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Papers by Antonio Martínez-riera
Majorensis: Revista Electrónica de Ciencia y Tecnología, 2018
Resumen Piomisitis por salmonella en un paciente inmunocompetente Describimos el caso de un pacie... more Resumen Piomisitis por salmonella en un paciente inmunocompetente Describimos el caso de un paciente de 16 años, previamente sano, quien tras un cuadro autolimitado de diarrea desarrolla un cuadro febril de hasta 39º y dolor en cadera derecha tras ejercicio intenso. Se aísla en el hemocultivo una salmonella y se aprecia en ecografía y resonancia magnética una sacroileítis y miositis que afecta a glúteos, piramidal y psoas derecho. El paciente evolucionó de forma favorable con tratamiento antibiótico, sin necesidad de desbridamiento quirúrgico.
Drug and Alcohol Dependence, May 1, 2019
In the manuscript entitled "Alcohol consumption and S-Klotho plasma levels in sedentary healthy m... more In the manuscript entitled "Alcohol consumption and S-Klotho plasma levels in sedentary healthy middle-aged adults", Jurado-Fasoli et al. (2018) analyze the relationship between soluble Klotho (s-Klotho) levels and the intensity of ethanol consumption in a cohort of healthy individuals, drinkers of "safe" amounts of ethanol (approximately 11 g/ day, with an upper limit of the 95% confidence interval of about 48 g for men and 20 for women, roughly the mean +2sD of the values shown in Table 1 of the mentioned article, although one individual drank > 60 g (Fig. 1)). They found an inverse correlation between ethanol consumption and s-Klotho levels, in contrast with the results derived from our series composed of 124 heavy alcoholic men, aged 59.31 ± 11.23 years, drinkers of 158 g ethanol daily (interquartile(IQ) range = 100-248 g) during 32.5 years (IQ = 25-40 years). In this cohort s-Klotho was increased in alcoholic cirrhotics (but not in non-cirrhotics) compared with controls (González-Reimers et al., 2018). The patients drank only wine (n = 59), wine and spirits (n = 42), only spirits (n = 10), or only beer (n = 4). We observed a direct correlation between the daily ethanol consumption and s-Klothos (ρ = 0.18; p = 0.044), especially among the 73 non-cirrhotic patients included in the sample (ρ = 0.29; p = 0.012), but no relationship between s-Klotho and age (ρ = 0.02; p = 0.80). Among 88 patients who underwent total body composition analysis, s-Klotho was not related to total fat mass (ρ = 0.13; p = 0.022), but with total lean mass (ρ = 0.23; p = 0.035), a signification that disappeared when patients with ascitis were excluded (ρ = 0.18; p = 0.13). Interestingly, a significant direct correlation was observed between TNF-α and s-Klotho (ρ = 0.23; p = 0.023). This relationship was even closer among only-wine drinkers (ρ = 0.36; p = 0.013). Jurado-Fasoli et al. concluded that plasma levels of s-Klotho are negatively associated with ethanol consumption in middle-aged sedentary adults. While this assertion is fully sustained by the results presented by the authors, and may be valid in a normal healthy population, their results are in sharp contrast with what we here report. Ethanol consumption leads to a proinflammatory situation (main mechanisms: increased intestinal permeability, oxidative damage, cytokine secretion, among others), but it is not known if there is a cutoff point that marks that this inflammatory state is clinically relevant. Klotho exerts an antioxidant effect, enhancing the expression of superoxide dismutase (Yamamoto et al., 2005) so that mice overexpressing Klotho are protected against oxidative damage (Kim et al., 2017). Also Klotho overexpression reduces the production of proinflammatory cytokines (Zhou et al., 2017) and some clinical studies show increased levels of Klotho in inflammatory conditions (tumors or sepsis), even directly related to increased mortality (Abdelmalik et al., 2018). It is tempting to speculate that, at least in some instances, inflammation triggers overexpression of Klotho gene in an attempt to compensate the enhanced proinflammatory state. Therefore, possibly a dual effect may define the relationship of ethanol and Klotho: low doses of ethanol may lead to decreased Klotho levels, but high doses may increase Klotho secretion, perhaps as a homeostatic mechanism directed to regulate enhanced ethanol-mediated inflammation.
PubMed, Apr 1, 1996
Aim: To determine the clinical and prognostic value of serum laminin in chronic alcoholic liver d... more Aim: To determine the clinical and prognostic value of serum laminin in chronic alcoholic liver disease and to discern whether laminin, alone or in combination with serum N-terminal type III collagen propeptide, and/or biochemical parameters, is useful in estimating the histomorphometrically determined amount of fibrosis. Study design: Prospective. Patients: 121 (80 of them cirrhotics), 107 followed up for a variable periods ranging from 1 to 1440 days. Results: Serum laminin was higher in cirrhotic patients belonging to Child's C group and, in cirrhotic patients, it significantly correlated with Pugh's score (r = 0.32, p < 0.01), prothrombin activity (r = 0.23, p < 0.05), serum albumin (r = -0.35, p < 0.001) and bilirubin (r = 0.30, p < 0.01), and also with the degree of fibrosis (r = 0.49, p < 0.001). Serum laminin over 3.5 U/ml were associated to higher mortality rates in the total population (Log rank test = 4.9, p = 0.022), but not in cirrhotics. Stepwise multiple regression analysis showed that laminin is useless in the estimation of liver fibrosis in cirrhotics, although in non-cirrhotic alcoholics, serum laminin together with alkaline phosphatase and GGT roughly estimates the amount of liver fibrosis (r = 0.72, p < 0.001, standard error = 7.29). Conclusions: Laminin is not useful in estimating the total amount of fibrosis neither in prognostic assessment of cirrhotics. However, serum laminin-values over 3.5 U/ml were associated with higher mortality rates in patients with chronic alcoholic liver disease, and serum laminin together with alkaline phosphatase and GGT correlated with the amount of fibrosis in the non-cirrhotic subgroup.
