[Incidental aneurysms and perimesencephalic subarachnoid haemorrhages]. / Aneurismas incidentales en el contexto de hemorragias subaracnoideas perimesencefálicas.

A perimesencephalic subarachnoid hemorrhage refers to the presence of bleeding around the midbrain with a normal angiography, meeting the well established clinical criteria and radiological criteria. Unlike the aneurysmal subarachnoid hemorrhage, it has a good prognosis, the recovery in most cases being complete and satisfactory. On the other hand, between 2 and 5% of the population will develop an intracranial aneurysm in the course of their life, most of them asymptomatic, with the likelihood of finding an incidental aneurysm in patients who have suffered a perimesencephalic hemorrhage. The importance of a proper diagnosis governs the course to follow, being a challenge for vascular treatment teams who must analyse the findings in detail and individualize treatment decisions.

Integrative sediment assessment at Atlantic Spanish harbours by means of chemical and ecotoxicological tools.

This study refers to the integrative assessment of sediment quality in three harbour areas at the Spanish Atlantic Coast: Vigo (Northwestern Spain), Bilbao and Pasajes (Northern Spain). At each site, two lines of evidence have been considered: chemical analyses (metal, PAH and PCB concentrations in sediments and ammonia concentration in bioassays) and toxicity tests (Microtox®, Corophium sp. marine amphipod and Paracentrotus lividus sea urchin larvae). Chemical and ecotoxicological results have been integrated by means of a tabular matrix and a multivariate factorial analysis (FA). Highly toxic samples have been characterised in Vigo and Pasajes harbours while Bilbao samples present toxicity levels ranging from non-toxic to moderately toxic. High toxicity is associated with high levels of contaminants whereas confounding factors (ammonia, organic matter and mud) have been identified to be the main cause of low to moderate toxicity. Based on the obtained results, it can be concluded that deriving potential toxicity of sediments based on comparison with Sediment Quality Guidelines (SQGs) is in agreement to toxicity results in areas presenting high levels of contaminants. However, at lower levels of toxicity (low to moderate), the mismatch between the potential toxicity (SQG approach) and the toxicity measured by bioassays is greater, as the former only accounts for chemical concentrations, without considering the interaction between contaminants and the effect of confounding factors. Contrarily, the multivariate analysis seems to be a robust tool for the integration and interpretation of different lines of evidence in areas affected by different sources of contamination.

Hypoplastic left heart syndrome diagnosed in fetal life: associated findings, pregnancy outcome and results of palliative surgery.

OBJECTIVES: To analyze the main prenatal characteristics of hypoplastic left heart syndrome (HLHS), its association with extracardiac anomalies including increased nuchal translucency (NT) and the outcome of affected patients. METHODS: We searched our database for classical forms of HLHS (aortic atresia, mitral and aortic atresia and critical aortic stenosis evolved to a severely hypoplastic left ventricle) prenatally diagnosed between 1998 and 2006. Data on 101 fetuses were retrieved and analyzed. RESULTS: The main reason for referral was suspected heart defect on a routine ultrasound scan (82%). The mean gestational age at diagnosis was 21 weeks. Most cases were detected at < or = 22 weeks (72%), the upper limit for termination of pregnancy (TOP) in our country (Spain). An intact atrial septum was diagnosed in 11 of the 58 fetuses (19%) in which pulmonary vein blood flow was assessed, and this diagnosis was proved to be correct in the six liveborn babies. Most fetuses (68%) had an isolated HLHS. Fourteen fetuses (14%) were chromosomally abnormal and all had associated extracardiac defects. NT was above the 95th centile in 21 of the 74 cases (28%) in which this measurement was available. 79% (58/73) of the cases in which HLHS was detected at < or = 22 weeks were terminated, and no differences in the rate of TOP were found through the study period. Among the 43 continuing pregnancies, seven fetuses died in utero and there were 36 live births; in 12 cases the parents opted for compassionate care and 24 chose to have the infant surgically treated. In the cohort of intention-to-treat cases, the overall survival rate was 36% (9/25). This rate improved from 18% (2/11) in the period 1998-2002 to 50% (7/14) in 2003-2006. There were no survivors in cases with intact atrial septum or when there were associated defects. At follow-up, 2/9 survivors suffered from significant neurological morbidity. CONCLUSIONS: Fetal echocardiography allows an accurate diagnosis of HLHS, which is made in most instances in the first half of pregnancy. Despite the advantage offered by the prenatal detection of HLHS, which provides the opportunity to plan perinatal management, our up-to-date results show that the outlook for these fetuses is still poor, and highlight the importance of presenting these figures when counseling parents with affected fetuses.

