[Risk of osteoporotic fracture and hip fracture in patients with chronic obstructive pulmonary disease]. / Riesgo de fractura osteoporótica y de cadera en pacientes con enfermedad pulmonar obstructiva crónica.

AIM: Osteoporosis is a frequent comorbidity in patients with chronic obstructive pulmonary disease (COPD). We have studied the risk of major osteoporotic fracture and hip fracture in patients with COPD. PATIENTS AND METHODS: A multicenter cross-sectional study was performed in Spain in 26 hospitals of 16 regional communities. Patients diagnosed with COPD who required admission to the Internal Medicine Service due to exacerbation of their respiratory disease were enrolled. COPD was confirmed by post-bronchodilator spirometry in stable state: maximum expiratory volume in the first second (FEV1) < 80% of the theoretical value and quotient FEV(1)/FVC < 0.70 and percent predicted after the administration of a bronchodilator. Dyspnea was evaluated with the modified Medical Research Council (mMRC) dyspnea scale. The principal variable was the likelihood of fracture evaluated with the FRAX® tool for the Spanish population. RESULTS: Three hundred and ninety two patients, 347 (88%) men, with a mean (SD) age of 73.7 (8.9) years and a mean FEV1 of 1.23 liters (43.3% of predicted) were enrolled. Only 37 patients (9.4%), 27 men and 10 women had been diagnosed previously of osteoporosis. Overall, 1.8% (95% CI: 0.9-3.6) had a 10-year probability of major osteoporotic fracture ≥ 20% and 49.7% (95% CI: 44.8-54.7) had a probability of hip fracture ≥ 3%. No relationship was observed between the probability of fracture and GOLD stage or mMRC dyspnea scale. CONCLUSIONS: The diagnosis of osteoporosis is uncommon in our COPD patients. However, half of them have a high probability of a hip fracture in the next 10 years.

[Study of the comorbidities in hospitalized patients due to decompensated chronic obstructive pulmonary disease attended in the Internal Medicine Services. ECCO Study]. / Estudio de las comorbilidades en pacientes hospitalizados por descompensación de la enfermedad pulmonar obstructiva crónica atendidos en los servicios de Medicina Interna. Estudio ECCO.

OBJECTIVE: Evaluate comorbidity in patients hospitalized due to COPD in the Internal Medicine services. METHODS: An observational, prospective and multicenter study. The Charlson index and a specific questionnaire were used. RESULTS: A total of 398 patients, 353 men (89%), with mean age of 73.7 years (8.9) and mean FEV(1) of 43.2% (12.5), were included. The most frequent comorbidities were: arterial hypertension (55%), arrhythmias (27%) and diabetes mellitus (26%). A total of 27% suffered heart failure, 17% coronary disease and 9% previous myocardial infarction. The number of associated chronic diseases was 3.6 (1,8). Score on Charlson index was 2.72 (2). CONCLUSIONS: The patients hospitalized due to decompensated COPD had an elevated comorbidity.

Clinical ultrasonography in chronic obstructive pulmonary disease. / Ecografía clínica en la enfermedad pulmonar obstructiva crónica.

COPD is a highly prevalent disease and one of the most common reasons for hospitalization in Internal Medicine departments. COPD also has significant associated morbidity and mortality. In recent years, multiorgan clinical ultrasonography (pulmonary, cardiac and vascular) has emerged as a tool of considerable usefulness in managing patients with COPD in numerous situations, including the differential diagnosis of dyspnoea of uncertain origin, the assessment of the aetiology in episodes of exacerbation, detecting concomitant heart failure or associated pulmonary hypertension and as support in managing cardiovascular risk factors such as subclinical atherosclerosis. This study summarises the most important evidence regarding this approach and proposes future scenarios for the use of ultrasonography that will help improve the diagnosis, prognostic estimations and the selection of the optimal treatment for this type of patient.

Consensus for managing patients with chronic obstructive pulmonary disease according to the CODEX index. / Consenso para el manejo de pacientes con EPOC según el índice CODEX.

The comorbidity, obstruction, dyspnoea, exacerbations (CODEX) index is the first multicomponent scale designed to predict the risk of readmissions and mortality at 1 year for patients hospitalised for chronic obstructive pulmonary disease (COPD). The index includes the comorbidities (C) (measured by the Charlson index), the degree of obstruction (O) (assessed by the forced expiratory volume in 1 second percentage), dyspnoea (D) (stratified according to the modified Medical Research Council scale) and exacerbations (EX) in the previous year. Our objective was to prepare recommendations based on the index's various components for personalised therapeutic management. To this end, we performed a literature search based on guidelines, consensuses and systematic reviews, as a basis for preparing recommendations on basic concepts, comorbidities, dyspnoea, pulmonary obstruction, exacerbations and follow-up. The recommendations were then subjected to an external assessment process by a multidisciplinary group of 62 experts. In total, 108 recommendations were created, 96 of which achieved consensus, including the recommendation that COPD be considered a high-risk cardiovascular disease, as well as several specific recommendations on managing the various comorbidities. A consensus was reached on the recommended treatments in the guidelines for the various levels of obstruction, dyspnoea and exacerbations, adapted to the CODEX scores. Advice is also offered for patient follow-up after hospital discharge, which includes aspects on assessment, treatment and care coordination.

