Descending aorta to right atrial fistula: Transcatheter embolization of a very rare anomaly with coils.

Key Clinical Message: Descending aorta to right atrial (RA) fistula is a rare and distinct clinical entity mimicking patent ductus arteriosus (PDA) and it may lead to rapid development of pulmonary vascular disease. Correct diagnosis and treatment, especially in the presence of other congenital heart defects, is very important. Interventional management is the treatment of choice. Abstract: We present a case report of a trisomy 21 infant with atrial and ventricular septal defects and small patent ductus arteriosus (PDA) complicated by the presence of descending aorta to right atrial (RA) fistula with large left to right shunt leading to rapid increase in pulmonary vascular resistance. Transcatheter occlusion of the fistula followed by closure of the PDA with Nit-Occlud coil systems led to decreased pulmonary pressure and resistance permitting successful surgical repair of the patient's intracardiac defects with good outcome over 3 years of follow-up. Descending aorta to RA fistula is a rare and distinct clinical entity mimicking PDA and its correct diagnosis and treatment, especially in the presence of other congenital heart defects, is very important as it may lead to rapid development of pulmonary vascular disease.

Multiple myocardial bridges causing severe ischaemia in adolescent with pulmonary stenosis.

Myocardial bridges are often asymptomatic but may need therapy when causing ischaemia. They have rarely been reported in children or in association with CHD, where symptomatology may be mistakenly attributed to the CHD. We report a case of multiple myocardial bridges causing ischaemia in an adolescent with pulmonary stenosis and discuss management.

Plasma Beta-Glucuronidase Activity: A Novel Tool to Distinguish Type 1 from Type 2 Amiodarone-Induced Thyrotoxicosis?

BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) is a common and deleterious side effect of amiodarone use. There are two types of AIT, characterized by distinct pathogenic mechanisms and, hence, different treatments. Discriminating between type 1 (AIT1) and type 2 (AIT2) AIT is often very challenging. Beta-glucuronidase (ß-G) is a lysosomal enzyme released into the extracellular fluid during inflammation. OBJECTIVES: To examine whether the determination of the plasma activity of ß-G is useful in distinguishing AIT1 from AIT2. METHODS: The study included 67 subjects: 9 with AIT1, 9 with AIT2, 14 with hyperthyroidism due to Grave's disease or toxic multinodular goiter, 14 with subacute thyroiditis, and 21 euthyroid controls. Thyroid function tests and plasma ß-G activity were determined in all participants, while thyrotoxic patients also underwent thyroid ultrasound/scintigraphy and urine iodine excretion assessment. RESULTS: Plasma ß-G activity (expressed as mean ± SD in nmol 4-methylumbelliferone [4-MU]/mL plasma/h) in AIT2 was higher compared to AIT1 (2,263.6 ± 771 vs. 1,101.8 ± 201.9, p < 0.05) and similar to subacute thyroiditis (2,263.6 ± 771 vs. 2,083.2 ± 987.5, p = ns). ß-G activity did not differ significantly between AIT1 and controls (1,101.8 ± 201.9 vs. 954.6 ± 248.6, p = ns). ROC curve analysis revealed that ß-G activity had a high predictive value for destructive processes, namely AIT2 and subacute thyroiditis (AUC 0.846, 95% CI 0.748-0.943) and a cut-off value of 1,480.5 nmol 4-MU/mL plasma/h was able to discriminate between destructive and non-destructive thyroid conditions with 74% sensitivity and 82% specificity. CONCLUSION: In our study, plasma ß-G activity performed well in distinguishing AIT1 from AIT2. Further studies are warranted to establish its usefulness as a discriminator between the two AIT types.

Ambulatory Intravenous Inotropic Support and or Levosimendan in Pediatric and Congenital Heart Failure: Safety, Survival, Improvement, or Transplantation.

End-stage heart failure (HF) frequently needs continuous inotropic support in hospital and has high morbidity and mortality in absence of heart transplantation. This study reports outcome, efficacy, and safety of continuous ambulatory inotropes (AI) and/or periodic levosimendan (LS) infusions in pediatric HF patients. The study included 27 patients, median age 9.4 (0.1-26.1) years, with severe HF (6 myocarditis, 13 dilated cardiomyopathy, 2 restrictive cardiomyopathy, 6 repaired congenital heart disease). Dobutamine and milrinone AI were administered in 21 patients through a permanent central catheter for median duration 1.0 (0.3-3.7) years. Additionally, 14 AI patients and the remaining 6 study patients received periodic LS infusions for median duration 1.1 (0.2-4.2) years. During median follow-up 2.1 (0.3-21.3) years, 4 patients died of worsening HF after 0.8-2.1 years AI, 6 patients underwent heart transplantation with only 3 survivors, while the rest remained stable out of the hospital with complications 4 line infections treated with antibiotics and 4 catheter reinsertions due to dislodgement. Severe pulmonary hypertension was reversed with AI in 2 patients, allowing successful heart-only transplantation. Therapy with AI was discontinued after 1.4-0.4 years in 6 improved myocarditis and 3 cardiomyopathy patients without deterioration. In conclusion, prolonged AI and/or LS infusions in HF are safe and beneficial even in small infants, allowing stabilization and reasonable social and family life out of the hospital. It may provide precious time for heart transplantation or myocardial remodeling, improvement, and possible discontinuation even after long periods of support.

