Disorders of serum sodium in emergency patients: salt in the soup of emergency medicine

Electrolyte disorders are common and potentially fatal laboratory findings in emergency patients. Approximately 20 % of patients in the emergency department present with either hyponatremia or hypernatremia. Recently it was shown that disorders of serum sodium are not only an expression of the severity of the underlying disease but independent predictors for the outcome of patients. They directly influence patient daily life by causing not only gait and concentration disturbances but also an increased tendency to fall together with a reduced bone mass. Given these new data it is even more important to detect and adequately correct dysnatremia in patients in the emergency department. Acute, symptomatic dysnatremia should be corrected promptly by use of 3 % NaCl for hyponatremia and 5 % glucose for hypernatremia. A close monitoring of serum sodium concentration is, however, essential in any case of correction of hyponatremia or hypernatremia in order to avoid rapid overcorrection and subsequent complications. A profound knowledge of the mechanisms underlying the development of hyponatremia, e.g. diuretics, syndrome of inappropriate antidiuretic hormone secretion (SIADH), heart failure and cirrhosis of the liver and hypernatremia, e.g. dehydration, infusions, diuretics and osmotic diuresis is essential. The present article describes the epidemiology, etiology and correction of hyponatremia and hypernatremia on the basis of current knowledge with special emphasis on emergency department patients.

Evaporation of free water causes concentrational alkalosis in vitro

BACKGROUND The development of metabolic alkalosis was described recently in patients with hypernatremia. However, the causes for this remain unknown. The current study serves to clarify whether metabolic alkalosis develops in vitro after removal of free water from plasma and whether this can be predicted by a mathematical model. MATERIALS AND METHODS Ten serum samples of healthy humans were dehydrated by 29 % by vacuum centrifugation corresponding to an increase of the contained concentrations by 41 %. Constant partial pressure of carbon dioxide at 40 mmHg was simulated by mathematical correction of pH [pH(40)]. Metabolic acid-base state was assessed by Gilfix' base excess subsets. Changes of acid-base state were predicted by the physical-chemical model according to Watson. RESULTS Evaporation increased serum sodium from 141 (140-142) to 200 (197-203) mmol/L, i.e., severe hypernatremia developed. Acid-base analyses before and after serum concentration showed metabolic alkalosis with alkalemia: pH(40): 7.43 (7.41 to 7.45) vs 7.53 (7.51 to 7.55), p = 0.0051; base excess: 1.9 (0.7 to 3.6) vs 10.0 (8.2 to 11.8), p = 0.0051; base excess of free water: 0.0 (- 0.2 to 0.3) vs 17.7 (16.8 to 18.6), p = 0.0051. The acidifying effects of evaporation, including hyperalbuminemic acidosis, were beneath the alkalinizing ones. Measured and predicted acid-base changes due to serum evaporation agreed well. CONCLUSIONS Evaporation of water from serum causes concentrational alkalosis in vitro, with good agreement between measured and predicted acid-base values. At least part of the metabolic alkalosis accompanying hypernatremia is independent of renal function.

Improved Localization of Implanted Subdural Electrode Contacts on MRI Using an Elastic Image Fusion Algorithm in Invasive EEG Recording

BACKGROUND: Accurate projection of implanted subdural electrode contacts in presurgical evaluation of pharmacoresistant epilepsy cases by invasive EEG is highly relevant. Linear fusion of CT and MRI images may display the contacts in the wrong position due to brain shift effects. OBJECTIVE: A retrospective study in five patients with pharmacoresistant epilepsy was performed to evaluate whether an elastic image fusion algorithm can provide a more accurate projection of the electrode contacts on the pre-implantation MRI as compared to linear fusion. METHODS: An automated elastic image fusion algorithm (AEF), a guided elastic image fusion algorithm (GEF), and a standard linear fusion algorithm (LF) were used on preoperative MRI and post-implantation CT scans. Vertical correction of virtual contact positions, total virtual contact shift, corrections of midline shift and brain shifts due to pneumencephalus were measured. RESULTS: Both AEF and GEF worked well with all 5 cases. An average midline shift of 1.7mm (SD 1.25) was corrected to 0.4mm (SD 0.8) after AEF and to 0.0mm (SD 0) after GEF. Median virtual distances between contacts and cortical surface were corrected by a significant amount, from 2.3mm after LF to 0.0mm after AEF and GEF (p<.001). Mean total relative corrections of 3.1 mm (SD 1.85) after AEF and 3.0mm (SD 1.77) after GEF were achieved. The tested version of GEF did not achieve a satisfying virtual correction of pneumencephalus. CONCLUSION: The technique provided a clear improvement in fusion of pre- and post-implantation scans, although the accuracy is difficult to evaluate.

