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Jose L Hernandez

Hospital Marques de Valdecilla. Santander. Spain.
hernandezjluis@gmail.com

Journal articles

2010
José M Olmos, José L Hernández, Josefina Martínez, Jesús Castillo, Carmen Valero, Isabel Pérez Pajares, Daniel Nan, Jesús González-Macías (2010)  Bone turnover markers and bone mineral density in hypertensive postmenopausal women on treatment.   Maturitas Feb  
Abstract: OBJECTIVE: To evaluate bone mineral density (BMD) and bone metabolism in hypertensive postmenopausal women, and to differentiate the effect of thiazides from that of other antihypertensive agents. SUBJECTS AND METHODS: A community-based population of 636 postmenopausal women, 293 with hypertension (160 receiving thiazides, and 133 receiving other antihypertensive treatments), and 343 control women, were evaluated. Serum levels of aminoterminal propeptide of type I collagen (P1NP), C-terminal telopeptide of type I collagen (beta-CTX), 25-hydroxivitamin D, and intact parathyroid hormone were measured by electrochemiluminiscence. BMD was determined by DXA, and heel quantitative ultrasound measurements (QUS) with a gel-coupled device. RESULTS: BMD expressed as Z-score was higher in both groups of hypertensive women at all locations. Expressed as g/cm(2), it was also higher in patients on thiazides at femoral neck and lumbar spine. Only in the latter site, differences remained significant after adjusting for potential confounding variables, including BMI. Bone turnover markers were lower in both groups of hypertensive women, although the difference was greater in those on thiazides. After adjusting for potential confounders, differences remained significant only in the thiazide group. CONCLUSIONS: Our results add evidence to the idea that thiazides are beneficial to prevent bone loss.
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José L Hernández, José M Olmos, Carmen Ramos, Josefina Martínez, Julia de Juan, Carmen Valero, Daniel Nan, Jesus González-Macías (2010)  Serum lipids and bone metabolism in Spanish men: the Camargo cohort study.   Endocr J 57: 1. 51-60 10  
Abstract: There is growing evidence of a link between lipid and bone metabolism, although data on this association in European men are scarce. This cross-sectional study from a community-based prospective cohort aims to explore the association of serum lipids with different aspects of bone metabolism in Spanish men. Demographic and anthropometric measurements, biochemical parameters including serum lipids, bone remodelling markers and calciotropic hormones, bone mineral density (BMD) assessed by dual X-ray absorptiometry and heel quantitative ultrasound, and prevalent vertebral and non-vertebral fractures, were evaluated in 289 men. Calciotropic hormones or bone markers were not associated with serum lipids. Serum total (TC) and LDL cholesterol, as well as LDL/HDL ratio were positively correlated to BMD at lumbar spine and hip. No significant correlation was noted for triglycerides or HDL. We observed a positive association between triglycerides, LDL/HDL ratio and BUA, and between TC/HDL ratio and both, QUI and BUA. BMD at the femoral neck and total hip was significantly higher in men with hypercholesterolemia after controlling for all the covariates (p=0.007). We did not observe any association between serum lipids and prevalent vertebral fractures. However, we found that TC (p=0.03) and LDL (p=0.04) were lower in subjects with non-vertebral fractures. In conclusion, we have found that a more unfavorable lipid profile (mainly higher LDL-C levels) is associated with higher BMD at lumbar spine and hip in Spanish men. Moreover, we did not observe any association between hypercholesterolemia and prevalent vertebral fractures, but we found lower serum TC and LDL-C levels in men with prevalent non-vertebral fractures.
