Infective endocarditis treated in a secondary hospital: epidemiological, clinical, microbiological characteristics and prognosis, with special reference to patients transferred to a third level hospital.

OBJECTIVE: To analyse the clinical and epidemiological characteristics and mortality-related factors of patients admitted to a secondary hospital with Infective Endocarditis (IE). METHODS: Observational study of a cohort of patients who have been diagnosed with IE in a secondary hospital and evaluated in accordance with a pre-established protocol. RESULTS: A total of 101 cases were evaluated (years 2000-2017), with an average age of 64 years and a male-to-female ratio of 2:1. 76% of the cases had an age-adjusted Charlson comorbidity index of >6, with 21% having had a dental procedure and 36% with a history of heart valve disease. The most common microorganism was methicillin-susceptible S. aureus (36%), with bacterial focus of unknown origin in 54%. The diagnostic delay time was 12 days in patients who were transferred, compared to 8 days in patients who were not transferred (p=0.07); the median surgery indication delay time was 5 days (IQR 13.5). The in-hospital mortality rate was 34.6% and the prognostic factors independently associated with mortality were: cerebrovascular events (OR 98.7%, 95% CI, 70.9-164.4); heart failure (OR 27.3, 95% CI, 10.2-149.1); and unsuitable antibiotic treatment (OR 7.2, 95% CI, 1.5-10.5). The mortality rate of the patients who were transferred and who therefore underwent surgery was 20% (5/25). CONCLUSIONS: The onset of cerebrovascular events, heart failure and unsuitable antibiotic treatment are independently and significantly associated with in-hospital mortality. The mortality rate was higher than the published average (35%); the diagnostic delay was greater in patients for whom surgery was indicated.

[Pneumonia in patients with SARS-CoV-2 infection: series of 17 cases in the region of Murcia]. / Neumonía neumocócica en pacientes con infección por SARS-CoV-2: serie de 17 casos en la Región de Murcia.

OBJECTIVE: Currently the prevalence of pneumococcal coinfection in patients with COVID-19 is unknown. In this work we present its clinical characteristics, evolution and treatment. METHODS: Retrospective data collection from August to October 2020 in two hospitals in the Murcia region. RESULTS: Eighteen patients had COVID-19 diagnosed by PCR and pneumococcal infection confirmed by antigenuria, which represented a prevalence of 2%. A total of 88% had radiological alterations upon admission (two patients had an X-ray within normality) and 29% had elevated procalcitonin. Mortality in our series was 12%. CONCLUSIONS: It could be reasonable to consider the start of antimicrobial therapy in those cases in which there is a moderate or high suspicion of bacterial coinfection, being essential the early suspension of antibiotic treatment if it is not confirmed.

Alcohol binge disrupts the rat intestinal barrier: the partial protective role of oleoylethanolamide.

BACKGROUND AND PURPOSE: Chronic alcohol consumption alters the gut-brain axis, but little is known about alcohol binge episodes on the functioning of the intestinal barrier. We investigated the influence of ethanol binges on bacterial translocation, gut inflammation and immunity, and tight junction (TJ) structure and the ability of the biolipid oleoylethanolamide (OEA) to prevent ethanol binge-induced intestinal barrier dysfunction. EXPERIMENTAL APPROACH: OEA was injected i.p. before repeated ethanol administration by oral gavage. Plasma, spleen, liver and mesenteric lymph nodes (MLN) were collected in sterile conditions for determination of bacterial load. Immune/inflammatory parameters, TJ proteins and apoptotic markers were determined in colonic tissue by RT-PCR and Western blotting. TJ ultrastructure was examined by transmission electron microscopy. KEY RESULTS: Ethanol binges induced bacterial translocation to the MLN (mainly) and spleen. Colonic tissues showed signs of inflammation, and activation of innate (Toll-like receptor-4) and adaptive (IgA) immune systems and TJ proteins (occludin and claudin-3) were decreased after ethanol binges. Pretreatment with OEA reduced intestinal inflammation and immune activation and partially preserved the TJ structure affected by alcohol binges but had no effect on alcohol-induced apoptosis. Ultrastructural analyses of colonic TJs revealed dilated TJs in all ethanol groups, with less electron-dense material in non-pretreated rats. The protective effects of i.p. OEA did not reduce bacterial translocation to the MLN. However, intragastric OEA administration significantly reduced plasma LPS levels and bacterial translocation to the MLN. CONCLUSION AND IMPLICATIONS: OEA-based pharmacotherapies could potentially be useful to treat disorders characterized by intestinal barrier dysfunction, including alcohol abuse.

