Management of Rapidly Progressive Precocious Puberty in a Patient with Mosaic Turner Syndrome.

CONTEXT: Rapidly progressive precocious puberty (RPPP) is a rare condition in Turner syndrome (TS), with no consensus on treatment and follow-up. Only 12 cases have been reported so far. OBJECTIVE: We aimed to evaluate the effects of the GnRH analog (GnRHa) on growth and anti-mullerian hormone (AMH) levels in TS and RPPP. DESIGN: The clinical and laboratory data was recorded at baseline and after treatment. SUBJECTS AND METHODS: An 8.1-year old girl with a karyotype of 45, X/46, XX presented with breast development at Tanner stage-2. Breast development advanced to Tanner stage-3 at the age of 8.7 years. Growth velocity (GV) was 8 cm/year. Bone age was 11 years with a predicted adult height of 152 cm. Luteinizing hormone (LH) was 1.69mIU/mL and estradiol was 33pg/mL, confirming the central puberty. AMH level was 6.33ng/mL. The sizes of ovaries and uterus were compatible with the pubertal stage, with an endometrial thickness of 5 mm. GnRHa was started for RPPP. RESULTS: After three months, GV declined to 0 cm/3 months and AMH level to 50% of the baseline. Growth hormone (GH) treatment was started for insufficient growth. GV improved with GH treatment, as well as a far more decreased AMH level. RESULTS: After three months, GV declined to 0 cm/3 months and AMH level to 50% of the baseline. Growth hormone (GH) treatment was started for insufficient growth. GV improved with GH treatment, as well as a far more decreased AMH level. CONCLUSION: GV usually declines before puberty in patients with TS, even if the mid-parental height is tall. RPPP should be considered if GV is increased. Excessive suppression of growth may be prevented with GH treatment. GnRHa treatment also plays a role in reducing AMH levels in patients with TS.

Characteristics of Turkish children with Type 2 diabetes at onset: a multicentre, cross-sectional study.

AIMS: To describe the baseline clinical and laboratory findings and treatment modalities of 367 children and adolescents diagnosed with Type 2 diabetes in various paediatric endocrinology centres in Turkey. METHODS: A standard questionnaire regarding clinical and laboratory characteristics at onset was uploaded to an online national database system. Data for 367 children (aged 6-18 years) newly diagnosed with Type 2 diabetes at 37 different paediatric endocrinology centres were analysed. RESULTS: After exclusion of the children with a BMI Z-score < 1 SD, those with genetic syndromes associated with Type 2 diabetes, and those whose C-peptide and/or insulin levels were not available, 227 cases were included in the study. Mean age was 13.8 ± 2.2 (range 6.5-17.8) years, with female preponderance (68%). Family history of Type 2 diabetes was positive in 86% of the children. The mean BMI was 31.3 ± 6.5 kg/m2 (range 18.7-61) and BMI Z-score was 2.4 ± 0.8 (range 1-5). More than half (57%) of the children were identified by an opportunistic diabetes screening due to existing risk markers without typical symptoms of diabetes. Only 13% (n = 29) were treated solely by lifestyle modification, while 40.5% (n = 92) were treated with metformin, 13% (n = 30) were treated with insulin, and 33.5% (n = 76) were treated with a combination of insulin and metformin initially. Mean HbA1C levels of the insulin and combination of insulin and metformin groups were 98 (11.1%) and 102 mmol/mol (11.5%), respectively, and also were significantly higher than the lifestyle modification only and metformin groups mean HbA1C levels (70(8.6%) and 67 mmol/mol (8.3%), respectively). CONCLUSIONS: An opportunistic screening of children who are at high risk of Type 2 diabetes is essential, as our data showed that > 50% of the children were asymptomatic at diagnosis. The other important result of our study was the high rate of exclusion from the initial registration (38%), suggesting that accurate diagnosis of Type 2 diabetes in youth is still problematic, even for paediatric endocrinologists.

Adolescents with Type 1 diabetes mellitus experience psychosensorial symptoms during hypoglycaemia.