Revista Clinica Espanola, 2002
European Journal of Internal Medicine, Oct 1, 2013
Objectives: Heart failure is the end stage of hypertensive, coronary and valvular cardiovascular ... more Objectives: Heart failure is the end stage of hypertensive, coronary and valvular cardiovascular disease. It is a major and growing problem because of the increasing size of the aging population and the prolonged lives of cardiac patients with modern therapy. The goal of our study was to investigate the relationship between different parameters with survival, in a cohort of heart failure elderly patients. Methods: We studied a cohort of 244 patients hospitalized with heart failure (diagnosed according to Framingham criteria) at the Internal Medicine unit of a country hospital of Cantabria (Tres Mares Hospital at Reinosa); 115 were men and 129 were women with an age range of 55 to 100 years (median age and quartiles of 85 and 79–89 years). Fourteen (5.7%) patients died during hospitalization. All patients were followed up by telephone with a median survival of 984 days. The variables included in our study were age, sex, cognitive status Mini Mental Status Examination (MMSE), Barthel index, coronary disease, stroke, peripheral arteriopathy, atrial fibrillation, diabetes mellitus, COPD, smoking, heart rate, ejection fraction, NYHA class, systolic blood pressure, body mass index, midarm circumference, midarm muscle area (MAMA), triceps skinfold, handgrip strength, hemoglobin, serum albumin, serum prealbumin, lymphocyte count, total cholesterol, serum creatinine, serum urea nitrogen and natremia. To know which variables yield long term independent predictive value, we included in survival analysis with covariates (Cox regression) those variables with long term significant value when assessed by Kaplan–Meier and long rank test analysis. Results: The data with an independent predictive value were NYHA III/IV versus I/II, RR 3.73 (2.07–6.71) (p b 0.001); hemoglobin b 11 g/dl, RR 3.15 (1.83–5.40) (p b 0.001); serum creatinine N 1.5 mg/dl, RR 2.71 (1.59–4.61) (p b 0.001); MMSE b 21, RR 3.95 (1.70–9.17) (p 0.001); ejection fraction, RR 2.11 (1.17–3.79) (p 0.013): heart rate b 90 beats/min, RR 1.77 (1.04–3.00) (p 0.034); and midarm muscle area (MAMA) b 95th percentile, RR 0.22 (0.05–0.93) (p 0.039). Conclusion:ANYHA class III or IV class, a hemoglobin lower than 11 g/dl, a serum creatinine over 1.5 mg/dl, cognitive impairment with a MMSE lower than 21 points, an Ejection Fraction below 40% and a heart rate greater than 90/m were associated with a higher mortality rate. As a protective factor we found a MAMA over the 95th percentile of the normal population.
Journal of Trace Elements in Medicine and Biology, Sep 1, 2020
Introduction: In chronic hepatitis C virus (HCV) infection there is increased iron absorption lea... more Introduction: In chronic hepatitis C virus (HCV) infection there is increased iron absorption leading to iron overload, a fact that may promote ferritin synthesis. Theoretically, increased ferritin should promote ongoing liver fibrosis but disparate results have been described. Objective: We analyze the behavior of iron metabolism-related variables, comparing them with fibrosis and inflammatory activity in liver biopsy in HCV infected patients. Patients and Methods: We analyzed among 90 HCV patients subjected to liver biopsy prior to antiviral treatment the relationships of serum levels of iron, ferritin, transferrin, transferrin saturation index (TSI) and total iron binding capacity (TIBC) with liver fibrosis and histological severity, assessed by Metavir-f, Metavir-a and Knodell indices, as well as with liver function, and also compared the aforementioned iron metabolism-related variables with 34 controls. Results: Patients showed higher values of sideremia (T = 2.04; p = 0.044) and transferrin (T = 2.29; p = 0.004) compared with controls; but not ferritin, that was significantly higher among the 33 patients who also consumed alcohol (Z = 2.05; p = 0.041). Most patients showed a well preserved liver function (86 cases, Child A). Patients with Child B or C showed higher ferritin levels (Z = 2.68; p = 0.007) and TSI (Z = 2.41; p = 0.016), but lower transferrin and TIBC (Z = 3.25; p = 0.001) than Child A patients. Transferrin and TIBC were directly related to albumin (ρ = 0.24; p = 0.026), whereas bilirubin showed direct relationships with iron (ρ = 0.25; p = 0.016), TSI (ρ = 0.39; p < 0.001) and ferritin (ρ = 0.36; p < 0.001). Both ferritin (ρ = −0.22; p = 0.04) and TSI (ρ = −0.25; p = 0.016) were related to platelet count. No relationships were observed between iron variables and Knodell index, but serum iron, serum transferrin, and TSI were directly related to Metavir-f score (ρ = 0.28; p = 0.009, ρ = 0.22; p = 0.044, and ρ = 0.22; p = 0.044, in this order). Conclusion: Alterations of iron related variables are relatively subtle in our series of 90 well compensated HCV patients. Serum ferritin was not related to liver fibrosis and increases only when alcoholism co-exists with HCV infection.
