Patterns of Brain Injury in Newborns Treated with Extracorporeal Membrane Oxygenation.

BACKGROUND AND PURPOSE: Neonates treated with extracorporeal membrane oxygenation are at risk for brain injury and subsequent neurodevelopmental compromise. Advances in MR imaging and improved accessibility have led to the increased use of routine MR imaging after extracorporeal membrane oxygenation. Our objective was to describe the frequency and patterns of extracorporeal membrane oxygenation-related brain injury based on MR imaging findings in a large contemporary cohort of neonates treated with extracorporeal membrane oxygenation. MATERIALS AND METHODS: This was a retrospective study of neonatal patients treated with extracorporeal membrane oxygenation from 2005-2015 who underwent MR imaging before discharge. MR imaging and ultrasound studies were reviewed for location and type of parenchymal injury, ventricular abnormalities, and increased subarachnoid spaces. Parenchymal injury frequencies between patients treated with venoarterial and venovenous extracorporeal membrane oxygenation were compared by χ2 tests. RESULTS: Of 81 neonates studied, 46% demonstrated parenchymal injury; 6% showed infarction, mostly in vascular territories (5% anterior cerebral artery, 5% MCA, 1% posterior cerebral artery); and 20% had hemorrhagic lesions. The highest frequency of injury occurred in the frontal (right, 24%; left, 25%) and temporoparietal (right, 14%; left, 19%) white matter. Sonography had low sensitivity for these lesions. Other MR imaging findings included volume loss (35%), increased subarachnoid spaces (44%), and ventriculomegaly (17% mild, 5% moderate, 1% severe). There were more parenchymal injuries in neonates treated with venoarterial (49%) versus venovenous extracorporeal membrane oxygenation (29%, P = .13), but the pattern of injury was consistent between both modes. CONCLUSIONS: MR imaging identifies brain injury in nearly half of neonates after treatment with extracorporeal membrane oxygenation. The frontal and temporoparietal white matter are most commonly affected, without statistically significant laterality. This pattern of injury is similar between venovenous and venoarterial extracorporeal membrane oxygenation, though the frequency of injury may be higher after venoarterial extracorporeal membrane oxygenation.

Distal radius fracture fixation with volar locking plates and additional bone augmentation in osteoporotic bone: a biomechanical study in a cadaveric model.

BACKGROUND: Fractures of the distal radius represent the most common fractures in adults. Volar locked plating has become a popular method for treating these fractures, but has been subject to several shortcomings in osteoporotic bone, such as loss of reduction and screw purchase. In order to overcome these shortcomings, cement augmentation has been proposed. METHODS: AO-type 23-A3.3 fractures were made in 8 pairs of fresh frozen osteoporotic cadaveric radial bones. All specimens were treated with volar plating, and divided into cement augmentation or non-augmentation groups (n = 8/group). Constructs were tested dynamically and load to failure, construct-stiffness, fracture gap movement and screw cutting distance were measured. RESULTS: Cement augmentation resulted in a significant increase in cycles and load to failure, as well as construct stiffness at loads higher than 325 N. When compared to the non-augmented group, fracture gap movement decreased significantly at this load and higher, as did screw cutting distance at the holes of the ulnar column. The cycles to failure depend on the BMD in the distal region of the radius. CONCLUSION: Cement augmentation improves biomechanical properties in volar plating of the distal radius.

A biomechanical evaluation of orthopaedic implants for hip fractures by finite element analysis and in-vitro tests.

The aim of this study was to test the hypothesis that a reinforced gamma nail for the fixation of subtrochanteric fractures would experience less stress during loading compared with a common gamma nail. The issue of whether the use of the stronger implant would result in more stress shielding in the surrounding bone was also addressed. A finite element analysis (FEA) of a synthetic bone was employed to calculate the stress distribution in implant and bone for two fracture types (AO 31-A3.1 and AO 31-A3.3). The FEA was validated by mechanical tests on six synthetic femurs. To test the hypothesis in vitro, mechanical tests on six pairs of fresh-frozen human femurs were conducted. The femurs were supplied with a common or a reinforced gamma nail in a cross-over study design. Strains were measured on the nail shaft to quantify the loading of the nail. The FEA resulted in 3-51 per cent lower stresses for the reinforced gamma nail. No increase in stress shielding could be observed. In the in-vitro tests, the reinforced gamma nail experienced less strain during loading (p < 0.016). The study demonstrated the benefit of a reinforced gamma nail in subtrochanteric fractures. It experienced less stress but did not result in more stress shielding.

