New results for monogenic diabetes with analysis of causative genes using next-generation sequencing: a tertiary centre experience from Turkey

International Journal of Diabetes in Developing Countries - Although monogenic diabetes accounts for a small proportion of diabetes cases, accurate diagnosis may significantly change treatment....     

Biliary stones and stenoses: diagnostic value of magnetic resonance cholangiography.

BACKGROUND/AIMS: To evaluate the accuracy of magnetic resonance cholangiography for detection of bile duct calculi and stenosis. METHODS: Half-Fourier single-shot rapid acquisition with relaxation enhancement sequence magnetic resonance cholangiography was performed prospectively in 68 patients who were suspected of having choledocholithiasis or biliary tree stenosis. On the basis of findings at ultrasound, computed tomography, endoscopic retrograde or percutaneous cholangiography, intraoperative cholangiography or choledocoscopy and exploration, final diagnoses were normal bile ducts (n=8), choledocholithiasis (n=28), benign or malignant stenosis (n=32). RESULTS: Choledocholithiasis was diagnosed with a sensitivity of 96% and a specificity of 98%. False negative readings occurred due to stones less than two mm at in size at the distal common bile duct. A false diagnosis of choledocholithiasis (single impacted stone) by magnetic resonance cholangiography occurred in only one case for whom the final diagnosis was main bile duct adenocarcinoma, suspected on endoscopic retrograde cholangiography and confirmed at surgery. Bile duct stenosis was diagnosed with a sensitivity of 97% and a specificity of 94%. CONCLUSIONS: With magnetic resonance cholangiography, bile duct calculi and stenosis can be diagnosed with high accuracy. It is a fast, accurate and noninvasive alternative to endoscopic retrograde cholangiography in the evaluation of biliary tract disease.     

Plasma thrombin-activatable fibrinolysis inhibitor (TAFI) antigen levels in diabetic foot ulcers

Plasma TAFI may participate in arterial thrombosis in cardiovascular diseases (CVD) and may be involved in the mechanism of vascular endothelial damage in diabetic patients. The aim of this study was to investigate the association of plasma TAFI antigen level in the development of diabetic foot ulcer in Type 2 diabetes. The TAFI antigen levels were determined in 50 patients with diabetic foot ulcers and 34 patients without diabetic foot ulcers and 25 healthy individuals. We measured TAFIa/ai antigen in plasma samples with a commercially available ELISA Kit. Diabetic foot ulcer group and diabetic group were similar in terms of mean age and sex distribution. Diabetes duration, retinopathy, neuropathy, macrovascular disease and infection were related to diabetic foot ulcers. HbA1c, HDL-cholesterol and Folic Acid levels were decreased in the diabetic foot ulcer group. TAFI levels were 99.44?±?55.94% in control group, 135.21?±?61.05% in diabetic foot ulcer group, 136.75?±?59.38% in diabetic group and was statistically different (P??0.05). No significant difference in plasma TAFI levels were seen between diabetic foot ulcer stages. TAFI antigen levels are increased in Type 2 diabetic patients, but are not related to diabetic foot ulcer development.     

Unusual presentation: pulmonary hemosiderosis with celiac disease and retinitis pigmentosa in a child

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease characterized by anemia, hemoptysis and recurrent alveolar hemorrhage. The combination of IPH and celiac disease (CD) is extremely rare. We report a 9-year-old boy with Lane-Hamilton syndrome, co-occurrence of pulmonary hemosiderosis with CD. This presentation is unique presentation because he has also retinal pigmentation.     

The importance of anti-insulin antibody in patients with type 1 diabetes mellitus treated with continuous subcutaneous insulin infusion or multiple daily insulin injections therapy

To investigate the influence of two insulin administration modalities, continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) therapy with insulin analogues, on the development of insulin antibodies (IAs) in patients with type 1 diabetes mellitus and to assess the impact of IAs on glucose control and hypoglycaemia. 96 patients with type 1 diabetes mellitus treated with CSII (n = 48) or MDI (n = 48) were included in the study. Age, duration of diabetes, A1c, preprandial and postprandial blood glucose and hypoglycaemic events were compared between IA positive and negative patients. IA levels were higher in the CSII group (% 24.6 ± 14.2) than the MDI group (% 13.2 ± 9.9). Duration of diabetes and age were not associated with IA positiveness. While A1c, preprandial blood glucose and the frequency of hypoglycaemic events were similar in two groups, postprandial blood glucose was lower in IA positive group (P = 0.03). Patients with type 1 diabetes mellitus treated with CSII with insulin analogues had higher IA levels when compared to MDI therapy. However, the development of IAs did not impair the glycaemic control.     

Nifedipine therapy for preterm labor: effects on placental, fetal cerebral and atrioventricular Doppler parameters in the first 48 hours.