Pulmonary vasodilator therapy in tetralogy of Fallot with pulmonary atresia and major aortopulmonary collaterals: case series and review of literature.

We present the use of pulmonary vasodilators in three adult patients with unrepaired tetralogy of Fallot, pulmonary atresia, aortopulmonary collaterals, and segmental pulmonary arterial hypertension. Patients improved by 1-2 NYHA classes with modest exercise-tolerance increase, and remained stable without side effects during 2.5, 10, and 14 years. Literature review revealed five studies with pulmonary vasodilators in heterogeneous, mostly repaired patient populations.

Growth velocity and final height in elite female rhythmic and artistic gymnasts.

PURPOSE: The aim of this study was to determine the impact of intensive training on adult final height in elite female rhythmic and artistic gymnasts. METHODS: The study included 215 rhythmic gymnasts (RG) and 113 artistic gymnasts (AG). RESULTS: AG were below the 50th percentile, while RG were taller than average. Final adult height was lower than target height in AG, while in RG, it exceeded target height. AG started training earlier than RG (p<0.001) and reported lower intensity of training (p<0.001). RG were taller than AG, with higher target height, greater Δ final height-target height and lower body fat and BMI (p<0.001). Using multiple regression analysis, the main factors influencing final height were weight SDS (p<0.001), target height SDS (p<0.001) and age of menarche (p<0.001) for RG, and weight SDS (p<0.001) and target height SDS (p<0.001) for AG. CONCLUSION: In both elite female RG and AG, genetic predisposition to final height was not disrupted and remained the main force of growth. Although in elite RG genetic predisposition for growth was fully preserved, in elite female AG final adult height falls shorter than genetically determined target height, though within the standard error of prediction.

Feto-maternal risks associated with pregnancy achieved through oocyte donation in a woman with Turner syndrome.

We report a case of a 40-year-old primipara Caucasian woman with Turner syndrome (TS) and Hashimoto thyroiditis who had underwent a successful IVF-ET cycle with oocyte donation and single embryo transfer. All pregnancies in women with TS are considered as high risk, with cardiovascular complications being the most dangerous. Our case represents a typical case of fetal growth restriction with gradual slowing down of fetal growth after 28 weeks. At 37 + 3 gestational weeks, a healthy male newborn weighing 2240 g, with artery pH of 7.32 was delivered by cesarean section. The neonate was small for gestational age. Women with TS who become pregnant need close surveillance from a multidisciplinary team of cardiologists, obstetricians and endocrinologists. The primary goal is to prevent maternal complications and to improve perinatal outcome. In doing so, a thorough evaluation of fetal growth and uteroplacental and fetal circulation should by no means be omitted, after 26-28 weeks of gestation. The examinations should be at monthly or even shorter intervals to find early signs of growth restriction and act accordingly.

Treating iodine deficiency: long-term effects of iodine repletion on growth and pubertal development in school-age children.

BACKGROUND: Iodine deficiency (ID) is still a major universal health problem. Iodine deficiency disorders (IDDs) affect people of all ages, among whom the most vulnerable are children and adolescents. The aim of the present study was to assess the long-term effects on growth and pubertal development of correcting severe ID in areas of Azerbaijan between 1999 and 2000. METHODS: Iodized oil was administered orally to 293,000 children, aged 6-16 years. Among those, 364 children were randomly selected and were examined 1 year before the administration of iodized oil (Group I-neg, iodine negative) and 295 children (Group I-Rx, iodine treated) were examined 4 years (Group I-R x 4, iodine treated 4 years later; n = 173) or 5 years (Group I-R x 5, iodine treated 5 years later; n = 122) after the last dose of iodide. RESULTS: In Group I-neg the median urine iodine concentration (UIC) (mcg/L) was 36 (mean: 36.272 +/- 11.036) and increased significantly (p < 0.001) in Group I-R x 4: 188 (mean: 230.969 +/- 155.818) and in Group I-R x 5: 175 (mean: 201.176 +/- 130.369). The prevalence of goiter was 99% in Group I-neg and 2% in Group I-R x 4. Children in Group I-Rx had a greater standard deviation score (SDS) for height (-0.1364 +/- 1.279, n = 294) than children in Group I-neg (-0.5019 +/- 1.17, n = 363) (p < 0.001, t = -3.817), which was more significant for boys. SDS for weight was similar in both groups (Group I-neg: -0.17 +/- 0.78, n = 363; Group I-Rx: -0.115 +/- 0.917, n = 294). The rate of puberty development as judged by the development of breast and pubic hair was normalized in both sexes after the correction of ID. CONCLUSIONS: Our results demonstrate that long-term correction of severe ID leads to sustained improvement of linear growth accompanied by a normalization of the time of onset of pubertal development for both sexes.