European Journal of Internal Medicine, Oct 1, 2013
due to other causes besides left heart dysfunction were excluded from this survey. Results: 32 pa... more due to other causes besides left heart dysfunction were excluded from this survey. Results: 32 patients with PH and HF. 5 males (average age of 70.6 years), 27 females (average age of 76.3 years). Two of the patients have both HF and chronic pulmonary obstructive disease; 15 patients have HF secondary to hypertensive cardiomyopathy; 7 patients have HF secondary to ischemic cardiomyopathy and 10 patients have HF due to valvular cardiomyopathy. When evaluated EF, 19 patients have normal EF (EF ≥ 55%), 7 patients have preserved EF (EF [40%,55%]) and 6 patients have impaired global systolic function with EF b40%. Among the 32 evaluated patients, 17 patients have mild tricuspid insufficiency (TI), 10 patients have moderate TI and 3 patients have severe TI. PH tends to be more severe in patients with normal (median PASP = 51.68 mmHg) and preserved (median PASP = 52.21 mmHg) EF, than in patients with reduced global systolic function (median PASP 44.17 mmHg). Conclusions: The results of our retrospective analysis support the ongoing studies in which patients with HFpEF accounted for a significant percentage of patients with PH and right-sided heart dysfunction. The processes underlying the development of PH in HFpEF are still unclear.
Digestive and Liver Disease, Jun 1, 2023
The New England Journal of Medicine, Apr 25, 1996
Alcohol, Jul 1, 1998
This study was performed to analyze the relative and combined effects of ethanol and protein defi... more This study was performed to analyze the relative and combined effects of ethanol and protein deficiency on bone histology and mineral metabolism in 4 groups of 7 animals each which were pair-fed during 8 weeks with 1) a nutritionally adequate diet; 2) a 36% (as energy) ethanol containing isocaloric diet; 3) a 2% protein, isocaloric diet; and 4) a 36% ethanol 2% protein isocaloric diet, respectively, following the Lieber-DeCarli model. Another group of five rats were fed ad libitum the control diet. The first and second lumbar vertebrae were removed after sacrifice, and processed for histomorphometrical analysis of undecalcified bone samples. Blood and 24-h urine were also collected. Protein malnutrition, but not ethanol, leads to osteoporosis and reduced osteoid synthesis, whereas ethanol and protein malnutrition both lead to impaired bone mineral apposition and increased urinary hydroxyproline excretion. These changes are accompanied by an increase in serum parathormone and serum 1,25 dihydroxy vitamin D3, a slight hypomagnesemia, hypercalciuria and hyperphosphaturia; protein deficiency plays an independent role in these alterations, whereas both ethanol and protein deficiency exert independent effects on decreasing serum testosterone levels; this last alteration may contribute to the bone changes mentioned before.
Alcohol and Alcoholism, Feb 13, 2006
Objectives: Osteoprotegerin (OPG) is a decoy receptor that binds RANK-ligand (RANKL) and prevents... more Objectives: Osteoprotegerin (OPG) is a decoy receptor that binds RANK-ligand (RANKL) and prevents osteoclast activation. Oestrogens, androgens, corticosteroids, parathyroid hormone (PTH), vitamin D, and several cytokines exert their effects on bone modulating the OPG/RANKL system. Since these substances become altered in chronic alcoholic liver disease, we investigated the OPG/RANKL system in alcoholic liver disease, its relation with bone mineral density (BMD) and with several hormones and cytokines. Methods: Serum OPG, RANKL, C-terminal cross-linking telopeptide of type 1 collagen, osteocalcin, insulin-like growth factor 1 (IGF-1), 1,25 dihydroxyvitamin D, IL-6, tumour necrosis factor (TNF)-a, PTH, estradiol, free testosterone and corticosterone were measured in 77 male alcoholic patients, 25 of them cirrhotics. All these patients underwent assessment of BMD at lumbar spine and left hip by a Hologic QDR-2000 (Waltham, MA) bone densitometer. Nineteen non-drinkers male sanitary workers of similar age served as controls. Results: Serum OPG levels were higher in patients (12.66 ± 6.44 pmol/l) than in controls (6.59 ± 1.58 pml/l, P < 0.005), especially in cirrhotics (15.97 ± 7.03 pmol/l) vs non-cirrhotics (10.96 ± 5.45 pmol/l, P < 0.001). Patients also showed higher telopeptide levels (0.60 ± 0.36 vs 0.20 ± 0.10 nmol/100 ml,
Alcohol and Alcoholism, 1994
Revista española de las enfermedades del aparato digestivo, 1989
To establish the prevalence of liver enzyme alterations in the course of serious infections of di... more To establish the prevalence of liver enzyme alterations in the course of serious infections of diverse origin, 112 patients were studied retrospectively for the levels of GOT, GPT, LDH, GGT, alkaline phosphatase (FA) and bilirubin (BIL). Cases in which the values might be altered due to causes other than the infectious process were previously excluded. The prevalence of affectation of each of the parameters was the following: GGT, 39.1%; LDH, 33.3%; FAL, 30.1%; GOT, 29.5%; GPT, 24.8%; BIL, 18.3%. Seventy percent had at least one of these values changed. No significant differences were found in the incidence or intensity of the analytic alterations in function of the origin of the of infection, which suggests that these modification are nonspecific. Bilirubin levels were found to be significantly higher in the patients who died. On realizing the linear correlation analysis between the diverse parameters studied, a good correlation was found between them, suggesting a common pathogene...
Revista española de enfermedades digestivas : organo oficial de la Sociedad Española de Patología Digestiva, 1996
To determine the clinical and prognostic value of serum laminin in chronic alcoholic liver diseas... more To determine the clinical and prognostic value of serum laminin in chronic alcoholic liver disease and to discern whether laminin, alone or in combination with serum N-terminal type III collagen propeptide, and/or biochemical parameters, is useful in estimating the histomorphometrically determined amount of fibrosis. Prospective. 121 (80 of them cirrhotics), 107 followed up for a variable periods ranging from 1 to 1440 days. Serum laminin was higher in cirrhotic patients belonging to Child's C group and, in cirrhotic patients, it significantly correlated with Pugh's score (r = 0.32, p < 0.01), prothrombin activity (r = 0.23, p < 0.05), serum albumin (r = -0.35, p < 0.001) and bilirubin (r = 0.30, p < 0.01), and also with the degree of fibrosis (r = 0.49, p < 0.001). Serum laminin over 3.5 U/ml were associated to higher mortality rates in the total population (Log rank test = 4.9, p = 0.022), but not in cirrhotics. Stepwise multiple regression analysis showed t...
