Alteration of Exon Definition Causes Amelogenesis Imperfecta.

Amelogenesis imperfecta (AI) is a collection of genetic disorders affecting the quality and/or quantity of tooth enamel. More than 20 genes are, so far, known to be responsible for this condition. In this study, we recruited 3 Turkish families with hypomaturation AI. Whole-exome sequence analyses identified disease-causing mutations in each proband, and these mutations cosegregated with the AI phenotype in all recruited members of each family. The AI-causing mutations in family 1 were a novel AMELX mutation [NM_182680.1:c.143T>C, p.(Leu48Ser)] in the proband and a novel homozygous MMP20 mutation [NM_004771.3:c.616G>A, p.(Asp206Asn)] in the mother of the proband. Previously reported compound heterozygous MMP20 mutations [NM_004771.3:c.103A>C, p.(Arg35=) and c.389C>T, p.(Thr130Ile)] caused the AI in family 2 and family 3. Minigene splicing analyses revealed that the AMELX missense mutation increased exonic definition of exon 4 and the MMP20 synonymous mutation decreased exonic definition of exon 1. These mutations would trigger an alteration of exon usage during RNA splicing, causing the enamel malformations. These results broaden our understanding of molecular genetic pathology of tooth enamel formation.

In vitro antioxidant/prooxidant effects of combined use of flavonoids.

The present study was undertaken to investigate the individual and combined antioxidant or prooxidant effects of genistein, daidzein and quercetin in human erythrocytes and rat microsomes in vitro. Their reducing potential against oxidation of a redox sensitive fluorescent probe, their protective effect against H2O2-induced membrane lipid peroxidation and their inhibitory effect on AAPH-induced hemolysis were evaluated. Genistein and daidzein were prooxidant in erythrocytes but antioxidant in microsomes where their metabolites might have been formed which suggests the importance of metabolic capacity in in vitro models to predict the physiological situation. Quercetin showed antioxidant effects in all models and conditions. Prooxidant effect of 'genistein-daidzein mixture', at their concentrations reflecting the real life, was suppressed by addition of quercetin to the mixture. Our study shows that flavonoids can exert prooxidant effects depending on the conditions, but the mixture effect should be considered while assessing their effects and safety in humans.

Poorly understood and often miscategorized congenital umbilical cord hernia: an alternative repair method.

PURPOSE: Umbilical cord hernia is poorly understood and often miscategorized as "omphalocele minor". Careless clamping of the cord leads to iatrogenic gut injury in the situation of umbilical cord hernia. This study aimed to determine the characteristics and outcomes of umbilical cord hernias. We also highlight an alternative repair method for umbilical cord hernias. METHODS: We recorded 15 cases of umbilical cord hernias over 10 years. The patients' data were retrospectively reviewed, and preoperative preparation of the newborn, gestational age, birth weight, other associated malformations, surgical technique used, enteral nutrition, and length of hospitalization were recorded. RESULTS: This study included 15 neonates with umbilical cord hernias. The mean gestational age at the time of referral was 38.2 ± 2.1

Malignant epignathus including a nephroblastoma component and successful management.

A male infant was born to a 24-year-old mother (gravida 1 para 1) by cesarean delivery at 33 1/7 weeks of gestation. The physical examination revealed a large mass protruding from the baby's mouth, which appeared to be attached to the palate. Tracheostomy was performed immediately in the delivery room. A partial surgical excision was performed on the second postnatal day, removing most of the teratoma (epignathus), which was attached to the back of the pharynx and protruding from the baby's mouth measuring 13×11×9 cm and weighing 545 g. The final pathological diagnosis was "malignant epignathus with nephroblastoma component." According to our knowledge, this is the first case that have malignant epignathus including nephroblastoma component in the literature.

Tuberculous meningoencephalitis with severe neurological sequel in an immigrant child.

Central nervous system tuberculosis (TB) is the most devastating manifestation of TB. It is a challenge for clinicians because of the difficulty in making an early diagnosis and the severe consequences of delayed treatment. The aim of this report is to point out the relation between migration and TB based on a 14-year-old child with tuberculous meningoencephalitis (TBM) of an immigrant family. Migration, crowded living conditions and positive family history contribute to the severe course of TB as TBM and miliary TB forms. TB control may prevent these severe manifestations of the disease among immigrants. Prompt diagnosis with helpful early diagnostic tools like polymerase chain reaction in TBM is crucial due to the high mortality and morbidity.

Significant loss of hepatitis A Ab after allogeneic hematopoietic SCT in pediatric patients.

