Rehabilitation bei Kindern und Jugendlichen mit Diabetes mellitus

Background

Medical rehabilitation plays a special role in the treatment of children and adolescents with diabetes mellitus: services which are difficult to implement in an out-patient or an acute in-patient setting can be provided. The study analyzed changes over a period of 12 years.

Methods

In a monocentric, retrospective cross-sectional analysis, all (n = 2001) children and adolescents with diabetes (52% girls, age 12.6 ± 4.9 years) who were admitted to a specialist clinic for rehabilitation during the period 01/2004–12/2016 were examined.

Results

The duration of medical rehabilitation was 27.3 ± 6.1 days. In all, 1980 of 2001 (98.9%) children and adolescents had type 1 diabetes, while 21 of 2001 (1.1%) had type 2 diabetes. Mean HbA1c was 7.87 ± 1.47%. Overall, 1897 of 2001 (95%) patients had an intensified insulin therapy, of which 633 (32%) used insulin pumps (CSII). They injected 0.86 ± 0.47?I.?U. insulin/kg body weight/day and performed 37.6 ± 11.4 blood glucose self-tests/week. The number of patients who participated in medical rehabilitation decreased: In 2016 it was 68% lower than in 2007, the year of the highest number of patients (p < 0.05). Parameters of metabolic control hardly changed. The proportion of patients with CSII increased (p < 0.05). In particular, young children used CSII more frequently (59% in <4 year olds vs 24% in 16–17 year olds, p < 0.05). Changes also occurred in cultural status: The percentage of patients from German families decreased (p < 0.05); the proportion of patients from mixed-cultural families increased (p < 0.05). The number of patients living together with both parents also decreased (p < 0.05 for the tendency); the number of patients living with single parents increased (p < 0.05 for the tendency). In young children, HbA1c values were the lowest. From the beginning of puberty (about 10 years), HbA1c increased (8.5 ± 1.9% in 16–17 year olds). There were no correlations/associations between metabolic control and the incidences of hypoglycemia/ketoacidoses.

Conclusions

There has been a change in medical rehabilitation: The number of patients has decreased, the proportion of patients using CSII has increased, the number of patients living with single parents and the percentage of patients from a culturally mixed families has also increased. Thus, there are new challenges in medical rehabilitation.

     

Wie häufig werden Patienten mit depressiven Störungen in der hausärztlichen Praxis erkannt?

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Hausärzte sind als Primärversorger für Patienten mit depressiven Störungen entscheidende Weichensteller...     

Tabakassoziierte Krebserkrankungen in Deutschland – Entwicklung der Inzidenz und Mortalität seit 1995

Background and Objectives

Tobacco consumption is the most important cancer risk factor. In Germany, about 15% of all new cancer cases can be attributed to smoking. The aim of this paper is to analyze the incidence and mortality trends in tobacco-associated cancer cases in Germany for the last two decades.

Materials and Methods

Age standardized incidence and mortality rates were calculated for tumors of the upper aerodigestive tract and lower urinary tract for the period from 1995 to 2014/2015. In addition, average annual percentage changes were calculated with joinpoint regression analysis. Regarding lung cancer, trends in incidence and mortality rates were also stratified by different age groups and trends in mortality rates were analyzed by birth cohorts.

Results

The incidence and mortality rates among men are declining for all tobacco-associated cancers except esophageal cancer. Lung cancer mortality rates showed the greatest decrease with ?1.9% on average per year. The incidence rates among women increased for all tobacco-associated cancers except lower urinary tract cancers. The increase in lung cancer incidence was greatest with 3.3% on average per year. Among men there was a continuous decline over all birth cohorts regarding the chance of dying of lung cancer at a certain age. Among women, the chance of dying of lung cancer increased for all birth cohorts until 1960.

Conclusions

The present analyses regarding tobacco-associated cancers in Germany reflect the changes in smoking prevalence with a deferment of multiple decades.

