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In representation of A. baumannii eradication program., [Background] Acinetobacter baumannii causes frequently nosocomial infections worldwide. Its ability to survive on dry surfaces facilitates its spread and the persistence of endemic situations, especially in the intensive care units (ICUs). The objective of this paper is to describe a multicomponent intervention program designed to control a hyperendemic persistence of multidrug-resistant A. baumannii (MDR-Ab) and to characterize its impact. [Methods] Design: Quasi-experimental intervention study based on open cohorts. Setting: Public tertiary referral centre. Period: January 2009–August 2017. Intervention: multifaceted program based on environmental decontamination, hand hygiene, antimicrobial stewardship, contact precautions, active surveillance, weekly reports and regular meetings. Analysis: joinpoint regression and interrupted time-series analysis. [Results] The intervention was successfully implemented. Through the study period, the compliance with contact precautions changed from 0 to 100% and with hand hygiene, from 41.8 to 82.3%. Between 2012 and 2016, the antibiotic consumption decreased from 165.35 in to 150.44 daily-defined doses/1000 patients-days in the ICU. The incidence density of MDR-Ab in the ICU was 10.9 cases/1000 patients-days at the beginning of the intervention. After this moment, the evolution of the incidence density of MDR-Ab was: between months 0 and 6°, it remained stable; between months 7° and 10°: there was an intense decrease, with an average monthly percentage change (AMPC) = − 30.05%; from 11° month until the end, the decrease was lighter but continuous (AMPC:-2.77%), achieving an incidence density of 0 cases/1000 patients-days on the 18° month, without any new case for 12 months. From the 30° month until the end of the study period, several little outbreaks of MDR-Ab were detected, all of them rapidly controlled. The strains of MDR-Ab isolated during these outbreaks were not clonally related with the previously endemic one, which supports its eradication from the environmental reservoirs. [Conclusion] The multicomponent intervention performed by a multidisciplinary team was effective to eradicate the endemic MDR-Ab.

Introduction The SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance study monitors antimicrobial susceptibility and extended spectrum β-lactamases (ESBLs) in Gram-negative bacilli recovered from intra-abdominal infections (IAI). Material and methods Antimicrobial susceptibility of 5,343 isolates from IAI recovered in 11 centres during the 2011-2015 SMART-Spain program was analysed by standard microdilution (EUCAST criteria) and compared with that from 2002-2010. ESBLs were phenotypically detected. Results Escherichia coli, the most common isolate, significantly decreased in community acquired IAI (60.9% 2002-2010 vs. 56.1% 2011-2015, P=0.0003). It was followed in prevalence by Klebsiella pneumoniae that increased both in the community (8.9% vs. 10.8%, P=0.016) and nosocomial (9.2% vs. 10.8%, P=0.029) IAI and P. aeruginosa, which significantly increased in community acquired IAI (5.6% vs. 8.0%, P=0.0003). ESBLs were more prevalent in K. pneumoniae (16.3%) than in E. coli (9.5%) of nosocomial origin and were more frequently isolated from elderly patients (>60 years). Considering all Enterobacteriaceae, ertapenem (92.3-100%) and amikacin (95.5%-100%) were the most active antimicrobials. Ertapenem activity, unlike amoxicillin-clavulanate or piperacillin-tazobactam, remained virtually unchanged in ESBL (100%) and non-ESBL (98.8%) E. coli producers. Its activity decreased in ESBL-K. pneumoniae (74.7%) but was higher than that of amoxicillin-clavulanate (14.0%) and piperacillin-tazobactam (24.0%). Interestingly, ertapenem susceptibility was maintained in >60% of ESBL isolates that were resistant to amoxicillin-clavulanate, piperacillin-tazobactam or fluoroquinolones. Conclusions SMART-Spain results support current guidelines which include ertapenem as empiric treatment in mild-moderate community-acquired IAI, particularly with ESBL producers. These recommendations will need to be updated with the recently introduction of new antimicrobials.

Dactylitis is a typical feature of psoriatic arthritis. However, dactylitis was included as a spondyloarthritis (SpA) feature for both (axial and peripheral) of the ASAS classification criteria, but data about its prevalence are scarce, especially in patients with a recent onset of the disease. Our objective was to determine the prevalence and characteristics associated with dactylitis in patients with early SpA.A baseline dataset from the ESPeranza cohort was used. This programme included patients who were suspected of having SpA (age45 years, symptoms duration of 3-24 months and with inflammatory back pain, or asymmetrical arthritis, or spinal/joint pain plus ≥1 of the SpA features). For this study, 609 patients who were diagnosed with SpA by their physician were included. Descriptive, univariable and multivariable logistic regression analyses were employed to investigate the association between the presence of dactylitis and the characteristics associated with SpA.Fifty-eight (9.5%) patients currently or previously had dactylitis. In the multivariable analysis, dactylitis was independently associated with peripheral arthritis (OR= 4.83; p0.001), enthesitis (OR= 2.49; p=0.01), psoriasis (OR= 3.62; p0.01) and the physician's visual analogue scale (OR= 0.82; p=0.01). However, 67% of the patients who had dactylitis did not have peripheral arthritis or psoriasis and 15% had predominantly axial disease.Dactylitis is a frequent manifestation in patients with SpA, even during the early stages of the disease. Its presence is mainly associated with peripheral manifestations and psoriasis. Nevertheless, dactylitis is not exclusive of patients with PsA or peripheral manifestations.

A patient with functionally defective fibrinogen has been studied. Fibrinogen Almeria I was found to have a prolonged of latency time (LT) and a decrease in rate of gelation (RG) when plasma or isolated fibrinogen were activated by thrombin or reptilase. This fibrinogen also has the unusual formation of cross-linked fibrin; the existence of unpolymerized alpha chains was confirmed.