Effect of sphingosine and stearylamine on the interaction of phosphatidylserine with calcium. A study using DSC, FT-IR and 45Ca(2+)-binding.

The lamellar gel to lamellar liquid-crystalline phase transition of dipalmitoylphosphatidylserine (DPPS) multilamellar membranes is abolished by the presence of Ca2+ at DPPS/Ca2+ molar ratios of 2:1 or lower. However, when equimolar sphingosine (SPH) or stearylamine (SA), which are positively charged at the pH studied in this work, were included in DPPS vesicles, the phase transition of DPPS was still observed by differential scanning calorimetry, even in the presence of very high Ca2+ concentrations such as a DPPS/Ca2+ molar ratio of 1:10. According to that, delta H was similar for samples formed by equimolar DPPS and SPH and SA, either in the presence or in the absence of Ca2+, whereas no phase transition was observed for the pure phospholipid in the presence of Ca2+ at molar ratios lower than DPPS/Ca2+ 2:1. 45Ca(2+)-binding experiments showed that for DPPS/SPH or DPPS/SA molar ratios of 2:1, only half of the Ca2+ was bound to DPPS with respect to pure DPPS, i.e., in the absence of SPH or SA. At concentrations of SPH or SA equimolar with DPPS, the Ca2+ binding was nearly abolished. The effect of SPH and SA on the the apparent pKapp of the carboxyl group of DPPS was also studied in the presence and in the absence of Ca2+ by using Fourier transform infrared spectroscopy. The dehydration of the phosphate group of DPPS induced by the binding of Ca2+ was followed through the observation of the PO2- antisymmetric stretching, and the percentage of dehydrated PO2- groups quantitatively assayed. It was again confirmed that, in the presence of equimolar concentrations of SPH or SA, Ca2+, at concentrations which are saturating for pure DPPS, was not bound at all to DPPS. It was also found that the pKapp was considerably shifted to lower values in the presence of the amino bases, decreasing from 4.6 in pure DPPS to 2.1 and 2.2 for the equimolar mixtures of DPPS with SPH and SA, respectively. These results show that SPH and SA, being positively charged molecules anchored in the membrane, are able of preventing the binding of positively charged ions such as Ca2+ through an electrostatic charge neutralization.

A phase behavior study of mixtures of sphingosine with zwitterionic phospholipids.

The interactions of sphingosine (SPH) with dipalmitoylphosphatidylcholine (DPPC) and dielaidoylphosphatidylethanolamine (DEPE) have been studied by means of differential scanning calorimetry (DSC) and 31P-nuclear magnetic resonance (31P-NMR). Experiments were carried out with the fully protonated form of SPH, at pH 6.0. DSC studies showed that the main Tc transition temperature of DPPC was perturbed by the presence of SPH so that Tc of the mixture was higher than those of pure components at concentrations of SPH up to 50 mol%, with an azeotropic point at 30 mol% of SPH. At higher concentrations solid phase separations were observed from 70 to 95 mol% of SPH with an eutectic point at 90 mol% of SPH. 31P-NMR showed lamellar phases in DPPC/SPH mixtures, at all the range of concentrations. The behavior of DEPE/SPH mixtures was somewhat different since no azeotropic point was detected, the gel to liquid-crystalline transition being depressed by the presence of SPH, and an eutectic point was detected at 60 mol%. Solid phase immiscibilities were present between 50 mol% and 85 mol% of SPH. It is also remarkable that the liquid-crystalline to hexagonal HII phase transition of DEPE was only slightly shifted to lower temperatures at concentrations of SPH lower than 33 mol% of SPH but, this transition disappeared at concentrations of SPH higher than 33 mol% of SPH, so that isotropic phases were formed instead, as seen through 31P-NMR. The present results show the importance of taking into account the effects appearing in mixtures of SPH with zwitterionic phospholipids when considering their influence on the organization of biomembranes.

Interaction of sphingosine and stearylamine with phosphatidylserine as studied by DSC and NMR.