     

Differently designed playgrounds and preschooler’s physical activity play

New playground concepts – favouring natural play characteristics – emerge. The aim of our free play study is to explore the relation between newly established natural playgrounds and the widely spread contemporary ones in terms of physical activity levels. The playground features differ in vegetation, topography, size and play equipment. The children’s locomotive activity was measured with the StepWatch? Activity Monitor – a pedometer. Research with known groups of preschool children on urban playgrounds should serve a future transfer of results to institutional play areas. Within this pilot study, results indicate that there is no significant difference in mean locomotive activity during free play on diverse playgrounds. However, results show high variability of activity between the playgrounds in terms of active children and rather sedentary ones. In conclusion, kindergarten environments should be more diverse incorporating elements of nature and contemporary playgrounds to serve all levels of activity.     

The role of Müller cell glucocorticoid signaling in diabetic retinopathy

Graefe's Archive for Clinical and Experimental Ophthalmology - Diabetic retinopathy (DR) is a sight-threatening complication associated with the highly prevalent diabetes disorder. Both the...     

Triple (GGTA1, CMAH,B2M) modified pigs expressing an SLA class Ilow phenotype—Effects on immune status and susceptibility to human immune responses

Porcine xenografts lacking swine leukocyte antigen (SLA) class I are thought to be protected from human T cell responses. We have previously shown that SLA class I deficiency can be achieved in pigs by CRISPR/Cas9‐mediated deletion of β₂‐microglobulin (B2M). Here, we characterized another line of genetically modified pigs in which targeting of the B2M locus did not result in complete absence of B2M and SLA class I but rather in significantly reduced expression levels of both molecules. Residual SLA class I was functionally inert, because no proper differentiation of the CD8⁺ T cell subset was observed in B2M^low pigs. Cells from B2M^low pigs were less capable in triggering proliferation of human peripheral blood mononuclear cells in vitro, which was mainly due to the nonresponsiveness of CD8⁺ T cells. Nevertheless, cytotoxic effector cells developing from unaffected cell populations (eg, CD4⁺ T cells, natural killer cells) lysed targets from both SLA class I⁺ wildtype and SLA class I^low pigs with similar efficiency. These data indicate that the absence of SLA class I is an effective approach to prevent the activation of human CD8⁺ T cells during the induction phase of an anti‐xenograft response. However, cytotoxic activity of cells during the effector phase cannot be controlled by this approach.     

Molecular diagnosis of kidney transplant failure based on urine

In light of the organ shortage, there is a great responsibility to assess postmortal organs for which procurement has been consented and to increase the life span of transplanted organs. The former responsibility has moved many centers to accept extended criteria organs. The latter responsibility requires an exact diagnosis and, if possible, omission of the harmful influence on the transplant. We report the course of a kidney transplant that showed a steady decline of function over a decade, displaying numerous cysts of different sizes. Clinical workup excluded the most frequent causes of chronic transplant failure. The filed allocation documents mentioned the donor’s disease of oral‐facial‐digital syndrome, a rare ciliopathy, which can also affect the kidney. Molecular diagnosis was performed by culturing donor tubular cells from the recipient´s urine more than 10 years after transplantation. Next‐generation panel sequencing with DNA from tubular urinary cells revealed a novel truncating mutation in OFD1, which sufficiently explains the features of the kidney transplants, also found in the second kidney allograft. Despite this severe donor disease, lifesaving transplantation with good long‐term outcome was enabled for 5 recipients.     