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Javier Velasco, Jose L Hernandez, Jose L Perez-Castrillon, Maria T Zarrabeitia, Maria A Alonso, Jesus Gonzalez-Macias, Jose A Riancho (2010)  Haplotypes of intron 4 of the estrogen receptor alpha gene and hip fractures: a replication study in Caucasians.   BMC Med Genet 11: 1. Jan  
Abstract: ABSTRACT: BACKGROUND: Despite their great impact, few genetic association studies have used hip fractures as an endpoint. However, the association of two polymorphisms on intron 4 of estrogen receptor alpha (ESR1) with hip fractures was recently reported in a Chinese population. The aim of this study was to investigate whether such association is also present in Caucasians. METHODS: We analyzed those two SNPs and another neighbour SNP located on the exon 4 of ESR1 in 787 patients with hip fractures and 953 controls from Spain. RESULTS: The allelic frequencies differed markedly from those reported in Asian populations. Nevertheless, haplotypes including the rs3020314 and rs1884051 loci in intron 4 showed a significant association with hip fractures (omnibus test p= 0.006 in the whole group and 0.00005 in women). In the sex-stratified analysis, the association was significant in females, but not in males. In women, the CA haplotype appeared to have a protective influence, being present in 6.5% of the controls, but only in 3% of patients with fractures (odds ratio 0.39; 95% confidence interval 0.26-0.59; estimated population preventive fraction 3.5%). The inclusion of the rs1801132 SNP of exon 4 further increased the statistical significance of the association (odds ratio 0.17; 95% CI 0.08-0.37; p=0.00001). Each SNP appeared to contribute independently to the association. No genotype-related differences in gene expression were found in 42 femoral bone samples. CONCLUSIONS: This study confirms the association of some polymorphisms in the region of exon 4/intron 4 of ESR1 and hip fractures in women. However, there are marked differences in allele frequencies between Asian and Caucasian populations.
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2009
Miguel Angel Núñez Viejo, Ana Fernández Montes, Javier Velasco Montes, José Javier Gómez-Román, Carmen García Ibarbia, José Luis Hernández Hernández (2009)  Rapid resolution of nitrofurantoin-induced interstitial lung disease   Arch Bronconeumol 45: 7. 352-355 Jul  
Abstract: We report the case of a 40-year-old woman diagnosed with interstitial lung disease due to long-term nitrofurantoin therapy. Despite severely distorted bronchiolar architecture and honeycombing confirmed by computed tomography of the thorax, transbronchial biopsy showed a pattern of acute/subacute interstitial pneumonitis and the symptoms and radiographic findings disappeared within 1 month after administration of prednisone. This case shows that nitrofurantoin-induced lung disease may run a benign course and respond favorably to corticosteroids, even when there is radiographic evidence of established lung fibrosis. Transbronchial biopsy might be useful for assessing the reversibility of pulmonary lesions associated with nitrofurantoin.
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J J Napal, J L Hernández, J Alonso, E Casuso (2009)  Differential factors of tumor etiology for iron deficiency anemia of probable gastrointestinal origin   Rev Clin Esp 209: 6. 265-269 Jun  
Abstract: BACKGROUND: Diagnosis of iron deficiency anemia (IDA) of probably gastrointestinal (GI) tract origin is a difficult task for the clinician. OBJECTIVE: To know the incidence of GI lesions in our setting; the possibility to predict cancer with clinical and laboratory parameters; the diagnostic utility of capsule endoscopy, and the follow-up in those patients. PATIENTS AND METHOD: We performed a prospective study in our Internal Medicine Department, from April 2005 to December 2007, of patients with IDA. RESULTS: A total of 129 patients (42 men, 87 women) were studied. There was 27 (20.9%) malignancies (21 colon, 5 stomach, 1 esophagus ); 39 (30.2%) benign upper GI lesions; 12 (9.3%) benign lower GI disorders; 16(12.4%) synchronous GI lesions; 2 (1.6%) celiac sprue, and 33 (25.6%) without identifiable lesions. We found significant differences between patients with and without malignancy in NSAID use, weight loss, leukocyte and platelet count, and alkaline phosphatase levels. Diagnosis sensitivity of capsule endoscopy in obscure GI bleeding was 27%. We did not found any malignancy during the follow-up of patients without an initial diagnosis. CONCLUSIONS: In IDA, colonoscopy (or contrast barium enema in certain circumstances) is the most important exploration to rule out malignancy. Only NSAID use is useful to exclude cancer. Patients without identifiable lesions have a favorable prognosis. A moderate frequency of synchronous lesions was found. We recommend a complete conventional GI endoscopic study if no evident bleeding lesion is found during the initial endoscopic procedure. Capsule endoscopy and celiac disease serology are useful in obscure gastrointestinal bleeding.