International Journal of Colorectal Disease, Mar 30, 2016
Dear Editor: Carcinoid tumors are slow-growing neoplasms derived from enterochromaffin cells or K... more Dear Editor: Carcinoid tumors are slow-growing neoplasms derived from enterochromaffin cells or Kulchintsky cells being thus neuroendocrine in nature. They may arise anywhere in the gastrointestinal tract, in the bronchi, and occasionally elsewhere (ovary, central nervous system). Within the gastrointestinal tract, most carcinoid tumors arise in the small intestine (45 %, most commonly in the ileum), followed by rectum (20 %), appendix (16 %), colon (11 %), and stomach (7 %). Carcinoid syndrome is the term applied to a set of symptoms mediated by different humoral factors elaborated by some carcinoid tumors (diarrhea, cutaneous flushing, cardiac valvular lesions, bronchospasm, and intermittent abdominal pain). These tumors synthesize, store, and release a variety of polypeptides, biogenic amines, and prostaglandins. Some of these tumor products are responsible for the carcinoid syndrome. The relative contribution and the specificity of each of the particular components of the syndrome are uncertain. It seems that among patients with intestinal carcinoid tumors, the carcinoid syndrome does not occur in the absence of liver metastases. In contrast, bronchial and other extraintestinal carcinoids, whose bioactive products are not immediately cleared by the liver, can rarely cause the syndrome in the absence of metastatic disease. Metastases of carcinoid tumors in peripheral nerve are extremely rare. All of them come from supradiaphragmatic
Colorectal Disease, Nov 1, 2016
Aim Very few studies have compared the epidemiological characteristics of patients with familial ... more Aim Very few studies have compared the epidemiological characteristics of patients with familial colorectal cancer Type X (FCCTX) with those of sporadic colorectal cancer (S-CRC). The aim of this study was to compare clinicopathological characteristics and survival between FCCTX and S-CRC in patients from a historically isolated geographical region. Method A retrospective study was carried out of patients with S-CRC and FCCTX treated in the Canary Islands. Family and personal history of colorectal cancer (CRC) were recorded, together with genetic (microsatellite instability), immunohistochemical and clinical variables. Results Forty-eight (10.6%) of 451 patients were classified as FCCTX and the remaining 403 (89.4%) as S-CRC. Age at the diagnosis of tumour was significantly lower in FCCTX than in S-CRC (64.06 AE 12.65 years vs 69.13 AE 10.80 years; P = 0.01; Z = À2.48). Patients with FCCTX had a larger number of synchronous tumours (P = 0.09). Recurrence was significantly higher in FCCTX than in S-CRC (18.7% vs 8.6%; P = 0.01). Survival correlated significantly with the number of first-degree and second-degree relatives with CRC (
Archivos De Bronconeumologia, May 1, 1992
Alcohol and Alcoholism, Mar 1, 1996
A hypermetabolic state with increased oxygen consumption has been described in alcoholic hepatiti... more A hypermetabolic state with increased oxygen consumption has been described in alcoholic hepatitis, playing a major role in ethanol-induced liver damage. Based on its ability to decrease oxygen consumption, propylthiouracil (PTU) has been proposed as a therapeutic agent in this context. On the other hand, several muscle changes have been described in hypothyroidism. including both atrophy and hypertrophy of muscle fibres. The aim of this experimental study was to analyse the effects of PTU on the alcohol-induced changes in muscle fibre size and proportion, also taking into account the presence or absence of protein deficiency. The study was performed on 64 male Wistar rats divided into eight groups, fed with: (1) Lieber-DeCarli control diet: (2) an isocaloric 36% cthanol-containing diet: (3) an isocaloric 2% protein-containing diet: (4) an isocaloric 36% ethanol 2% protein-containing diet, without and with PTU. respectively. Right gastrocnemius muscle was removed 2 months later and histochemical and morphometric studies were performed Type lib fibre atrophy was observed both in the alcoholic and protein-deficient animals, but not in the PTU-treated animals. The combination of protein deficiency and ethanol led to a more marked type lib atrophy, with PTU reversing this effect. Malnutrition led to a decrease in type I fibre diameter: ethanol and PTU caused an increase in its size and PTU reversed the effect of protein deficiency. Proportion of type lib fibres decreased in the three experimental groups without PTU with respect to the control, especially in the alcoholic protein-deficient animals. PTUtreated animals, especially those fed a low-protein diet, showed a more marked reduction in type lib fibre proportion than that presented by the groups without PTU. However, an increase in type I fibre proportion was observed in the PTU-treated animals, especially marked in those fed a low-protein diet Thus. PTU seems to ameliorate ethanol-induced changes on type lib muscle fibres.
Biomolecules, Aug 20, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of the American Geriatrics Society, Apr 1, 2016
Although the number of subjects reported here is too small to draw definitive conclusions, this e... more Although the number of subjects reported here is too small to draw definitive conclusions, this experience suggests that, if salsalate is to be used in older individuals, especially those who may be frail or prefrail, practitioners should be especially alert to the possibility of renal failure especially in the context of diarrhea and dehydration. An additional concern is that these adverse events occurred at a dose half that used in reported trials. Given that older adults are frequently underrepresented in clinical trials, these observations highlight the importance of having sufficient numbers of older adults in trials of agents likely to be used in that population.
