Cytokine activation and disease progression in patients with stable moderate chronic heart failure

BACKGROUND: Activation of the cytokine and the complement system is associated with disease progression in severe congestive heart failure (CHF). Magnitude and prognostic relevance of cytokine and complement activation remain uncertain in patients with moderate CHF. OBJECTIVES: Measurement of cytokine and complement activation in patients with moderate CHF and testing whether C-reactive protein (CRP) can serve as a surrogate marker of their activation, adding independent prognostic information when co-measured with B-type natriuretic peptide (BNP). METHODS: The 118 study participants were separated into three groups based on pre-determined CRP and BNP levels: Group I (n = 27; CRP > 5 mg/liter, BNP > or = 200 pg/ml); Group II (n = 46; CRP < or = 5 mg/liter, BNP > or = 200 pg/ml); and Group III (n = 45; CRP < or = 5 mg/liter, BNP < 200 pg/ml). RESULTS: Mortality was high in Group I (30%; log-rank p < 0.001) but low in Groups II and III (2% and 4%, respectively; log rank, p = 0.7). No differences were observed for left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD) between Groups I and II (31 +/- 16 vs 32 +/- 14% and 66 +/- 16 vs 65 +/- 11 mm, respectively), whereas in Group III LVEF was higher (42 +/- 17%, p = 0.002) with smaller LVEDD (57 +/- 13 mm, p = 0.012). Cytokine sCD14 and tumor necrosis factor (TNF)-alpha levels were not different between the three groups. However, interleukin-6 levels (9.75 +/- 8.17 pg/ml, p = 0.001) and the terminal complement complex C5b-9 (109.9 +/- 68 ng/ml; p = 0.04) were elevated in Group I, both correlating with CRP (interleukin-6: r = 0.5, p < 0.001; C5b-9: r = 0.41, p = 0.001). CONCLUSIONS: CRP may be used as a surrogate parameter for interleukin-6 and complement activation in moderate CHF. CRP in combination with BNP identifies a high-risk group with a tendency for poor outcome not discriminated by cardiac function.

Sedation and weaning from mechanical ventilation: effects of process optimization outside a clinical trial

PURPOSE: We studied the effects of reorganization and changes in the care process, including use of protocols for sedation and weaning from mechanical ventilation, on the use of sedative and analgesic drugs and on length of respiratory support and stay in the intensive care unit (ICU). MATERIALS AND METHODS: Three cohorts of 100 mechanically ventilated ICU patients, admitted in 1999 (baseline), 2000 (implementation I, after a change in ICU organization and in diagnostic and therapeutic approaches), and 2001 (implementation II, after introduction of protocols for weaning from mechanical ventilation and sedation), were studied retrospectively. RESULTS: Simplified Acute Physiology Score II (SAPS II), diagnostic groups, and number of organ failures were similar in all groups. Data are reported as median (interquartile range).Time on mechanical ventilation decreased from 18 (7-41) (baseline) to 12 (7-27) hours (implementation II) (P = .046), an effect which was entirely attributable to noninvasive ventilation, and length of ICU stay decreased in survivors from 37 (21-71) to 25 (19-63) hours (P = .049). The amount of morphine (P = .001) and midazolam (P = .050) decreased, whereas the amount of propofol (P = .052) and fentanyl increased (P = .001). Total Therapeutic Intervention Scoring System-28 (TISS-28) per patient decreased from 137 (99-272) to 113 (87-256) points (P = .009). Intensive care unit mortality was 19% (baseline), 8% (implementation I), and 7% (implementation II) (P = .020). CONCLUSIONS: Changes in organizational and care processes were associated with an altered pattern of sedative and analgesic drug prescription, a decrease in length of (noninvasive) respiratory support and length of stay in survivors, and decreases in resource use as measured by TISS-28 and mortality.