AIM: To describe mood and psychosensorial symptoms of hypoglycaemia in adolescents with Type 1 diabetes mellitus in two countries with different cultures, Turkey and the USA. METHODS: We developed a 68-item questionnaire assessing physical, behavioural, mood and psychosensorial symptom frequency and ratings ['good', 'bad', or 'both' (sometimes good, sometimes bad)]. Adolescents with Type 1 diabetes were recruited from paediatric diabetes clinics at the University of North Carolina at Chapel Hill in the USA and Kocaeli University in Turkey. The percentages of participants at each clinic who endorsed individual symptoms, symptom categories and symptom ratings were calculated and compared. RESULTS: Cronbach's α values were > 0.7 for each real symptom category. No symptom items were excluded from the questionnaire analysis based on item-total correlation results which were all > 0.2. Data were collected from 132 participants (69 from University of North Carolina, 63 from Kocaeli University, 54% male). The mean (SD) age of the participants was 14.9 (1.9) years, HbA1c level was 8.7 (1.8) % and duration of Type 1 diabetes was 5.8 (3.7) years. On average, each physical symptom was experienced by 65.2% of participants, each behavioural symptom by 46.5%, each mood symptom by 42.8%, and each psychosensorial symptom by 48.9%. On average, each physical, behavioral, mood and psychosensorial symptom was rated as 'good' or 'both' by 23.0, 29.1, 36.9 and 37.2% of participants, respectively. There were no symptom differences between the groups in each country. CONCLUSIONS: In addition to the classic physical symptoms experienced during hypoglycaemia, adolescents with Type 1 diabetes report psychosensorial, mood and behavioral symptoms, and some describe them as positive experiences. Symptom experiences were similar in these two countries with different cultures.

Diffusion-weighted MRI in acute stroke within the first 6 hours: 1.5 or 3.0 Tesla?

OBJECTIVES: To compare the sensitivity and specificity of 1.5-T and 3.0-T diffusion-weighted MRI (DWI) to detect hyperacute ischemic stroke lesions. METHODS: We blindly reviewed the DWI of 135 acute stroke patients and 34 controls performed at 1.5 T (n = 108) or 3.0 T (n = 61). The stroke patients all had subsequently proved carotid territory ischemic stroke and were imaged within the first 6 hours after stroke onset. Four readers (2 neuroradiologists and 2 stroke neurologists) blinded to clinical data and magnetic field strength recorded the presence of ischemic lesions on DWI and apparent diffusion coefficient (ADC) maps if necessary. Sensitivity, specificity, and false-negative rates were computed. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and DWI contrasts were calculated at both field strengths. RESULTS: The accuracy of DWI in stroke diagnosis was superior at 1.5 T (98.8%) than at 3.0 T (90.9%, p = 0.03). The sensitivity decreased from 99.1% at 1.5 T to 92.5% at 3.0 T (p = 0.06) and the specificity from 97.8% to 84.1% (p = 0.002). ADC map readings did not improve accuracy, sensitivity, or specificity. The false-negative rate was 0.6% at 1.5 T and 6.1% at 3.0 T. Type of readers, stroke severity, and type of the coil did not affect diagnosis value. SNR and CNR were significantly higher at 3 T (p < 0.0001) but DWI contrast was lower (p = 0.04). CONCLUSIONS: Blind reading by 4 experts of a large series of images shows that 1.5-T diffusion-weighted MRI (DWI) is better than 3.0-T DWI for the imaging of hyperacute stroke during the therapeutic window of thrombolysis.

Adenosine A1 receptor, a target and regulator of estrogen receptoralpha action, mediates the proliferative effects of estradiol in breast cancer.

Estrogen receptor-alpha (ERalpha) and its ligand estradiol (E2) has critical roles in breast cancer growth and are key therapeutic targets. In this study, we report a novel dual role of the adenosine A1 receptor (Adora1) as an E2/ERalpha target and a regulator of ERalpha transcriptional activity. In ERalpha-positive breast cancer cells, E2 upregulated Adora1 messenger RNA (mRNA) and protein levels, an effect that was reversed by the E2 antagonist ICI 182 780. Small interference RNA ablation of Adora1 in ERalpha-positive cells reduced basal and E2-dependent proliferation, whereas Adora1 over-expression in an ERalpha-negative cell line induced proliferation. The selective Adora1 antagonist, DPCPX, reduced proliferation, establishing Adora1 as a mediator of E2/ERalpha-dependent breast cancer growth. Intriguingly, Adora1 ablation decreased both mRNA and protein levels of ERalpha and, consequently, estrogen-responsive element-dependent ERalpha transcriptional activity. Moreover, Adora1 ablation decreased binding activity of ERalpha to the promoter of its target gene TFF1 and led to reduced TFF1 promoter activity and mRNA levels, suggesting that Adora1 is required for full transcriptional activity of ERalpha on E2 stimulation. Taken together, we showed a short feed-forward loop involving E2, ERalpha and Adora1 that favors breast cancer growth. These data suggest that Adora1 may represent an important target for therapeutic intervention in hormone-dependent breast cancer.