The stability of a hip fracture determines the fatigue of an intramedullary nail.

The purpose of this study was to address the question of how the stability of a proximal hip fracture determines the fatigue and failure mechanism of an intramedullary implant. To answer this question, mechanical experiments and finite element simulations with two different loading scenarios were conducted. The two load scenarios differed in the mechanical support of the fracture by an artificial bone sleeve, representing the femoral head and neck. The experiments confirmed that an intramedullary nail fails at a lower load in an unstable fracture situation in the proximal femur than in a stable fracture. The nails with an unstable support failed at a load 28 per cent lower than the nails with a stable support by the femoral neck. Hence, the mechanical support of a fracture is crucial to the fatigue failure of an implant. The simulation showed why the fatigue fracture of the nail starts at the aperture of the lag screw. It is the location of the highest von Mises stress, which is the failure criterion for ductile materials.

Targeted, PCR-based gene disruption in cyanobacteria: inactivation of the polyhydroxyalkanoic acid synthase genes in Synechocystis sp. PCC6803.

A PCR-based method is described for the efficient construction of targeted gene disruptions and gene fusions in the cyanobacterium Synechocystis sp. PCC6803. In a simple two-step PCR approach, a gene conversion cassette was synthesized targeting the polyhydroxyalkanoic acid (PHA) synthase genes. Upon transformation, PHA production in Synechocystis under normal as well as high production culture conditions was undetectable. The application of this method to the genetic inactivation of the phaE-C(Syn) gene cluster demonstrates its potential for genetic engineering of cyanobacteria and the study of functional genomics in Synechocystis.

Identification and analysis of the polyhydroxyalkanoate-specific beta-ketothiolase and acetoacetyl coenzyme A reductase genes in the cyanobacterium Synechocystis sp. strain PCC6803.

Synechocystis sp. strain PCC6803 possesses a polyhydroxyalkanoate (PHA)-specific beta-ketothiolase encoded by phaA(Syn) and an acetoacetyl-coenzyme A (CoA) reductase encoded by phaB(Syn). A similarity search of the entire Synechocystis genome sequence identified a cluster of two putative open reading frames (ORFs) for these genes, slr1993 and slr1994. Sequence analysis showed that the ORFs encode proteins having 409 and 240 amino acids, respectively. The two ORFs are colinear and most probably coexpressed, as revealed by sequence analysis of the promoter regions. Heterologous transformation of Escherichia coli with the two genes and the PHA synthase of Synechocystis resulted in accumulation of PHAs that accounted for up to 12.3% of the cell dry weight under high-glucose growth conditions. Targeted disruption of the above gene cluster in Synechocystis eliminated the accumulation of PHAs. ORFs slr1993 and slr1994 thus encode the PHA-specific beta-ketothiolase and acetoacetyl-CoA reductase of Synechocystis and, together with the recently characterized PHA synthase genes in this organism (S. Hein, H. Tran, and A. Steinbüchel, Arch. Microbiol. 170:162-170, 1998), form the first complete PHA biosynthesis pathway known in cyanobacteria. Sequence alignment of all known short-chain-length PHA-specific acetoacetyl-CoA reductases also suggests an extended signature sequence, VTGXXXGIG, for this group of proteins. Phylogenetic analysis further places the origin of phaA(Syn) and phaB(Syn) in the gamma subdivision of the division Proteobacteria.

Identification and characterization of three differentially expressed genes, encoding S-adenosylhomocysteine hydrolase, methionine aminopeptidase, and a histone-like protein, in the toxic dinoflagellate Alexandrium fundyense.