Multiple spinal extradural meningeal cysts presenting as acute paraplegia. Case report and review of the literature

Multiple spinal extradural meningeal cysts are rare. To the authors' knowledge, there have been only four reported cases in the world literature. The authors report a case of multiple spinal extradural meningeal cysts in a 31-year-old woman presenting with acute paraplegia. Magnetic resonance imaging of the thoracolumbar spine revealed multiple extradural cystic lesions extending from T-7 to T-8 and from T-12 to L-3. Intraoperative findings demonstrated a white, fibrous, and tense cyst filled with cerebrospinal fluid-like colorless fluid. Excision of the posterior wall of the symptomatic cyst was followed by immediate neurological improvement. The examination of the pathological specimen showed a thick duralike layer of collagen and an inner membrane of arachnoid that is often not found in these lesions. The final diagnosis was based on combined imaging, intraoperative, and histopathological findings. The authors review the literature and discuss the etiological, diagnostic, and therapeutic aspects of this lesion.

[Psychophysiologic manifestations, psychological and somatic risk factors and the physician-patient relationship in patients with heart diseases]

In daily medicine we often see patients complaining about thoracic pain. There is little doubt about the etiology in the most cases, but several patients continue posing diagnostic problems. There are different pathophysiological views to understand the situation of those patients, and it is important to determine their mental and psychological conditions. For this purpose, the focus on transference and countertransference phenomena has to be stressed. With these elements it will be possible to determine the diagnostic and therapeutic approach to those patients to reassure them and to justify investigations.

[Childhood Henoch-Schönlein syndrome--common and uncommon features, complications, Finkelstein-Seidlmayer variant and management]

Although Henoch-Schönlein syndrome can occur at any age, it is overwhelmingly a disease of childhood. Indeed, Henoch-Schönlein syndrome is the most common vasculitis that affects children. The clinical features of this vasculitis are well documented, and the diagnosis is generally not difficult. This article briefly reviews both common and uncommon clinical aspects of the condition and information concerning therapy. A further focus of this review is recent information concerning abnormalities of immunoglobulin IgA1 glycosylation and the role of aberrantly glycosylated immunoglobulins in the development of Henoch-Schönlein syndrome. The final focus of the article is acute hemorrhagic edema, a benign vasculitis limited to the skin, which is characterized by circinate, medallion-like purpura, and ecchymoses and occurs in children younger than 4 years of age. The nosologic position of acute hemorrhagic edema, which has also been called Finkelstein-Seidlmayer syndrome, as a variant of Henoch-Schönlein syndrome is the subject of considerable debate, but most authors agree that there are sufficient clinical and prognostic differences to consider it a separate entity.

Three dimensional finite element simulation of polymer melting and flow in a single-screw extruder : optimization of screw channel geometry

Single-screw extrusion is one of the widely used processing methods in plastics industry, which was the third largest manufacturing industry in the United States in 2007 [5]. In order to optimize the single-screw extrusion process, tremendous efforts have been devoted for development of accurate models in the last fifty years, especially for polymer melting in screw extruders. This has led to a good qualitative understanding of the melting process; however, quantitative predictions of melting from various models often have a large error in comparison to the experimental data. Thus, even nowadays, process parameters and the geometry of the extruder channel for the single-screw extrusion are determined by trial and error. Since new polymers are developed frequently, finding the optimum parameters to extrude these polymers by trial and error is costly and time consuming. In order to reduce the time and experimental work required for optimizing the process parameters and the geometry of the extruder channel for a given polymer, the main goal of this research was to perform a coordinated experimental and numerical investigation of melting in screw extrusion. In this work, a full three-dimensional finite element simulation of the two-phase flow in the melting and metering zones of a single-screw extruder was performed by solving the conservation equations for mass, momentum, and energy. The only attempt for such a three-dimensional simulation of melting in screw extruder was more than twenty years back. However, that work had only a limited success because of the capability of computers and mathematical algorithms available at that time. The dramatic improvement of computational power and mathematical knowledge now make it possible to run full 3-D simulations of two-phase flow in single-screw extruders on a desktop PC. In order to verify the numerical predictions from the full 3-D simulations of two-phase flow in single-screw extruders, a detailed experimental study was performed. This experimental study included Maddock screw-freezing experiments, Screw Simulator experiments and material characterization experiments. Maddock screw-freezing experiments were performed in order to visualize the melting profile along the single-screw extruder channel with different screw geometry configurations. These melting profiles were compared with the simulation results. Screw Simulator experiments were performed to collect the shear stress and melting flux data for various polymers. Cone and plate viscometer experiments were performed to obtain the shear viscosity data which is needed in the simulations. An optimization code was developed to optimize two screw geometry parameters, namely, screw lead (pitch) and depth in the metering section of a single-screw extruder, such that the output rate of the extruder was maximized without exceeding the maximum temperature value specified at the exit of the extruder. This optimization code used a mesh partitioning technique in order to obtain the flow domain. The simulations in this flow domain was performed using the code developed to simulate the two-phase flow in single-screw extruders.

