Insulin detemir improves glycemic control and reduces hypoglycemia in children with type 1 diabetes: findings from the Turkish cohort of the PREDICTIVE™ observational study

Background: Insulin detemir is a basal insulin analog designed to produce a superior pharmacokinetic profile to basal formulations of human insulin. It has shown consistently improved tolerability in comparison to neutral protamine Hagedorn (NPH) insulin in adult cohorts, but there are relatively few publications involving pediatric cohorts. Methods: The efficacy and safety of insulin detemir in children with type 1 diabetes was assessed using data from the Turkish cohort of PREDICTIVE? (a large, multinational, observational) study. The children investigated were using basal–bolus therapy involving NPH insulin or insulin glargine at baseline but were switched to insulin detemir as part of routine clinical care by their physicians. Results: Twelve weeks of treatment with insulin detemir significantly reduced mean hemoglobin A1c (9.7–8.9%, p < 0.001) and mean fasting glucose [185–162 mg/dL (10.3–9 mmol/L), p < 0.01]. Fasting glucose variability was also lower after treatment with insulin detemir than previously (on either NPH or glargine, p < 0.05). The frequencies of total, major and nocturnal hypoglycemic events were significantly reduced with insulin detemir relative to baseline, with an estimated mean of 6.89 fewer events/patient/yr overall (p < 0.001) and 2.6 fewer nocturnal events/patient/yr (p < 0.01). Weight and insulin dose remained relatively unchanged. Conclusions: Twelve weeks of treatment with insulin detemir improved glycemic control and reduced hypoglycemia in children with type 1 diabetes. This improved tolerability might allow further dose titration and therefore additional improvements in glucose control.     

NEUROPSYCHOLOGIC SEQUELAE IN THE LONG-TERM SURVIVORS OF CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA

The neurotoxicity of either systemic chemotherapy or central nervous system prophylaxis was studied in 19 children treated for acute lymphoblastic leukemia (ALL). They had completed ALL therapy at least a year before and survived more than 5 years after diagnosis. The duration between age at diagnosis and age at investigation was 8.6 2.7 years (5-15 years). Neuropsychologic tests, cranial magnetic resonance imaging (MRI), and evoked potentials (EP) were studied. Seventeen healthy siblings were taken as a control group. Emotional evaluation was done using the childhood depression inventory and Beck depression inventory. Cognitive functions were evaluated using Wechsler's Intelligence Scale for Children-Revised (WISC-R) or the Wechsler's Adult Intelligence Scale-Revised (WAIS-R) tests, which were adapted to Turkish children. Performance and total IQ scores (94.0 16.8 and 92.2 16.5) were significantly low as compared to the control group (112.1 18.9 and 105.4 14.2) (p=.007 and p=.02). Abnormal MRI findings were found in 33.3% (6/18). Three out of 18 patients (16.6%) had abnormal auditory while 5 out of 17 patients (29.5%) displayed abnormal visual EPs. Abnormal findings in MRI, cognitive examination, and electrophysiologic testing were not associated with age at diagnosis, radiotherapy doses, intermediate/high-dose systemic methotrexate administration or central nervous system involvement. But more patients must be studied to demonstrate discrete outcomes of neurotoxicity in long-term survivors of childhood leukemia.     

A comparative analysis of arterial blood flow in unexplained infertility,tubal infertility and fertile groups

We aimed to compare ovarian (O), uterine (U) and spiral (S) artery (A) resistance of patients diagnosed as fertile, unexplained infertility (UI) and tubal factor infertility (TFI) in the peri-implantation period and independent from the impact of the treatment. UI (n?=?70), TFI (n?=?75) and fertile (n?=?72) patients’ ovarian, uterine and spiral artery pulsatility index (PI), resistance index (RI) and the endometrial thickness, serum estradiol and progesterone levels were compared. The specificity and sensitivity values were calculated according to determined cutoff values. Both TFI and control groups’ UA PI values were significantly lower than the UI group’s PI values. The highest UA RI values were found in UI group and the lowest values were in the control group. UI and TFI groups’ OA PI/RI values were significantly higher than the control group. Both the control and TFI groups’ SA PI/RI values were significantly lower than UI group’s PI/RI values. UI patients’ uterine and spiral arteries PI values >1.86 and >0.85, RI values >0.80 and >0.53 can be used as a valuable test showing reduced uterine perfusion. Ovarian artery PI values >0.96 and RI values >0.58 can be used as tests showing decreased ovarian perfusion in patients with TFI. In these patients, embryo cryopreservation can be considered.     