Role of uterine artery Doppler in interpreting low PAPP-A values in first-trimester screening for Down syndrome in pregnancies at high risk of impaired placentation.

OBJECTIVES: Low maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) are associated with both increased risk of aneuploidies and impaired trophoblastic invasion, while high uterine artery (UtA) resistance is associated with impaired trophoblastic invasion but not with an increased risk of aneuploidies. The aim of this study was to determine whether high UtA resistance plays a role in explaining low PAPP-A levels in the absence of aneuploidies. METHODS: This was a prospective study of 116 singleton pregnancies at high risk for impaired placentation (having at least one major risk factor: prior history of pre-eclampsia, pregestational diabetes mellitus, chronic hypertension, chronic kidney disease, body mass index >30, autoimmune disorder, thrombophilia or recurrent pregnancy loss), booked for routine assessment of risk for aneuploidies by means of the first-trimester combined screening test (nuchal translucency thickness (NT) + PAPP-A + beta-human chorionic gonadotropin (beta-hCG)). Measurement of NT and the mean UtA pulsatility index (PI) were carried out at the 11 to 13 + 6-week scan. All values were calculated in multiples of the median (MoM) adjusted for gestational age. A cut-off risk of 1/270 at time of sampling was adopted to differentiate high- from low-risk groups for trisomy 21. RESULTS: There were 108 patients deemed to be at low risk for trisomy 21 and eight at high risk. None had chromosomal defects, giving a false-positive rate for trisomy 21 of 6.9%. The greatest differences between patients at low risk and those at high risk for trisomy 21 were found in their PAPP-A (0.98 vs. 0.38 MoM, P < 0.01) and beta-hCG (1.09 vs. 1.77 MoM, P = 0.04) values. Greater NT thickness (1.02 vs. 0.90 MoM) and higher mean UtA-PI (1.05 vs. 0.96 MoM) were recorded in the high-risk group, although the differences did not reach statistical significance (P = 0.19 and 0.40, respectively). After log-transformation there were no significant correlations between mean UtA-PI and NT and between mean UtA-PI and beta-hCG. There was a significant negative linear correlation between mean UtA-PI and PAPP-A (r = -0.331; P < 0.01). After adjusting the PAPP-A values by UtA-PI, the false-positive rate for trisomy 21 decreased to 2.6%. CONCLUSION: Mean UtA-PI at the 11 to 13 + 6-week scan may be an effect-modifier variable for PAPP-A that should be taken into account in the first-trimester combined screening for aneuploidies, at least in pregnancies at high risk for impaired placentation.

Prenatal diagnosis of right aortic arch: associated findings, pregnancy outcome, and clinical significance of vascular rings.

OBJECTIVES: To analyze the characteristics and clinical implications of right aortic arch (RAA) detected in fetal life. METHODS: Retrospective study of all cases of RAA diagnosed prenatally in high-risk patients who underwent fetal echocardiography between 2000 and 2007. RESULTS: There were 48 RAA; 18 had vascular ring (Group 1), including 15 RAA with aberrant left subclavian artery and 3 double aortic arch, and 30 had not vascular ring (Group 2), all RAA with mirror-image branching. The prenatal diagnosis was confirmed in 94%. In Group 1 most fetuses had normal heart (89%), and none had 22q11 deletion. There were 16 live births and all infants but one are asymptomatic (mean follow-up of 31 months). In Group 2 almost all fetuses had congenital heart defects (CHDs) (97%), and five were chromosomally abnormal (17%), including four 22q11 deleted. The 1-year survival rate was 69%, which was significantly higher in Group 1 (89% vs 57%, p < 0.05). CONCLUSIONS: RAA can be accurately diagnosed by fetal echocardiography. The outlook for these patients largely depends on the presence of associated defects, mainly CHDs, and their severity. If isolated, aortic arch anomalies are asymptomatic vascular variants in most cases. This information is important to assist parental counseling in pregnancy.