ObjetivoDiseñar y validar un cuestionario autoadministrado evaluador de la función sexual en la mujerDiseñoEstudio transversal y multicéntricoEmplazamientoAtención primaria. Realizado en 9 centros sanitarios de la Comunidad ValencianaParticipantesMujeres sin riesgo de disfunción sexual, seleccionadas por muestreo consecutivo. Muestra inicial: 600; muestra válida: 212IntervencionesDiseño del cuestionario, de 14 preguntas a cumplimentar en 5–10 min, por un comité de expertos. Las participantes lo realizan en 2 ocasiones (test y retest) con un intervalo de 4 semanas. Evaluación diagnóstica por un comité de observadoresMediciones principalesFiabilidad entre preguntas de test y retest: a) una a una, mediante análisis de concordancia con índice kappa. Variaciones significativas mediante la prueba de la χ2 de bondad de ajuste; b) de las sumas de respuestas: comparación de medias (Wilcoxon) y posterior análisis mediante el coeficiente de correlación intraclase (CCI). La consistencia interna se determinó con el α de Cronbach y para la validez de contenidos se consideraron el consenso de expertos, la correlación interobservadores (CCI) y el análisis factorialResultadosFiabilidad entre preguntas una a una: kappa=0,597–0,743; χ2 no significativa. Fiabilidad entre sumas totales (Wilcoxon): no significativa (z=-0,312; p=0,755) (confianza del 95%). CCI: r=0,9587 (intervalo de confianza del 95%, 0,9460–0,9685), correlación significativa (confianza del 99%). Consistencia interna: a de Cronbach en el test de 0,8954 y en el retest de 0,8973. Correlación interobservadores (CCI): r=0,9498 (intervalo de confianza del 95%, 0,9386- 0,9611), significativa (confianza del 99%). Análisis factorial: agrupaciones de los ítems 9, 13 y 14; 1, 2, 3 y 10; 5, 6, 7 y 8ConclusionesEl cuestionario es estable, válido y fiable. Evalúa las fases de la respuesta sexual, la iniciativa y el grado de comunicación sexual. Recoge datos descriptivos acerca del desempeño sexual y resulta útil en la exploración y el diagnóstico de las disfunciones sexualesObjectiveTo design and validate a self-administered questionnaire to evaluate sexual function in womenDesignCross-sectional, multi-centre studySettingPrimary care, in 9 health centres of the Community of ValenciaParticipantsWomen not at risk of sexual dysfunction, selected by consecutive sampling. Initial sample 600, valid sample 212InterventionsQuestionnaire of 14 questions to be filled out in 5–10 minutes, designed by a committee of experts. The participants filled it out on two occasions (test and retest) with an interval of 4 weeks. Diagnostic assessment by a committee of observersMain measurementsReliability between test and retest questions:- One to one: analysis of concordance: kappa index. Significant variations: χ2 goodness of fit- On the sum of replies: comparison of means (Wilcoxon) and subsequent analysis: intra-class correlation coefficient (ICC). Internal consistency: Cronbach's alpha. Validity of contents: consensus of experts. Inter-observer correlation: ICC and factor analysisResultsReliability: one to one: Kappa from 0.597 to 0.743. χ2 not significant (ns). Between total sums (Wilcoxon), ns (z=-0.312, P=.755) (95% confidence). ICC: r=0.9587 (95% CI, 0.9460–0.9685), significant correlation (99% confidence). Internal consistency: Cronbach's alpha test: 0.8954, retest: 0.8973. Inter-observer correlation: ICC: r=0.9498 (CI, 0.9386–0.9611) significant (confidence 99%). Factor analysis: groupings of items 9, 13, 14; 1, 2, 3, 10; 5, 6, 7, 8ConclusionsThe questionnaire is stable, valid and reliable. It evaluates the stages of sexual response, initiative and degree of sexual communication. It collects data on sexualperformance. It is useful for exploring and diagnosing sexual dysfunction

Erythrocyte aggregability was determined by a laser backscattering light technique in 23 beta minor thalassemia carriers and in 36 age and sex matched controls. The aggregation time (Ta) was statistically higher in cases than in controls (2.8 +/- 1.0 vs 2.3 +/- 0.4, p0.05) and the aggregation index at 10 sec (AI10) was statistically lower (25.1 +/- 5.7 vs 28.2 +/- 3.8, p0.05), suggesting both parameters a statistically lower erythrocyte aggregability tendency. However, the total disaggregation threshold (gammaD) was statistically higher in cases than in controls (134.4 +/- 34.1 vs 105.1 +/- 33.1, p0.05), indicating that once aggregates are formed a higher shear rate is needed to break them up. No differences were observed in plasmatic factors, i.e., fibrinogen, total cholesterol and triglycerides, that could have influenced erythrocyte aggregation. A negative statistically significant correlation was found between erythrocyte indexes and the total disaggregation threshold. The lower erythrocyte aggregation found in minor thalassemia carriers could be attributed in part to the morphological alterations, although others mechanisms such as modifications in the membrane structure of the RBC can not be ruled out.

Abnormally high levels of von Willebrand factor (VWF) have been described as a response to physiologic and chronic alterations. It is therefore of great interest to have sensitive, accurate, fast and easy to use assays to quantify VWF. The aim of this study was to evaluate the performance characteristics of the immunoturbidimetric assay IL Test VWF:Ag and the use of this determination in the study of vascular dysfunction.The reproducibility, accuracy and linearity of the method were determined. A method comparison study was performed using an ELISA as the reference test. The assay reference range and its age-dependence were established. To evaluate the utility of the assay in vascular dysfunction, a cohort of 30 type 1 diabetes mellitus (DM) patients were analyzed, 11 of whom showed microvascular complications.The linearity range found was 10-150 IU/dL. Reported values above 150 IU/dL should be diluted and reanalyzed, expanding the range up to 600 IU/dL. The coefficients of variation were below 5% and inaccuracies below +/-15% within the linearity range. The comparison with the reference ELISA showed a good correlation coefficient (r = 0.985, VWF values from 5-680 IU/dl). The reference range was found to be 40.8 - 158.1 IU/dL. Significant differences between the DM type 1 patients with microvascular complications and a sex-age matched control group were observed. This difference was not observed for the DM patients not showing vascular alterations.The method is reproducible, accurate and linear. The assay correlates well with the reference ELISA. There is a relationship between patients showing microvascular diabetic complications and high levels of VWF:Ag. The assay is easy to perform, fully automated, and suitable for analyzing a small number of samples.