[Design and implementation of an outpatient parenteral antimicrobial therapy program in primary care: the experience at a second level hospital]. / Design and implementation of an outpatient parenteral antimicrobial therapy program in primary care: the experience at a second level hospital.

OBJECTIVE: Outpatient parenteral antimicrobial therapy (OPAT) programs are a good assistance option in a wide variety of infectious diseases. Our aim was to design and implement an OPAT program in the area of influence of a second-level hospital, with no Home Hospitalization Service available, being necessary close collaboration between hospitalization and Primary Care teams, describe our cohort, analyse the antimicrobial treatment indicated and evaluate the prognostic and risk factors associated with readmission and mortality. METHODS: Prospective study cohorts of patients admitted to the OPAT programme, from 1 January 2012 to 31 May 2015. RESULTS: During the period of study a total of 98 episodes were recorded. The average age of the cohort was 66 years. The most frequent comorbidity was immunosuppression (33.67 %), with an overall average of Charlson index of 5.21 ± 3.09. The most common source of infection was respiratory (33.67 %). Microbiological isolation was achieved in fifty-eight patients (59.18 %) being Escherichia coli the most frequently isolated (25%). The average number of days of antibiotics administration at home was 10.42 ± 6.02 (SD), being carbapenems (43.48%) the more administered. Eighty-six patients (87.75%) completed the treatment successfully. Thirty-two patients (32.65%) were readmitted within 30 days after being discharged and seven patients (7.14%) died. A statistically significant association was only found in the readmission with variables: elderly patients (p=0.03), being carriers of Porth-a-Cath (p=0.04) and treatment termination related with infection (p<0.05). CONCLUSIONS: This is the first programme of OPAT administration not dependent on Home Hospitalization Service in Spain, which could allow to optimize the hospital and primary care resources available. Nevertheless this pilot study results are poor in terms of optimization of antibiotics choice, transition to oral administration, de-escalation and duration.

Multiscale design of cell-type-specific pharmacokinetic/pharmacodynamic models for personalized medicine: application to temozolomide in brain tumors.

Optimizing anticancer therapeutics needs to account for variable drug responses in heterogeneous cell populations within the tumor as well as in organs of toxicity. To address cell heterogeneity, we propose a multiscale modeling approach-from in vitro to preclinical and clinical studies-to develop cell-type-specific pharmacokinetic-pharmacodynamic (PK-PD) models. A physiologically based mechanistic modeling approach integrating data from aqueous solutions, U87 glioma cells, mice, and cancer patients was utilized to characterize the brain disposition of temozolomide (TMZ), the cornerstone of chemotherapy against glioblastoma multiforme. The final model represented intracellular normal brain and brain tumor compartments in which TMZ pH-dependent conversion to the DNA-alkylating species leads to the formation of DNA adducts that serve as an entry point for a PD model. This multiscale protocol can be extended to account for TMZ PK-PD in different cell populations, thus providing a critical tool to personalize TMZ-based chemotherapy on a cell-type-specific basis.

Diagnostic and predictive value of urine PCA3 gene expression for the clinical management of patients with altered prostatic specific antigen.

