thyroid autoimmunity may not play an important role in the development of CH in Iran.

[Hemorrhagic strokes in children: etiology and management]. / Accidents vasculaires cérébraux hémorragiques spontanés chez l'enfant: etiologies et prise en charge.

Pediatric particularities and management of pediatric hemorrhagic strokes are reviewed. Etiologies of hemorrhagic strokes in children are quite different than in adults. Arterio-venous malformations are much more frequently encountered than aneurysms, cavernous malformations and other non structural causes. Modem imagery allows to diagnose the cause of the hemorrhage with a good security and the management is based on the association of neurosurgery, interventional neuroradiology and radiosurgery. These cases must be handled in specialized tertiary care hospital where these three modalities of treatment are available 24 hours/day.

Urine and milk iodine concentrations in healthy and congenitally hypothyroid neonates and their mothers.

INTRODUCTION: In view of the high prevalence of Congenital Hypothyroidism (CH) in Iran, in this study we evaluated the role of iodine in the aetiology of CH by comparing urine and milk iodine concentrations in healthy and congenitally hypothyroid neonates and their mothers. MATERIAL AND METHODS: In a cross-sectional study, urinary iodine concentrations (UIC) in newborns with CH, as well as UIC and the milk iodine concentrations (MIC) of their mothers, were measured and compared with a control group. The lower, mid, and upper range of UIC for neonates and lactating mothers was considered to be < 150 µg/L, 150-230 µg/L, and > 230 µg/L, and lower, mid, and upper range of MIC was considered to be < 150 µg/L, 150-180 µg/L, and > 180 µg/L, respectively. RESULTS: The median UICs in subjects with CH (n = 68) and healthy subjects (n = 179) were 300.5 and 290.5 µg/L, respectively (P > 0.05). The median UICs in the case and control groups were 150 and 130 µg/L, respectively (P > 0.05). The median MIC in the case group was higher than in the control group (210 µg/L v. 170 µg/L, P < 0.05).There was a positive correlation between newborn UIC and MIC. There was no significant correlation between newborn UIC and serum TSH, maternal UIC and maternal MIC, or newborn UIC and serum TSH. CONCLUSIONS: There is no inadequacy in iodine intake in the studied population. Iodine excess could be a possible risk factor for CH, but there were findings, such as lack of correlation between maternal MIC and UIC, and the median neonatal UIC, which was similar in the two groups, so, drawing conclusions should be done with some caution and requires further studies.

Nonsurgical Endodontic Treatment of Necrotic Teeth Resolved Apical Lesions on Adjacent Implants with Retrograde/Apical Peri-implantitis: A Case Series with 2-year Follow-up.

Retrograde (or apical/periapical) peri-implantitis (RPI) presents with radiographic signs of bone loss at the periapical area of endosteal implants and may also present with clinical signs of abscess formation or a sinus tract traceable to the implant periapex. The lesion may form days up to several years after the initial implant placement. In contrast to marginal peri-implantitis, which has a prevalence of 19.83%, RPI may be underreported because many clinicians are currently not aware of this type of lesion. The etiology, although not fully understood, may be attributed to endodontic infection of an adjacent tooth or residual microorganisms present after the extraction of an infected tooth at the implant site. There are several treatment modalities available for the management of RPI. Nonsurgical root canal treatment may be an option if the implant RPI etiology is suspected to be related to an adjacent endodontically involved tooth. In a previous report, surgical treatment modalities to correct RPI were described. This current case series presents 2 cases of RPI in which nonsurgical treatment of the necrotic adjacent teeth resulted in full radiographic and clinical resolution of the adjacent apical peri-implant lesions with 18-month and 2-year follow-ups, respectively. RPI may be prevented by evaluating the endodontic status of natural teeth adjacent to the implants and by addressing endodontic infections near the implant sites. Certain types of implant RPI may successfully be resolved nonsurgically by addressing adjacent endodontic infections as shown by this case series.

Management of Retrograde Peri-Implantitis Using an Air-Abrasive Device, Er,Cr:YSGG Laser, and Guided Bone Regeneration.