Majorensis: Revista Electrónica de Ciencia y Tecnología, 2018
Resumen Piomisitis por salmonella en un paciente inmunocompetente Describimos el caso de un pacie... more Resumen Piomisitis por salmonella en un paciente inmunocompetente Describimos el caso de un paciente de 16 años, previamente sano, quien tras un cuadro autolimitado de diarrea desarrolla un cuadro febril de hasta 39º y dolor en cadera derecha tras ejercicio intenso. Se aísla en el hemocultivo una salmonella y se aprecia en ecografía y resonancia magnética una sacroileítis y miositis que afecta a glúteos, piramidal y psoas derecho. El paciente evolucionó de forma favorable con tratamiento antibiótico, sin necesidad de desbridamiento quirúrgico.
Drug and Alcohol Dependence, May 1, 2019
In the manuscript entitled "Alcohol consumption and S-Klotho plasma levels in sedentary healthy m... more In the manuscript entitled "Alcohol consumption and S-Klotho plasma levels in sedentary healthy middle-aged adults", Jurado-Fasoli et al. (2018) analyze the relationship between soluble Klotho (s-Klotho) levels and the intensity of ethanol consumption in a cohort of healthy individuals, drinkers of "safe" amounts of ethanol (approximately 11 g/ day, with an upper limit of the 95% confidence interval of about 48 g for men and 20 for women, roughly the mean +2sD of the values shown in Table 1 of the mentioned article, although one individual drank > 60 g (Fig. 1)). They found an inverse correlation between ethanol consumption and s-Klotho levels, in contrast with the results derived from our series composed of 124 heavy alcoholic men, aged 59.31 ± 11.23 years, drinkers of 158 g ethanol daily (interquartile(IQ) range = 100-248 g) during 32.5 years (IQ = 25-40 years). In this cohort s-Klotho was increased in alcoholic cirrhotics (but not in non-cirrhotics) compared with controls (González-Reimers et al., 2018). The patients drank only wine (n = 59), wine and spirits (n = 42), only spirits (n = 10), or only beer (n = 4). We observed a direct correlation between the daily ethanol consumption and s-Klothos (ρ = 0.18; p = 0.044), especially among the 73 non-cirrhotic patients included in the sample (ρ = 0.29; p = 0.012), but no relationship between s-Klotho and age (ρ = 0.02; p = 0.80). Among 88 patients who underwent total body composition analysis, s-Klotho was not related to total fat mass (ρ = 0.13; p = 0.022), but with total lean mass (ρ = 0.23; p = 0.035), a signification that disappeared when patients with ascitis were excluded (ρ = 0.18; p = 0.13). Interestingly, a significant direct correlation was observed between TNF-α and s-Klotho (ρ = 0.23; p = 0.023). This relationship was even closer among only-wine drinkers (ρ = 0.36; p = 0.013). Jurado-Fasoli et al. concluded that plasma levels of s-Klotho are negatively associated with ethanol consumption in middle-aged sedentary adults. While this assertion is fully sustained by the results presented by the authors, and may be valid in a normal healthy population, their results are in sharp contrast with what we here report. Ethanol consumption leads to a proinflammatory situation (main mechanisms: increased intestinal permeability, oxidative damage, cytokine secretion, among others), but it is not known if there is a cutoff point that marks that this inflammatory state is clinically relevant. Klotho exerts an antioxidant effect, enhancing the expression of superoxide dismutase (Yamamoto et al., 2005) so that mice overexpressing Klotho are protected against oxidative damage (Kim et al., 2017). Also Klotho overexpression reduces the production of proinflammatory cytokines (Zhou et al., 2017) and some clinical studies show increased levels of Klotho in inflammatory conditions (tumors or sepsis), even directly related to increased mortality (Abdelmalik et al., 2018). It is tempting to speculate that, at least in some instances, inflammation triggers overexpression of Klotho gene in an attempt to compensate the enhanced proinflammatory state. Therefore, possibly a dual effect may define the relationship of ethanol and Klotho: low doses of ethanol may lead to decreased Klotho levels, but high doses may increase Klotho secretion, perhaps as a homeostatic mechanism directed to regulate enhanced ethanol-mediated inflammation.
PubMed, Apr 1, 1996
Aim: To determine the clinical and prognostic value of serum laminin in chronic alcoholic liver d... more Aim: To determine the clinical and prognostic value of serum laminin in chronic alcoholic liver disease and to discern whether laminin, alone or in combination with serum N-terminal type III collagen propeptide, and/or biochemical parameters, is useful in estimating the histomorphometrically determined amount of fibrosis. Study design: Prospective. Patients: 121 (80 of them cirrhotics), 107 followed up for a variable periods ranging from 1 to 1440 days. Results: Serum laminin was higher in cirrhotic patients belonging to Child's C group and, in cirrhotic patients, it significantly correlated with Pugh's score (r = 0.32, p < 0.01), prothrombin activity (r = 0.23, p < 0.05), serum albumin (r = -0.35, p < 0.001) and bilirubin (r = 0.30, p < 0.01), and also with the degree of fibrosis (r = 0.49, p < 0.001). Serum laminin over 3.5 U/ml were associated to higher mortality rates in the total population (Log rank test = 4.9, p = 0.022), but not in cirrhotics. Stepwise multiple regression analysis showed that laminin is useless in the estimation of liver fibrosis in cirrhotics, although in non-cirrhotic alcoholics, serum laminin together with alkaline phosphatase and GGT roughly estimates the amount of liver fibrosis (r = 0.72, p < 0.001, standard error = 7.29). Conclusions: Laminin is not useful in estimating the total amount of fibrosis neither in prognostic assessment of cirrhotics. However, serum laminin-values over 3.5 U/ml were associated with higher mortality rates in patients with chronic alcoholic liver disease, and serum laminin together with alkaline phosphatase and GGT correlated with the amount of fibrosis in the non-cirrhotic subgroup.
