[Depressed fractures of the base of the middle phalanges of the fingers : Evaluation of a percutaneous, intramedullary surgical technique]. / Mittelgliedbasisimpressionsfrakturen der Finger : Evaluation eines perkutanen, intramedullären Operationsverfahrens.

BACKGROUND: Depressed fractures of the base of the middle phalanges are problematic because of frequent subluxations and centrally depressed fragments. There are two minimally invasive procedures available: 1) the less known intramedullary padding technique according to Hintringer and 2) the widely used distraction fixator of Suzuki. This article describes the technique and outcome of these two procedures. METHODOLOGY: The follow-up collective included 42 patients after treatment of a depressed fracture of the base of the middle phalanx. An intramedullary padding with percutaneous Kirschner wire retention was performed 28 times (group A) and treatment with a Suzuki fixator 14 times (group B). The study examined the hand function, the radiological results and the subjective pain level. RESULTS: According to the American Society for Surgery of the Hand (ASSH) classification 81% of the patients in group A achieved a good result but in group B the same result was achieved by only 50% of the patients. The median range of movement in the proximal interphalangeal joint was 82.5° after intramedullary padding and 47.5° after Suzuki fixator. In median, the impression was reduced from 2.35 mm to 0.5 mm in group A, but only from 1.6 mm to 1.15 mm in group B. Pain was a limiting factor in 2 out of 28 patients in group A and 1 out of 14 patients in group B. CONCLUSION: The intramedullary padding technique according to Hintringer enables good treatment of depressed fractures of the base of the middle phalanx of the finger. Repositioning of dorsal subluxations can be performed and centrally impressed fragments can be reduced better than by using the Suzuki dynamic fixator. In addition, the radiological course assessments can be assessed better than with the distraction fixator.

[Treatment of flexor tendon injuries in children]. / Behandlung von Beugesehnenverletzungen bei Kindern.

Injuries to the flexor tendons in children are less common than in adults. The clinical examination and diagnostics require extensive experience. Leaving flexor tendons untreated will result in growth disorders of the affected finger. Therefore, the indications for operative exploration of any type of open injury in a child's hand should be liberally applied. As for adults the primary treatment of flexor tendon injuries as an emergency is rarely indicated. In the recent literature various tendon suture techniques and rehabilitation protocols have been differently assessed. According to the Ulm algorithm flexor tendon injuries in children are treated by a 2-strand core stitch technique followed by a continuous circular suture. Children under 6 years of age are postoperatively immobilized for 3 weeks with a fist bandage. Children older than 6 years are treated like adults with a dynamic aftercare as described by Kleinert for 5 weeks. The results are comparable with those of other aftercare protocols.

Endosomal-Lysosomal Cholesterol Sequestration by U18666A Differentially Regulates Amyloid Precursor Protein (APP) Metabolism in Normal and APP-Overexpressing Cells.

Amyloid ß (Aß) peptide, derived from amyloid precursor protein (APP), plays a critical role in the development of Alzheimer's disease. Current evidence indicates that altered levels or subcellular distribution of cholesterol can regulate Aß production and clearance, but it remains unclear how cholesterol sequestration within the endosomal-lysosomal (EL) system can influence APP metabolism. Thus, we evaluated the effects of U18666A, which triggers cholesterol redistribution within the EL system, on mouse N2a cells expressing different levels of APP in the presence or absence of extracellular cholesterol and lipids provided by fetal bovine serum (FBS). Our results reveal that U18666A and FBS differentially increase the levels of APP and its cleaved products, the α-, ß-, and η-C-terminal fragments, in N2a cells expressing normal levels of mouse APP (N2awt), higher levels of human wild-type APP (APPwt), or "Swedish" mutant APP (APPsw). The cellular levels of Aß1-40/Aß1-42 were markedly increased in U18666A-treated APPwt and APPsw cells. Our studies further demonstrate that APP and its cleaved products are partly accumulated in the lysosomes, possibly due to decreased clearance. Finally, we show that autophagy inhibition plays a role in mediating U18666A effects. Collectively, these results suggest that altered levels and distribution of cholesterol and lipids can differentially regulate APP metabolism depending on the nature of APP expression.

The Effects of Extracellular Serum Concentration on APP Processing in Npc1-Deficient APP-Overexpressing N2a Cells.

Amyloid precursor protein (APP) is cleaved by a set of proteases including α-/ß-/γ- and recently identified η-secretases, generating C-terminal fragments (CTFs) of varying lengths and amyloid ß (Aß) peptides, which are considered to play a pivotal role in Alzheimer's disease (AD) pathogenesis. Cellular cholesterol content/distribution can regulate the production/clearance of APP metabolites and hence modify AD pathology. To determine the functional relation between endosomal-lysosomal (EL) cholesterol sequestration and APP metabolism, we used our recently developed mouse N2a-ANPC cells that overexpress Swedish mutant human APP in the absence of cholesterol-trafficking Niemann-Pick type C1 (Npc1) protein. Here, we report that neither increased levels nor EL cholesterol sequestration altered APP holoprotein levels but caused the intracellular accumulation of APP α-/ß-/η-CTFs and Aß1-40/42 peptides. The levels of APP-cleaved products increased as a function of extracellular serum concentration in N2a-ANPC cells, which are more vulnerable to death than the control cells. Additionally, we show that pH of the lysosomal vesicles in N2a-ANPC cells shifted to a less acidic range with increasing serum concentrations, thus making them less efficient functionally. Interestingly, the addition of cholesterol to the culture media not only increased the levels of cellular cholesterol and APP-cleaved products but also rendered the cells more vulnerable to toxicity. Collectively, our results suggest that extracellular cholesterol concentration in serum under conditions of Npc1 deficiency can influence intracellular cholesterol content/distribution and lysosomal efficacy, triggering the accumulation of toxic APP-cleaved products, eventually leading to cell death.

Characterisation of proteins differentially present in the plasma of Biomphalaria glabrata susceptible or resistant to Echinostoma caproni.

Snail immune responses towards a trematode infection are known to rely on both plasmatic and cellular host factors. As an approach to further investigate the suspected involvement of plasmatic factors in Biomphalaria glabrata resistance/susceptibility to Echinostoma caproni, we compared protein patterns of plasma collected from susceptible and resistant snails. This proteomic approach revealed that 13 plasmatic proteins exhibited significant differences in their apparent representativity. The genes corresponding to five of them were characterised by a combination of mass spectrometry and molecular cloning. They encode two isoforms of a glycolytic enzyme, two isoforms of a calcium binding protein and an inhibitor of cysteine protease. Furthermore, we investigated gene expression in parasite-exposed or -unexposed snails as well as in various tissues by quantitative PCR. This study showed that: (i) differential representation of plasma proteins between the snail strains was correlated with a differential level of transcripts; (ii) expression of these genes after parasite exposure was differentially regulated in the two strains; and (iii) these genes were expressed predominantly in the albumen gland.