Stacking of discontinuous regional palaeoclimate records: Chironomid-based summer temperatures from the Alpine region

Since multi-site reconstructions are less affected by site-specific climatic effects and artefacts, regional palaeotemperature reconstructions based on a number of sites can provide more robust estimates of centennial- to millennial-scale temperature trends than individual, site-specific records. Furthermore, reconstructions based on multiple records are necessary for developing continuous climate records over time scales longer than covered by individual sequences. Here, we present a procedure for developing such reconstructions based on relatively short (centuries to millennia), discontinuously sampled records as are typically developed when using biotic proxies in lake sediments for temperature reconstruction. The approach includes an altitudinal correction of temperatures, an interpolation of individual records to equal time intervals, a stacking procedure for sections of the interval of interest that have the same records available, as well as a splicing procedure to link the individual stacked records into a continuous reconstruction. Variations in the final, stacked and spliced reconstruction are driven by variations in the individual records, whereas the absolute temperature values are determined by the stacked segment based on the largest number of records. With numerical simulations based on the NGRIP δ18O record, we demonstrate that the interpolation and stacking procedure provides an approximation of a smoothed palaeoclimate record if based on a sufficient number of discontinuously sampled records. Finally, we provide an example of a stacked and spliced palaeotemperature reconstruction 15000–90 calibrated 14C yr BP based on six chironomid records from the northern and central Swiss Alps and eastern France to discuss the potential and limitations of this approach.

Diagnosis and management of developmental dysplasia of the hip from triradiate closure through young adulthood

Abstract The current treatment of painful hip dysplasia in the mature skeleton is based on acetabular reorientation. Reorientation procedures attempt to optimize the anatomic position of the hyaline cartilage of the femoral head and acetabulum in regard to mechanical loading. Because the Bernese periacetabular osteotomy is a versatile technique for acetabular reorientation, it is helpful to understand the approach and be familiar with the criteria for an optimal surgical correction. The femoral side bears stigmata of hip dysplasia that may require surgical correction. Improvement of the head-neck offset to avoid femoroacetabular impingement has become routine in many hips treated with periacetabular osteotomy. In addition, intertrochanteric osteotomies can help improve joint congruency and normalize the femoral neck orientation. Other new surgical techniques allow trimming or reducing a severely deformed head, performing a relative neck lengthening, and trimming or distalizing the greater trochanter.  An increasing number of studies have reported good long-term results after acetabular reorientation procedures, with expected joint preservation rates ranging from 80% to 90% at the 10-year follow-up and 60% to 70% at the 20-year follow-up. An ideal candidate is younger than 30 years, with no preoperative signs of osteoarthritis. Predicted joint preservation in these patients is approximately 90% at the 20-year follow-up. Recent evidence indicates that additional correction of an aspheric head may further improve results.

Temperature dependence of postmortem MR quantification for soft tissue discrimination.