Revista Clinica Espanola, 2002
European Journal of Internal Medicine, Oct 1, 2013
Objectives: Heart failure is the end stage of hypertensive, coronary and valvular cardiovascular ... more Objectives: Heart failure is the end stage of hypertensive, coronary and valvular cardiovascular disease. It is a major and growing problem because of the increasing size of the aging population and the prolonged lives of cardiac patients with modern therapy. The goal of our study was to investigate the relationship between different parameters with survival, in a cohort of heart failure elderly patients. Methods: We studied a cohort of 244 patients hospitalized with heart failure (diagnosed according to Framingham criteria) at the Internal Medicine unit of a country hospital of Cantabria (Tres Mares Hospital at Reinosa); 115 were men and 129 were women with an age range of 55 to 100 years (median age and quartiles of 85 and 79–89 years). Fourteen (5.7%) patients died during hospitalization. All patients were followed up by telephone with a median survival of 984 days. The variables included in our study were age, sex, cognitive status Mini Mental Status Examination (MMSE), Barthel index, coronary disease, stroke, peripheral arteriopathy, atrial fibrillation, diabetes mellitus, COPD, smoking, heart rate, ejection fraction, NYHA class, systolic blood pressure, body mass index, midarm circumference, midarm muscle area (MAMA), triceps skinfold, handgrip strength, hemoglobin, serum albumin, serum prealbumin, lymphocyte count, total cholesterol, serum creatinine, serum urea nitrogen and natremia. To know which variables yield long term independent predictive value, we included in survival analysis with covariates (Cox regression) those variables with long term significant value when assessed by Kaplan–Meier and long rank test analysis. Results: The data with an independent predictive value were NYHA III/IV versus I/II, RR 3.73 (2.07–6.71) (p b 0.001); hemoglobin b 11 g/dl, RR 3.15 (1.83–5.40) (p b 0.001); serum creatinine N 1.5 mg/dl, RR 2.71 (1.59–4.61) (p b 0.001); MMSE b 21, RR 3.95 (1.70–9.17) (p 0.001); ejection fraction, RR 2.11 (1.17–3.79) (p 0.013): heart rate b 90 beats/min, RR 1.77 (1.04–3.00) (p 0.034); and midarm muscle area (MAMA) b 95th percentile, RR 0.22 (0.05–0.93) (p 0.039). Conclusion:ANYHA class III or IV class, a hemoglobin lower than 11 g/dl, a serum creatinine over 1.5 mg/dl, cognitive impairment with a MMSE lower than 21 points, an Ejection Fraction below 40% and a heart rate greater than 90/m were associated with a higher mortality rate. As a protective factor we found a MAMA over the 95th percentile of the normal population.
Journal of Trace Elements in Medicine and Biology, Sep 1, 2020
Introduction: In chronic hepatitis C virus (HCV) infection there is increased iron absorption lea... more Introduction: In chronic hepatitis C virus (HCV) infection there is increased iron absorption leading to iron overload, a fact that may promote ferritin synthesis. Theoretically, increased ferritin should promote ongoing liver fibrosis but disparate results have been described. Objective: We analyze the behavior of iron metabolism-related variables, comparing them with fibrosis and inflammatory activity in liver biopsy in HCV infected patients. Patients and Methods: We analyzed among 90 HCV patients subjected to liver biopsy prior to antiviral treatment the relationships of serum levels of iron, ferritin, transferrin, transferrin saturation index (TSI) and total iron binding capacity (TIBC) with liver fibrosis and histological severity, assessed by Metavir-f, Metavir-a and Knodell indices, as well as with liver function, and also compared the aforementioned iron metabolism-related variables with 34 controls. Results: Patients showed higher values of sideremia (T = 2.04; p = 0.044) and transferrin (T = 2.29; p = 0.004) compared with controls; but not ferritin, that was significantly higher among the 33 patients who also consumed alcohol (Z = 2.05; p = 0.041). Most patients showed a well preserved liver function (86 cases, Child A). Patients with Child B or C showed higher ferritin levels (Z = 2.68; p = 0.007) and TSI (Z = 2.41; p = 0.016), but lower transferrin and TIBC (Z = 3.25; p = 0.001) than Child A patients. Transferrin and TIBC were directly related to albumin (ρ = 0.24; p = 0.026), whereas bilirubin showed direct relationships with iron (ρ = 0.25; p = 0.016), TSI (ρ = 0.39; p < 0.001) and ferritin (ρ = 0.36; p < 0.001). Both ferritin (ρ = −0.22; p = 0.04) and TSI (ρ = −0.25; p = 0.016) were related to platelet count. No relationships were observed between iron variables and Knodell index, but serum iron, serum transferrin, and TSI were directly related to Metavir-f score (ρ = 0.28; p = 0.009, ρ = 0.22; p = 0.044, and ρ = 0.22; p = 0.044, in this order). Conclusion: Alterations of iron related variables are relatively subtle in our series of 90 well compensated HCV patients. Serum ferritin was not related to liver fibrosis and increases only when alcoholism co-exists with HCV infection.