BACKGROUND: The placement of an implant in a previously infected site is an important etiologic factor contributing to implant failure. The aim of this case report is to present the management of retrograde peri-implantitis (RPI) in a first maxillary molar site, 2 years after the implant placement. The RPI was treated using an air-abrasive device, Er,Cr:YSGG laser, and guided bone regeneration (GBR). CASE DESCRIPTION: A 65-year-old Caucasian male presented with a draining fistula associated with an implant at tooth #3. Tooth #3 revealed periapical radiolucency two years before the implant placement. Tooth #3 was extracted, and a ridge preservation procedure was performed followed by implant rehabilitation. A periapical radiograph (PA) showed lack of bone density around the implant apex. The site was decontaminated with an air-abrasive device and Er,Cr:YSGG laser, and GBR was performed. The patient was seen every two weeks until suture removal, followed by monthly visits for 12 months. The periapical X-rays, from 6 to 13 months postoperatively, showed increased bone density around the implant apex, with no signs of residual clinical or radiographic pathology and probing depths ≤4 mm. CONCLUSIONS: The etiology of RPI in this case was the placement of an implant in a previously infected site. The use of an air-abrasive device, Er,Cr:YSGG, and GBR was utilized to treat this case of RPI. The site was monitored for 13 months, and increased radiographic bone density was noted.

Wlds-mediated protection of dopaminergic fibers in an animal model of Parkinson disease.

Parkinson disease (PD) is characterized by the progressive degeneration of substantia nigra dopaminergic neurons projecting to the striatum. Since the deficit in striatal dopamine is the main cause of PD symptoms, it appears critical to preserve axon terminals. Significant axon protection from peripheral nerve Wallerian degeneration is observed in Wlds mice, a phenotype conferred by a spontaneous dominant mutation. To assess any Wlds-mediated rescue of dopamine fibers in a PD model, the nigrostriatal pathway of Wlds mice was lesioned with 6-hydroxydopamine (6-OHDA), a catecholaminergic neurotoxin. Following 6-OHDA injection in the medial forebrain bundle, Wlds mice showed remarkable dopamine fiber protection in the striatum. Drug-induced rotational behavior confirmed the nigrostriatal fiber ability to release dopamine, although revealing an abnormal neurotransmitter control presumably due to disrupted axonal transport. Following 6-OHDA injection in the midstriatum, only a protection trend was observed. Strikingly, no protection of Wlds nigral dopaminergic cell bodies was obtained following either nigrostriatal lesion. Besides showing subtle differences in the degeneration process between subcellular compartments, the reported Wlds-mediated protection of the dopamine axon terminals in an animal model of PD may lead to the understanding of mechanisms underlying axon loss and to the development of new therapeutic approaches.

Classification and Clinical Management of Retrograde Peri-implantitis Associated with Apical Periodontitis: A Proposed Classification System and Case Report.

Biological complications involving dental implants include peri-implant diseases such as peri-implant mucositis and peri-implantitis. The latter presents with progressive bone loss from the alveolar crest in a coronal apical direction. However, a separate disease entity termed retrograde peri-implantitis (RPI), which presents with progressive bone loss at the periapex of the implant, also exists and may be of particular interest to endodontists because it typically presents with periapical pathology of both the implant and adjacent tooth or at a site that previously housed an endodontically treated tooth. The reported prevalence of retrograde peri-implantitis is 0.26%, which is much lower than the prevalence of marginal peri-implantitis; however, its incidence increases to 7.8% when teeth adjacent to the implant exhibit an endodontic infection. It is positively correlated with a shorter distance between the implant and the adjacent tooth and a shorter time elapsed from the endodontically treated adjacent tooth to implant placement. This case report describes a patient diagnosed with an RPI lesion (RPI) associated with an adjacent endodontically treated tooth with a persistent periapical radiolucent lesion. The diagnosis, possible etiology, and management of the RPI lesion is thoroughly reported including follow-up visits showing complete resolution after subsequent periodontal and endodontic therapy. Endodontic evaluation of teeth adjacent to the implant site should be performed for primary prevention of RPI. Proper classification of RPI will aid in determining the course of treatment; class 1 and 2 cases require endodontic therapy of the involved teeth for healing to occur.

Etiology of congenital hypothyroidism in Isfahan: Does it different?