The interaction of sphingosine (SP) and stearylamine (SA) with dipalmitoylphosphatidylserine (DPPS) has been studied by using differential scanning calorimetry (DSC) and phosphorus nuclear magnetic resonance (31P-NMR). DSC showed that SP and SA rigidified the membranes, forming an azeotropic mixture with DPPS. The azeotropic mixture which was formed between DPPS and SP was found at a DPPS/SP molar ratio of 2:1 whereas SA and DPPS formed an azeotropic mixture at a DPPS/SA molar ratio of 1:1. An eutectic point was observed at 85 mol% of SP and 90 mol% of SA in DPPS. 31P-NMR showed the presence of a lamellar phase at DPPS/SP and DPPS/SA molar ratios lower than 1:1, whereas at higher molar ratios and at high temperatures, besides the lamellar phase, an isotropic component was detected. It was found that, at physiological pH, both SP and SA were protonated in a large extent, i.e., positively charged, since their apparent pK in the membrane were 9.1 and 8.9, respectively. The results reported in this work may be relevant to understand a number of biological effects produced by these positively charged molecules, due to their electrostatic interaction with negatively charged phospholipids.

Infrared spectroscopic study of the interaction of diacylglycerol with phosphatidylserine in the presence of calcium.

The interaction of 1,2-dipalmitoylglycerol (DPG) with dipalmitoylphosphatidylserine (DPPS) has been studied in aqueous dispersion in the presence and in the absence of Ca2+ by using Fourier transform infrared spectroscopy (FT-IR) and 45Ca(2+)-binding. FT-IR showed that DPG increased the phase transition of DPPS and induced a rigidification of the DPPS/DPG-Ca2+ complex. In the absence of Ca2+, the incorporation of DPG produced an increase in the proportion of dehydrated carbonyl groups in the mixture of DPPS plus DPG whereas, in the presence of Ca2+, DPG suppressed the solid-solid phase transition of phosphatidylserine-Ca2+ complexes. The phosphate band of DPPS was analyzed using a multivariate statistical analysis, indicating that DPG induced a higher dehydration of the PO2- group in the presence of subsaturating Ca2+ concentrations. Even very low concentrations of DPG, such as 2 mol%, already produced a significant effect. In the presence of both DPG and Ca2+, dehydration of DPPS increased, so that full dehydration was reached at a DPPS/Ca2+ molar ratio of 2.94 instead of 2.04 as observed for pure DPPS. However, the stoichiometry of the binding of Ca2+ to DPPS was not significantly altered by the inclusion of DPG as revealed by 45Ca(2+)-binding experiments, indicating that, in this situation, full dehydration of the PO2- groups of DPPS was reached when approx. 2 out of every 3 molecules of DPPS were binding Ca2+. The effects reported here for the interaction of DPG with DPPS may be significant for a number of biological situations where Ca2+, phosphatidylserine and diacylglycerols are involved, such as fusion of membranes or the activation of protein kinase C, where the dehydration effect produced by diacylglycerols may explain, at least in part, their effects.

Diacylglycerol, phosphatidylserine and Ca2+: a phase behavior study.

The interaction of 1,2-dipalmitoylglycerol (1,2-DPG) with dipalmitoylphosphatidylserine (DPPS) has been studied in the presence and in the absence of Ca2+ by using differential scanning calorimetry (DSC) and 31P-nuclear magnetic resonance (31P-NMR). In the absence of Ca2+, DSC showed that 1,2-DPG increased the phase transition of DPPS, effect already noticed at very low 1,2-DPG concentrations, whereas lipid immiscibilities were detected at concentrations of 1,2-DPG higher than about 30 mol%. 31P-NMR indicated that lamellar phases were always present at concentration of 1,2-DPG lower than about 35 mol%, but at higher concentrations non-lamellar phases may be present in the fluid phase. As observed by DSC, the apparent pKa of the carboxyl group of DPPS was increased slightly in the presence of 1,2-DPG. In the presence of Ca2+, the effect of 1,2-DPG was to further increase the temperature of the onset of the phase transition, indicating an stabilization of the most rigid phase in the DPPS/1,2-DPG/Ca2+ samples. Even concentrations of 1,2-DPG as low as 1 mol% of the total lipid already produced a noticeable effect. Moreover, lipid immiscibilities were apparent at concentrations of 1,2-DPG higher than 20 mol%. Furthermore, the transition of the DPPS/Ca2+ complex observed by DSC at 155 degrees C was perturbed by the presence of 1,2-DPG, indicating a change in the structure of the crystalline complex. Interestingly, the effect of non-saturating Ca2+ concentrations on the DPPS phase transition was enhanced by the presence of 1,2-DPG. The effect reported here may be significant for a number of situations where Ca2+, phosphatidylserine and diacylglycerols are involved, such as fusion of membranes, where diacylglycerol may facilitate Ca(2+)-induced fusion, or the activation of enzymes such as protein kinase C and phospholipases.