OBJECTIVE: Analyze the impact of the introduction of the study of PCA3 gene in post-prostatic massage urine in the clinical management of patients with PSA altered, evaluating its diagnostic ability and predictive value of tumor aggressiveness. METHODS: Observational, prospective, multicenter study of patients with suspected prostate cancer (PC) candidates for biopsy. We present a series of 670 consecutive samples of urine collected post-prostatic massage for three years in which we determined the "PCA3 score" (s-PCA3). Biopsy was only indicated in cases with s-positive PCA3. RESULTS: The s-PCA3 was positive in 43.7% of samples. In the 124 biopsies performed, the incidence of PC or atypical small acinar proliferation was 54%, reaching 68,6% in s-PCA3≥100. Statistically significant relationship between the s-PCA3 and tumor grade was demonstrated. In cases with s-PCA3 between 35 and 50 only 23% of PC were high grade (Gleason≥7), compared to 76.7% in cases with s-PCA3 over 50. There was a statistically significant correlation between s-PCA3 and cylinders affected. Both relationships were confirmed by applying a log-linear model. CONCLUSIONS: The incorporation of PCA3 can avoid the need for biopsies in 54% of patients. s-PCA3 positivity increases the likelihood of a positive biopsy, especially in higher s-PCA3 100 (68.6%). s-PCA3 is also an indicator of tumor aggressiveness and provides essential information in making treatment decisions.

Cancer chronotherapeutics: experimental, theoretical, and clinical aspects.

The circadian timing system controls cell cycle, apoptosis, drug bioactivation, and transport and detoxification mechanisms in healthy tissues. As a consequence, the tolerability of cancer chemotherapy varies up to several folds as a function of circadian timing of drug administration in experimental models. Best antitumor efficacy of single-agent or combination chemotherapy usually corresponds to the delivery of anticancer drugs near their respective times of best tolerability. Mathematical models reveal that such coincidence between chronotolerance and chronoefficacy is best explained by differences in the circadian and cell cycle dynamics of host and cancer cells, especially with regard circadian entrainment and cell cycle variability. In the clinic, a large improvement in tolerability was shown in international randomized trials where cancer patients received the same sinusoidal chronotherapy schedule over 24h as compared to constant-rate infusion or wrongly timed chronotherapy. However, sex, genetic background, and lifestyle were found to influence optimal chronotherapy scheduling. These findings support systems biology approaches to cancer chronotherapeutics. They involve the systematic experimental mapping and modeling of chronopharmacology pathways in synchronized cell cultures and their adjustment to mouse models of both sexes and distinct genetic background, as recently shown for irinotecan. Model-based personalized circadian drug delivery aims at jointly improving tolerability and efficacy of anticancer drugs based on the circadian timing system of individual patients, using dedicated circadian biomarker and drug delivery technologies.

[Can home prophylaxis for venous thromboembolism reduce mortality rates in patients with chronic obstructive pulmonary disease?]. / Puede reducir la mortalidad de los pacientes con EPOC la profilaxis domiciliaria de la enfermedad tromboembólica venosa?

OBJECTIVE: The incidence of venous thromboembolism (VTE) in patients with chronic obstructive pulmonary disease (COPD) ranges from 20% to 60% in different studies and the mortality rates are higher for patients with both conditions. Heparin prophylaxis is therefore usually prescribed for COPD patients who are hospitalized for exacerbation. Once their situation becomes stable, however, they are discharged to home without prophylaxis even though the low level of physical activity their disease allows continues to put them at risk for VTE. The aim of this study was to test the efficacy of home heparin prophylaxis on reducing the incidence of VTE and on the overall mortality rate in patients with severe COPD. PATIENTS AND METHODS: We conducted a prospective, randomized controlled trial of 87 patients with severe COPD who required home oxygen therapy (> or =18 h/d) and whose physical activity was highly restricted. A total of 44 patients received low molecular weight heparin (3500 IU/d of bemiparin) subcutaneously for 6 months. The outcome measures were incidence of VTE and mortality at 3 and 6 months. RESULTS: Four patients (9.1%) died in the heparin group and 9 (20.4%) died in the control group; the difference was not statistically significant (P=.23). VTE without pulmonary embolism developed in 1 patient (2%) in each group. Slight bleeding complications appeared in 9 patients (20.4%) in the heparin group and 1 patient (2.3%) in the control group, a difference that was statistically significant (P=.015). CONCLUSIONS: Home prophylaxis with heparin does not reduce the incidence of VTE or overall mortality in patients with severe COPD.

¿Puede reducir la mortalidad de los pacientes con EPOC la profilaxis domiciliaria de la enfermedad tromboembólica venosa? / Can home prophylaxis for venous thromboembolism reduce mortality rates in patients with Chronic Obstructive Pulmonary disease?