To evaluate the influence of several factors, including age, prostate volume, total PSA (PSA-T), clinical stage and Gleason on the PSA:alpha 1ACT/PSA-T (C/T) ratio.Using in-house assays, we measured plasma levels of PSA-T and PSA:alpha 1ACT complex in 622 patients with benign prostate hyperplasia (BPH) (455 with hystological confirmation and 167 with clinical evidence of absence of malignance) and in 255 patients with prostate cancer (CaP), and determined the correlation between different parameters.In BPH patients, PSA-T and PSA:alpha 1ACT significantly increased with age. There was a positive correlation between age and PSA-T (r = 0.161, p0.0001) and PSA:alpha 1ACT (r = 0.141, p = 0.001). In contrast, the C/T ratio remained constant and below 70% in all decades. Similar results were obtained in CaP patients. In BPH patients, there was a positive correlation between prostate volume and PSA-T and PSA:alpha 1ACT, but not with the C/T ratio. In CaP patients, however, there was a negative correlation between prostate volume and the C/T ratio. An excellent correlation was found between PSA-T and PSA:alpha 1ACT, and a good correlation between PSA-T and the C/T ratio and between PSA:alpha 1ACT and C/T ratio. A multiple regression analysis showed that, in HBP and CaP patients, PSA-T and PSA:alpha 1ACT complex were the only parameters that significantly and independently influenced the C/T ratio.The C/T ratio is independent of age, prostate volume, Gleason and clinical stage. Therefore, these factors need not to be considered when using the C/T ratio.

The incidence of coronary artery disease (CAD) is higher in post-menopausal than in pre-menopausal women. Epidemiological studies suggest that hormone replacement therapy (HRT) decreases the risk of cardiovascular disease in post-menopausal women. HRT could modify the cardiovascular risk via several mechanisms, including modifications in the fibrinolytic system and lipoprotein (a) levels. Our study was aimed at investigating some of these modifications.In the cross-sectional part of the study we evaluated several components of the fibrinolytic system, coagulation inhibitors and lipid profile in premenopausal (n=15) and post-menopausal women (n=64) with CAD and compared these parameters with those of healthy pre-menopausal (n=31) and post-menopausal women (n=88). The prospective part of the study analyzed the effect of HRT with transdermal estrogen with or without progestogen in post-menopausal women with CAD.Pre- and postmenopausal women with CAD showed significant lower fibrinolytic activity and higher plasminogen activator inhibitor type 1 (PAI-1) levels than their control groups. Lp(a) levels were higher in premenopausal women with CAD than in healthy premenopausal women. In post-menopausal women with CAD, HRT induced a significant decrease in PAI-1 and Lp(a) levels. No significant differences were observed in any parameter studied between the groups treated with transdermal estrogen with and without progestogen.CAD is associated with a decrease in fibrinolytic activity, possibly due to an increase in PAI-1 levels. An increase in fibrinolytic activity and a decrease in PAI-1 and Lp(a) levels were observed in CAD women receiving transdermal HRT and these changes may have a favorable impact on the risk of new cardiovascular events in post-menopausal CAD women.

The prothrombin G20210A mutation and factor V Leiden have been found to be associated with an increased risk of venous thrombosis, but the reported prevalences of the prothrombin gene variant both in the normal population and in patients with deep venous thrombosis (DVT) vary greatly in the literature. Moreover, the influence of oral contraceptives (OC) on thrombotic events in patients with the prothrombin G20210A variant has not been well established. In this study we evaluate both circumstances.A case-control study was run on 229 patients with DVT and 246 healthy controls. The patients' history of thrombosis and acquired thrombotic risk factors, especially OC, were recorded. Prothrombin G20210A mutation, factor V Leiden, antithrombin, heparin II cofactor, plasminogen and proteins C and S were evaluated.Seven and a half percent of the patients and 2.9% of the controls were carriers of the prothrombin mutation, while 12.2% of the patients and 1.6% of the controls had factor V Leiden. Among the 229 DVT patients there were 130 patients with clinically suspected thrombophilia (first thrombotic event occurring before the age of 45 years or positive family history of thrombosis or recurrent venous thrombosis). Ten percent of these 130 patients were carriers of the prothrombin G20210A mutation and 18.5% had the factor V Leiden mutation. The odds ratios (OR) for DVT risk were: 2.4 (95% CI, 1.0-6.3) for the total DVT patients and 5.2 (95% CI, 1.4-19.5) for the patients with clinically suspected thrombophilia with the prothrombin mutation. The risk of thrombosis was 6.9 (95% CI, 2.3-20.6) for the DVT patients and 14.3 (95% CI, 3.3-64.6) for the patients with clinically suspected thrombophilia with factor V Leiden. Fifty-five percent of the patients with combined congenital defects (prothrombin mutation G20210A plus another congenital defect) had recurrent thrombosis. In women receiving OC the risk of DVT was 3.5 (95% CI, 1.5-8.2) that of the patients not receiving OC. When women with combined defects were also taking OC, the risk of thrombosis increased significantly.The prevalence of the prothrombin G20210A mutation in the healthy population in our study is similar to that observed in other southern European countries. The prothrombin G20210A mutation does not by itself seem to be a high thrombotic risk factor. However, when it is present together with other thrombotic risk factors, the predicted risk of thrombotic events increases. The use of OC by women with the prothrombin G20210A variant or FV Leiden, either alone or combined with other thrombotic risk factors, was associated with a significant increase in the risk of venous thrombosis.