OBJECTIVES To investigate and correct the temperature dependence of postmortem MR quantification used for soft tissue characterization and differentiation in thoraco-abdominal organs. MATERIAL AND METHODS Thirty-five postmortem short axis cardiac 3-T MR examinations were quantified using a quantification sequence. Liver, spleen, left ventricular myocardium, pectoralis muscle and subcutaneous fat were analysed in cardiac short axis images to obtain mean T1, T2 and PD tissue values. The core body temperature was measured using a rectally inserted thermometer. The tissue-specific quantitative values were related to the body core temperature. Equations to correct for temperature differences were generated. RESULTS In a 3D plot comprising the combined data of T1, T2 and PD, different organs/tissues could be well differentiated from each other. The quantitative values were influenced by the temperature. T1 in particular exhibited strong temperature dependence. The correction of quantitative values to a temperature of 37 °C resulted in better tissue discrimination. CONCLUSION Postmortem MR quantification is feasible for soft tissue discrimination and characterization of thoraco-abdominal organs. This provides a base for computer-aided diagnosis and detection of tissue lesions. The temperature dependence of the T1 values challenges postmortem MR quantification. Equations to correct for the temperature dependence are provided. KEY POINTS • Postmortem MR quantification is feasible for soft tissue discrimination and characterization • Temperature dependence of the T1 values challenges the MR quantification approach • The results provide the basis for computer-aided postmortem MRI diagnosis • Diagnostic criteria may also be applied for living patients.

Antisense properties of tricyclo-DNA.

Tricyclo (tc)-DNA belongs to the class of conformationally constrained DNA analogs that show enhanced binding properties to DNA and RNA. We prepared tc-oligonucleotides up to 17 nt in length, and evaluated their binding efficiency and selectivity towards complementary RNA, their biological stability in serum, their RNase H inducing potential and their antisense activity in a cellular assay. Relative to RNA or 2'-O-Me-phosphorothioate (PS)-RNA, fully modified tc-oligodeoxynucleotides, 10-17 nt in length, show enhanced selectivity and enhanced thermal stability by approximately 1 degrees C/modification in binding to RNA targets. Tricyclodeoxyoligonucleotides are completely stable in heat-deactivated fetal calf serum at 37 degree C. Moreover, tc-DNA-RNA duplexes are not substrates for RNase H. To test for antisense effects in vivo, we used HeLa cell lines stably expressing the human beta-globin gene with two different point mutations in the second intron. These mutations lead to the inclusion of an aberrant exon in beta-globin mRNA. Lipofectamine-mediated delivery of a 17mer tc-oligodeoxynucleotide complementary to the 3'-cryptic splice site results in correction of aberrant splicing already at nanomolar concentrations with up to 100-fold enhanced efficiency relative to a 2'-O-Me-PS-RNA oligonucleotide of the same length and sequence. In contrast to 2'-O-Me-PS-RNA, tc-DNA shows antisense activity even in the absence of lipofectamine, albeit only at much higher oligonucleotide concentrations.

Only Neochordoplasty Achieves Physiological Trans-valvular Pressure Gradients After Repair Of Acute Posterior Leaflet Prolapse In Porcine Mitral Valves

Objective: Minimizing resection and preserving leaflet tissue has been previously shown to be beneficial for mitral valve function and leaflet kinematics after repair of acute posterior leaflet prolapse in porcine valves. We examined the effects of different additional methods of mitral valve repair (neochordoplasty, ring annuloplasty, edge-to-edge repair and triangular resection) on hemodynamics at different heart rates in an experimental model. Methods: Severe acute P2 prolapse was created in eight porcine mitral valves by resecting the posterior marginal chordae. Valve hemodynamics was quantified under pulsatile conditions in an in vitro heart simulator before and after surgical manipulation. Mitral regurgitation was corrected using four different methods of repair on the same valve: neochordoplasty with expanded polytetrafluoroethylene sutures alone and together with ring annuloplasty, edge-to-edge repair and triangular resection, both with non-restrictive annuloplasty. Residual mitral valve leak, trans-valvular pressure gradients, flow and cardiac output were measured at 60 and 80 beats/min. A validated statistical linear mixed model was used to analyze the effect of treatment. The p values were calculated using a two-sided Wald test. Results: Only neochordoplasty with expanded polytetrafluoroethylene sutures but without ring annuloplasty achieved similar hemodynamics compared to those of the native mitral valve (p range 0.071-0.901). Trans-valvular diastolic pressure gradients were within a physiologic range but significantly higher than those of the native valve following neochordoplasty with ring annuloplasty (p=0.000), triangular resection (p=0.000) and edge-to-edge repair (p=0.000). Neochordoplasty alone was significantly better in terms of hemodynamic than neochordoplasty with a ring annuloplasty (p=0.000). These values were stable regardless of heart rate or ring size. Conclusions: Neochordoplasty without ring annuloplasty is the only repair technique able to achieve almost native physiological hemodynamics after correction of leaflet prolapse in a porcine experimental model of acute chordal rupture.