Gestational diabetes mellitus in a cohort of HIV-1 infected women.

OBJECTIVES: We undertook a prospective study to estimate the prevalence of gestational diabetes mellitus (GDM) and associated risk factors in a cohort of 669 HIV-1 infected women. METHODS: The O'Sullivan and glucose tolerance tests were performed during regular visits of 609 mothers. RESULTS: The median age of the cohort was 30.7 years (range 16-44), with most women having had heterosexual contact (67%). The majority were in Centers for Disease Control (CDC) category A (71%) and 53% exhibited hepatitis C co-infection. Median viral load and CD4 count at third trimester were 545 cells/microL (range 139-1690 cells/microL) and 1.9 log (range 1.7-5.4), respectively. Seventy-four per cent of the patients were treated with highly active antiretroviral therapy (HAART), of whom 41% received a protease inhibitor (PI). An above-average prevalence of 7% [95% confidence interval (CI) 5.2-9.5] for positive GDM diagnosis was found. Risk factors associated with GDM in univariate analysis included older age, hepatitis C co-infection, stavudine and PI exposure. However, only older age [adjusted odds ratio (AOR) 1.09, 95% CI 1-1.1] and PI exposure (AOR 2.4, 95% CI 1-5.3) remained as independent risk factors for GDM development in multivariate analysis. CONCLUSIONS: In our cohort, the prevalence of GDM appears to be increased, with older age and PI exposure contributing as significant independent risk factors.

Predictive value of fetal hepatic biometry for birth weight and cord blood markers in gestational diabetes.

OBJECTIVE: The objective of this study is to evaluate third-trimester fetal liver biometry, to predict birth weight and cord markers at birth in diabetic pregnancies. STUDY DESIGN: Fetal liver biometry (liver diameters, area and volume) was obtained between 32 and 34 weeks. A blood sample was obtained from cord after birth. Receiver operating characteristic (ROC) curve models were evaluated for 75th and 90th birth weight percentile. Univariate and multivariate models were used. RESULT: All the hepatic diameters, area and sectional volume demonstrated significant differences in both birth weight percentile ⩾75 and ⩾90. All ROC curves showed significant values. A significant association was observed for all measurements with birth weight. In multivariate model, liver area volume gave significant values for predicting birth weight. Cord leptin, c-peptide and ferritin were related to fetal hepatic size. CONCLUSION: The hepatic changes in gestational diabetes were valid to predict birth weight and metabolic changes at birth.

[Impact of Lean methodology to improve care processes and levels of satisfaction in patient care in a clinical laboratory]. / Impacto de la metodología Lean en la mejora de procesos asistenciales y niveles de satisfacción en la atención de pacientes en un laboratorio clínico.

INTRODUCTION: The application of the Lean methodology in health institutions is an effective tool to improve the capacity and workflow, as well as to increase the level of satisfaction of patients and employees. OBJECTIVE: To optimise the time of outpatient care in a clinical laboratory, by implementing a methodology based on the organisation of operational procedures to improve user satisfaction and reduce the number of complaints for delays in care. MATERIAL AND METHODS: A quasi-experimental before and after study was conducted between October 2011 to September 2012. XBar and S charts were used to observe the mean service times and standard deviation. The user satisfaction was assessed using service questionnaires. RESULTS: A reduction of 17 minutes was observed in the time of patient care from arrival to leaving the laboratory, and a decrease of 60% in complaints of delay in care. Despite the high staff turnover and 38% increase in the number of patients seen, a culture of empowerment and continuous improvement was acquired, as well as greater efficiency and productivity in the care process, which was reflected by maintaining standards 12 months after implementation. CONCLUSION: Lean is a viable methodology for clinical laboratory procedures, improving their efficiency and effectiveness.