Most exercise testing is performed in adults with known or suspected ischemic heart disease. In the last few years cardiac imaging techniques have been applied in this field, improving the information obtained with the procedure. However, the exceptions to this rule are emerging rapidly not only in healthy people (asymptomatic individuals, athletes, handicapped people) but also in cardiac patients (advanced congestive heart failure, hypertension, rhythm disorders, congenital heart disease, etc.). All the-se issues justify the need for a multidisciplinary consensus document in Spain. This paper reviews and updates the methodological aspects of the stress test, including those related to oxygen consumption measurements. The main aim of this review was to determine the role of exercise testing in the evaluation of ischemic heart disease as well as the applications of imaging stress testing. The usefulness of this test in other non-ischemic cardiac disorders and in selected subsets of healthy people is also reviewed.

We describe the thrombophilic and clinical characteristics of a group of patients who suffered venous thrombosis (VT) (n = 36) and ischemic stroke (n = 8) while taking oral contraceptives (OC). Our purpose is to ascertain whether there are differences between users of second and third generation progestogen and to investigate the influence of concurrent congenital and acquired risk factors (other than OC) on the onset of the thrombosis. The group of patients included 36 women with VT and eight with ischemic stroke. The patients' recognized predisposing factors were recorded. We also considered age, length of time on OC, types of OC, rethrombosis, family history of VT, and the presence of thrombophilic genetic defects. In the group of patients with VT, 54% were treated with second generation OC (n = 23), and 30% (n = 11) were treated with third generation OC. We found no significant statistical differences with respect to age and length of time on OC between the two types of OC. The prevalence of genetic defects in these patients--factor V (FV) Leiden, prothrombin G20210A mutation and protein S deficiency--was 19% (n = 7), 17% (n = 6), and 8% (n = 3) respectively. We observed the shortest time lapse between initiating OC and the first thrombotic event in carriers of FV Leiden and in patients with combined defects, but the differences were not significant. In patients with ischemic stroke, 50% were treated with second generation OC and 50% were treated with third generation OC. Prothrombin G20210A mutation was detected in two patients. In both patients,the stroke occurred earlier than in the rest of the patients, but these differences were not statistically significant. With respect to preventing thrombotic events in these patients, our data suggest that OC therapy should be avoided in patients with a previous history of thrombosis and in patients with an evident thrombotic tendency in the family. In patients in whom the family history of thrombosis is not very evident, it would be recommended to screen for FV Leiden, prothrombin G20210A mutation, and protein S, and to rule out OC if the patient does in fact have one of these risk factors. Moreover, if a patient develops a thrombotic complication while taking OC, an evaluation to search for a thrombophilic defect is warranted, and at the same time, alternative methods of contraception should be considered.

A D-dimer assay can be helpful to rule out thromboembolism provided it is sensitive, reliable, fast and easy to perform. Tests based on the ELISA methodology have a high diagnostic sensitivity, and are therefore adequate for excluding deep venous thrombosis (DVT). The drawbacks are their long assay times, unsuitability to be run on single samples and cost. New methods have been developed, based either on the same principle, by immunofiltration or by microlatex immunoturbidimetric assays which seem to reach the high sensitivity and negative predictive value (NPV) required, but allowing fast and quantitative single sample analysis. The aim of this work was to evaluate one rapid test, a fully automated quantitative assay (IL Test D-dimer, run on an ACL 7000 coagulation analyzer, Instrumentation Laboratory).We compared the diagnostic value of IL Test for DVT with that of an ELISA (Dimertest Gold EIA Agen Biomedical Limited, Acacia Ridge, Australia). Eighty-six patients (43 men, 43 women, mean age: 61 years) showing DVT symptoms formed the population for this non-randomized controlled trial in a referral center. The diagnosis of DVT based on the clinical history, was confirmed by serial compression ultrasonography (CUS) with Doppler flow in 62 patients.The IL Test D-dimer proved to be rapid, automated and well suited for individual tests with a good reproducibility in three control plasmas with different concentrations of D-dimer (coefficient of variation range 0.54-3. 87%). Its performance was comparable to that of the Dimertest Gold EIA, as indicated by the areas under the receiver operating characteristic curves (Dimertest Gold EIA 0.748; IL Test D-dimer 0.70). On the basis of kappa coefficients, there was a good concordance between the Dimertest Gold EIA and IL Test D-dimer when the receiver operating characteristic (ROC) curves suggested cut-offs were used. The sensitivity (98.3%) and NPV (88.9%) shown by IL Test D-dimer are comparable or even better than those obtained for EIA (95%, 80%, respectively).This study shows that the new method can be included in prospective clinical trials to test the utility of D-dimer measurement in combination with other non-invasive diagnostic procedures in the management of DVT diagnosis.

The effect of a binifibrate (Biniwas Retard, Wasserman) on the plasma lipids and hemorheological profile of 30 primary hyperlipemic patients was studied. Our results indicate that the patients under study had evident rheological alterations as well as the expected lipid alterations. Treatment with Biniwas (2 x 550 mg/day) for six months not only substantially improved the alterations in the lipid balance but also tended to normalize the patients' hemorheological alterations, and there was a statistically significant correlation between the two effects. Apart from the decrease in plasma viscosity (1.20 +/- 0.05 vs 1.29 +/- 0.07 mPa.s, p0.001), the most noteworthy effects of Biniwas treatment were the decrease in red blood cell aggregability (8.7 +/- 1.2 vs 9.3 +/- 1.1, p0.05) and increased deformability (55 +/- 3 vs 47 +/- 5%, p0.001). Both changes may be due to modifications in the lipid composition of the erythrocyte membrane due to cell-plasma lipid exchange.