Intra-articular therapy of experimental arthritis with a derivative of triamcinolone acetonide incorporated in liposomes.

Triamcinolone acetonide-21-palmitate was synthesized and incorporated into liposomes for intra-articular treatment of an experimentally-induced arthritis in the knee joints of rabbits. The liposomal formulation was more efficient than free triamcinolone acetonide in solution in suppressing the arthritis. Using radioactive tracers, it was found that triamcinolone acetonide-21-palmitate incorporated into liposomes was retained in the articular cavity, together with the liposomal lipids, for a much longer period than free triamcinolone acetonide, and this correlated with its anti-inflammatory effect.

[A reversible posterior leukoencephalopathy syndrome]. / Síndrome de leucoencefalopatía posterior reversible.

INTRODUCTION AND METHOD: The reversible posterior leukoencephalopathy (RPLS) was initially described by Hinchey et al in patients hospitalized due to different acute process that cause hypertension and renal disease that were being treated with immunosuppressive agents. Clinically it produces an acute or subacute encephalopathy that usually agrees with a fast increase of blood pressure. Neuroimaging technique demonstrated abnormalities involving the white matter, especially bilateral edema in the posterior portions of the cerebral hemispheres, although it can also affect to any other cerebral area, trunk or cerebellum. The production mechanism is not well know. In case of hypertensive encephalopathy and eclampsia of pregnancy it is believed to be caused by vascular and endothelial autoregulation alterations, and when it's related to immunosuppressors the edema seems to have a cytotoxical origin. The particularity that defines the RPLS is that, in most cases, neurological symptoms and white matter lesions disappear after anti hypertensive treatment or when immunosuppressive agents is ceased. CONCLUSION: The RPLS is an uncommon neurological complication, however each time more news cases appear in the medical literature. The excellent evolution and treatment response that these patients show and the full clinical and radiological recuperation suggest the need of its early identification to avoid unnecessary diagnostic studies or wrong treatments.

[Pulmonary lymphangioleiomyomatosis. Description and course of 2 cases]. / Linfangioleiomiomatosis pulmonar. Descripción y evolución de dos casos.

Pulmonary lymphangioleiomyomatosis (LAM) is a rare, serious, chronic disease whose etiology is unknown and which affects young women almost exclusively. It produces typical clinical and radiological characteristics. Diagnosis is confirmed on finding histological evidence of irregular proliferation of the smooth muscle cells of the lungs. Treatment is not usually effective and there is rapid worsening of the pulmonary function leading to serious respiratory failure which often results in the patients death. We present two cases of LAM in women, one of whom was 33 and the other 38. In the first case the patient had all the pulmonary findings described in the literature, while the second also had bilateral renal angiomyolipomas. We discuss the histological, radiological and clinical characteristics and evolution of both cases, as well as the treatment given. We also review the literature. It is concluded that LAM should be suspected in young women who have dyspnea, cough and/or hemoptysis and an interstitial radiological pattern, especially when associated with a pleural effusion or pneumothorax.

Comorbidity and gender-related differences in patients hospitalized for COPD. The ECCO study.

RATIONALE: Patients hospitalized for a COPD exacerbation are usually of advanced age, with functional deterioration, and suffering an increased number of associated conditions, but little is known about gender differences. Our hypothesis is that the frequency and type of comorbidities differ in male and female COPD patients. MATERIAL AND METHODS: A cross-sectional, multicentre study of patients hospitalized for a COPD exacerbation. All of them had COPD confirmed by baseline forced spirometry with a bronchodilator test. Comorbidity information was collected using the Charlson index, and an ad hoc questionnaire that included other common conditions not included in the Charlson index. RESULTS: We studied 398 patients, 353 men (89%) and 45 women (11%), with a mean (S.D.) age of 73.7 (8.9) years and a percent predicted FEV(1) of 43.2 (12.5). The mean score of the Charlson index was 2.7 (2.0), with no differences by gender; in contrast, the mean number of all comorbid conditions assessed was 3.7 (1.7) in men and 1.8 (1.8) in women (p < 0.05). Overall, 55% of the patients had arterial hypertension, 26% diabetes mellitus, 27% chronic heart failure, and 17% ischemic heart disease. Female COPD patients had a lower prevalence of ischemic heart disease (p = 0.008) and alcoholism (p = 0.03), but presented more frequently with chronic heart failure (p = 0.03), osteoporosis (p = 0.007) and diabetes mellitus without complications (p = 0.02). CONCLUSIONS: Comorbidities are common in patients hospitalized for a COPD exacerbation, but their relative distribution varies by gender. The exclusive use of the Charlson index underestimates comorbidities in COPD patients.