Genes showing differential expression related to the early G(1) phase of the cell cycle during synchronized circadian growth of the toxic dinoflagellate Alexandrium fundyense were identified and characterized by differential display (DD). The determination in our previous work that toxin production in Alexandrium is relegated to a narrow time frame in early G(1) led to the hypothesis that transcriptionally up- or downregulated genes during this subphase of the cell cycle might be related to toxin biosynthesis. Three genes, encoding S-adenosylhomocysteine hydrolase (Sahh), methionine aminopeptidase (Map), and a histone-like protein (HAf), were isolated. Sahh was downregulated, while Map and HAf were upregulated, during the early G(1) phase of the cell cycle. Sahh and Map encoded amino acid sequences with about 90 and 70% similarity to those encoded by several eukaryotic and prokaryotic Sahh and Map genes, respectively. The partial Map sequence also contained three cobalt binding motifs characteristic of all Map genes. HAf encoded an amino acid sequence with 60% similarity to those of two histone-like proteins from the dinoflagellate Crypthecodinium cohnii Biecheler. This study documents the potential of applying DD to the identification of genes that are related to physiological processes or cell cycle events in phytoplankton under conditions where small sample volumes represent an experimental constraint. The identification of an additional 21 genes with various cell cycle-related DD patterns also provides evidence for the importance of pretranslational or transcriptional regulation in dinoflagellates, contrary to previous reports suggesting the possibility that translational mechanisms are the primary means of circadian regulation in this group of organisms.

Coupling of saxitoxin biosynthesis to the G1 phase of the cell cycle in the dinoflagellate Alexandrin fundyense: temperature and nutrient effects.

The correlation between changes in length of the different cell cycle stages and the toxicity of Alexandrium fundyense Balech was studied in semi-continuous cultures. Growth rates ranging from 0.031 d(-1) to 0.36 d(-1) were established at different temperatures or levels of phosphate limitation. In all treatments, G1 was the phase with the longest duration. Decrease in growth rate was associated with an increase in duration of the different cell cycle stages. Toxin content was always directly correlated to the duration of the G1 phase. In both the temperature treatments and the phosphate limitation experiments, toxin production rates remained constant for the respective range of conditions, implying that the variations in toxin content observed were a result of increasing periods of biosynthetic activity. Toxin accumulation was directly correlated to protein biosynthesis in all temperature treatments. In contrast, toxin content showed little correlation with protein content as phosphate limitation increased. Significant differences in toxin composition were observed between the temperature and phosphate treatments. Total concentrations of GTX II and III and C I and II were significantly higher in the phosphate-limited cultures, while the levels of STX, NEO and gonyautoxins I and IV remained virtually unchanged. We conclude that toxin biosynthesis in A. fundyense is coupled to the G1 phase of the cell cycle, that toxin synthesis is not down-regulated by phosphate deprivation and that interconversions among saxitoxin derivatives are influenced by the availability of phosphate.

[Osmolar and mechanic resistance of erythrocytes in chronic liver diseases]. / Die osmotische und mechanische Resistenz der Erythrozyten bei chronischen Lebererkrankungen

Out of 120 patients with chronic liver diseases (45 liver cirrhosis, 38 chronic hepatitis, 15 fatty degeneration of the liver and 22 stasis liver) the osmotic resistance of the erythrocytes after Hennemann and the mechanic resistance after Schubothe was determined. 24% of the patients had a decreased osmotic resistance of the erythrocytes, even 55% a decreased incubation resistance. 16% of the patients with liver diseases had a decreased mechanic resistance of the erythrocytes. The comparison of the groups of disease and the stages of the diseases resulted in an increased mechanical resistance of the erythrocytes only for the decompensated liver cirrhosis. A positive correlation was the result between the degree of the haemolysis and the spherical index of the erythrocytes.

[Patholgenesis of anemias in chronic liver diseases]. / Zur Pathogenese der Anämien bei chronischen Lebererkrankungen

In a complex examination of clinically healthy persons, with postprandial glucosuria or affected with a hereditary diabetes mellitus differences were found in the dynamics of the insulin secretion in oral and venous glucose tolerance dependent on the character of the glucose tolerance. With the deterioration of the latter the insulinaemia increase and prolongs in oral tolerance, in venous tolerance, however, it will be lower and lower. The through analysis of the results refers to the pathogenetic role of the peripheral resistance to the insulin as well as the disturbed secretory function of the islet apparatus. The established connections allow of the derivation of pathogenetically proved criteria for the differentiation of normal, subnormal and pathologic glucose tolerance. The confronting of the insulinaemia with the adiposity of the persons examined detects the fundamental difference between persons with normal and disturbed carbohydrate tolerance. The increase of weight contributes to the manifestation of the genetic defect. From the prophylactic point of view apart from the significance of the adequate dietetic regimen the attention is also drawn to the effect of biguanides.