In order to ascertain whether young asymptomatic patients with heterozygous familial hypercholesterolemia (FH) but without clinical signs of atherosclerosis have increased plasma thrombomodulin (TM) levels expressing early endothelial damage, we determined TM in 23 heterozygous FH subjects (aged 28-44 years, x: 32 +/- 6) and in a well matched control group (CG). In addition, carotid Doppler ultrasonography was done in all the patients and controls in order to assess the state of the vascular tree. Results show a tendency for FH subjects to have higher TM values than the CG (37.8 +/- 14.2 ng/ml vs. 30.1 +/- 11.2 ng/ml), although the differences are not statistically significant. When taken together the results of TM and carotid ultrasound, the sensitivity and specificity of the former were only 66% and 80%, respectively. The fact that only 66% of the FH patients with atherosclerotic injury had high TM values eliminates the possibility of using this as an early marker of atherosclerosis in FH individuals.

Epidemiological studies suggest that hormone replacement therapy (HRT) decreases the risk of cardiovascular disease in postmenopausal women via several mechanisms, including modifications in the fibrinolytic system and lipoprotein(a) [Lp(a)] levels. The aim of this study was to examine the influence of the levels and isoforms of Lp(a) on fibrinolytic activity in 91 postmenopausal women in comparison with premenopause and analyze the effect of HRT on those parameters. In postmenopause, an increase in plasma Lp(a) and plasminogen activator inhibitor-1 (PAI-1) levels was found. A significant inverse correlation was observed between Lp(a) or PAI-1 levels and plasmin generation. Plasma samples with low molecular weight (MW) apo(a) isoforms showed higher plasmin inhibition than plasmas with high MW apo(a) isoforms and similar levels of total Lp(a) and PAI-1. HRT induced a significant decrease in Lp(a) and PAI-1 levels and an increase in estradiol levels, as well as an increase in fibrinolytic activity. A significant correlation was found between the percentages of variation in Lp(a) levels and in plasmin generation and between the percentages of variation in PAI-1 levels and in the euglobulin lysis time under HRT. In conclusion, the increase in fibrinolytic activity observed in women under HRT could be explained by two independent mechanisms: (a) the decrease in PAI-1 and (b) the decrease in the inhibition of plasmin generation due to the decrease in Lp(a) levels.

We describe the case of a 39-year-old woman who suffered two iliofemoral venous thromboses, a cerebral ischemic infarct and recurrent fetal loss. Initial studies showed high levels of antiphospholipid antibodies (APAs) and a moderate thrombocytopenia. After her second miscarriage, laboratory diagnosis revealed that the woman was heterozygous for the factor V Leiden mutation and had a functional protein S deficiency as well as anti-protein S and anti-beta 2-glycoprotein I antibodies. The impairment of the protein C pathway at various points could well explain the recurrent thromboses in the patient and supports the role of a disturbed protein C system in the pathophysiology of thrombosis in patients with APAs.

Deep vein thrombosis (DVT) seems to be related to a hypercoagulation and definite hemorheological alterations, but the importance of these alterations in the development of thrombotic events in the deep vein system has not been established. The present study examines both aspects in a group of 55 patients with DVT; the presence of a hypercoagulable state was assessed by quantifying the prothrombin fragment 1+2 (F1+2) and the thrombin-antithrombin III complex (T-AT), and the main hemorheological parameters were evaluated in the acute state and 6 and 12 months later. The results show marked hemorheological, F1+2, and TAT alterations in the acute phase. After 12 months the pattern shows a modest improvement, but erythrocyte aggregation, fibrinogen, F1+2 and T-AT remain increased with respect to the control group (8.51 +/- 1.43; 331 +/- 81 mg/dl; 1.33 +/- 0.60 nmol/l; 3.54 +/- 1.71 ng/ml vs. 8.10 +/- 1.40; 230 +/- 38; 0.94 +/- 0.40; 1.56 +/- 0.59, respectively). These data suggest that the thrombotic event could be influenced by the previous rheological situation and hypercoagulable state.

In order to ascertain whether young familial hypercholesterolemic subjects without atherosclerotic lesions demonstrable on a carotid echo-Doppler show decreased erythrocyte deformability, we determined the erythrocyte elongation index (EEI) by means of a shear stress diffractometer (Rheodyn SSD) in twenty-four children with heterozygous familial hypercholesterolemia (FH), aged 12 +/- 3 years, and their corresponding affected parent. The parents were twenty-three adults with heterozygous FH aged, 32 +/- 6 years. The control group was made up of a similar number of well matched healthy volunteers. The EEI at 6, 12, 30 and 60 Pa showed no statistical differences between FH children and their control group, or between FH parents and their control group. No correlations were found between EEI and plasma lipids or lipoproteins at any of the shear stresses used. These results suggest that the red blood cells of young familial hypercholesterolemic subjects who show no deterioration of the vascular tree are not less deformable than those of healthy normolipemic subjects, and that dyslipemia itself does not produce alterations that damage the rheological properties of the red blood cell.

In order to ascertain whether the increased aggregability observed in the red blood cells of diabetic patients is induced exclusively by plasma factors or is also influenced by membrane lipids, we examined the phospholipids of the erythrocyte membrane, the plasma fibrinogen concentration and erythrocyte aggregation in 86 insulin and non insulin-dependent diabetic patients. The data obtained show that the erythrocyte aggregability of the diabetic patients is higher than that of the control group (10.0+/-2.4 vs. 7.8+/-1.6%). This increased aggregability correlates not only with a higher fibrinogen concentration but also with changes observed in the membrane phospholipids. The percentage of sphingomyelin (SP) in the patients is higher than in the controls (22.6+/-6.8 vs. 18.4+/-5.4%) and that of phosphatidylserine (PS) is lower (9.5+/-6.1 vs. 12.1+/-5.1%). No differences in the percentages of the other two phospholipids identified (phosphatidylcholine, PC, and phosphatidylethanolamine, PE) were observed. The increase in the saturated nature of the phospholipids of the erythrocyte membrane, which can be measured by the (SP + PC)/(PE + PS) ratio, is statistically related (r = 0.39; p0.05) to the increased red blood cell aggregability observed in these patients.