Objetivo: La incidencia de enfermedad tromboembólica venosa (ETV) en pacientes con enfermedad pulmonar obstructiva crónica (EPOC) oscila entre el 20 y el 60% según las series, y la mortalidad por ETV es superior en estos enfermos. Por ello suele prescribirse profilaxis con heparina a los pacientes con EPOC hospitalizados por una agudización. Sin embargo, una vez que se estabiliza su situación, se les remite a su domicilio sin dicha profilaxis, a pesar de que la escasa actividad física que les permite su enfermedad sigue constituyendo un factor de riesgo para la aparición de ETV. El objetivo de este estudio ha sido analizar si la profilaxis domiciliaria con heparina reduce la aparición de ETV y la mortalidad global en los enfermos con EPOC evolucionada. Pacientes y métodos: Se ha realizado un ensayo clínico prospectivo aleatorizado con 87 pacientes afectados de EPOC grave que precisaban oxigenoterapia domiciliaria (18 h o más al día), con una alta limitación de la actividad física. Un total de 44 sujetos recibió heparina de bajo peso molecular (HBPM; 3.500 U/día de bemiparina) por vía subcutánea durante 6 meses. Las variables estudiadas fueron la incidencia de ETV y la mortalidad a los 3 y 6 meses. Resultados: Durante el estudio fallecieron 4 pacientes del grupo que recibió HBPM (9,1%) y 9 del grupo control (20,4%); las diferencias entre ambos grupos no fueron estadísticamente significativas (p = 0,23). Presentó trombosis venosa profunda sin embolia pulmonar un paciente de cada grupo (2%). Aparecieron complicaciones hemorrágicas leves en 9 pacientes del grupo con HBPM (20,4%), frente a una en el grupo control (2,3%), diferencia que fue estadísticamente significativa (p = 0,015). Conclusiones: La profilaxis domiciliaria con heparina no reduce la aparición de ETV ni la mortalidad global en los pacientes con EPOC avanzada

Objective: The incidence of venous thromboembolism (VTE) in patients with chronic obstructive pulmonary disease (COPD) ranges from 20% to 60% in different studies and the mortality rates are higher for patients with both conditions. Heparin prophylaxis is therefore usually prescribed for COPD patients who are hospitalized for exacerbation. Once their situation becomes stable, however, they are discharged to home without prophylaxis even though the low level of physical activity their disease allows continues to put them at risk for VTE. The aim of this study was to test the efficacy of home heparin prophylaxis on reducing the incidence of VTE and on the overall mortality rate in patients with severe COPD. Patients and methods: We conducted a prospective, randomized controlled trial of 87 patients with severe COPD who required home oxygen therapy (>=18 h/d) and whose physical activity was highly restricted. A total of 44 patients received low molecular weight heparin (3500 IU/d of bemiparin) subcutaneously for 6 months. The outcome measures were incidence of VTE and mortality at 3 and 6 months. Results: Four patients (9.1%) died in the heparin group and 9 (20.4%) died in the control group; the difference was not statistically significant (P=.23). VTE without pulmonary embolism developed in 1 patient (2%) in each group. Slight bleeding complications appeared in 9 patients (20.4%) in the heparin group and 1 patient (2.3%) in the control group, a difference that was statistically significant (P=.015). Conclusions: Home prophylaxis with heparin does not reduce the incidence of VTE or overall mortality in patients with severe COPD

S-100beta and MIA in advanced melanoma in relation to prognostic factors.

We compared the sensitivity and specificity of S-100 and MIA in advanced melanoma, in 96 patients with no evidence of disease (NED) and 86 patients with metastatic melanoma. Abnormal S100 (>0.2 microg/l) and MIA (>14 ng/ml) results were found in 1.1% and 3.2% of NED patients and in 59.3% and 54.6% of the patients with active melanoma (p<0.001). Using both tumor markers simultaneously, the sensitivity increased up to 69.8% with the same specificity 96.8%. S100 serum levels were not related to growth patterns. By contrast, MIA levels seemed to be related to the growth pattern, with higher levels in nodular melanoma (60.6+/-87.1 ng/ml) compared with acral-lentigous melanoma (11.9+/-5.4 ng/ml) (p=0.02). Likewise, S100 was related to the metastases site with significantly higher sensitivity and mean concentrations in patients with brain metastases (p=0.01) with the lowest in those with lung MI. MIA was related to the same metastases locations but without statistical significance. In summary, both S100 and ML4 are useful markers related to prognostic factors, being more effective when used in combination.