Computational study of internal and external condensing flows and experimental synthesis to investigate their attainability and stability in ground-based and space-based environments

This doctoral thesis presents the computational work and synthesis with experiments for internal (tube and channel geometries) as well as external (flow of a pure vapor over a horizontal plate) condensing flows. The computational work obtains accurate numerical simulations of the full two dimensional governing equations for steady and unsteady condensing flows in gravity/0g environments. This doctoral work investigates flow features, flow regimes, attainability issues, stability issues, and responses to boundary fluctuations for condensing flows in different flow situations. This research finds new features of unsteady solutions of condensing flows; reveals interesting differences in gravity and shear driven situations; and discovers novel boundary condition sensitivities of shear driven internal condensing flows. Synthesis of computational and experimental results presented here for gravity driven in-tube flows lays framework for the future two-phase component analysis in any thermal system. It is shown for both gravity and shear driven internal condensing flows that steady governing equations have unique solutions for given inlet pressure, given inlet vapor mass flow rate, and fixed cooling method for condensing surface. But unsteady equations of shear driven internal condensing flows can yield different “quasi-steady” solutions based on different specifications of exit pressure (equivalently exit mass flow rate) concurrent to the inlet pressure specification. This thesis presents a novel categorization of internal condensing flows based on their sensitivity to concurrently applied boundary (inlet and exit) conditions. The computational investigations of an external shear driven flow of vapor condensing over a horizontal plate show limits of applicability of the analytical solution. Simulations for this external condensing flow discuss its stability issues and throw light on flow regime transitions because of ever-present bottom wall vibrations. It is identified that laminar to turbulent transition for these flows can get affected by ever present bottom wall vibrations. Detailed investigations of dynamic stability analysis of this shear driven external condensing flow result in the introduction of a new variable, which characterizes the ratio of strength of the underlying stabilizing attractor to that of destabilizing vibrations. Besides development of CFD tools and computational algorithms, direct application of research done for this thesis is in effective prediction and design of two-phase components in thermal systems used in different applications. Some of the important internal condensing flow results about sensitivities to boundary fluctuations are also expected to be applicable to flow boiling phenomenon. Novel flow sensitivities discovered through this research, if employed effectively after system level analysis, will result in the development of better control strategies in ground and space based two-phase thermal systems.

Surgical approach for synovial cyst of the atlantoaxial joint: a case report and review of the literature

STUDY DESIGN: Case report and review of the literature. OBJECTIVE: We describe the first case of a synovial cyst arising from pseudarthrosis of a previous dens fracture. The literature is reviewed and etiological, diagnostic, and therapeutic options of atlantoaxial cysts are discussed. SUMMARY OF BACKGROUND DATA: Symptomatic synovial cysts of the atlantoaxial joint are rare. To the authors' knowledge only 24 cases have been reported.A 60-year-old patient presented with bilateral hand numbness, quadrihyperreflexia, and gait deterioration. Magnetic resonance imaging of the cervical spine disclosed a cystic mass located at the transverse ligament of dens axis causing bulbomedullary compression. METHODS: Surgery was performed via transoral image guided approach. The ventral atlas arch, dens, transverse ligament, tectorial membrane, and the compressing cyst were removed, followed by a C0-C3 fusion. RESULTS: Two months postsurgery the patient recovered completely from the cervical myelopathy with transient remnant dysparesthesia of the finger tips. CONCLUSION: Magnetic resonance imaging findings are not specific enough to establish a preoperative diagnosis. Radical resection via image-guided transoral route followed by posterior fusion allows complete resection of the cystic lesion and results in excellent long-term decompression.