It has been observed that the apo(a) isoforms of low molecular weight predict the family history of premature ECV. Our objective was to study the relationship between the levels of Lp(a) and the isoforms of apo(a) in parents and children.Twenty-four families, where at least one of the children had been diagnosed with familial or polygenic hypercholesterolemia and at least one of these children and one parent had Lp(a)or = 30 mg/dl, were studied. They were classified according to whether Lp(a) wasor =30 mg/dl, with 44 and 38 subjects in each group, respectively. The total cholesterol, triglycerides, HDL and LDL, the Lp(a) and apo(a) isoforms were determined, as well as the relative concentration of the latter.The molecular weight average of the major isoform was lower in the group with high Lp(a) levels (592 +/- 38 vs 656 +/- 65 kD, p0.001). An inverse correlation between Lp(a) levels and the major isoform size was found (r = -0.522, p0.001). The correlation of the Lp(a) levels in the child with that of his or her "best fit" (the best fit parent was that whose level was closer to that of the child) was very significant (r = 0.61, p0.01), but lower than the corresponding paternal apo(a) isoform levels (r = 0.801, p0.01). The study of the apo(a) isoforms in parents and their children suggests not only that the isoform is inherited, but also its concentration.Subjects with small size apo(a) isoforms have higher Lp(a) levels. There is a better correlation between parents and children in the phenotypes of the apo(a) than in Lp(a) levels. The determination of these parameters allows the identification of a risk population.

Investigation of the urethral flora in men with urethritis, with particular reference to anaerobic bacteria.Multiple cultures were performed on three urethral samples from 110 men attending the STD Clinic of the School of Medicine in Seville: 35 with no evidence of urethritis (control group), and 75 with urethritis (17 gonococcal urethritis (GU) and 58 non-gonococcal urethritis (NGU)). In the 58 men with NGU, Chlamydia trachomatis was isolated in 16 (27.5%), Ureaplasma urealyticum in 18 (31%), Trichomonas vaginalis in two (3.4%) and no pathogens were isolated in the remaining 22 (38%) patients.Aerobic flora, mainly Staphylococcus spp., were isolated less frequently (41%) in patients with GU than in the control group (80%), and those with NGU (72%). Anaerobic flora were isolated in 62% of patients, with similar isolation rates in each group. Gram-negative anaerobes were more frequently isolated in men with urethritis, especially NGU, compared to controls (P0.05). Prevotella spp. and Bacteroides spp. were significantly more frequently isolated in patients with NGU, including Chlamydia-negative NGU. Fusobacterium spp. were more frequent in the Chlamydia-positive NGU than in the controls (P0.05). P. magnus was the most frequent anaerobic species found in the control group, while P. prevotii was most frequently seen in the urethritis group. B. ureolyticus, P. prevotii and P. tetradius were more frequent on the NGU group (P0.05). B. ureolyticus was commoner in patients with Chlamydia-negative NGU, while P. tetradius and P. asaccharolytica was commoner in those where C. trachomatis was isolated than in the control group.Urethral microflora isolated showed ten bacterial genus and 25 different species of anaerobes. The spectrum of these microflora changed with the presence of urethritis and varied with its aetiology.

Increased levels of lipoprotein (a) [Lp(a)] have been considered an independent risk factor for cardiovascular disease, but the mechanism behind this relationship is not completely understood. A high concentration of Lp(a) may interfere with fibrinolysis because of the structural similarity between apo(a) and plasminogen. The aim of the present study was to examine the influence of apo(a) levels and isoforms on fibrinolytic activity in 82 subjects from 24 families in which the Lp(a) levels wereor =30 mg/dl in at least one child and one parent. Several fibrinolytic parameters, including plasmin generation by fibrin-bound tissue plasminogen activator, the lipid profile and apo(a) isoforms were studied. Subjects with high circulating Lp(a) levels (n = 44) had significantly reduced plasmin generation compared with their relatives with normal Lp(a) levels (n = 38). A significant inverse correlation between Lp(a) levels and plasmin generation was observed. The individuals with a combination of high levels of plasma Lp(a) and a major apo(a) isoformor =580 kD molecular weight show the lowest fibrinolytic activity. A high correlation was found between the levels of apo(a) isoforms in children and the levels of the corresponding parental apo(a) isoforms. We conclude that the antifibrinolytic effect of Lp(a) in subjects with two apo(a) isoforms may depend not only on the total plasma level of Lp(a) but also on the relative concentration of the small apo(a) isoform.

The authors describe a false outbreak of tuberculosis by contamination in sample processing.The longitudinal polymorphisms of restriction fragments (RFLPs) of 6 strains of Mycobacterium tuberculosis isolated in different patients over a three week period and which were apparently implicated in an outbreak of tuberculosis were analyzed.Four of the strains studied presented identical restriction pattern and the remaining two presented totally different patterns. Following study of the clinical histories and the epidemiologic relationships three cases of tuberculosis were confirmed. The other three strains isolated corresponded to contamination during the sampling process.In a possible outbreak of six cases of tuberculosis, molecular techniques have allowed identification of three true cases of tuberculosis and have demonstrated contamination during the sampling process in three other cases. The latter could not have been shown with the clinical and phenotypical data of the strains.