Sensitivity of splice sites to antisense oligonucleotides in vivo.

A series of HeLa cell lines which stably express beta-globin pre-mRNAs carrying point mutations at nt 654, 705, or 745 of intron 2 has been developed. The mutations generate aberrant 5' splice sites and activate a common 3' cryptic splice site upstream leading to aberrantly spliced beta-globin mRNA. Antisense oligonucleotides, which in vivo blocked aberrant splice sites and restored correct splicing of the pre-mRNA, revealed major differences in the sensitivity of these sites to antisense probes. Although the targeted pre-mRNAs differed only by single point mutations, the effective concentrations of the oligonucleotides required for correction of splicing varied up to 750-fold. The differences among the aberrant 5' splice sites affected sensitivity of both the 5' and 3' splice sites; in particular, sensitivity of both splice sites was severely reduced by modification of the aberrant 5' splice sites to the consensus sequence. These results suggest large differences in splicing of very similar pre-mRNAs in vivo. They also indicate that antisense oligonucleotides may provide useful tools for studying the interactions of splicing machinery with pre-mRNA.

Postmortem quantitative 1.5-T MRI for the differentiation and characterization of serous fluids, blood, CSF, and putrefied CSF.

The purpose of the present study was to investigate whether serous fluids, blood, cerebrospinal fluid (CSF), and putrefied CSF can be characterized and differentiated in synthetically calculated magnetic resonance (MR) images based on their quantitative T 1, T 2, and proton density (PD) values. Images from 55 postmortem short axis cardiac and 31 axial brain 1.5-T MR examinations were quantified using a quantification sequence. Serous fluids, fluid blood, sedimented blood, blood clots, CSF, and putrefied CSF were analyzed for their mean T 1, T 2, and PD values. Body core temperature was measured during the MRI scans. The fluid-specific quantitative values were related to the body core temperature. Equations to correct for temperature differences were generated. In a 3D plot as well as in statistical analysis, the quantitative T 1, T 2 and PD values of serous fluids, fluid blood, sedimented blood, blood clots, CSF, and putrefied CSF could be well differentiated from each other. The quantitative T 1 and T 2 values were temperature-dependent. Correction of quantitative values to a temperature of 37 °C resulted in significantly better discrimination between all investigated fluid mediums. We conclude that postmortem 1.5-T MR quantification is feasible to discriminate between blood, serous fluids, CSF, and putrefied CSF. This finding provides a basis for the computer-aided diagnosis and detection of fluids and hemorrhages.

Callus massage after distraction osteogenesis using the concept of lengthening then dynamic plating.

Correction of complex deformities is a challenging procedure. Long-term wearing of a fixator after correction and lengthening are inconvenient and has a high rate of complication. The goals of the surgical treatment in the presented case were: (1) correction of the deformity and lengthening of the left leg by the Taylor spatial frame (TSF, Smith and Nephew, Marl, Germany); (2) reduction in the time the patient wears the TSF by changing the fixation system to a plate (lengthening then plating-LTP) and using a locking compression plate in conjunction with the 5.0 dynamic locking screws in order to accelerate bone healing.

Osteotomy of the distal femur. Surgical technique using the LCP Pediatric Condylar Plate 90°.