Symptomatic retroperitoneal cyst: a diagnostic challenge

Retroperitoneal cystic masses pose an important diagnostic and therapeutic challenge. Simple drainage, internal or external, is usually not sufficient. We report a case of a large symptomatic retroperitoneal cyst and its management.

Coordinated Lot-sizing and Dynamic Prizing under a Supplier All-units Quantity Discount

We consider an economic order quantity model where the supplier offers an all-units quantity discount and a price sensitive customer demand. We compare a decentralized decision framework where selling price and replenishment policy are determined independently to simultaneous decision making. Constant and dynamic pricing are distinguished. We derive structural properties and develop algorithms that determine the optimal pricing and replenishment policy and show how quantity discounts not only influence the purchasing strategy but also the pricing policy. A sensitivity analysis indicates the impact of the fixed-holding cost ratio, the discount policy, and the customers' price sensitivity on the optimal decisions.

Ranking of tests for pain hypersensitivity according to their discriminative ability in chronic neck pain

BACKGROUND AND OBJECTIVES Quantitative sensory testing (QST) is widely used to investigate peripheral and central sensitization. However, the comparative performance of different QST for diagnostic or prognostic purposes is unclear. We explored the discriminative ability of different quantitative sensory tests in distinguishing between patients with chronic neck pain and pain-free control subjects and ranked these tests according to the extent of their association with pain hypersensitivity. METHODS We performed a case-control study in 40 patients and 300 control subjects. Twenty-six tests, including different modalities of pressure, heat, cold, and electrical stimulation, were used. As measures of discrimination, we estimated receiver operating characteristic curves and likelihood ratios. RESULTS The following quantitative sensory tests displayed the best discriminative value: (1) pressure pain threshold at the site of the most severe neck pain (fitted area under the receiver operating characteristic curve, 0.92), (2) reflex threshold to single electrical stimulation (0.90), (3) pain threshold to single electrical stimulation (0.89), (4) pain threshold to repeated electrical stimulation (0.87), and (5) pressure pain tolerance threshold at the site of the most severe neck pain (0.86). Only the first 3 could be used for both ruling in and out pain hypersensitivity. CONCLUSIONS Pressure stimulation at the site of the most severe pain and parameters of electrical stimulation were the most appropriate QST to distinguish between patients with chronic neck pain and asymptomatic control subjects. These findings may be used to select the tests in future diagnostic and longitudinal prognostic studies on patients with neck pain and to optimize the assessment of localized and spreading sensitization in chronic pain patients.

Flow-R, a model for susceptibility mapping of debris flows and other gravitational hazards at a regional scale

The development of susceptibility maps for debris flows is of primary importance due to population pressure in hazardous zones. However, hazard assessment by process-based modelling at a regional scale is difficult due to the complex nature of the phenomenon, the variability of local controlling factors, and the uncertainty in modelling parameters. A regional assessment must consider a simplified approach that is not highly parameter dependant and that can provide zonation with minimum data requirements. A distributed empirical model has thus been developed for regional susceptibility assessments using essentially a digital elevation model (DEM). The model is called Flow-R for Flow path assessment of gravitational hazards at a Regional scale (available free of charge under http://www.flow-r.org) and has been successfully applied to different case studies in various countries with variable data quality. It provides a substantial basis for a preliminary susceptibility assessment at a regional scale. The model was also found relevant to assess other natural hazards such as rockfall, snow avalanches and floods. The model allows for automatic source area delineation, given user criteria, and for the assessment of the propagation extent based on various spreading algorithms and simple frictional laws. We developed a new spreading algorithm, an improved version of Holmgren's direction algorithm, that is less sensitive to small variations of the DEM and that is avoiding over-channelization, and so produces more realistic extents. The choices of the datasets and the algorithms are open to the user, which makes it compliant for various applications and dataset availability. Amongst the possible datasets, the DEM is the only one that is really needed for both the source area delineation and the propagation assessment; its quality is of major importance for the results accuracy. We consider a 10 m DEM resolution as a good compromise between processing time and quality of results. However, valuable results have still been obtained on the basis of lower quality DEMs with 25 m resolution.