European Journal of Internal Medicine, Oct 1, 2013
due to other causes besides left heart dysfunction were excluded from this survey. Results: 32 pa... more due to other causes besides left heart dysfunction were excluded from this survey. Results: 32 patients with PH and HF. 5 males (average age of 70.6 years), 27 females (average age of 76.3 years). Two of the patients have both HF and chronic pulmonary obstructive disease; 15 patients have HF secondary to hypertensive cardiomyopathy; 7 patients have HF secondary to ischemic cardiomyopathy and 10 patients have HF due to valvular cardiomyopathy. When evaluated EF, 19 patients have normal EF (EF ≥ 55%), 7 patients have preserved EF (EF [40%,55%]) and 6 patients have impaired global systolic function with EF b40%. Among the 32 evaluated patients, 17 patients have mild tricuspid insufficiency (TI), 10 patients have moderate TI and 3 patients have severe TI. PH tends to be more severe in patients with normal (median PASP = 51.68 mmHg) and preserved (median PASP = 52.21 mmHg) EF, than in patients with reduced global systolic function (median PASP 44.17 mmHg). Conclusions: The results of our retrospective analysis support the ongoing studies in which patients with HFpEF accounted for a significant percentage of patients with PH and right-sided heart dysfunction. The processes underlying the development of PH in HFpEF are still unclear.
Digestive and Liver Disease, Jun 1, 2023
The New England Journal of Medicine, Apr 25, 1996
Alcohol, Jul 1, 1998
This study was performed to analyze the relative and combined effects of ethanol and protein defi... more This study was performed to analyze the relative and combined effects of ethanol and protein deficiency on bone histology and mineral metabolism in 4 groups of 7 animals each which were pair-fed during 8 weeks with 1) a nutritionally adequate diet; 2) a 36% (as energy) ethanol containing isocaloric diet; 3) a 2% protein, isocaloric diet; and 4) a 36% ethanol 2% protein isocaloric diet, respectively, following the Lieber-DeCarli model. Another group of five rats were fed ad libitum the control diet. The first and second lumbar vertebrae were removed after sacrifice, and processed for histomorphometrical analysis of undecalcified bone samples. Blood and 24-h urine were also collected. Protein malnutrition, but not ethanol, leads to osteoporosis and reduced osteoid synthesis, whereas ethanol and protein malnutrition both lead to impaired bone mineral apposition and increased urinary hydroxyproline excretion. These changes are accompanied by an increase in serum parathormone and serum 1,25 dihydroxy vitamin D3, a slight hypomagnesemia, hypercalciuria and hyperphosphaturia; protein deficiency plays an independent role in these alterations, whereas both ethanol and protein deficiency exert independent effects on decreasing serum testosterone levels; this last alteration may contribute to the bone changes mentioned before.
Alcohol and Alcoholism, Feb 13, 2006
Objectives: Osteoprotegerin (OPG) is a decoy receptor that binds RANK-ligand (RANKL) and prevents... more Objectives: Osteoprotegerin (OPG) is a decoy receptor that binds RANK-ligand (RANKL) and prevents osteoclast activation. Oestrogens, androgens, corticosteroids, parathyroid hormone (PTH), vitamin D, and several cytokines exert their effects on bone modulating the OPG/RANKL system. Since these substances become altered in chronic alcoholic liver disease, we investigated the OPG/RANKL system in alcoholic liver disease, its relation with bone mineral density (BMD) and with several hormones and cytokines. Methods: Serum OPG, RANKL, C-terminal cross-linking telopeptide of type 1 collagen, osteocalcin, insulin-like growth factor 1 (IGF-1), 1,25 dihydroxyvitamin D, IL-6, tumour necrosis factor (TNF)-a, PTH, estradiol, free testosterone and corticosterone were measured in 77 male alcoholic patients, 25 of them cirrhotics. All these patients underwent assessment of BMD at lumbar spine and left hip by a Hologic QDR-2000 (Waltham, MA) bone densitometer. Nineteen non-drinkers male sanitary workers of similar age served as controls. Results: Serum OPG levels were higher in patients (12.66 ± 6.44 pmol/l) than in controls (6.59 ± 1.58 pml/l, P < 0.005), especially in cirrhotics (15.97 ± 7.03 pmol/l) vs non-cirrhotics (10.96 ± 5.45 pmol/l, P < 0.001). Patients also showed higher telopeptide levels (0.60 ± 0.36 vs 0.20 ± 0.10 nmol/100 ml,
Alcohol and Alcoholism, 1994
Revista española de las enfermedades del aparato digestivo, 1989
To establish the prevalence of liver enzyme alterations in the course of serious infections of di... more To establish the prevalence of liver enzyme alterations in the course of serious infections of diverse origin, 112 patients were studied retrospectively for the levels of GOT, GPT, LDH, GGT, alkaline phosphatase (FA) and bilirubin (BIL). Cases in which the values might be altered due to causes other than the infectious process were previously excluded. The prevalence of affectation of each of the parameters was the following: GGT, 39.1%; LDH, 33.3%; FAL, 30.1%; GOT, 29.5%; GPT, 24.8%; BIL, 18.3%. Seventy percent had at least one of these values changed. No significant differences were found in the incidence or intensity of the analytic alterations in function of the origin of the of infection, which suggests that these modification are nonspecific. Bilirubin levels were found to be significantly higher in the patients who died. On realizing the linear correlation analysis between the diverse parameters studied, a good correlation was found between them, suggesting a common pathogene...
Revista española de enfermedades digestivas : organo oficial de la Sociedad Española de Patología Digestiva, 1996
To determine the clinical and prognostic value of serum laminin in chronic alcoholic liver diseas... more To determine the clinical and prognostic value of serum laminin in chronic alcoholic liver disease and to discern whether laminin, alone or in combination with serum N-terminal type III collagen propeptide, and/or biochemical parameters, is useful in estimating the histomorphometrically determined amount of fibrosis. Prospective. 121 (80 of them cirrhotics), 107 followed up for a variable periods ranging from 1 to 1440 days. Serum laminin was higher in cirrhotic patients belonging to Child's C group and, in cirrhotic patients, it significantly correlated with Pugh's score (r = 0.32, p < 0.01), prothrombin activity (r = 0.23, p < 0.05), serum albumin (r = -0.35, p < 0.001) and bilirubin (r = 0.30, p < 0.01), and also with the degree of fibrosis (r = 0.49, p < 0.001). Serum laminin over 3.5 U/ml were associated to higher mortality rates in the total population (Log rank test = 4.9, p = 0.022), but not in cirrhotics. Stepwise multiple regression analysis showed t...