Jab1 expression is associated with TGF-β1 signaling in chronic rhinosinusitis and nasal polyposis

Jab1, which is a fifth component of COP9 signalosome, plays an essential role in cell growth and proliferation. Jab1 is also shown to regulate transforming growth factor-beta (TGF-β) signaling in carcinoma cells. The aim of the present study was to investigate the expression and the correlation of Jab1 and TGF-β1 in chronic rhinosinusitis and nasal polyposis. Here, we show the elevated expression of Jab1 and TGF-β1 in diseased mucosa without nasal polyps and a correlation between Jab1 and TGF-β1 expression. Forty-six samples (26 patients with nasal polyps, 10 patients with chronic rhinosinusitis and 10 control subjects) were included to this study. Immunohistochemistry and Western blotting were performed for the assessment of Jab1 and TGF-β1 localization and the expression of proteins. Double staining of both proteins showed that Jab1 and TGF-β1 were colocalized in the epithelium, inflammatory cells and the vascular endothelium of nasal mucosa. There was a significant increase in the expression of TGF-β1 and Jab1 in patients without nasal polyps and a significant decrease in patients with nasal polyps compared to controls. Moreover, correlation was detected between the expression of Jab1 and TGF-β1 in chronic rhinosinusitis and nasal polyposis. Our results demonstrate that chronic rhinosinusitis is characterized by elevated expression of Jab1 and TGF-β1 compared to nasal polyposis and Jab1 may play a vital role in the pathogenesis of both chronic rhinosinusitis and nasal polyposis.     

A novel ITGB2 variant with long survival in patients with leukocyte adhesion defect type-I

Leukocyte adhesion deficiency is an autosomal recessive primary immunodeficiency that has been divided into three types: LAD1 (beta-2 integrin (CD18) family deficiency/defect), LAD2 (absence of fucosylated carbonhydrate ligands for selectins) and LAD3 (defective activation of all beta integrins). However, recently LAD4 has been described in cystic fibrosis patients, with a defect in integrin activation reported in monocytes. LAD-I is the most common type and prevalence of 1 in 1,000,000 live births. Clinical features of LAD patients are recurrent bacterial and fungal infections, omphalitis with delayed umbilical stump separation, significant leukocytosis especially neutrophilia during infection periods, impaired pus formation, and delayed traumatic or surgical wound healing. Flow cytometry is considered a useful tool for rapid diagnosis of the disease. The study of CD18 and CD11 (a, b, c) expression patterns in peripheral blood leukocytes helps to distinguish different phenotypes of LAD-I. In general, patients with ≥ 2% CD18 expression tend to have a less severe infection and often survive until adulthood, whereas < 2% CD18 expression often results in death in infancy. In this case report, three siblings, 10, 15, and 17 years old, diagnosed with leukocyte adhesion defect type 1 in adolescence age group, are presented.

     

Trace elements, heavy metals and vitamin levels in patients with coronary artery disease

Aim: In the present study, we aimed to assess serum concentrations of zinc (Zn), copper (Cu), iron (Fe), cadmium (Cd), lead (Pb), manganese (Mn), vitamins A (retinol), D (cholecalciferol) and E (α-tocopherol) in patients with coronary artery disease (CAD) and to compare with healthy controls.Methods: A total of 30 CAD patients and 20 healthy subjects were included in this study. Atomic absorption spectrophotometry (UNICAM-929) was used to measure heavy metal and trace element concentrations. Serum α-tocopherol, retinol and cholecalciferol were measured simultaneously by high performance liquid chromatography (HPLC).Results: Demographic and baseline clinical characteristics were not statistically different between the groups. Serum concentrations of retinol (0.3521±0.1319 vs. 0.4313±0.0465 mmol/I, p=0.013), tocopherol (3.8630±1.3117 vs. 6.9124±1.0577 mmol/I, p<0.001), cholecalciferol (0.0209±0.0089 vs. 0.0304±0.0059 mmol/I, p<0.001) and Fe (0.5664±0.2360 vs. 1.0689±0,4452 µg/dI, p<0.001) were significantly lower in CAD patients. In addition, while not statistically significant serum Cu (1.0164±0.2672 vs. 1.1934±0.4164 µg/dI, p=0.073) concentrations were tended to be lower in patients with CAD, whereas serum lead (0.1449±0.0886 vs. 0.1019±0.0644 µg/dI, p=0.069) concentrations tended to be higher.Conclusions: Serum level of trace elements and vitamins may be changed in patients with CAD. In this relatively small study we found that serum levels of retinol, tocopherol, cholecalciferol, iron and copper may be lower whereas serum lead concentrations may be increased in patients with CAD.     