Loss of specific immunity after hematopoietic SCT (HSCT) is well documented for polio, measles, mumps and tetanus. There are limited studies reporting the loss of Hepatitis A virus immunity and no reports evaluating the effect of donor immunity on Hepatitis A virus (HAV) immunity loss after HSCT. A total of 49 of the 81 patients who received HSCT at the Ankara University Pediatric HSCT Unit from January 1997 to December 2006 had HAV serology tested before HSCT and were evaluated for seroprevalence, and 30 of 49 patients were evaluated for the loss of Ab and for the effect of donor immunity on the loss of HAV Abs. The seroprevalence before HSCT was 75.5%. Loss of Ab was detected in 43.5% (10/23) of the patients. The median time to loss of Ab was 12 months (12-32 months), and 60% of these patients were seronegative at 12 months after HSCT. After HSCT, 46.7% of the patients were seronegative. Loss of Ab was higher in the seronegative donor group (75 vs 26%). The loss of HAV Ab is high after allogeneic HSCT for pediatric patients. Reimmunization should be considered for the continuation of individual and community immunity. Further studies with larger study groups are warranted to clarify the role of donor immunity on the loss of HAV immunity.

The value of the levels of acute phase reactants for the prediction of familial Mediterranean fever associated amyloidosis: a case control study.

In order to determine the role of levels of acute phase proteins (APPs) for the development of amyloidosis in familial Mediterranean fever (FMF) patients, the levels of serum amyloid A (SAA), C reactive protein (CRP), fibrinogen and erythrocyte sedimentation rate were measured in paired sera of 36 FMF patients during and in between acute attacks, 39 of their healthy parents (obligate heterozgotes), and 15 patients with FMF associated amyloidosis. To compare the levels of APPs, 39 patients with chronic infections or inflammatory diseases who may develop secondary amyloidosis, 20 patients with acute infections who are known to have elevated acute phase response but will never develop amyloidosis and 19 healthy controls were included. The median levels of all APPs are increased in the patients with FMF during attacks and a significant decrease was observed after the attack was over. The level of SAA was above reference range in all FMF patients during the attack free period and the level of at least one other APP was also above normal in 64% of the patients. Both CRP and SAA levels were found to be higher in obligate heterozygotes compared to controls. The levels of SAA in patients with FMF during the attack-free period, obligate heterozygotes and patients with FMF-amyloidosis were found to be similar. The levels in each group were found to be higher than SAA levels found in healthy controls yet lower than the levels measured in the patients with acute infections and patients with chronic inflammation or chronic infections. In conclusion, our results show that SAA level reflects subclinical inflammation with high sensitivity but its value for the prediction of amyloid formation process seems to be low.

Do sexual dysfunctions get better during dialysis? Results of a six-month prospective follow-up study from Turkey.

Dialysis improves most symptoms of end-stage renal disease (ESRD), yet many patients continue to experience sexual dysfunction (SD) during the dialysis treatment. The aim of this preliminary study was to evaluate the frequency and the course of SD during a 6-month dialysis treatment. Additionally, relationships between the level of depression, cognitive impairment and biochemical parameters of SD were also assessed. The subjects were 43 ESRD (25 male and 18 female) on dialysis treatment for at least 12 months. SD was assessed using the Arizona Sexual Experiences Scale (ASEX); the level of depression and cognitive impairment were assessed using the Hamilton Depression Rating Scale (HDRS) and Mini Mental Status Exam (MMSE). Several biochemical parameters were also assessed. All assessments were carried out at baseline and repeated at 6-month follow-up. Of 43 patients, 20 (47%) and 18 (42%) complained of SD at baseline and at 6-month assessments, respectively. Of 25 males, nine (36%) and seven (28%) patients described SD at baseline and 6-month assessments, respectively; erectile dysfunction was the most frequent complaint. Of 18 females, 11 (61%) and 11 (61%) patients reported SD at baseline and 6-month assessments, respectively; difficulties with arousal and reaching orgasm were the most frequent complaints. Both total and item-by-item comparisons of baseline and 6 months ASEX scores did not reveal any significant changes during 6-month period, indicating that patient's sexual functions do not improve with dialysis treatment. For female patients, HDRS scores were significantly higher in patients with SD at baseline (t = 2.15, P = 0.05) and at 6-month follow-up (t = 2.44, P = 0.03) assessments; after excluding the effects of age and duration of dialysis for females using regression analysis, HDRS still significantly (t = 4.02, P = 0.003) associated with the SD. This preliminary prospective study suggests that SD is frequent in dialysis patients, does not remit with dialysis treatment, associated with depression in female patients, and much clinical attention is indicated.