BACKGROUND: Considering the higher prevalence of congenital hypothyroidism (CH) in Iran and the importance of determination of the etiology of CH for assessing appropriate treatment strategies, understanding the pathogenesis of CH and the implications of its inheritance and prognosis, the aim of this study was to determine the etiology of CH 7 years after initiation of the program in Isfahan province. MATERIALS AND METHODS: In this cross-sectional study, children with a primary diagnosis of CH studied. They clinically examined and their medical files were reviewed by a Pediatric Endocrinologist. Considering screening and follow-up lab data and radiologic findings the etiology of CH was determined. Screening properties of different etiologies of CH was compared. RESULTS: In this study, 437 patients with permanent CH (PCH) were studied. Etiology of PCH in 316 (72.3%) and 121 (27.7%) of cases was thyroid dyshormonogenesis and thyroid dysgenesis, respectively. Prevalence of agenesis, ectopia, hypoplasia and hemiagenesis in thyroid dysgenetic patients was 13.3%, 6.4%, 4.3% and 3.7% respectively. Mean of thyroid stimulating hormone in screening, recall and after discontinuing treatment at 3 years of age was significantly lower in dyshormonogenetic CH patients than dysgenetic ones(P < 0.01). CONCLUSION: Seven years of our experiences in CH screening program indicated that the etiology of CH in Isfahan, with a higher rate of CH, with a predominance of thyroid dyshormonogenesis is different from most of the studies world-wide and similar to other reports from Iran. The findings of the current study provide us baseline information for determination of CH pathogenesis in this region.

Fractionated stereotactic radiotherapy with static field conformal and non coplanar arcs for pediatric patients with craniopharyngioma: analysis of long term visual outcome and endocrine toxicity.

We assessed the efficacy and the toxicity for pediatric craniopharyngioma patients of fractionated stereotactic radiotherapy (FSRT). Between May 2000 and May 2009, 9 patients (male to female ratio, 5:4) with craniopharyngiomas underwent FSRT (median dose, 54 Gy). Among the 9 patients, 6 received radiation therapy (RT) for recurrent tumors and 3 for residual disease as adjuvant therapy after incomplete surgery. Median tumor volume was 2.3 cm3 (range, 0.1-5.8). The median target coverage was 93.7% (range 79.3-99.8%). The median conformity index was 0.94 (range, 0.6-1.4). Dose to the hippocampal region was assessed for all patients.After a median follow-up of 62.5 months (range, 32-127)the treated volume decreased in size in four of eight patients (50%). One patient was lost to follow-up. Local control and survival rates at 3 years were 100% and there were no marginal relapses. One patient, with a chronic bilateral papillary oedema after surgery, visual defect deteriorated after FSRT to a complete hemianopsia. One male patient with normal pituitary function before FSRT presented with precocious puberty at the age of 7.4 years, 24 months after FSRT. Four patients (50%) were severely obese at their last visit. FSRT is a safe treatment option for craniopharyngioma after incomplete resection.

Prevalence of permanent congenital hypothyroidism in isfahan-iran.

BACKGROUND: Considering the importance to determine the reasons for the higher occurrence of congenital hypothyroidism (CH) in Iran, in this study we report the prevalence of permanent CH (PCH) in Isfahan province 7 years after initiation of CH screening program in Isfahan. METHODS: In this cross-sectional study, children with a primary diagnosis of CH studied. They clinically examined and their medical files were reviewed by a pediatric endocrinologist. Considering screening and follow-up lab data, radiologic findings and the decision of pediatric endocrinologists the final diagnosis of PCH was determined. RESULTS: A total of 464,648 neonates screened in Isfahan province. The coverage percent of the CH screening and recall rate was 98.9% and 2.1%, respectively. A total of 1990 neonates were diagnosed with primary CH. PCH was diagnosed in 410 neonates. The prevalence of PCH and transient CH (TCH) was 1 in 1133 and 1 in 294 live births. The most common etiology of CH was thyroid dyshormonogenesis. CONCLUSIONS: Though the prevalence of PCH is high, but the higher prevalence of CH in Isfahan is commonly due to cases with TCH. Hence, the necessity of determining new strategies for earlier diagnosis of patients with TCH is recommended.

Growth and specialized growth charts of children with congenital hypothyroidism detected by neonatal screening in isfahan, iran.

Objectives. The aim of the current study was to investigate the growth status of CH, generate specialized growth charts of CH infants, and compare them with their counterparts of regional normal infants. Methods. In this prospective cohort study, 760 (345 girls and 415 boys) neonates born in 2002-2009 diagnosed by neonatal CH screening program in Isfahan were followed up from the time of diagnosis. 552 healthy children were recruited as a control group. The empirical 3rd, 15th, 50th, 85th, and 97th percentiles for height, weight, and head circumference of both sexes were determined and compared with their counterpart values of the control group. The relative frequency of patients with impaired growth for each studied variable was determined. Also, specialized growth charts of CH patients were generated. Results. The percentiles of weight, height, and head circumference of studied patients are significantly different from regional healthy children (P < 0.001). The relative frequency of impaired head circumference was decreased to less than 3% at the 3rd year of age and for height it reached gradually 3% and 9% at the 5th year of age for boys and girls, respectively (P < 0.05); however for weight still it was statistically more than 3% in both sexes. Conclusion. CH patients had impaired growth development which was improved during follow up, but the catch-up time was earlier for head circumference and later for weight.