[The French version of the FOUR score: A new coma score]. / Le FOUR score en français, un nouveau score d'évaluation de la profondeur du coma.

BACKGROUND: Comatose state is a major cause for admission to the intensive care unit. The most commonly used assessment score is the Glasgow coma scale (GCS). Although widely accepted, this score has several limitations. Recently, the full outline of unresponsiveness score (FOUR) has been validated and tested as reliable as the GCS. METHODS: We translated this score in French and tested its reliability in a neurological critical care unit. This study included eight critical care patients and eight intensive care patients. The patients were successively evaluated by two neurologists, four experienced nurses and five inexperienced nurses; a total of 176 evaluations were performed. The weighted kappa (kappa(W)) was used to determine the reliability of the evaluation for both the FOUR score and the GCS. RESULTS: The mean age of the patients was 62 years. The interobserver reliability of the French version of the FOUR score was high (kappa(W)=0.86; IC 95%: 0.83-0.89) comparable to that of the GCS (kappa(W)=0.85; IC 95%: 0.82-0.88). CONCLUSION: The French version of the FOUR score has an excellent interobserver reliability. This score is easy to perform and well accepted, only requiring simple and short training.

In vivo timing of onset of transgene expression following adenoviral-mediated gene transfer.

Recombinant adenoviruses are efficient gene transfer vehicles that could be used for treatment of acute diseases. However, the time required for adenoviruses to produce physiologically relevant levels of transgene in vivo is unknown. To address this question rat lungs were infected with an E1a(-)/E3a(-) adenovirus that contains an hCMV-driven human beta(2)-adrenergic receptor (beta(2)AR) cDNA. Human beta(2)AR message and protein expression were noted 2-4 h postinfection without evidence of pseudotransduction. beta(2)AR function (cAMP production) was increased at 6 h postinfection. To determine when beta(2)AR gene transfer affects downstream catecholamine-sensitive pathways, we measured lung Na,K-ATPase expression and alveolar fluid clearance (AFC). beta(2)AR gene transfer increased Na,K-ATPase number by 80% at 6 h, and AFC by 20% at 8 h postinfection. These data indicate that recombinant adenoviruses can produce physiologically significant levels of transgene within hours of infection and that they may be suitable for gene therapies for acute, rapidly progressive diseases.

beta(2)-adrenergic receptor overexpression increases alveolar fluid clearance and responsiveness to endogenous catecholamines in rats.

beta-Adrenergic agonists accelerate the clearance of alveolar fluid by increasing the expression and activity of epithelial solute transport proteins such as amiloride-sensitive epithelial Na(+) channels (ENaC) and Na,K-ATPases. Here we report that adenoviral-mediated overexpression of a human beta(2)-adrenergic receptor (beta(2)AR) cDNA increases beta(2)AR mRNA, membrane-bound receptor protein expression, and receptor function (procaterol-induced cAMP production) in human lung epithelial cells (A549). Receptor overexpression was associated with increased catecholamine (procaterol)-responsive active Na(+) transport and increased abundance of Na,K-ATPases in the basolateral cell membrane. beta(2)AR gene transfer to the alveolar epithelium of normal rats improved membrane-bound beta(2)AR expression and function and increased levels of ENaC (alpha subunit) abundance and Na,K-ATPases activity in apical and basolateral cell membrane fractions isolated from the peripheral lung, respectively. Alveolar fluid clearance (AFC), an index of active Na(+) transport, in beta(2)AR overexpressing rats was up to 100% greater than sham-infected controls and rats infected with an adenovirus that expresses no cDNA. The addition of the beta(2)AR-specific agonist procaterol to beta(2)AR overexpressing lungs did not increase AFC further. AFC in beta(2)AR overexpressing lungs from adrenalectomized or propranolol-treated rats revealed clearance rates that were the same or less than normal, untreated, sham-infected controls. These experiments indicate that alveolar beta(2)AR overexpression improves beta(2)AR function and maximally upregulates beta-agonist-responsive active Na(+) transport by improving responsiveness to endogenous catecholamines. These studies suggest that upregulation of beta(2)AR function may someday prove useful for the treatment of pulmonary edema.

GI complications in patients receiving mechanical ventilation.