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José M Olmos, Carmen Valero, Andrés Gómez Del Barrio, José A Amado, José L Hernández, José Menéndez-Arango, Jesús González-Macías (2009)  Time course of bone loss in patients with anorexia nervosa.   Int J Eat Disord Aug  
Abstract: OBJECTIVE:: To evaluate the time course of bone mineral density (BMD) in women with anorexia nervosa (AN) during 2-year follow-up. METHOD:: We prospectively studied 51 female with AN aged 18-38 years, and 40 age-matched healthy women (19-34 years). BMD was measured in lumbar spine (LS), femoral neck (FN), and total hip (TH) by DXA. RESULTS:: At baseline, weight, body mass index, and lumbar and hip BMD were significantly (p < .001) lower in AN patients than in controls. Patients who gain weight showed a significant increase in BMD at FN (+1.6%; p < .05), and TH (+4.4%; p < .05) and lower nonsignificant changes in LS (+1.3%). Weight at entry, and percent change of weight were significant determinants (p < .05) of the variability in percent change of BMD at FN and TH, whereas weight at entry was the main determinant of bone modifications at lumbar spine. DISCUSSION:: Our data emphasize the influence of weight gain in recovery of bone mass in AN patients, especially at the hip. (c) 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2009.
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Josefina Martínez, José M Olmos, José L Hernández, Gabriel Pinedo, Javier Llorca, Eduardo Obregón, Carmen Valero, Jesús González-Macías (2009)  Bone turnover markers in Spanish postmenopausal women: the Camargo cohort study.   Clin Chim Acta 409: 1-2. 70-74 Nov  
Abstract: BACKGROUND: This cross-sectional study was performed to determine the reference ranges for two bone turnover markers--aminoterminal propeptide of type I collagen (P1NP) and C-terminal telopeptide of type I collagen (beta-CrossLaps, beta-CTX)--in normal postmenopausal Spanish women as determined in serum by automated methods. METHODS: A community-based population of 1080 healthy postmenopausal women was evaluated. Data regarding risk factors for osteoporosis and fractures were collected by means of a structured questionnaire. Fasting serum levels of P1NP, beta-CTX, 25-Hydroxivitamin D (25OHD), and intact parathyroid hormone (iPTH) were measured on the Elecsys 2010 automated analyzer (Roche). BMD at lumbar spine, femoral neck and total hip was determined by DXA. RESULTS: The mean age of subjects was 63+/-9. Logarithmic transformation of both markers was performed to allow for normal distributions. Mid-95% ranges for P1NP and beta-CTX were 19-100 ng/ml and 0.112-1.018 ng/ml, respectively. Mean values of P1NP (47.7+/-19.9 ng/ml) were similar to those previously determined by the manufacturer of the assays, whereas beta-CTX mean values (0.387+/-0.197 ng/ml) were lower. Both markers were higher among osteoporotic women. CONCLUSIONS: Values obtained from this well-characterized population study provide reference ranges for serum automated P1NP and beta-CTX in normal Spanish postmenopausal women.
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2008
José Luis Hernández Hernández, José Antonio Riancho Moral, Jesús González Macías (2008)  Metabolic syndrome: how about bone?   Med Clin (Barc) 130: 19. 745-750 May  
Abstract: In the last decades, the association between cardiovascular disease and osteoporosis has been a matter of an extensive clinical and basic investigation, and in fact, common pathogenic links have been recently proposed. The metabolic syndrome includes a series of cardiovascular risk factors that confer a high risk of morbimortality. On the other hand, osteoporosis and its more serious consequence, fracture, represent a true epidemic nowadays. The aim of the present article is to perform a brief update of the association between the individual components of the metabolic syndrome and bone metabolism, and to analyze the publications that have studied the same association, but considering the metabolic syndrome as a whole.