Renal dysgenesis and KAL1 gene defects in patients with sporadic Kallmann syndrome.

OBJECTIVE: To correlate the presence of renal agenesis/dysgenesis to the prevalence of KAL1 gene defects in patients with sporadic Kallmann syndrome (KS). DESIGN: Prospective assessment of renal structure and DNA sequence analysis of the KAL1 gene. SETTING: Outpatient clinics of the divisions of endocrinology of university hospitals. PATIENT(S): Sixteen male patients with sporadic KS. INTERVENTION(S): Assessment of renal structure by abdominal ultrasounds scans and DNA extraction, polymerase chain reaction amplification, and DNA sequence analysis of all 14 exons of the KAL1 gene. MAIN OUTCOME MEASURE(S): KAL 1 gene structure and presence of renal dysgenesis. RESULT(S): Renal dysgenesis was identified in only two of 16 KS patients. Genetic defects were found in only two patients with KS, that is, in those with the identified renal dysgenesis. The first gene defect was identified in a patient with associated right renal agenesis who had two point mutations in the KAL1 gene: the first was a G to A transition in exon 11, turning codon 514 encoding glutamic acid into lysine; and the second was a G to A transition in exon 13, turning codon 660 encoding alanine into threonine. The second gene defect was identified in a patient with ichthyosis, right renal agenesis, and mirror movements of the upper limbs (synkinesia) and comprised a deletion of exons 5-10 of the KAL1 gene and a complete deletion of the steroid sulphatase gene. CONCLUSION(S): The phenotype of renal agenesis/dysgenesis strongly indicates the existence of KAL1 gene defects in the genotype of patients with sporadic KS, providing evidence for the X-linked mode of inheritance and offering the opportunity for genetic counseling.

The gonadotropin-releasing hormone (GnRH)-1 gene, the GnRH receptor gene, and their promoters in patients with idiopathic hypogonadotropic hypogonadism with or without resistance to GnRH action.

The study included 26 patients with idiopathic hypogonadotropic hypogonadism (24 sporadic and 2 familial). The Pro146Ser mutation was identified in the gonadotropin-releasing hormone receptor (GnRHR) gene in two sisters as well as in their mother, and one polymorphism in the GnRH1 gene (the Trp16Ser) was identified in four patients. No mutations in transcription factor-binding sites of their promoters were identified. Three patients (one male and two sisters) were found with resistance to GnRH action. No mutations were identified in the male, whereas in the females the mutation Pro146Ser in the GnRHR was identified in heterozygosity.

Delayed but normally progressed puberty is more pronounced in artistic compared with rhythmic elite gymnasts due to the intensity of training.

CONTEXT: Elite gymnasts are subjected to intense training, which may alter pubertal development. OBJECTIVE: The objective of the investigation was to study the impact of gymnastics on pubertal development in rhythmic (RGs) and artistic gymnasts (AGs). DESIGN: Evaluation of somatometric parameters, pubertal stage, and intensity of training in the competition field were studied. SETTING: The study was conducted at European and world championships of years 1997-2004. SUBJECTS: Subjects included 433 elite RGs and 427 AGs, aged 11-23 yr. INTERVENTION: There were no interventions. MAIN OUTCOME MEASURES: Mean chronological and bone ages of each pubertal stage and their relation to the intensity of training were measured. RESULTS: AGs and RGs showed a delay in skeletal maturation (Delta age-bone age, 2.13 and 1.28, respectively; P < 0.001). AGs were subjected to higher levels of physical training. Thelarche occurred at 12.9 yr for RGs and 13.2 yr for AGs (P = 0.003) and pubarche at 12.5 and 12.9 yr, respectively (P = 0.002). Puberty was delayed but normally progressed. AGs entered each pubertal stage later than RGs. The delay was influenced by the amount of energy output. Menarcheal age was 14.6 yr for RGs and 14.9 yr for AGs. Menarche was influenced in AGs by bone age (b = 0.333; t = 2.521; P = 0.020), pubarche (b = 0.322; t = 2.401; P = 0.026), and body fat (b = -0.458; t = -3.412; P = 0.003) and in RGs by bone age (b = 0.378; t = 3.689; P < 0.001) and pubarche (b = 0.525; t = 6.017; P < 0.001). CONCLUSION: In RGs and AGs, pubertal development was shifted to a later age, maintaining a normal rate of progression, which followed the bone age. AGs, who were exposed to a greater and more sustained energy output than RGs, presented a more pronounced delay in both skeletal maturation and pubertal development.