Dihydroxynitrobenzaldehydes and hydroxymethoxynitrobenzaldehydes: synthesis and biological activity as catechol-O-methyltransferase inhibitors.

A series of nitro derivatives of dihydroxy- and hydroxymethoxybenzaldehyde was synthesized and tested as potential inhibitors of partially purified pig liver catechol-O-methyltransferase (COMT). All the dihydroxynitrobenzaldehydes prepared were potent inhibitors of COMT, but only one hydroxymethoxynitrobenzaldehyde (3-hydroxy-4-methoxy-5-nitrobenzaldehyde) showed activity as a COMT inhibitor. Although previously reported data showed that the presence of electron-withdrawing substituents at position 5 seemed to be very important for activity as COMT inhibitor, our results suggest that the requirement necessary to enhance the activity of the dihydroxyni-trobenzaldehyde derivatives toward COMT is the presence of the nitro group in a position ortho with respect to one hydroxyl group. The assayed compounds showed a reversible inhibition of COMT, which was mixed for all the dihydroxynitro derivatives but noncompetitive for 3-hydroxy-4-methoxy-5-nitrobenzaldehyde when pyrocatechol was the variable substrate and uncompetitive in all the inhibitors with respect to S-adenosyl-L-methionine.

In vivo effects of new inhibitors of catechol-O-methyl transferase.

1. The effects of two new synthetic compounds showing in vitro catechol-O-methyl transferase (COMT) inhibitor properties were studied in vivo and compared with the effects of nitecapone and Ro-41-0960. 2. QO IA (3-(3-hydroxy-4-methoxy-5-nitrobenzylidene)-2,4-pentanedione), QO IIR ([2-(3,4-dihydroxy-2-nitrophenyl)vinyl]phenyl ketone), nitecapone and Ro-41-0960 (30 mg kg(-1), i.p.) were given to reserpinized rats 1 h before the administration of L-DOPA/carbidopa (LD/CD, 50:50 mg kg(-1), i.p.). Locomotor activity was assessed 1 h later. All the COMT inhibitors (COMTI), with the exception of QO IA, markedly potentiated LD/CD reversal of reserpine-induced akinesia. Similar results were obtained when the COMTI were coadministered with LD/CD. The effect of compound QO IIR was dose-dependent (7.5-30 mg kg(-1), i.p.). 3. The COMTI (30 mg kg(-1), i.p.) potentiated LD/CD reversal of both catalepsy and hypothermia of reserpinized mice. 4. QO IIR, nitecapone and Ro-41-0960 (30 mg kg(-1), i.p.) reduced striatal 3-methyl-DOPA (3-OMD) levels and increased dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels. Compound QO IA was devoid of any effect on striatal amine levels. In contrast to the other inhibitors, Ro-41-0961 reduced HVA levels as well. The effect of QO IIR on striatal amine levels was dose-dependent (7.5-60 mg kg(-1), i.p.) 5. These results suggest that the new compound QO IIR is an effective peripherally acting COMT inhibitor in vivo.

Inhibition of catechol-O-methyltransferase by 1-vinyl derivatives of nitrocatechols and nitroguaiacols. Kinetics of the irreversible inhibition by 3-(3-hydroxy-4-methoxy-5-nitro benzylidene)-2,4-pentanedione.