OBJECTIVE: To assess the effect of nifedipine tocolysis on Doppler parameters of the uterine, umbilical and fetal middle cerebral arteries and atrioventricular valves in the first 48 h of therapy. METHODS: Doppler waveforms of uterine, umbilical and middle cerebral arteries and both atrioventricular valves were measured from 28 pregnant women and fetuses prior to and during nifedipine therapy for preterm labor. Maternal and fetal heart rates (FHR), maternal systolic and diastolic blood pressure, and the Doppler pulsatility index (PI) of the uterine, umbilical and middle cerebral arteries were measured. The cerebroplacental ratio (middle cerebral artery PI/umbilical artery PI) was calculated. The total time velocity integrals (TVIs) of tricuspid and mitral valves and their E- and A-wave peak velocity ratio (E/A) were measured. Friedman repeated-measures analysis of variance was used to compare the variables before and after nifedipine therapy. If significant differences were found, Wilcoxon's signed ranks test was used to analyze the difference between the two variables. A P-value of < 0.05 was considered significant. RESULTS: Nifedipine maintenance was associated with a significant decline in maternal systolic and diastolic blood pressure after 24 h, while maternal heart rate and FHR were unaffected. The uterine artery PI had decreased significantly at 24 and 48 h, while the umbilical artery PI did not change significantly. The middle cerebral artery PI had decreased significantly at 24 and again at 48 h. A significant fall in the cerebroplacental Doppler ratio was maintained beyond 24 h. The mean E/A values, TVIs and TVI x FHR values at 24 and 48 h were unchanged from the baseline values. CONCLUSIONS: Nifedipine maintenance tocolysis is associated with a significant decline in uterine artery and middle cerebral artery Doppler indices 24 h after the first dose. Fetal cardiac diastolic function is unaffected and the significant redistribution observed after 24 h is likely to be attributable to altered cerebral blood flow.     

Changes in protein turnover, IGF-I and IGF binding proteins in children with cancer

Changes in insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBPs) were correlated with protein synthesis and breakdown using [1- ¹³C]leucine before chemotherapy and during subsequent febrile neutropenia (FN) in eight children with cancer, aged 6.3–17.5 y. IGF-I levels were similar to age-matched controls before chemotherapy (mean ±SEM: 250 ±28 and 228 ±22 μg l^-1, respectively). During FN, IGF-I fell to 156 ±22 /ng l ^-1(p= 0:02), and rose to 276 ±27 μ g l ^-1 with recovery at 6 months (p = 0:004). Similarly, IGFBP-3 decreased from 4.0 ±0.2mgl^-1 before chemotherapy to 3.0 ±0.3 mgl^-1 during FN (p= 0:01), and returned to 4.1 ±0.2mgl ^-1 at 6 months (p= 0:01). IGF-I correlated with IGFBP-3 (r=+0:7, p <0:001). Scanning densitometry showed a decrease in IGFBP-3 from 94 to 54% during FN, when the presence of IGFBP-3 protease activity was observed. Compared with normal human serum, IGFBP-2 was elevated throughout the study. IGFBP-1 increased from 14.6 ±3.5 to 30.6 ±2.8/ngl^-1 (p = 0:004), whereas serum insulin decreased from 26.5 ±6.8 to 7.8 ±0.8 mUl^-1 (p= 0:03) before and during FN, respectively. Whilst IGF-I and IGFBP-3 fell, daytime growth hormone increased from 3.3 ±0.6 to 6.7±0.8mUl ^-1 (p= 0:01), and cortisol from 197 ±48 to 594±98nmoll ^-1 (p = 0:005). Albumin decreased from 47 ±2 to 38 ±2gl^-1 (p= 0:004) and improved to 47 ±2gl^-1 with recovery (p= 0:003). Protein synthesis increased from 4.5 ±0.4 to 5.0 ±0.6gkg^-1 d^-1 before chemotherapy and during FN, while protein breakdown rose from 5.4 ±0.4 to 6.3 ±0.4kg^-1d^-1. Increasing protein breakdown was related to falling IGF-I and IGFBP-3 levels. Modification of IGFBP-3 by circulating proteolytic activity may alter IGF bioavailability, allowing protein synthesis to increase during periods of severe catabolic stress.     

Spinal cord compression–do we miss it?

Four children with spinal cord compression due to malignant tumours are presented. The severity of the condition was not initially recognized by parents, or the nature of the likely cause by the initial physicians. Lower limb asymmetrical weakness, clear-cut sensory levels, and marked pain indicate need for urgent imaging and exclusion of a space occupying lesion. In 1997 diagnosis of Guillain-Barré syndrome should not be made without careful prior spinal imaging.     

HLA-DR typing of women with recurrent late spontaneous abortion and unsuccessful cervical cerclage

The release of certain cytokines, e.g. tumour necrosis factor (TNF)- alpha, in the amniotic fluid has been suggested to be a cause of preterm birth. The predisposition to excessive liberation of cytokines from peripheral leukocytes has been shown to depend partly on the individual's HLA-DR genotype. The HLA-DR1 and -DR3 alleles have previously been reported as being associated with a TNF-alpha high responder status and have also been associated with unexplained recurrent spontaneous abortions. In the present study, HLA-DR typing was performed in 10 women who had experienced recurrent very early preterm births resulting in perinatal death, or late spontaneous abortions under a clinical picture resembling that traditionally attributed to cervical incompetence. All patients had had at least one mid-trimester miscarriage in spite of the insertion of a cervical cerclage. Nine out of 10 (90%) patients had the HLA-DR phenotypes DR1 and/or DR3 compared with 37% in the background population (P < 0.005). The results suggest that HLA-DR-associated immunological factors might play a part in recurrent late spontaneous abortions and extremely preterm births under a cervical incompetence-like picture, at least in the subset of cases not treatable by cervical cerclage.