Growth, pubertal development, skeletal maturation and bone mass acquisition in athletes.

The genetic potentials for growth can be fully expressed only under favourable environmental conditions. Excessive physical training may negatively affect growth, especially during puberty. Sports that require a strict control of energy input in the presence of a high energy output are of particular concern. In gymnastics, a different pattern in skeletal maturation was observed, leading to an attenuation of growth potential ins Artistic Gymnasts (AG), more pronounced in males than in females, whereas in female Rhythmic Gymnasts (RG) the genetic predisposition to growth was preserved because of a late catch-up growth phenomenon. In all other sports not requiring strict dietary restrictions, no deterioration of growth has been documented. Intensive physical training and negative energy balance modify the hypothalamic pituitary set point at puberty, prolong the prepubertal stage and delay pubertal development and menarche in a variety of sports. In elite RG and AG the prepubertal stage is prolonged and pubertal development is entirely shifted to a later age, paralleling the bone age rather than the chronological age. Bone formation, and, consequently, BMD are enhanced by physical activity. In athletes, high-impact loading activities have been shown to improve BMD, while in sports requiring a lean somatotype, the delay in skeletal maturation and pubertal development, resulting from hypoestrogenemia, predisposes athletes to osteopenia. In AG, an increase in bone density is observed using the bone age as denominator.

Kallmann's syndrome and schizophrenia.

OBJECTIVE: Kallmann's Syndrome is a heritable disorder characterized by the association of hypogonadotropic hypogonadism and anosmia or hyposmia. A common pathogenesis for KS and schizophrenia had been proposed based on shared pathologies of these two disorders, although no such clinical associations have ever been reported. METHOD: We report a 35 year old man with schizophrenia and Kallmann's Syndrome. The patient presented with signs and symptoms of hypogonadism, severe hyposmia and normal endocrine functions of the anterior pituitary. Hyposmia has been attributed to the absence of the olfactory bulbs and tracts and atrophy of the olfactory gyri, but normal olfactory mucosa. The patient presented with paranoid schizophrenia with persecutory delusions, auditory hallucinations, thought disorder, depersonalization, and gradual but marked global deterioration. RESULTS: Psychiatric evaluation revealed an entirely different psychopathological and personality profile between the patient and the six other Kallmann patients studied. Cycle sequencing analysis revealed a normal sequence of all 14 exons of the KAL gene. In conclusion, based on the presented case, Kallmann's Syndrome and schizophrenia represent a rare clinical association rather than a syndrome with a common pathogenesis, which if present should be confined to the olfactory dysfunction.

Identification of iodine deficiency in the field by the rapid urinary iodide test: comparison with the classic Sandell-Kolthoff reaction method.

The two traditional methods for the assessment of iodine deficiency in a given area are the estimation of urinary excretion of iodine, and the prevalence of goiter. In field studies, the estimation of urinary iodine excretion (UIE) in random urine specimens provides an adequate assessment of a population's iodine nutrition. The recommended method is the classic one, based on Sandell-Kolthoff reaction (Method A). Recently, a new semi-quantitative method has been introduced (rapid urinary iodide test [RUIT]). We performed a field study in a developing country (Azerbaijan) in order to compare the classic Method A to RUIT. The study included 942 schoolchildren, to whom UIE was estimated by RUIT. Comparing the two methods, (n = 260), the sensitivity of RUIT using as gold standard Method A, was 96% and the specificity was 61%. The correlation between median values UIE estimated by RUIT and by Method A was excellent (r = 0.98, p < 0.001). An agreement in iodine deficiency classification according to the World Health Organization-United Nations Children's Fund-International Council for the Control of Iodine-Deficiency Disorders (WHO-UNICEF-ICCIDD) between the two methods was observed in eight of nine areas. In conclusion, RUIT is a suitable method for UIE estimation in field studies of suspected iodine deficiency. The test is relatively inexpensive, easy to perform, and does not require sophisticated instruments.