A contemporary approach to the musculoskeletal problems associated with hemophilia.

ABSTRACT: It is essential that joint bleeds be treated in a hematologically and orthopedically optimal manner so as to arrest the bleeding as soon as possible and prevent potentially irreversible joint damage from setting in. The main goal of rehabilitation in the context of hemophilia is above all prevention and treatment of the consequences of musculoskeletal bleeding. Rehabilitation of acute joint bleeding episodes, that is, hemarthrosis, is based on three fundamental pillars: arthrocentesis, PRICE measures, and rehabilitation protocols.

Missed opportunities in early diagnosis of symptomatic colorectal cancer.

OBJECTIVE: delays in diagnosis of symptomatic colorectal cancer are a reality in our context. This study aims at identifying missed diagnostic opportunities, describing events, clinical clues and most common mistakes, and quantifying delays. MATERIAL AND METHODS: an observational descriptive study was performed in order to review all case histories. Two experts reviewed the case histories of all the patients from the 4th Catchment Area of Asturias diagnosed with colorectal cancer in 2009. All data were analysed using bivariate and multivariate logistic regression. RESULTS: full information on 119 patients out of 143 patients was collected. 34.45% had a clinical missed opportunity -confidence interval (CI) 95%: 30.92-39.68-. Outcomes show an average of 2.41 missed opportunities and 2.61 diagnostic clinical clues per patient. The number of patients with missed opportunities was significantly higher. The total amount of co-morbidities was higher in patients with missed opportunities (2.7). This was the main determinant. The main diagnostic key was iron-deficiency anaemia (46.3%). It produced the longest delay (300 days). Not having requested diagnostic tests was the most common mistake (43.3%). Having at least one missed opportunity entailed an average delay of 235.8 days between the first visit to the office and the referral to a consultant. CONCLUSIONS: in clinical practice, missed opportunities to start a diagnostic assessment in patients with presumptive diagnosis of colorectal cancer are common. The most significant clinical clue and the one generating the longest delay is iron-deficiency anaemia. The diagnostic delay is important and is caused mainly by not identifying symptoms.

Asymptomatic hypertransaminasemia in patients in primary care.

INTRODUCTION AND OBJECTIVE: asymptomatic hypertransaminasemia (AH) is a common finding in clinical practice. We propose to determine the prevalence of AH in our environment, its epidemiology and its evolution. MATERIAL AND METHODS: we studied a random sample of 1,136 blood tests undertaken in 2006, excluding patients with known hepatic disease or symptoms or signs of liver disease, and following the evolution of the AHs until 2009. Data was analyzed using bivariate and multivariate logistic regression. RESULTS: the percentage of patients found with a AH was 15.24% (95% CI 13.52 to 16.96%). The rates of AST and ALT, were 6.93% (95% CI 5.71 to 8.15%) and 14.31% (95% CI 12.65 to 15.97%) respectively. The percentage of normalization of transaminase values in a second analytical control was a 31.81% (95% CI: 26.21 to 37.4%). An association was found between AH and BMI (OR: 1.129, 95% CI 1.062 to 1.199) and between the persistence of AH and GGT (OR: 1.011, 95% CI 1.003 to 1.018). Fundamental tests such as hepatitis serology or ultrasound were performed on only 50% of patients (with 32% of steatohepatitis). CONCLUSIONS: the prevalence found in our study of AH was relatively high (15.24%), being more frequently encountered in obese subjects. Nearly a third of the AHs is normalized in a subsequent blood test. The high GGT is associated with persistence of AH. There is great variability in terms of additional testing in patients with AH and the application of such tests is not protocol.

Thirteen week feeding study with transgenic maize grain containing event DAS-Ø15Ø7-1 in Sprague-Dawley rats.