It is well known that activated alkene derivatives react with thiol groups according to a Michael's addition reaction. On the basis of the presence of at least one thiol group essential for the activity of catechol-O-methyltransferase (COMT), several 1-vinyl derivatives of nitrocatechol and nitroguaiacol were synthesized and tested as potential irreversible active site-directed inhibitors of COMT. All the synthesized products were potent inhibitors of partially purified pig liver COMT. However, the inhibition was reversible in most cases, with the exception of 3-(3-hydroxy-4-methoxy-5-nitrobenzylidene)-2,4-pentanedione (compound 2) which inhibited COMT in an irreversible manner. When the inhibition of COMT was measured as a function of the length of time of pre-incubation with 2, biphasic kinetics were observed, suggesting the modification of at least two thiol groups which are essential for COMT activity. The analysis of the two parts of the inhibition curve as a function of the inhibitor concentration showed that compound 2 modified the more reactive group in a non-specific manner, while it behaved as an active site-directed inhibitor on the second slow-reacting thiol group. Importantly, a saturating concentration of S-adenosyl-L-methionine (AdoMet) in the pre-incubation mixture gave pseudo-first order kinetics, suggesting total protection of one thiol group. Magnesium ions had no effect on the protection of COMT by AdoMet. In the presence of 3,5-dinitrocatechol (DNC) slight protection of COMT was observed; when the inactivation of both groups was analysed independently, protection of the specifically modified group was detected, while the reaction with the other group was faster in the presence of DNC. When both AdoMet and DNC were present, inactivation of COMT by 2 was not observed, suggesting that both reacting groups are located at or near the active site.

Synthesis and biological studies of glycosyl dopamine derivatives as potential antiparkinsonian agents.

A new approach to deliver dopamine into the central nervous system, based on the use of D-glucose as transportable agent, has been studied. Glycosyl dopamine derivatives bearing the sugar moiety linked to either the amino group or the catechol ring of dopamine through amide, ester or glycosidic bonds were synthesised as potential antiparkinsonian agents. Studies on the binding to dopamine D2 receptor, in vitro stability, and locomotive effect in mice of the synthetic glycoconjugates are reported.

Determination of tackiness of chitosan film-coated pellets exploiting minimum fluidization velocity.

The tackiness of aqueous chitosan film coatings and effects of anti-sticking agents on sticking tendency, were evaluated. A novel rapid method exploiting minimum fluidization velocity to determine tackiness was introduced and tested. The pressure difference over the miniaturized fluidized-bed was precisely recorded as a function of velocity of fluidization air. High molecular weight chitosan plasticized with glycerol was used as a film-forming agent. Magnesium stearate, titanium dioxide, colloidal silicon dioxide and glyceryl-1-monostearate (GMS) were studied as anti-sticking agents. Film coatings were performed in a miniaturized top-spray coater. The incorporation of anti-sticking agents led to a clear decrease in tackiness of the chitosan films, and magnesium stearate and GMS were shown the most effective. Film-coated pellets containing magnesium stearate and GMS as an anti-sticking agent were very easily fluidized (showing very low values of minimum fluidization velocity) and were thus classified as the best flowing and the least sticking samples. Both these additives were found anti-sticking agents of choice for aqueous chitosan film coatings. Determination of the experimental minimum fluidization velocity in a fluidized bed, is a useful and sensitive method of measuring the tackiness tendency of film-coated pellets.

Use of 4-chloro-7-nitrobenzofurazane as a derivative reagent for the determination of amino acids by cathodic stripping square wave voltammetry in biological fluids.

The rapid and simple reaction of 4-chloro-7-nitrobenzofurazane with amino acids allows the determination of amino acids in urine using cathodic stripping square wave voltammetry. The obtained compounds are adsorbed on a hanging mercury drop electrode for determination by voltammetric methods using phosphate buffer at pH 2.0 as supporting electrolyte. The proposed method allows determination with an error of 5.68%. A limit of detection (3sigma) of 3.64 nM (0.766 ng ml(-1)) and a limit of determination (10sigma) of 12.12 nM (2.55 ng ml(-1)) are obtained for arginine determination. The proposed method has been applied to the determination of amino acids in urine.

Characterisation of human foetal liver Zn-metallothioneins using differential pulse polarography.