Vascular endothelial growth factor +405 C/G polymorphism is highly associated with an increased risk of endometriosis in Turkish women

Objective  

Endometriosis is a chronic gynecological disease characterized by the growth of hormonally responsive, endometrial tissue outside the uterine cavity. The present study aims to analyze two vascular endothelial growth factor (VEGF) polymorphisms (−460 C/T and +405 C/G) in Turkish women with and without endometriosis.     

Mortality from asthma in children and young adults in Louisiana.

BACKGROUND: Asthma mortality rates have been increasing despite our improved understanding of the pathophysiology of asthma and advanced methods of treatment. Although there are many national studies of asthma mortality rates, few studies have concentrated on subnational regions such as individual states. OBJECTIVES: We sought to determine the trends in asthma mortality in children and young adults during the last 15 years in Louisiana. METHODS: Asthma mortality data were acquired from the Louisiana State Center for Health Statistics for the years 1983 through 1997. All asthma deaths coded International Classification of Disease, Ninth Revision 493 were included in the data set along with year, sex, and rate characteristics. State population estimates obtained from the United States Bureau of Census for three 5-year periods (1983 to 1987, 1988 to 1992, and 1993 to 1997) were used to calculate crude and adjusted mortality rates. These time periods were compared with one another and with the period 1983 to 1987, which was used as a baseline. RESULTS: For all residents, the mortality rate increased from 0.41 deaths per 100,000 persons during the 1983 to 1987 time period to 0.49 and 0.63 deaths per 100,000 persons during 1988 to 1992 and 1993 to 1997 time periods, respectively. Mortality rates have increased in both the white and non-white populations over the 15-year study period, with the most pronounced increases among the non-white population. CONCLUSION: Asthma mortality rates in Louisiana have increased, particularly among the non-white population, over the last 15 years, although the results are not statistically significant. When compared with other states, asthma mortality in Louisiana is lower than in the northeast and central north states.     

The effects of iloprost, a prostacyclin analogue, in experimental ischaemia/reperfusion injury in rat ovaries

Ovarian torsion is a surgical emergency affecting not only the ipsilateral ovary but also contralateral ovary. Although the conventional treatment is salpingo-oophorectomy, recent studies advocate detorsion. We hypothesized that iloprost, an analogue of prostacyclin with cytoprotective properties, may prevent the harmful effects of ischaemia–reperfusion injury in bilateral ovaries after unilateral ovarian torsion–detorsion in rat. In this study, 24 female Wistar-albino female rats were divided into four groups. Ovarian torsion was produced by applying vascular clamps to right ovaries. In Group I, bilateral oophorectomy was performed. In group II, bilateral oophorectomy was performed after a unilateral torsion period of 4 h. In group III, bilateral ovaries were removed, following unilateral torsion–detorsion periods each lasted for 4 h. Saline was injected i.p. 30 min before detorsion. In group IV, same experimental protocol, which was conducted in group III, was repeated. Iloprost was injected i.p. 30 min before detorsion instead of saline in group IV. Tissue levels of malondialdehyde (MDA) and nitric oxide (NO), which are the indicators for oxidative stress were determined and histopathological evaluation was performed in bilateral ovaries in all groups. The MDA and NO levels for ipsilateral ovaries of four groups were compared and no significant difference was found (p>0.05). The same comparison were done for the contralateral sides and no difference was seen either (p>0.05). In histological examination, iloprost produced improvement in I/R-induced alterations in ipsilateral and contralateral ovaries. In conclusion, these results showed that iloprost has beneficial effect on the histological appearences in both the ipsilateral and contralateral rat ovaries after unilateral torsion–detorsion.