Maize line 1507, containing event DAS-Ø15Ø7-1 (1507), is a genetically modified (GM) maize plant that expresses the cry1F gene from Bacillus thuringiensis (Bt) sbsp. aizawai and the phosphinothricin-N-acetyltransferase (pat) gene from Streptomyces viridochromogenes throughout the plant including in the grain expression of the Cry1F protein confers in planta resistance to the European corn borer (ECB; Ostrinia nubilalis Hübner: Crambidae) and other lepidopteran pests. Expression of the PAT protein confers tolerance to the herbicidal active ingredient glufosinate-ammonium. The current study evaluated the nutritional performance of rats fed diets containing 1507 maize grain in a subchronic rodent feeding study. The grains in this study, 1507, its near-isogenic control (33P66), and a non-GM commercial hybrid (33J56) contained similar amounts of proximates, amino acids, minerals, anti-nutrients, and secondary metabolites. The subchronic feeding study compared standard toxicology response variables in rats fed diets containing 1507 maize grain with those in rats fed diets containing non-GM maize grains. All diets were prepared according to the specifications of PMI Nutrition International, LLC Certified Rodent LabDiet 5002 (PMI) 5002). Diets were fed ad libitum to Sprague-Dawley rats for approximately 90 days. In-life response variables included indicators of dietary performance and weekly evaluations for clinical signs of toxicity. No toxicologically significant differences were observed in the nutritional performance variables, clinical and neurobehavioral signs, ophthalmology, clinical pathology (hematology, clinical chemistry, coagulation, and urinalysis), organ weights, and gross and microscopic pathology between any pair of treatment groups. These results demonstrate that 1507 maize grain is as safe and as nutritious as non-GM maize grain.

Effect of adrenaline and glucocorticoids on monocyte cAMP-specific phosphodiesterase (PDE4) in a monocytic cell line.

An increase in phosphodiesterase 4 (PDE4) in blood mononuclear white cells of patients with atopic dermatitis (AD) has been described. This and other skin disorders worsen during stress, during which there are increased circulating levels of adrenaline and glucocorticoids. The aim of this study was to analyse the effect of both these hormones on PDE4 in inflammatory cells. The human monocyte cell line U-937 was used as a model of blood mononuclear leucocytes. For this purpose, (1) the effect of adrenaline on PDE4 activity was determined, (2) the receptor mediating adrenaline actions was characterized, (3) the role of intracellular cAMP in PDE4 activation was investigated and (4) the effect of glucocorticoids on PDE4 activity was also ascertained. Adrenaline at a concentration of 1 micro M produced a two- to threefold selective increase in PDE4 activity in U-937 cells after 4 h of incubation with the hormone. This stimulation was reversible, as well as concentration- and time-dependent. Cycloheximide (10 micro M) induced a blockade of adrenaline-induced stimulation of PDE4. The stimulatory effect was inhibited by propranolol, but not by atenolol or phentolamine, in a concentration-dependent manner and was mimicked by salbutamol. The stimulation of PDE4 was paralleled by an increase in intracellular levels of cAMP. 8-Br-cAMP and forskolin also increased PDE4 activity. After 4 h of incubation in the presence of adrenaline, inhibition of cAMP degradation by rolipram further increased cAMP levels by about 300% and also enhanced PDE4 activity. These results suggest that adrenaline-induced stimulation of PDE4 is mediated by the beta(2)-adrenoceptor and is related to intracellular levels of cAMP, which might trigger expression and synthesis of the enzyme. The synthetic glucocorticoid dexamethasone (in the concentration range 10(-8) to 10(-6) M) showed no effect on PDE4 activity or on the cAMP accumulation induced by adrenaline, even after prolonged (24 h) incubation with the cells. Of the two stress hormones assayed, PDE4 activity was shown to be sensitive to adrenaline elevation but resistant to changes in glucocorticoid levels in the U-937 monocytic cell line.

Striatal interaction among dopamine, glutamate and ascorbate.

Despite evidence suggesting the interaction among glutamate (GLU), dopamine (DA) and ascorbic acid (AA) in the striatum, their actions are often studied separately. Microdialysis was used here to quantify the extracellular interaction among GLU-DA-AA in the striatum of rats, an interaction which was compared with those studied in the substantia nigra (SN). Perfusion of GLU by reverse microdialysis increased DA and decreased 3,4-dihydroxyphenylacetic acid (DOPAC) in the extracellular medium of the striatum, but increased both DA and DOPAC in the SN. The increase of extracellular DA-concentration induced by the local DA-perfusion decreased the extracellular level of GLU and glutamine, an effect that, as suggested by the GLU and glutamine increase observed after the haloperidol administration, probably involves the D2 dopamine receptor. Local administration of AA increased the extracellular DA, decreased DOPAC and had no effect on GLU and glutamine. Present data suggest that, in the striatum, GLU-release inhibits DA-uptake, DA-release inhibits GLU-release, and AA-release prevents DA-oxidation increasing its extracellular diffusion. These effects were different in the SN where GLU probably promoted the DA-release instead of inhibiting the DA-uptake as presumably occurred in the striatum. Present data denote a marked GLU-DA-AA interaction in the striatum, which might be relevant for the pharmacological control of basal ganglia disorders.