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M A Hernández-Hernández, M A Ballesteros-Sanz, M Gutiérrez-Cuadra, C González-Fernández, R Martín-Láez, J L Hernández-Hernández (2008)  Analysis of subdural intracraneal empyemas in a third level hospital   Rev Neurol 46: 6. 336-339 Mar  
Abstract: INTRODUCTION: Intracranial subdural empyema (ISE) is an infrequent infectious disorder of diverse etiology and difficult to diagnose because of its non-specific clinical features. PATIENTS AND METHODS: Retrospective study of patients diagnosed of ISE in a third-level university hospital in a 15-year period. RESULTS: Five men were included (mean age: 39.3 years). The most frequent primary source of infection was otic and sinusal (60%). The initial clinical manifestations were fever, headache, alteration of consciousness, and neurological focal symptoms. The mean time elapsed between onset of symptoms and diagnosis was 3.6 days. Diagnosis was performed by computed tomography in all patients. ISE was localized in the left hemisphere in 60% of cases mainly affecting the parietal lobe (80%). Anaerobic and streptococci germs were the most frequently isolated microorganisms. Therapy was based on antibiotics and surgical drainage in 100% of the cases. The surgical procedure used in the evacuation of empyema was craniotomy in all the patients. The mean time elapsed between diagnosis and surgery was 8.4 days. The mean Intensive Care Unit stay was 12.8 days, whereas the overall mean in-hospital stay was 45.2 days. Mortality was 40%. CONCLUSION: ISE, although infrequent, displays a high morbimortality that can be reduced with an early therapeutic approach which may include the surgical evacuation in all the cases.
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Ciro Ramos-Estébanez, Ignacio Moral-Arce, Roberto Muñoz-Arrondo, Andrés González-Mandly, Pedro Matorras-Galán, Jesús González-Macias, José Luis Hernández-Hernández (2008)  Vascular cognitive impairment: prodromal stages of ischemic vascular dementia.   Dement Geriatr Cogn Disord 25: 5. 451-460 04  
Abstract: BACKGROUND/AIMS: To describe the natural history of the prodromal stages of ischemic vascular dementia (pVaD). METHODS: A sample of 314 inpatients with pVaD or a clini- cal diagnosis of vascular dementia (VaD; lacunar state, Binswanger's disease, pure cortical VaD, corticosubcortical and strategic infarctions) admitted to a teaching tertiary center during a 13-year period was assessed (retrospectively n = 88, prospectively n = 226). Prospective neuropsychological assessment consisted of Mini Mental State Examination, Revised Wechsler Adult Intelligence Scale, Exit-25, Trail Making tests, Blessed Dementia Scale and Camdex H, Global Depression Scale and Hamilton Depression Rating Scale tests. Univariate analysis and logistic regressions are displayed. Results: An unrecognized pVaD was related with a clinical onset with cognitive impairment no dementia (CIND) versus symptomatic cerebrovascular events (p < 0.0001), and with being under therapy with anticoagulant or antiplatelet agents (p < 0.01). Age <85 years at diagnosis of VaD (p < 0.01) correlated with a delayed pVaD diagnosis. CIND onset was associated with a longer prodromal stage (p < 0.01), no clinical strokes during pVaD (p < 0.001), silent ischemia (p < 0.01) and Binswanger's disease (p < 0.01). CONCLUSIONS: Vascular cognitive impairment remains an underdiagnosed, yet treatable entity. A brief neuropsychological examination and informant interviews should become standard practice in elderly populations with vascular risk factors. Small-vessel disease is a prevalent condition with a distinct natural history.
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José M Olmos, Luis A Vázquez, José A Amado, José L Hernández, Jesús González Macías (2008)  Mineral metabolism in obese patients following vertical banded gastroplasty.   Obes Surg 18: 2. 197-203 Feb  
Abstract: BACKGROUND: Bone disease has been described in patients after surgical treatment for obesity, but few studies have dealt with the impact of vertical banded gastroplasty on mineral metabolism. We have examined bone mineral metabolism in morbidly obese patients before and after 3 months after vertical banded gastroplasty without vitamin D supplementation. METHODS: Sixteen morbidly obese patients (14 women, 2 men) with a mean (+/-SD) age of 38 +/- 9 years and a body mass index (BMI) of 47.1 +/- 8.1 kg/m2 were studied. No vitamin D supplementation was given. Body weight, fat mass, calcium, 25OHD, iPTH, bone remodeling markers, and leptin levels were measured at baseline and after weight loss. RESULTS: Mean weight loss was 28 +/- 11 kg; BMI and body fat mass decreased by 20 and 35%, respectively. Bone resorption markers and albumin-corrected serum calcium increased after operation, whereas iPTH fell. Serum 25OHD levels rose. Leptin levels decreased. Serum iPTH was positively correlated with weight, BMI, and fat mass before operation (p < 0.05), and its decline after weight reduction was negatively associated with the increase in bone resorption markers (p < 0.01). Leptin concentration was correlated with BMI and body fat mass (p < 0.05) both before and after surgery. CONCLUSIONS: Weight reduction obtained in morbidly obese subjects 3 months after vertical banded gastroplasty increases bone turnover markers and decreases PTH secretion. Serum 25OHD levels rose. Therefore, no reasons for a metabolic bone disease related to hypovitaminosis D were readily apparent. However, an increase in bone turnover, which is generally regarded as a potential risk factor for osteoporosis, was observed. Further work is needed to clarify the importance of this turnover increase in the long run.