A study on electrochemical characterisation of three isoforms of human foetal liver Zn-metallothioneins, labelled MT-0, MT-1 and MT-2, has been performed by using differential pulse polarography (DPP). Two different peaks, attributed to two different Zn complexes with metallothioneins, have been detected. The electrochemical behaviour is similar for the three studied isoforms. Studies on the addition of Cd(2+) and Zn(2+) as well as studies as a function of pH have been carried out. The association and dissociation equilibria of metal ions with MTs are reversible in the studied pH range. The behaviour of Zn complexes in human foetal liver Zn-metallothioneins is comparable to the Cd complexes obtained using other mammalian Cd, Zn-metallothioneins, particularly as a function of pH.

Effect of humic acids on speciation and toxicity of copper to Paracentrotus lividus larvae in seawater.

The effects of humic acid (HA) on the toxicity of copper to sea urchin Paracentrotus lividus larvae were studied in chemically defined seawater. Square Wave Anodic Stripping Voltammetry (SWASV) was employed to study the complexation of copper in seawater medium. A simple complexation model assuming one ligand type and a 1:1 reaction stoichiometry successfully explained the inverse titration experiments. A conditional stability constant of 6.53+/-0.05 and a complexating capacity of 230+/-7 micromol Cu/g HA were obtained. Sea urchin bioassay tests with two endpoints, embryogenesis success and larval growth were carried out in order to study the toxicity of dissolved copper in both the presence and absence of HA. The toxicity data obtained fitted well into a logistic model, and the high sensitivity of both endpoints (EC(50) were 41.1 microg Cu/l and 32.9 microg Cu/l, respectively) encourages their use for biomonitoring. The HA had a clearly protective effect, reducing the toxicity of Cu to the sea urchin larvae. The labile copper, rather than the total copper concentrations, explained the toxicity of the Cu-HA solutions, and the Cu-HA complexes appeared as non-toxic forms. These results are in agreement with the Free Ion Activity Model, because the labile Cu concentrations in this buffered and chemically defined medium covary with the free ion activity of the Cu, validating the model to naturally occurring HA in the marine environment.

Glutathione S-transferase, glutathione peroxidase and acetylcholinesterase activities in mussels transplanted to harbour areas.

As part of an integrative monitoring campaign involving water and sediment chemistry, in situ bioassays, and mussel bioaccumulation and biomarkers, Mytilus galloprovincialis mussels of standard size were transplanted from a clean location to five sites in two important harbours from the Atlantic coast of Spain (Vigo and Pasaia). After a 30-day field exposure, the concentrations of major contaminants (trace metals, polychlorinated biphenyls and polycyclic aromatic hydrocarbons) accumulated in mussel tissues were measured at each site, and a mussel bioaccumulation index (MBI) was calculated. The enzymatic activity levels of glutathione S-transferase (GST), glutathione peroxidase (GPx) and acetylcholinesterase (AChE) were quantified in the gills of transplanted mussels (n=12). Mussels from the most polluted sites consistently exhibited significantly higher GST and GPx activities compared to the control site, whereas AChE activity was significantly inhibited. The responses of the GST and GPx activities were related to MBI, trace metals and PAH concentrations in mussels, whereas AChE activity was related to the trace metals concentrations in mussels. The above results suggest that GST and AChE activities can be used as potential biomarkers for active monitoring in marine coastal ecosystems. However, at this moment, GPx activity is not robust enough to be applicable to harbour areas.

Application of Toxicity Identification Evaluation (TIE) procedures for the characterization and management of dredged harbor sediments.

This study refers to the performance of Phase I Toxicity Identification Evaluation (TIE) procedures to identify the contaminants (i.e. organic compounds, metals and ammonia) exerting toxicity in marine sediments from the Pasaia harbor (Oiartzun estuary, northern Spain). The effectiveness of the manipulations to reduce toxicity was proved with the marine amphipod survival test (whole-sediment) and the sea urchin embryo-larval assay (elutriates). By means of TIEs it was concluded that organic compounds were the major contaminants exerting toxicity, although toxic effects by metals was also demonstrated. Additionally, the combination of Phase I treatments allowed to investigate the toxicity changes associated to the mobility of contaminants during dredging activities. Therefore, the performance of TIE procedures as another line of evidence in the decision-making process is recommended. They show a great potential to be implemented at different steps of the characterization and management of dredged harbor sediments.