International Journal of Colorectal Disease, Mar 30, 2016
Dear Editor: Carcinoid tumors are slow-growing neoplasms derived from enterochromaffin cells or K... more Dear Editor: Carcinoid tumors are slow-growing neoplasms derived from enterochromaffin cells or Kulchintsky cells being thus neuroendocrine in nature. They may arise anywhere in the gastrointestinal tract, in the bronchi, and occasionally elsewhere (ovary, central nervous system). Within the gastrointestinal tract, most carcinoid tumors arise in the small intestine (45 %, most commonly in the ileum), followed by rectum (20 %), appendix (16 %), colon (11 %), and stomach (7 %). Carcinoid syndrome is the term applied to a set of symptoms mediated by different humoral factors elaborated by some carcinoid tumors (diarrhea, cutaneous flushing, cardiac valvular lesions, bronchospasm, and intermittent abdominal pain). These tumors synthesize, store, and release a variety of polypeptides, biogenic amines, and prostaglandins. Some of these tumor products are responsible for the carcinoid syndrome. The relative contribution and the specificity of each of the particular components of the syndrome are uncertain. It seems that among patients with intestinal carcinoid tumors, the carcinoid syndrome does not occur in the absence of liver metastases. In contrast, bronchial and other extraintestinal carcinoids, whose bioactive products are not immediately cleared by the liver, can rarely cause the syndrome in the absence of metastatic disease. Metastases of carcinoid tumors in peripheral nerve are extremely rare. All of them come from supradiaphragmatic
Colorectal Disease, Nov 1, 2016
Aim Very few studies have compared the epidemiological characteristics of patients with familial ... more Aim Very few studies have compared the epidemiological characteristics of patients with familial colorectal cancer Type X (FCCTX) with those of sporadic colorectal cancer (S-CRC). The aim of this study was to compare clinicopathological characteristics and survival between FCCTX and S-CRC in patients from a historically isolated geographical region. Method A retrospective study was carried out of patients with S-CRC and FCCTX treated in the Canary Islands. Family and personal history of colorectal cancer (CRC) were recorded, together with genetic (microsatellite instability), immunohistochemical and clinical variables. Results Forty-eight (10.6%) of 451 patients were classified as FCCTX and the remaining 403 (89.4%) as S-CRC. Age at the diagnosis of tumour was significantly lower in FCCTX than in S-CRC (64.06 AE 12.65 years vs 69.13 AE 10.80 years; P = 0.01; Z = À2.48). Patients with FCCTX had a larger number of synchronous tumours (P = 0.09). Recurrence was significantly higher in FCCTX than in S-CRC (18.7% vs 8.6%; P = 0.01). Survival correlated significantly with the number of first-degree and second-degree relatives with CRC (
Archivos De Bronconeumologia, May 1, 1992
Alcohol and Alcoholism, Mar 1, 1996
A hypermetabolic state with increased oxygen consumption has been described in alcoholic hepatiti... more A hypermetabolic state with increased oxygen consumption has been described in alcoholic hepatitis, playing a major role in ethanol-induced liver damage. Based on its ability to decrease oxygen consumption, propylthiouracil (PTU) has been proposed as a therapeutic agent in this context. On the other hand, several muscle changes have been described in hypothyroidism. including both atrophy and hypertrophy of muscle fibres. The aim of this experimental study was to analyse the effects of PTU on the alcohol-induced changes in muscle fibre size and proportion, also taking into account the presence or absence of protein deficiency. The study was performed on 64 male Wistar rats divided into eight groups, fed with: (1) Lieber-DeCarli control diet: (2) an isocaloric 36% cthanol-containing diet: (3) an isocaloric 2% protein-containing diet: (4) an isocaloric 36% ethanol 2% protein-containing diet, without and with PTU. respectively. Right gastrocnemius muscle was removed 2 months later and histochemical and morphometric studies were performed Type lib fibre atrophy was observed both in the alcoholic and protein-deficient animals, but not in the PTU-treated animals. The combination of protein deficiency and ethanol led to a more marked type lib atrophy, with PTU reversing this effect. Malnutrition led to a decrease in type I fibre diameter: ethanol and PTU caused an increase in its size and PTU reversed the effect of protein deficiency. Proportion of type lib fibres decreased in the three experimental groups without PTU with respect to the control, especially in the alcoholic protein-deficient animals. PTUtreated animals, especially those fed a low-protein diet, showed a more marked reduction in type lib fibre proportion than that presented by the groups without PTU. However, an increase in type I fibre proportion was observed in the PTU-treated animals, especially marked in those fed a low-protein diet Thus. PTU seems to ameliorate ethanol-induced changes on type lib muscle fibres.
Biomolecules, Aug 20, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of the American Geriatrics Society, Apr 1, 2016
Although the number of subjects reported here is too small to draw definitive conclusions, this e... more Although the number of subjects reported here is too small to draw definitive conclusions, this experience suggests that, if salsalate is to be used in older individuals, especially those who may be frail or prefrail, practitioners should be especially alert to the possibility of renal failure especially in the context of diarrhea and dehydration. An additional concern is that these adverse events occurred at a dose half that used in reported trials. Given that older adults are frequently underrepresented in clinical trials, these observations highlight the importance of having sufficient numbers of older adults in trials of agents likely to be used in that population.