Elevated plasma levels of type 1 plasminogen activator inhibitor (PAI-1) have been implicated in mediating the fibrin deposition and occlusive lesions that occur within the placental vasculature in preeclampsia (PE) and intrauterine growth retardation (IUGR). In this report we identify the cells within the normal-appearing villous tissue that are responsible for the local production of PAI-1 in women with PE and IUGR. Levels for another fibrinolytic inhibitor (ie, type 2 plasminogen activator inhibitor [PAI-2]) were determined for comparative purposes. Elevated levels of PAI-1 were detected in placenta extracts from PE/IUGR patients (121 +/- 38 ng/mg, n = 8) when compared with the levels in placenta extracts from normal women (43 +/- 17 ng/mg, n = 10) or women with IUGR but not PE (51 +/- 22 ng/mg, n = 11). Immunohistochemical analysis of paraffin sections showed an increased immunoreactivity for PAI-1 in the placental villous syncytiotrophoblasts from PE/IUGR women compared with the immunostaining of placental samples from the normal or IUGR group. In contrast, antigen levels and immunostaining for PAI-2 were reduced in the placentas harvested from not only the PE/IUGR women (209 +/- 144 ng/mg) but also the IUGR group (169 +/- 106 ng/mg) in comparison with the PAI-2 levels in normal placentas (535 +/- 98 ng/mg). To document that the increased immunoreactivity for PAI-1 in PE/IUGR syncytiotrophoblasts was mediated by an increased production of PAI-1 within these cells, in situ hybridization analysis was performed. A strong positive signal for PAI-1 mRNA in villous syncytiotrophoblasts from PE patients (n = 5) was obtained after 2 weeks of exposure to the NTB2 emulsion in comparison with the weak signal for PAI-1 mRNA that required a 10-week exposure of the normal placenta sections (n = 10). Northern blotting for PAI-1 mRNA showed that both transcripts (ie, 3.2 and 2.3 kb) were elevated in samples of two PE patients in comparison with the PAI-1 mRNA transcripts present in a normal placenta and an IUGR placental sample. These results show increased PAI-1 and mRNA levels in placentas from PE patients and raise the possibility that localized elevated levels of PAI-1 may play a role in the initiation of placental damage, as well as in the thrombotic complications associated with this disease.

Pyomyositis (PMS) is a primary infection of striated muscle. Recent scanty reports suggest that non-tropical PMS may differ from classical tropical PMS. To address this question, 12 cases of nontropical PMS seen at two hospitals between 1976 and 1992 were reviewed and an English-literature search of similar cases was conducted. Both the series and reported cases are pooled together and herein reported. The age distribution of the 97 patients showed 30-50 and 60-70-year peaks, with a 3:1 (male-female) ratio. Fever, high erythrocyte sedimentation rate, and muscle stiffness or inflammation were present in more than 75% of patients. Muscles of the thigh (54%), back (13%), buttock (11%), arm (9%), or chest wall (4%) were involved. Staphylococci (61%), gram-negative bacilli (16%), streptococci (12%), and fungi (2%) were isolated from muscle specimens. Human immunodeficiency virus infection, diabetes mellitus, hemopoietic disorders, and other conditions with defective neutrophil function were present in 64 patients (66%). Drainage of pus and antibiotic therapy were the standard treatments. The mortality rate reached 10%. Analysis of patients classified by the comorbid condition showed differences in age, causative microorganisms, clinical features, and death rate. It is concluded that several clinical presentations of nontropical PMS are at variance with that of tropical PMS.

Erythrocytes promoted platelet reactivity in a plasma medium, as demonstrated in an in vitro system that independently evaluated the biochemistry of platelet activation and recruitment. The prothrombotic erythrocyte effects were metabolically regulated, as evidenced by lack of activity of ATP-depleted or glutaraldehyde-fixed erythrocytes. They occurred in the absence of cell lysis as verified by lactate dehydrogenase assays, and had an absolute requirement for platelet activation. The presence of erythrocytes induced a twofold increase in platelet thromboxane B2 (TXB2) synthesis upon collagen stimulation, indicating that erythrocytes modulated platelet eicosanoid formation. Cell-free releasates from stimulated platelet-erythrocyte suspensions, which exhibited increased recruiting capacity, contained 6.9-fold more ADP and 4.9-fold more ATP than releasates from stimulated platelets alone. Following aspirin ingestion, TXB2 formation was blocked, but erythrocyte promotion of platelet reactivity persisted at those doses of collagen that reinduced platelet activation. Moreover, when platelet mixtures consisted of as little as 10% obtained before aspirin plus 90% obtained post-aspirin ingestion, significant erythrocyte enhancement of platelet reactivity occurred, even at low agonist concentrations. These erythrocyte effects would decrease the therapeutic potential of inhibition of platelet cyclooxygenase by aspirin. The erythrocyte-induced modulation of platelet biochemistry and function emphasizes the importance of cell-cell interactions in stimulus-response coupling.

Red blood cells (RBC) increase the proaggregatory capacity of a cell-free supernatant obtained by stimulating platelet-rich plasma (PRP) samples with collagen (1 microgram/ml) as measured by the BASIC wave; this effect increases with the number of RBC and is proportionally greater with a lower number of platelets or when lower collagen concentrations are used. Aspirin (ASA) modifies the RBC behaviour in relation to their platelet-collagen interaction. This is demonstrated by the fact that when PRP and RBC obtained from the same subjects before and two hours after the ingestion of ASA (0.5 g) were mixed, it was found that non-ASA-RBC stimulate ASA-PRP, probably through a platelet cyclooxygenase independent pathway; ASA-RBC, however, stimulate non-ASA-PRP, but not ASA-PRP, which suggests that they may need an active platelet cyclooxygenase system for their action. This effect of ASA on RBC is not transient and was also observable 48 h after ASA ingestion. In addition, it was found that ASA-RBC greatly increase the activation of a mixture containing a small proportion of non-ASA-PRP in ASA-PRP, a situation that is expected to be encountered "in vivo" after ASA treatment. This effect of ASA-RBC on platelet activation may help to explain the sometimes contradictory clinical effect of aspirin as an antithrombotic drug.

The in vitro release of B-thromboglobulin (BTG) from platelets after stirring the platelet rich plasma (PRP) 5 min (37 degrees C/1000 rpm) was studied in a group of 13 healthy subjects before and after 'in vivo' aspirin ingestion, 1 g/d for 3 d. A significant reduction in the platelet BTG release (31%) was observed after aspirin ingestion in comparison to the pre-aspirin values, suggesting that the BTG release by stirring is related to a platelet activation process. Small doses of collagen (0.625 microgram/ml) and thrombin (0.1 U/ml) always released platelet BTG, whether or not there was a visible platelet aggregation, suggesting that platelet activation is not necessarily followed by visible platelet aggregation. A significant correlation was found between the BTG released by stimulation with collagen (2.5 microgram/ml) and thrombin (0.2 U/ml) and the maximum velocity and intensity of the aggregation curve parameters.