Long-term biochemical response after bisphosphonate therapy in Paget's disease of bone. Proposed intervals for monitoring treatment.

OBJECTIVES: To monitor the long-term evolution of Paget's disease activity after treatment with tiludronate by using serum total alkaline phosphatase (TAP) and more sensitive markers such as bone alkaline phosphatase (BAP), procollagen type I N propeptide (PINP) and urinary N-terminal cross-linking telopeptide of type I collagen (NTX); to analyse the predictors of long-term response to therapy; and to study the most appropriate intervals of time for monitoring the response to therapy. METHODS: Thirty-two patients with Paget's disease were included in the study. All received 400 mg of oral tiludronate daily for 3 months. A total of 21 patients completed the study. In these patients, serum TAP, BAP and PINP and urinary NTX were measured at baseline and at 1, 6, 12 and 24 months after discontinuation of therapy. Quantitative bone scintigraphy was performed at baseline and at 6 and 24 months after the end of treatment, obtaining a scintigraphic activity index (SAI). Patients were classified into two groups depending on the long-term response to treatment: Group 1, patients who presented a persistent and significant decrease in disease activity at this time, n = 12 (57%) and Group 2, patients who presented a relapse in the activity of the disease at 24 months after treatment, n = 9 (43%). The relapse of disease activity was defined as a significant increase of SAI (>13%) between 6 and 24 months after the end of treatment, whereas the response to therapy was defined as a significant reduction in SAI (>13%) at 6 months after the end of treatment. In addition, these results were compared with the biochemical evolution of bone markers. RESULTS: Biochemical markers and SAI decreased significantly after therapy and the nadir response was observed at 6 months. At this time 100% of patients responded to therapy. The persistent long-term response was associated with lower baseline indices of bone turnover (serum BAP<60 ng/ml or TAP<600 IU/l). The intervals of time for monitoring depended on the marker used: no patient from Group 1 presented a biochemical relapse in serum TAP at 1 and 2 yr after the end of treatment whereas 33 and 45% of these patients showed relapsed serum BAP at these time points. Moreover, all patients from Group 2 presented a biochemical relapse of serum BAP at 2 yr whereas in only 33% of these patients did serum TAP relapse at this time. CONCLUSION: Most of the Pagetic patients treated with tiludronate presented a long-term response, which persisted 2 yr after the end of treatment. The nadir response to treatment was observed 6 months after discontinuation of therapy whereas the relapse of disease activity was already observed 1 yr after the end of therapy and depended on both the baseline disease activity and the bone marker used in the evaluation.

Concentration of hydroxyproline in blood: a biological marker in occupational exposure to asbestos and its relationship with Pi*Z and Pi*S polymorphism in the alpha-1 antitrypsin gene.

BACKGROUND: Hydroxyproline (OHP) is one of the most abundant amino acids in collagen and, in general, it provides a good measure of overall collagen catabolism. METHODS: Asbestos workers suffering from asbestosis (cases n = 85); asbestos exposed workers without asbestosis (exposed controls, EC, n = 86), and non-exposed population (non-exposed controls, NEC, n = 122) were studied. The concentration of free OHP in whole blood was measured following the Pico-Tag procedure. RESULTS: Concentration of OHP in blood was significantly different in the three groups studied (P < 0.001), being higher in cases (19.8 +/- 14.7 micromol/L) than in EC (16 +/- 12.4) and NEC (13.5 +/- 6.7). When all individuals were grouped and stratified by the Pi*S and Pi*Z polymorphisms in the alpha-1-antitrypsin gene, the highest OHP levels were detected in the Pi*S homozygotes, one of the asbestosis-at risk-genotypes (Pi*S homozygotes, x = 24.5 +/- 11.7; Pi*S heterozygotes, x = 16.6 +/- 10.0; wild type, wt, x = 15.9 +/- 11.8). CONCLUSIONS: Blood OHP concentration could be used for monitoring human exposure to asbestos, either as a marker for occupational monitoring or as an additional clinical parameter in diagnostic exploration of asbestosis.