Osmosensitive response of glutamate in the substantia nigra.

Previous studies have suggested the increase of extracellular glutamate (GLU) in the substantia nigra (SN) as a cause of dopamine-cell degeneration (excitotoxicity) in Parkinson's disease (PD). However, the mechanisms involved in this increase remain unknown. The present work studied osmoregulation as a cause of GLU release in the SN. Microdialysis was used to change extracellular osmolarity, to administer drugs and to quantify the extracellular non-synaptic GLU (EnS-GLU). Two osmolarity modifications were performed, a moderate decrease (5%) resembling physiological modifications and a substantial decrease (>or=20% decrease) similar to that observed under pathological conditions. Hypo-osmolarity induced a dose-response (285-80 mOsm) increase of EnS-GLU which was detected after small osmolarity modifications (15 mOsm) and which was very marked (>1000%) after more intense osmolarity changes. This response disappeared after pre-treating rats with a P2 purinergic-receptor antagonist (pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid; 1 mM) suggesting ATP involvement in the osmosensitive EnS-GLU response. The EnS-GLU increase observed after administration of ATP (0.1-100 microM) and 2-methylthioadenosine triphosphate tetrasodium (P2-receptor agonist; 100 microM) and the lack of effects of adenosine administration (1 mM) suggest that the ATP action on P2 receptors is an amplificatory mechanism in the osmosensitive EnS-GLU response. The marked action of osmolarity on extracellular Glu suggests osmolarity regulation as a possible source for excitotoxicity in the SN.

A tiered system for assessing the risk of genetically modified plants to non-target organisms.

Representatives of the developers of modern agricultural biotechnology are proposing a tiered approach for conducting non-target organism risk assessment for genetically modified (GM) plants in Europe. The approach was developed by the Technical Advisory Group of the EuropaBio Plant Biotechnology Unit (http://www.europabio.org/TAG.htm) and complements other international activities to harmonize risk assessment. In the European Union (EU), the principles and methods to be followed in an environmental risk assessment for the placing on the market of GM plants are laid out in Annex II of Directive 2001/18/EC on the deliberate release into the environment of GMOs, Commission Decision 2002/623/EC and Regulation (EC) No. 1829/2003. Additional information is provided in the European Food Safety Authority guidance document of 2004. However, risk assessment for effects to non-target organisms could benefit from further clarification and remains the subject of much discussion in Europe. The industry-wide approach developed by EuropaBio is based on the fundamental steps of risk evaluation, namely hazard and exposure assessment. It follows a structured scheme including assessment planning, product characterization and assessment of hazard/exposure (Tier 0), single high dose and dose response testing (Tier 1), refined hazard characterization and exposure assessment (Tier 2) and further refined risk assessment experiments (Tier 3). An additional tier (Tier 4) was included to reflect the fact that post-market activities such as monitoring are required under Directive 2001/18/EC. The approach is compatible with conditions of commercial release in the EU and around the world.

Hospital Luis Calvo Mackenna: la calidad y la satisfacción usuaria, pilares estratégicos de cambio / Luis Calvo Mackenna hospital: quality and the patients satisfaction, strategies of change

El Hospital Luis Calvo Mackenna, inserto en un proceso de cambios relacionados con la búsqueda de la satisfacción del usuario y con la mejoría de la calidad de los servicios, construyó participativamente una misión y un plan. En éste último, uno de los objetivos estratégicos es la calidad. El hospital ha constituido un consejo de calidad multidisciplinario, quien ha explicitado sus valores-. compromiso con la vida y el ser humano. Y, a la calidad, la ha señalado como instrumento principal para el logro de la eficiencia social que nos impone ese compromiso valórico, lo que implica un cambio cultural profundo, que supone un proceso largo y paciente para consolidar una transformación de las costumbres y una modificación de los comportamientos, con el objetivo de responder a nuestros requerimientos éticos y asegurar la vialidad futura de] sistema público. Como ejemplo de lo anterior se señalan, entre otros, algunos avances en materia de calidad y satisfacción-usuario en áreas tales como participación usuaria, mejoría de la accesibilidad y de la calidad técnica de los servicios