Twenty adult surgical patients aged between 15 and 83 years (mean:45), 10 of whom had wound infections (one complicated with septicaemia), 2 with septicaemia, 1 with gynecological infection complicated with endocarditis, 5 with urinary tract infections and 2 with lower respiratory tract infections, were treated with parentally-administered cefotaxime. Aetiology was Proteus 7, E. coli 4, Pseudomonas 3, Enterobacter 2, Klebsiella 2 and 2 Serratia. Susceptibility testing was determined by the agar dilution method, with MIC values ranging from 0.01 to 5 microgram/ml, with two urinary isolates of Pseudomonas with MIC of 20 microgram/ml. Clinical responses were excellent in 13 (65 per cent) cases, moderate in 2 (10 per cent) and 3 (15 per cent) failed to respond to therapy. Clinical assessment was not possible in three patients. Bacteriological responses were excellent in 14 (70 per cent) cases, poor in 4 (20 per cent) and in two there was no follow-up. Systemic tolerance was good in all patients except one.

The relevance of mixed genital infections in our area was evaluated, and we report their clinical and epidemiological features for both viral types. We evaluated overall 54 Herpes simplex virus (HSV) isolates from 44 patients seen at the clinic of sexually transmitted diseases (STD) of the Sevilla School of Medicine during 1986 and 1987. The identification of the isolated strains was made by direct immunofluorescence with type-specific monoclonal antibodies. In those isolates where we detected both viral types confirmation was obtained with the endonuclease analysis: Hind III and Xho I. Four mixed infections were diagnosed, representing 7% of all HVS isolates of genital origin. Two were classified as initial nonprimary infections, and the remaining two were asymptomatic infections. Two patients showed simultaneous infections by other organisms.

It is shown that the supernatant of unstirred whole blood at 37 degrees C, stimulated by 1 microgram/ml of collagen for 10 sec, produces a rapid generation of pro and antiaggregatory compounds with a final proaggregatory activity which can be detected for more than 60 min on a platelet rich plasma (PRP) by turbidometric aggregometry. A reversible aggregation wave that we have called BASIC wave (for Blood Aggregation Stimulatory and Inhibitory Compounds) is recorded. The collagen stimulation of unstirred PRP produces a similar but smaller BASIC wave. BASIC's intensity increases if erythrocytes are added to PRP but decreases if white blood cells are added instead. Aspirin abolishes "ex vivo" the ability of whole blood and PRP to generate BASIC waves and dipyridamole "in vitro" significantly reduces BASIC's intensity in whole blood in every tested sample, but shows little effect in PRP.

Free erythrocyte protoporphirin (FEP), along with diverse haematologic and iron metabolism data, were determined in 60 carriers of the thalassaemic trait (29 beta and 31 delta beta). FEP rates were significantly higher in thalassaemia carriers (39.04 +/- 14.12 micrograms/dl) than in a control group (24.95 +/- 4.70 micrograms/dl) (p less than 0.05). No correlation between FEP and any other iron metabolism parameter, or the severity of anaemia, was found. No FEP differences appeared between the beta (41.06 +/- 16.5 micrograms/dl) and delta beta (37.1 +/- 11.06 micrograms/dl) traits, so, although FEP rates are increased in thalassaemia carriers, they are useless in differentiating between the commonest thalassaemic forms in our country.

Red-cell deformability was assessed with the Hanss' haemorheometer in 63 carriers of the thalassaemic trait (20 beta and 43 delta beta). Impaired deformability (rigidity index 10.5 +/- 1.4) was present in 80% of the carriers of both beta- and delta beta-traits, as compared with a control group (rigidity index 8.7 +/- 0.6). No correlation was found between such indices and several parameters capable of influencing upon red-cell deformability, namely, MCV, MCH, RDW and MDA. The possibility of any impairment of lipid compounds in red cell membrane is suggested as a cause of decreased deformability in thalassaemia carriers.

A total of 200 cases of thalassaemia trait, 102 of F thalassaemia and 98 of A2 thalassaemia were studied, evaluating haematometric, and morphological aspects of both groups. Significantly higher values were found in F thalassaemia for PCV, MCV and MCH, with 33.5% of women and 52% of men being found anaemic in F thalassaemia and 45% of women and 62% of men in A2 thalassaemia. Asthenia was usually present in A2 thalassaemia more so in women 50.9% as compared to 25% in man. Only 4% of F thalassaemia carriers were affected by asthenia. Cholecystectomy had been performed on 10% of the A2 thalassaemia group and on 5% of the F thalassaemia thamia group. Both groups show a high proportion of red cells with basophilic stippling (80%), the groups being morphologically indistinguishable. Intrafamilial segregation of Hb F values affected 22% of families carriers of F thalassaemia, whereas only 8% of families carriers of A2 thalassaemia showed segregation of HbA2 values. The values obtained in this study were compared with those of other authors.

The functional activity and active site of plasmin in full-term newborns have been studied and compared to those in adults in order to investigate the nature of the abnormality found in newborn plasminogen described in a previous paper. The functional activity of newborn plasminogen measured on chromogenic substrate was approximately 18% that of adult plasminogen when streptokinase was used as an activator and 12% when urokinase was used. Proteolysis of newborn plasminogen by urokinase yielding a two-chain plasmin form occurred normally, but the incorporation of diisopropylphosphorofluoridate into the light chain of newborn plasmin was approximately 23% of that observed in the light chain of adult plasmin. These observations suggest that the abnormality of full-term newborn plasminogen is located in the active site of the molecule.