Glucómetros de uso hospitalario: creación de un equipo pluridisciplinar para el proceso de selección y seguimiento Seis años de experiencia / Glucometers for hospital use: creation of a multi-disciplinary team for the selection and monitoring process

This work highlights what the authors consider to be critical aspects for setting up POCT (point-of-care testing) measurements, whether simple ones such as glucometers or critical ones such as those made with blood gas analyser (AU)

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Prospective evaluation of CEA and CA 15.3 in patients with locoregional breast cancer.

The tumor markers, CEA and CA 15.3, were prospectively studied in the sera of 1057 untreated patients with locoregional breast cancer diagnosed from 1983 to 2001. Abnormal CEA and CA 15.3 serum levels were found in 13% and 18.8% of the patients, respectively. One tumor marker or another was abnormal in 22.8% of the patients. Both tumor markers were correlated with tumor size and nodal involvement, with significantly higher concentrations in patients with larger tumors or in patients with nodal involvement. CEA was also related to the histological type and CA 15.3 with the histological grade. Univariate prognostic evaluation showed that tumor size, nodal involvement, histological grade, steroid receptors, adjuvant treatment, CEA, CA 15.3 and treatment before surgery were prognostic factors in both disease-free survival (DFS) and overall survival (OS). Similar results were obtained in node-positive patients, with the same factors being prognostic, excluding adjuvant treatment and CA 15.3, in both DFS and OS. Multivariate analysis showed that tumor size, nodal involvement, histological grade, ER and CEA were independent prognostic factors in both DFS and OS in the whole group as well as in node-positive patients. In contrast, tumor size was the only useful parameter in the prognosis of node-negative patients. CA 15.3 was useful for prognosis (OS) in node-negative patients. In summary, tumor markers are useful tools in the prognostic evaluation of patients with breast cancer.

Prospective evaluation of tumor markers (c-erbB-2 oncoprotein, CEA and CA 15.3) in patients with locoregional breast cancer.

Tumor markers were prospectively (CEA and CA 15.3) or retrospectively (c-erbB-2) studied in the sera of 503 untreated patients with breast cancer diagnosed from 1988 to 2001. Abnormal c-erbB-2 levels (> 15 U/ml) were found in 7%, CEA in 12% and CA 15.3 in 13% of the 503 patients. C-erbB-2 serum levels were only related to c-erbB-2 in tissue, with significantly higher concentrations in patients with positivity in tissue. All the tumor markers (c-erbB-2 only in patients with positivity in tissue) were correlated with tumor size, TNM and nodal involvement. CEA was also related to menopausal status, c-erbB-2 overexpression in tissue and ER. Univariate analysis (mean follow-up 8 years) showed that CEA and CA 15.3 were prognostic factors with significantly shorter disease-free survival (DFS) and overall survival (OS) in patients with pretreatment tumor marker positivity. Multivariate analysis in DFS and in OS showed that nodal involvement CEA and ER but not tumor size, menopausal status, histological grade, histology, CA 15.3, c-erbB-2, PgR, adjuvant treatment, p53 (345 patients) or c-erbB-2 in tissue are independent prognostic factors. In summary, tumor markers are a useful, inexpensive and reproducible tool for prognosis in breast cancer.

Serum osteoprotegerin and its ligand in Paget's disease of bone: relationship to disease activity and effect of treatment with bisphosphonates.