Pulmonary involvement in childhood-onset systemic lupus erythematosus: a report of five cases.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic systemic disease, which can involve multiple organs such as kidney, skin and brain. Lung is another organ that can be affected. A number of pulmonary complications including pleuritis, pneumonitis, infectious pneumonia, pulmonary haemorrhage, pulmonary hypertension and pneumothorax have been reported in patients with SLE. Pulmonary involvement is relatively frequent in adult patients; it has infrequently been reported in children with SLE. However, pulmonary manifestations may be an initial and/or life-threatening complication of SLE in children. In this paper we aim to emphasize the pulmonary involvement in childhood-onset SLE via description of our patients. METHODS: The patients, who were diagnosed with SLE at the Children's Hospital of Ankara University Medical School between 1993 and 2002, were retrospectively evaluated for evidence of pulmonary involvement. All patients fulfilled at least four of the classification criteria of the American Rheumatism Association. Using a standardized form, we obtained data regarding the age, sex and presenting complaints of the patients, previous therapies given, clinical and laboratory features, treatment and outcome. Informed consent was obtained from all patients. RESULTS: During the 10-yr study period, 16 patients were diagnosed with childhood-onset SLE. Five of them (31%) had pulmonary involvement including acute lupus pneumonitis, invasive pulmonary aspergillosis, cytomegalovirus pneumonia and pulmonary haemorrhage (in two patients). These 5 patients with lupus lung disease are presented in more detail.

Antistreptococcal response is exaggerated in children with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autosomal recessive disorder. Although the pathogenesis of the disease is not yet completely understood, enhanced acute-phase responsiveness is considered to be one of the most important mechanisms. The presence of high levels of antistreptolysin O (ASO) antibodies and streptococcus-associated diseases, such as acute poststreptococcal glomerulonephritis (AGN) and acute rheumatic fever (ARF), has been reported in patients with FMF. In order to better understand the effect of FMF on antistreptococcal antibody response, we measured ASO and antideoxyribonuclease B (anti-DNAse B) levels in patients with FMF and compared them with those in healthy controls. The study consisted of two parts. In the first step, antistreptococcal antibody levels were analysed in 44 patients with FMF and 165 healthy children who had no history or clinical evidence of upper respiratory tract infection (URTI) for the last 4 months. In the second step, antistreptococcal antibody levels were measured in 15 patients with FMF and 22 healthy controls in response to documented group A beta-haemolytic streptococcal pharyngitis. In the first part of the study, ASO and anti-DNAse B levels in patients with FMF were found to be significantly higher than those in healthy controls (P<0.001). In the second part, ASO and anti-DNAse B titres were found to be significantly higher in patients with FMF than in controls (P<0.001 and <0.05, respectively) 4 weeks after a positive throat culture. We concluded that patients with FMF have an exaggerated response to streptococcal antigens and might be prone to poststreptococcal non-suppurative complications, such as ARF.

Investigation of risk factors for penicillin-resistant Streptococcus pneumoniae carriage in Turkish children.

BACKGROUND: Nasopharyngeal colonization plays an important role for infections caused by Streptococcus pneumoniae. Emergence of penicillin resistance in this organism has made it difficult to treat pneumococcal infections. The objectives of this study were to investigate the risk factors for nasopharyngeal colonization with S. pneumonia and for nasopharyngeal colonization with penicillin-resistant S. pneumoniae. METHODS: Three hundred children with or without evidence of infection were investigated for various risk factors. Streptococcus pneumoniae isolated from children's nasopharyngeal swabs were examined for penicillin susceptibility. RESULTS: Day-care attendance (odds ratio OR=2.82, P=0.003) and upper respiratory tract infection within the last month (OR=1.83, P=0.02), have been determined to be risk factors for S. pneumoniae carriage. The use of antibiotics within the last 3 months (OR=81.07, P<0.001), the presence of more than five people living in the house of the child (OR=6.63, P=0.03), and having a sibling under 5-years-old (OR=4.60, P=0.03) have been determined to be risk factors for penicillin-resistant S. pneumoniae carriage. CONCLUSION: Some children are inevitably exposed to and colonized with penicillin susceptible or resistant S. pneumoniae. Changes in day-care organizations, better living conditions, and restriction of antibiotic use seems to be useful precautions to prevent the emerging and colonization with penicillin-susceptible or -resistant S. pneumoniae.

Effect of 5-aminoimidazole-4-carboxamide riboside (AICA-r) on isolated thoracic aorta responses in streptozotocin-diabetic rats.

