Lipoprotein-associated phospholipase A2 activity in obese adolescents with and without type 2 diabetes

Lipoprotein-associated phospholipase A2 (Lp-PLA2) was identified as a strong predictor for cardiovascular events. Furthermore, it is highly associated with obesity. The role of Lp-PLA2 in diabetes mellitus is controversial and analyses, especially in adolescents with type 2 diabetes (T2D), are missing. Therefore, we compared Lp-PLA2 activity between two obese age-, sex-, and BMI-matched cohorts of adolescents with and without T2D. Relationships between Lp-PLA2 activity and age, BMI, hemoglobin A1c, lipids, and adipokines were evaluated. Lp-PLA2 activity was analyzed in serum of 72 obese adolescents without T2D (mean age 15.2 ± 1.6 years) and in 65 obese adolescents with T2D (mean age 15.5 ± 1.8 years). Clinical data were obtained from the Diabetes-Patienten-Verlaufsdokumentation (DPV) registry. Surprisingly, obese adolescents with T2D had lower levels of Lp-PLA2 activity than obese children without T2D (160.2 ± 45.0 versus 180.9 ± 35.6 nmol/min/ml, p = 0.003), but this decrease could only be detected in male (158.8 ± 45.3 versus 190.8 ± 31.3 nmol/min/ml, p < 0.001) and not in female adolescents (162.1 ± 45.5 versus 167.7 ± 37.1 nmol/min/ml, p = 0.60). In multiple linear regression analysis, differences in Lp-PLA2 activity between cohorts remained large and significant (ß-coefficient: ?31.60, 95% confidence interval [?49.27;?13.93], p < 0.001). Furthermore, Lp-PLA2 activity was positively associated with BMI (ß-coefficient: 2.04 [0.68;3.40], p = 0.004) and negatively associated with the adipokines leptin (ß-coefficient: ?0.53 [?0.89;?0.17], p = 0.004) and adiponectin (ß-coefficient: ?3.06, [?5.63;?0.48], p = 0.02). Elevated mean glucose concentrations in adolescents with T2D were not associated with an increase but with a decrease of Lp-PLA2 activity. Hence, in young patients with T2D the Lp-PLA2 activity as a risk predictor for cardiovascular events needs further investigation.     

Injection of acidic or neutral insulin and pain: a single-center, prospective, controlled, noninterventional study in pediatric patients with type 1 diabetes mellitus

BACKGROUND: Pain resulting from injections has a potential influence on the acceptance and thus on the success of insulin treatment. Systematic investigation in humans has suggested that individuals perceive more pain during SC injection of acidic solutions than neutral solutions. Insulin glargine is a long-acting (up to 24-hour duration of effect), parenteral blood glucose-lowering agent. Unlike other insulins, it is injected as an acidic solution (pH 4). OBJECTIVE: The aim of this study was to assess whether the SC injection of insulin glargine is more painful than neutral insulin in a clinical setting. METHODS: This single-center, prospective, controlled, noninterventional study was performed in consecutively enrolled male and female pediatric patients (7-21 years) with type 1 diabetes mellitus who self-injected insulin >or=3 times per day and who had diabetes duration of >or=6 months. The study was conducted from September 1, 2005, to December 30, 2005, at the Diabetes Clinic, University Children's Hospital, Ulm, Germany. No changes to the patients' current insulin regimen were made. Based on their existing insulin treatment, patients were assigned to 1 of 2 treatment groups: (1) the acidic insulin group, which injected insulin glargine, and (2) the neutral insulin group, which injected neutral protamine Hagedorn or Semilente insulin. All patients also injected shortacting regular insulin or insulin analogs. Pain during SC insulin injection and during self-monitoring of blood glucose (SMBG) (the internal control) was assessed using a standardized, noninterventional protocol and optimized combined 10-cm visual analog scale and 5-point verbal rating scale (minimum = I cannot feel it at all; maximum = it hurts me). Patients were instructed to document pain immediately after insulin injection and SMBG at home 3 times a day on 3 different days. RESULTS: A total of 112 patients (mean [SD] age, 14.6 [3.0] years; sex, 60 [53.6%] male; mean [SD] glycosylated hemoglobin [HbA(1c)], 8.0% [1.4%]; mean [SD] diabetes duration, 6.1 [3.9] years) completed the study. Pain scores reported by the acidic group (n = 76) were not significantly different when compared with those of the neutral group (n = 36) (4.0 [2.0] vs 4.2 [1.9]). Pain scores were also similar for the injection of short-acting insulin in those from the acidic group when compared with those from the neutral group (3.7 [1.7] vs 4.1 [2.1]). Insulin injections were generally perceived as more painful than SMBG (3.9 [1.7] vs 2.9 [1.8]; P < 0.001). Using the Spearman rank correlation coefficient, pain perception was determined to be independent of age, gender, HbA(1c) level, and duration of diabetes. CONCLUSION: Despite its acidic formulation (pH 4), insulin glargine was not perceived as more painful during SC injection than neutral long-acting or shortacting insulin in these pediatric patients with type 1 diabetes mellitus.     