TMPRSS2-ERG Fusions Are Strongly Linked to Young Patient Age in Low-grade Prostate Cancer

Based on next-generation sequencing of early-onset prostate cancer (PCa), we earlier demonstrated that PCa in young patients is prone to rearrangements involving androgen-regulated genes—such as transmembrane protease, serine 2 (TMPRSS2)–v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion—and provided data suggesting that this situation might be caused by increased androgen signaling in younger men. In the same study, an accumulation of chromosomal deletions was found in cancers of elderly patients. To determine how age-dependent molecular features relate to cancer phenotype, an existing data set of 11 152 PCas was expanded by additional fluorescence in situ hybridization analyses of phosphatase and tensin homolog (PTEN), 6q15 and 5q21. The results demonstrate that the decrease in TMPRSS2–ERG fusions with increasing patient age is limited to low-grade cancers (Gleason ≤3 + 4) and that the significant increase in the deletion frequency with age was strictly limited to ERG-negative cancers for 6q15 and 5q21 but to ERG-positive cancers for PTEN. These data suggest that the accumulation of non–androgen-linked genomic alterations with advanced patient age may require an appropriate microenvironment, such as a positive or negative ERG status. The strong link of ERG activation to young patient age and low-grade cancers may help to explain a slight predominance of low-grade cancers in young patients.     

Population pharmacokinetics of artesunate and dihydroartemisinin during long-term oral administration of artesunate to patients with metastatic breast cancer

Purpose

The purpose of this study were firstly to characterize the population pharmacokinetics of artesunate (ARS) and its active metabolite dihydroartemisinin (DHA) in patients with metastatic breast cancer during long-term (>3 weeks) daily oral ARS administration and secondly to study the relationship between salivary and plasma concentrations of DHA.

Methods

Drug concentration-time data from 23 patients, receiving oral ARS (100, 150, or 200 mg OD), was analyzed using nonlinear mixed effects modeling. A combined drug-metabolite population pharmacokinetic model was developed to describe the plasma pharmacokinetics of ARS and DHA in plasma. Saliva drug concentrations were incorporated as being directly proportional to plasma concentrations.

Results

A first-order absorption model for ARS linked to a combined two-compartment disposition model for ARS and one-compartment disposition model for DHA provided the best fit to the data. No covariates were identified that could explain between-subject variability. A time-dependent increase in apparent elimination clearance of DHA was observed. Salivary DHA concentrations were proportionally correlated with total DHA plasma concentrations, with an estimated slope factor of 0.116.

Conclusions

Population pharmacokinetics of ARS and DHA in patients with breast cancer was well described by a combined drug-metabolite model without any covariates and with an increase in apparent elimination clearance of DHA over time. The estimated DHA saliva/plasma ratio was in good agreement with the reported DHA unbound fraction in human plasma. Saliva ARS concentrations correlated poorly with plasma concentrations. This suggests the use of saliva sampling for therapeutic drug monitoring of DHA. However, further studies are warranted to investigate the robustness of this approach.     

The starch-related R1 protein is an alpha -glucan,water dikinase

To determine the enzymatic function of the starch-related R1 protein it was heterologously expressed in Escherichia coli and purified to apparent homogeneity. Incubation of the purified protein with various phosphate donor and acceptor molecules showed that R1 is capable of phosphorylating glucosyl residues of alpha-glucans at both the C-6 and the C-3 positions in a ratio similar to that occurring naturally in starch. Phosphorylation occurs in a dikinase-type reaction in which three substrates, an alpha-polyglucan, ATP, and H(2)O, are converted into three products, an alpha-polyglucan-P, AMP, and orthophosphate. The use of ATP radioactively labeled at either the gamma or beta positions showed that solely the beta phosphate is transferred to the alpha-glucan. The apparent K(m) of the R1 protein for ATP was calculated to be 0.23 microM and for amylopectin 1.7 mg x ml(-1). The velocity of in vitro phosphorylation strongly depends on the type of the glucan. Glycogen was an extremely poor substrate; however, the efficiency of phosphorylation strongly increased if the glucan chains of glycogen were elongated by phosphorylase. Mg(2+) ions proved to be essential for activity. Incubation of R1 with radioactively labeled ATP in the absence of an alpha-glucan showed that the protein phosphorylates itself with the beta, but not with the gamma phosphate. Autophosphorylation precedes the phosphate transfer to the glucan indicating a ping-pong reaction mechanism.