Mechanical ventilation (MV) can be lifesaving by maintaining gas exchange until the underlying disorders are corrected, but it is associated with numerous organ-system complications, which can significantly affect the outcome of critically ill patients. Like other organ systems, GI complications may be directly attributable to MV, but most are a reflection of the severity of the underlying disease that required intensive care. The interactions of the underlying critical illness and MV with the GI tract are complex and can manifest in a variety of clinical pictures. Incorporated in this review are discussions of the most prevalent GI complications associated with MV, and current diagnosis and management of these problems.

Complications of mechanical ventilation.

Outcomes of critically ill patients are affected by the severity of the acute illnesses and by complications that may result from treatments. This article reviews the major complications associated with mechanical ventilation. Special emphasis is placed on recent advances in the understanding of ventilator-induced lung injury and strategies to avoid this life-threatening complication. In this update, the incidence, diagnosis, prevention, and management of complications associated with mechanical ventilation are discussed for each major organ system.

Laryngospasm and paradoxical bronchoconstriction after repeated doses of beta 2-agonists containing edetate disodium.

A 22-year-old woman with mild intermittent asthma, who had no previous history of an adverse reaction to an albuterol metered-dose inhaler, developed paradoxical bronchoconstriction after inhalation of the fourth dose of an albuterol nebulizer solution. She experienced the same symptoms and laryngospasm with repeated inhalations of albuterol and metaproterenol nebulizer solutions that contained edetate disodium. Each episode responded to racemic and subcutaneously administered epinephrine. To our knowledge, this is the first report of paradoxical bronchoconstriction and laryngospasm due to repeated doses of beta 2-agonist solutions with edetate disodium.

An unusual foreign body in the bowel lumen causing obstruction in a neonate.

Most of the foreign bodies swallowed by children pass the entire gastrointestinal tract without any complication. Neonatal intestinal foreign bodies are extremely rare. A newborn with a small bowel obstruction caused by a fresh grape is reported.

Factors that affect the rheologic properties of acrylic resin denture base materials.

The rheologic characteristics of different formulations of acrylic resin denture base materials are presented in this study. This is of practical significance in selecting resins with optimum rheologic properties for denture base construction. The materials are characterized in respect to their constituents, mean powder particle size and distribution, molecular weight averages and distributions, and glass transition temperature. A comparison of the polymers indicates that smaller particles saturate with monomer more readily, and this results in a higher viscosity. A higher viscosity for higher molecular weight and lower viscosity for lower molecular weight have been observed. Increasing the percentage of copolymerization increases the viscosity. No correlation has been found between the rheologic properties of denture base polymers and the powder glass transition temperature.

Human herpesvirus 6 and human herpesvirus 7 infections in renal transplant recipients and healthy adults in Turkey.

We explored the prevalence of human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) infections in 16 renal transplant recipients and 16 healthy controls by virus isolation, serology, polymerase chain reaction (PCR) followed by dot blot hybridization. HHV-6 variant A was isolated from one renal transplant recipient. Seven patients (44%) and six controls (38%) had HHV-6 variant B DNA in their peripheral blood mononuclear cells. The prevalence of HHV-7 DNA was found to be the same in patients and controls (19%).

Determination of doughing and manipulation times of acrylic resin denture base material and a proposal for a specification for a packing plasticity test.

The doughing and manipulation times of a range of acrylic resin denture base polymers are presented in this study. The methods evaluated were: (i) probing following American Society for testing materials specification, F451-76; (ii) hole penetration following British Standard, 2487: 1989 and International Standard Organisation, 1567: 1988; (iii) probing using a penetrometer employing a 20 g load and 1 mm diameter needle; (iv) oscillating rheometer apparatus used at a fixed frequency of 1 Hz by sweeping through a programmed linear increase in strain. The results indicate that each of the methods is capable of evaluating the doughing and manipulation times of the unprocessed polymers. It is concluded that the Bohlin VOR Oscillating Rheometer is excellent for investigating the flow properties of denture base polymers but it cannot be recommended for a standards specification test because of the high cost. The penetrometer method has been shown to be superior to the current standards specification test and would be ideal for a packing plasticity standards test.

Rheology of acrylic denture-base polymers.

The aim of this study was to investigate the changing rheological behavior of a denture-base polymer from mixing to setting. In addition, monomer evaporation and exothermic behavior of the mix were evaluated. The results show that the material behaves as a pseudoplastic fluid. It is shown that the viscosity increases at different rates with respect to lapsed time, and increases with higher temperature. Also, it is shown that polymerization and monomer evaporation both play a part in dough formation.