Adenosquamous carcinoma of the head and neck: report of 20 cases and review of the literature

PURPOSE To assess the clinical profile and prognostic factors in patients with adenosquamous carcinoma (ASC) of the head and neck treated by surgery and/or radiation therapy with or without chemotherapy. METHODS Data from 20 patients with stage I-II (n = 4), III (n = 5), or IVA (n = 11) head and neck ASC, treated between 1989 and 2010 were collected in a retrospective multicenter Rare Cancer Network study. Surgery was performed in 16 patients. Seventeen patients received combined modality treatment. RESULTS After a median follow-up of 15.5 months, 12 patients recurred. The 3-year and median overall survival, disease-free survival (DFS), and loco-regional control were 52% and 39 months, 32% and 12 months, and 47% and 33 months respectively. In multivariate analysis, DFS was negatively influenced by the presence of extracapsular extension and advanced stage. CONCLUSION Overall prognosis of locoregionally advanced ASC remains poor. However, early stage ASC patients managed with combined modality treatment may have prolonged DFS.

Characterization and Clinical Relevance of ALDHbright Populations in Prostate Cancer

PURPOSE High aldehyde dehydrogenase (ALDH) has been suggested to selectively mark cells with high tumorigenic potential in established prostate cancer cell lines. However, the existence of cells with high ALDH activity (ALDH(bright)) in primary prostate cancer specimens has not been shown so far. We investigated the presence, phenotype, and clinical significance of ALDH(bright) populations in clinical prostate cancer specimens. EXPERIMENTAL DESIGN We used ALDEFLUOR technology and fluorescence-activated cell-sorting (FACS) staining to identify and characterize ALDH(bright) populations in cells freshly isolated from clinical prostate cancer specimens. Expression of genes encoding ALDH-specific isoforms was evaluated by quantitative real-time PCR in normal prostate, benign prostatic hyperplasia (BPH), and prostate cancer tissues. ALDH1A1-specific expression and prognostic significance were assessed by staining two tissue microarrays that included more than 500 samples of BPH, prostatic intraepithelial neoplasia (PIN), and multistage prostate cancer. RESULTS ALDH(bright) cells were detectable in freshly excised prostate cancer specimens (n = 39) and were mainly included within the EpCAM((+)) and Trop2((+)) cell populations. Although several ALDH isoforms were expressed to high extents in prostate cancer, only ALDH1A1 gene expression significantly correlated with ALDH activity (P < 0.01) and was increased in cancers with high Gleason scores (P = 0.03). Most importantly, ALDH1A1 protein was expressed significantly more frequently and at higher levels in advanced-stage than in low-stage prostate cancer and BPH. Notably, ALDH1A1 positivity was associated with poor survival (P = 0.02) in hormone-naïve patients. CONCLUSIONS Our data indicate that ALDH contributes to the identification of subsets of prostate cancer cells of potentially high clinical relevance.

Diagnostic Imaging in Bovine Orthopedics.

Although a radiographic unit is not standard equipment for bovine practitioners in hospital or field situations, ultrasound machines with 7.5-MHz linear transducers have been used in bovine reproduction for many years, and are eminently suitable for evaluation of orthopedic disorders. The goal of this article is to encourage veterinarians to use radiology and ultrasonography for the evaluation of bovine orthopedic disorders. These diagnostic imaging techniques improve the likelihood of a definitive diagnosis in every bovine patient but especially in highly valuable cattle, whose owners demand increasingly more diagnostic and surgical interventions that require high-level specialized techniques.