OBJECTIVE Correction of all kind of deformities at the distal part of the femur (supracondylar). INDICATIONS Flexion, extension osteotomies, and varus or valgus, and external or internal rotation osteotomies, and shortening osteotomies of the distal femur or combined surgical procedures (e.g., extension and de-rotation osteotomy). CONTRAINDICATIONS Osteotomy through unknown bony process. SURGICAL TECHNIQUE LCP system provides angular stable fixation. POSTOPERATIVE MANAGEMENT Without concomitant surgical procedures of soft tissue (e.g., patellar tendon shortening), early functional rehabilitation is possible with immediate weight bearing (35 kg for small fragment plates and 70 kg for large fragment plates). RESULTS The surgical procedure is safe and is associated with few complications. Overall complication rate in this series of patients was 3%.

Caffeine affects the biological responses of human hematopoietic cells of myeloid lineage via downregulation of the mTOR pathway and xanthine oxidase activity.

Correction of human myeloid cell function is crucial for the prevention of inflammatory and allergic reactions as well as leukaemia progression. Caffeine, a naturally occurring food component, is known to display anti-inflammatory effects which have previously been ascribed largely to its inhibitory actions on phosphodiesterase. However, more recent studies suggest an additional role in affecting the activity of the mammalian target of rapamycin (mTOR), a master regulator of myeloid cell translational pathways, although detailed molecular events underlying its mode of action have not been elucidated. Here, we report the cellular uptake of caffeine, without metabolisation, by healthy and malignant hematopoietic myeloid cells including monocytes, basophils and primary acute myeloid leukaemia mononuclear blasts. Unmodified caffeine downregulated mTOR signalling, which affected glycolysis and the release of pro-inflammatory/pro-angiogenic cytokines as well as other inflammatory mediators. In monocytes, the effects of caffeine were potentiated by its ability to inhibit xanthine oxidase, an enzyme which plays a central role in human purine catabolism by generating uric acid. In basophils, caffeine also increased intracellular cyclic adenosine monophosphate (cAMP) levels which further enhanced its inhibitory action on mTOR. These results demonstrate an important mode of pharmacological action of caffeine with potentially wide-ranging therapeutic impact for treating non-infectious disorders of the human immune system, where it could be applied directly to inflammatory cells.

Visor Osteotomy of the Anterior Mandible

Current techniques for three-dimensional correction of the chin in patients with mandibular retrusion may increase mentolabial fold depth, but have limited effect on the lips. The authors present a single surgical technique to support the mentolabial fold and improve labial competence. The visor osteotomy is performed from canine to canine. The bone fragment pedicled to the lingual periosteum is coronally mobilized and fixed in the new position. Preserved vascularization is supposed to minimize the amount of bone resorbed. Visor osteotomy of the anterior mandible may improve the existing treatments for micrognathia by creating an aesthetic mentolabial fold and a competent lip seal.

Editorial genesis: From comparing texts (product) to interpreting rewritings (process)

In literary genetics, “editorial genetics” deals with the “public life” of texts, whereas the writing process is affected by edition and diffusion. Editorial genetics frequently has to deal with cases of “editorial rewriting”: in the literary domain for example, authors frequently modify previously published works, so that several versions may co-exist. We are especially interested in Balzac’s La Bourse (translated in English as The Purse) since we know three authorized versions of this specific work.By comparing different texts associated with a single work, the literary geneticist is facing different products that are themselves the result of a writing process. However, different specificities should be outlined: (1) the writing process does not leave any trace: we just have access to different products/texts and (2) since the texts we compare seem to be achieved, differences must be referred, not to programmatic or temporary linguistic structures, but to the reconfiguration of a pre-existing textuality.Do such products still reflect the processes that have given birth to them? Does the comparison between two texts considered as variations of a same text give access to this transformation’s processes? After describing the objects of this particular textual comparison and the terminology that permits to give an account of such phenomenon, this contribution suggests to express these questions differently, as a matter of poetics of transitions between texts, or, further digging, an hermeneutics of the transition between texts.