Transient striatal delivery of GDNF via encapsulated cells leads to sustained behavioral improvement in a bilateral model of Parkinson disease.

Numerous studies have shown the neuroprotective and regenerative benefits of glial cell line-derived neurotrophic factor (GDNF) in animal models of PD. Brain delivery of GDNF can, however, be associated with limiting side-effects in both primates and PD patients, rendering the duration of delivery a critical factor. In the present study, the effects of transient vs. sustained GDNF delivery by encapsulated cells were evaluated in a bilateral animal model, closely mimicking advanced PD. One week following bilateral striatal 6-hydroxydopamine injections in rats, capsules loaded with human fibroblasts genetically engineered to release GDNF were bilaterally implanted in the striatum. GDNF delivery resulted in a significant improvement of movement initiation and swimming performance in the lesioned animals, associated with striatal reinnervation of dopaminergic fibers. To test the sustainability of the behavioral improvement, GDNF-secreting capsules were withdrawn in a subgroup of animals, 7 weeks post-implantation. Strikingly, both the behavioral and morphological improvements were maintained until the sacrifice of the animals 6 weeks post-GDNF withdrawal. The sustained cellular and behavioral benefits after GDNF washout suggest the need for temporary delivery of the trophic factor in PD. Retrievable encapsulated cells represent an attractive delivery tool to achieve this purpose.

Long-term glial cell line-derived neurotrophic factor overexpression in the intact nigrostriatal system in rats leads to a decrease of dopamine and increase of tetrahydrobiopterin production.

Parkinson's disease (PD) is characterized by the progressive degeneration of the nigrostriatal dopaminergic system. Brain delivery of glial cell line-derived neurotrophic factor (GDNF) has been shown to protect and restore the dopaminergic pathway in various animal models of PD. However, GDNF overexpression in the dopaminergic pathway leads to a time-dependent down-regulation of tyrosine hydroxylase (TH), a key enzyme in dopamine synthesis. In order to elucidate GDNF-mediated biochemical effects on dopaminergic neurons, we overexpressed GDNF in the intact rat striatum using a lentiviral vector-mediated gene transfer technique. Long-term GDNF overexpression led to increased GTP cyclohydrolase I (GTPCH I) activity and tetrahydrobiopterin (BH4) levels. Further, we observed a down-regulation of TH enzyme activity in morphologically intact striatal dopaminergic nerve terminals, as well as a significant decrease of dopamine levels in striatal tissue samples. These results indicate that long-term GDNF delivery is a major factor affecting dopamine biosynthesis via a direct or indirect modulation of TH and GTPCH I and further underscore the importance of assessing both GDNF dose and delivery duration prior to clinical application in order to circumvent potentially adverse pharmacological effects on the biosynthesis of dopamine.

Lentiviral vector delivery of parkin prevents dopaminergic degeneration in an alpha-synuclein rat model of Parkinson's disease.

Parkinson's disease (PD) is characterized by a progressive loss of midbrain dopamine neurons and the presence of cytoplasmic inclusions called Lewy bodies. Mutations in several genes including alpha-synuclein and parkin have been linked to familial PD. The loss of parkin's E3-ligase activity leads to dopaminergic neuronal degeneration in early-onset autosomal recessive juvenile parkinsonism, suggesting a key role of parkin for dopamine neuron survival. To evaluate the potential neuroprotective role of parkin in the pathogenesis of PD, we tested whether overexpression of wild-type rat parkin could protect against the toxicity of mutated human A30P alpha-synuclein in a rat lentiviral model of PD. Animals overexpressing parkin showed significant reductions in alpha-synuclein-induced neuropathology, including preservation of tyrosine hydroxylase-positive cell bodies in the substantia nigra and sparing of tyrosine hydroxylase-positive nerve terminals in the striatum. The parkin-mediated neuroprotection was associated with an increase in hyperphosphorylated alpha-synuclein inclusions, suggesting a key role for parkin in the genesis of Lewy bodies. These results indicate that parkin gene therapy may represent a promising candidate treatment for PD.