Diabetes mellitus alters the vascular responsiveness to several vasoconstrictors and vasodilators. 5-amino-4-imidazole-carboxamide riboside (AICA-r), a nucleoside corresponding to AICA-ribotide and an intermediate of the de novo pathway of purine biosynthesis, was recently proposed as a new insulinotropic tool in non-insulin-dependent diabetes mellitus. The aim of the present study was to define whether AICA-r affects altered vascular responsiveness to vasoconstrictors and vasodilators in the thoracic aorta of neonatal streptozotocin (STZ)-diabetic rats. The results of this study indicate that a 1-month treatment with AICA-r significantly increases the body weight in diabetic rats; significantly decreases the blood glucose level of diabetic rats (from 302+/-47 to 135+/-11 mg/dL, p<0.001); does not significantly affect the fast, slow, and total components of responses to noradrenaline in all the experimental groups; reverses the increased Emax values of noradrenaline in diabetic rats to near-control values; reverses the completely abolished responses of acetylcholine (pD2 and percent relaxation) in diabetic rats to control values; and reverses the decreased pD2 values of sodium nitroprussiate in diabetic rats to control values. In conclusion, AICA-r treatment in neonatal STZ-diabetic rats improved increased blood glucose levels, accelerated weight gain, reversed endothelial dysfunction, and normalized vascular responses.

Effect of hyperoxia and metformin on vascular responses to vasoactive compounds in rats.

Exposure of cells to oxygen concentrations higher than normal (hyperoxia) damages the molecular components of cells, resulting in cellular dysfunction and death. Metformin, a biguanide molecule used for treating non-insulin-dependent diabetes, been shown to lower blood pressure. The aim of this study was to investigate the possible effects of hyperoxia and metformin on the vascular responses of thoracic aorta to vasoactive compounds, using an in vitro rat model. In the hyperoxia-control (HC) group, the response to acetylcholine was completely abolished, but metformin treatment before (MH) or after (HM) exposure to 100% oxygen restored the response to acetylcholine to near-control values. In aortas from HC, MH, or HM groups, no significant differences were found in pD2 values to the endothelium-dependent vasodilator sodium nitroprussiate. In aortic strips from metformin-treated rats, the pD2 values for noradrenaline in the presence of endothelium were significantly smaller than those in the normal control group. The maximal contractile responses to KCl were not significantly different among all experimental groups. The results of the present study show that in hyperoxia-exposed rats, metformin treatment reverses the abolished vascular relaxation to AChe.

Nasopharyngeal colonization with penicillin-resistant Streptococcus pneumoniae in Turkish children.

BACKGROUND: Streptococcus pneumoniae is one of the major infectious agents observed in children. In spite of the fact that penicillin is preferred in the treatment of infections caused by S. pneumoniae, there has been a world-wide increase in the frequency of penicillin-resistant S. pneumoniae. METHODS: One hundred and fifty sick children with a clinical diagnosis of pneumonia, meningitis, acute otitis media, acute sinusitis and septicemia or bacteremia, and 150 healthy children without any infection were examined. Streptococcus pneumoniae, which were isolated from the nasopharynx, were analyzed with respect to penicillin susceptibility using the agar dilution method. RESULTS: The S. pneumoniae carriage rate was observed to be 43.3% in the group of sick children and 30.0% in the control group (P < 0.05). The penicillin resistance of S. pneumoniae isolated from the nasopharynx was determined to be 35.4% from a total of 110 isolates, with an intermediate resistance of 32.7% and a high resistance of 2.7%. The penicillin resistance of S. pneumoniae carried in the nasopharynx was determined to be 41.5% in the group of sick children and 26.6% in the control group (P > 0.05). Resistance rates of other antibiotics were determined as follows: cefotaxime 2.7%, erythromycin 19%, clarithromycin 5.4%, tetracycline 21.8%, trimethoprim-sulfamethoxazole 4.5% and rifampin 0%. CONCLUSIONS: Penicillin resistance of S. pneumoniae has recently become a problem in Turkey. Because of this, we require new strategies to limit the spread of drug-resistant S. pneumoniae.

Hemorrhagic shock and encephalopathy syndrome: neurologic features.

Hemorrhagic shock and encephalopathy syndrome (HSES) is a severe disease that affects previously healthy infants of less than 1 year of age and is associated with significant mortality and neurologic morbidity. It is characterized by sudden onset of shock, convulsions and coma, bleeding due to severe coagulopathy, fever, diarrhea, metabolic acidosis, and hepatorenal dysfunction. Central nervous system involvement with recurrent seizures and brain edema is the most common cause of high mortality and neurological morbidity. In this report, we describe four patients of HSES and review the initial and follow-up neurological features, electroencephalography findings, and the results of neuroradiological examinations of this catastrophic illness.