Additional factor XII (hageman factor) deficiency in hemophilia a and in von willebrand syndrome

Summary Factor XII plasma levels were investigated with several methods in patients with hemophilia A and B and von Willebrand syndrome. There seem to be some families with hemophilia A or von Willebrand syndrome, who have an additional, congenital, partial lack of factor XII (Hageman factor). The mode of inheritance is independent of the other coagulation disorder. Frequently, the first indication of an additional factor XII deficiency is the disproportionate prolongation of the activated partial thromboplastin time (PTT) as regards the factor VIII level. The average factor XII level in patients with hemophilia A and von Willebrand syndrome is significantly lower than in normal subjects or patients with hemophilia B. It cannot be excluded that the frequently low levels of factor XII in patients with severe hemophilia are acquired and probably due to liver cell damage.Dedicated to Professor F. Hartmann, MD     

Klinische und molekulare Genetik des Schilddrüsenkarzinoms

Thyroid cancer represents a genetically and clinically heterogeneous group of neoplasias and understanding of its molecular aspects has improved significantly during recent years. In papillary cancer, and particularly in its radiation-induced variants, chromosomal rearrangements of the RET/PTC fusion oncogene have been identified as a key genetic event. PAX8-PPARγ rearrangements are a novel and specific oncogenic mechanism in follicular carcinomas. Anaplastic carcinomas are now believed to arise from differentiated tumors through secondary transformation. In medullary thyroid cancer, occurring in the context of familial MEN2 tumor syndrome in up to 30% of cases, activating point mutations of the RET proto-oncogene are a central mechanism. Using a two-step RET mutation analysis, affected family members may now be identified at a preclinical stage, with the option of surgical cure by prophylactic thyroidectomy.     

A novel dystrophin isoform is required for normal retinal electrophysiology

Dystrophin is present in the outer plexiform layer of the retinaand is required for normal retinal function as measured by electroretinography.We describe the identification of a novel isoform of dystrophln(Dp260) present in the mouse retina. The unIque 5' terminusof the mRNA originates from a newly identified exon and is splicedin frame to exon 30 of the Duchenne muscular dystrophy (DMD)gene. The retinal isoform of dystrophln has 13 novel amino acidsas its N-terminus followed by most of the dystrophin rod domainand the cysteine-rich C-terminal domains. Analysis of mousetissues indicated this isoform of dystrophin Is expressed inretina, brain and cardiac tissue. Comparison of retinal electrophysiologyin mdx and mdx^cv3 mouse suggests that Dp260 is required fornormal retinal function.     

Pilon fractures. Treatment protocol based on severity of soft tissue injury

One hundred seven pilon fractures in 107 patients were treated according to a staged prospective protocol. All pilon fractures were stabilized immediately by the application of calcaneal traction. Open fractures or fractures in patients with multiple injuries were stabilized with traveling traction that was applied in the operating room. A distraction computed tomography scan was obtained before definitive treatment. Treatment groups were based on the degree of soft tissue compromise. Forty-one patients with Tscherne Grade 0 or Grade I injuries underwent open reduction and internal fixation (open plating) using contemporary techniques and low-profile implants. Sixty-four patients with Tscherne Grade II and Grade III closed injuries and all patients with open fractures underwent definitive treatment with limited open reduction and stabilization using small wire circular external fixators. Clinical and radiographic evaluations were performed at an average 4.9 years after injury. For all fracture types (AO classification), 81% of the patients who were treated with external fixation and 75% of the patients who were treated with open plating had good or excellent results. For severe fracture patterns (Type C), patients in both groups had significantly poorer results than patients with Types A and B fractures. The patients in the open plating group had a significantly higher rate of nonunion, malunion, and severe wound complications compared with the patients who received external fixation for Type C fracture patterns. Because of the increased incidence of bony and soft tissue complications when treating open or closed Type C fractures, use of limited exposures and stabilization with small wire circular external fixators is recommended.