OBJECTIVE: To test the following hypotheses: 1) osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) serum levels in patients with Paget's disease are related to disease activity and are different from those in healthy individuals; 2) interleukin-6 (IL-6), a cytokine that has been shown to have higher levels in Paget's disease, modulates these factors; and 3) the antiresorptive effect of bisphosphonates in Paget's disease of bone may be mediated through these local factors. METHODS: The study group comprised 31 patients with Paget's disease who received 400 mg/day of oral tiludronate for 3 months. Serum levels of OPG, RANKL, IL-6, bone alkaline phosphatase (AP), N-terminal type I procollagen propeptide, urinary N-terminal crosslinking telopeptide of type I collagen, and urinary alpha-C-terminal crosslinking telopeptide of type I collagen were measured at baseline and 1 month after the end of therapy. In addition, the RANKL:OPG ratio was calculated, and disease activity was evaluated at baseline by quantitative bone scintigraphy. RESULTS: Mean baseline OPG values were higher in patients with Paget's disease than in healthy control subjects (P < 0.005), but RANKL and IL-6 values and RANKL:OPG ratios in the 2 groups were similar. OPG concentrations decreased significantly after treatment with tiludronate (P < 0.005), whereas no significant changes were observed in serum RANKL values. No correlation was found between either bone markers or quantitative scintigraphic indices and serum levels of OPG, RANKL, IL-6, and RANKL:OPG ratios. Serum OPG decreased significantly only in those patients with baseline OPG values >4.1 pM/liter. CONCLUSION: Serum OPG increases in Paget's disease and decreases after treatment with tiludronate, especially in patients with the highest OPG values. In contrast, RANKL serum levels and RANKL:OPG ratios are unmodified in patients with Paget's disease. Although serum OPG, RANKL, and IL-6 values were unrelated to disease activity, the increase in OPG may reflect a protective mechanism of the skeleton to compensate for increased bone resorption.

[Dynamic ultrasonography in the diagnosis of gallbladder dysfunction: reliability of a simple method with easy clinical application]. / Ultrasonografía dinámica en el diagnóstico de la disfunción vesicular: fiabilidad de un método sencillo de fácil aplicación clínica.

AIMS: Although the results of dynamic ultrasonography (DUS) are similar to those of dynamic cholescintigraphy (DCS) in the study of gallbladder function, the methodology required for this technique is laborious and sometimes complex. The aim of this study was to investigate the reliability of a simple method of DUS to evaluate gallbladder function using DCS as a reference. PATIENTS AND METHODS: Gallbladder function was studied using DUS and DCS in 80 consecutive patients with clinical findings compatible with gallbladder dysfunction. For DUS the ellipsoid method was used with measurement of three gallbladder diameters (transversal, longitudinal and anteroposterior) in basal conditions and after applying a cholecystokinetic stimulus (meal test); gallbladder emptying of less than 50% was considered abnormal. In DCS intravenous cholecystokinin (CCK) (0.40 IDU/kg in 20 minutes) was used as stimulus and an ejection fraction < or = 40% was considered abnormal. RESULTS: In 15 patients (19%; 95% CI, 11-29%) abnormal gallbladder response was found using DUS. The ejection fraction in the entire group of patients studied was 48 26.2%. Ejection fraction was abnormal in 41 patients (51%; 95% IC, 40-63%) with a value of 25 8.5% and was normal in 39 patients (49%; 95% IC, 40-63%) with a value of 71.5 14.5%. The correlation coefficient between the values of gallbladder emptying calculated with DUS and the ejection fraction obtained with DCS was 0.199 (p = 0.079). When patients were divided according to gallbladder emptying measured by DUS and the ejection fraction obtained with DCS the concordance was very low (k = 0.065; EE = 0.085). CONCLUSIONS: DUS performed using a simple technique lacks diagnostic value in gallbladder dysfunction when DCS is taken as a reference test

Pi*S and Pi*Z alpha 1 antitrypsin polymorphism and the risk for asbestosis in occupational exposure to asbestos.

Alpha 1 antitrypsin is a highly polymorphic anti-elastase enzyme, especially active in the protection of alveoli and liver. Here we studied the distribution of two deficient alleles Pi*Z and Pi* S, in 194 asbestos workers, of whom 100 were asbestosis cases, and 94 were controls without disease (exposed controls, EC). A second group of controls without asbestos exposure (non-exposed controls, NEC; n=122) was also included. Multivariate analysis adjusted by age and smoking habit showed ninefold risk for asbestosis in Pi*Z heterozygous individuals and 5.9-fold risk for Pi*S homozygous although differences were only significant in the first case (cases vs. EC: OR 8.9; p=0.04). Considering both genotypes (Pi*Z heterozygous, Pi*S homozygous) we obtained an OR of 8 (p=0.01). Our results suggest that the alpha 1 antitrypsin polymorphisms, especially Pi*Z, could help to predict asbestosis risk and confirm the high prevalence of the Pi*S allele in Spain.