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José L Hernández, Carlos M Garcés, Manuel Sumillera, Eugenio V Fernández-Aldasoro, Carmen García-Ibarbia, Jesús A Ortiz-Gómez, Jana Arozamena, María A Alonso, José A Riancho (2008)  Aromatase expression in osteoarthritic and osteoporotic bone.   Arthritis Rheum 58: 6. 1696-1700 Jun  
Abstract: OBJECTIVE: Estrogen deprivation is a central mechanism in the development of osteoporosis with aging. Results from recent studies also suggest the involvement of estrogens in the pathophysiology of osteoarthritis (OA). Aromatization of androgenic precursors in peripheral tissue is the main source of estrogens in postmenopausal women and in men. However, the importance of aromatase expression in bone is a subject of controversy. This study was undertaken to determine aromatase expression in bone samples from patients with hip fracture and patients with OA. METHODS: We studied 104 patients with hip fracture (n = 60) or primary hip OA (n = 44). Aromatase expression was determined in trabecular bone samples from the femoral neck and in osteoblast cultures grown by the primary explant technique (n = 62), using real-time reverse transcriptase-polymerase chain reaction. RESULTS: Aromatase RNA was detected in bone samples at levels similar to those found in adipose tissue. Transcript levels were significantly lower in bone tissue samples obtained from patients with OA than in those obtained from patients with fracture (P = 0.00001). Likewise, primary cultures of osteoblast cells from OA patients revealed lower aromatase expression than those of cells from fracture patients (P = 0.012). Results were independent of age or sex differences. CONCLUSION: Our findings indicate that the aromatase gene is expressed in bone tissue in high amounts, similar to those found in adipose tissue, but transcript levels are lower in tissue samples and osteoblast cultures from patients with OA than in those from patients with hip fracture. Since estrogens may help to prevent local cartilage degradation, it can be speculated that such a reduced expression of aromatase could facilitate the development of OA.
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C Valero, J L Pérez-Castrillón, M T Zarrabeitia, J L Hernández, M A Alonso, J del Pino-Montes, J M Olmos, J González-Macías, J A Riancho (2008)  Association of aromatase and estrogen receptor gene polymorphisms with hip fractures.   Osteoporos Int 19: 6. 787-792 Jun  
Abstract: Two polymorphisms of the aromatase and estrogen receptor genes appeared to interact to influence the risk of hip fractures in women. INTRODUCTION: Allelic variants of the aromatase gene have been associated with bone mineral density and vertebral fractures. Our objective was to analyze the relationship between two polymorphisms of the aromatase and estrogen receptor genes and hip fractures. METHODS: We studied 498 women with hip fractures and 356 controls. A C/G polymorphism of the aromatase gene and a T/C polymorphism of the estrogen receptor alpha gene were analyzed using Taqman assays. Aromatase gene expression was determined in 43 femoral neck samples by real-time RT-PCR. RESULTS: There were no significant differences in the overall distribution of genotypes between the fracture and control groups. However, among women with a TT genotype of the estrogen receptor, the CC aromatase genotype was more frequent in women with fractures than in controls (39 vs. 23%, p = 0.009). Thus, women homozygous for T alleles of estrogen receptor and C alleles of aromatase were at increased risk of fracture (odds ratio 2.0; 95% confidence interval 1.2-3.4). The aromatase polymorphism was associated with RNA levels in bone tissue, which were three times lower in samples with a CC genotype (p = 0.009). CONCLUSIONS: These common polymorphisms of the aromatase and estrogen receptor genes appear to interact, influencing the risk of hip fractures in women.
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2007
José L Fernández-Torre, José L Hernández-Hernández, Julio Jiménez-Bonilla, Andrés González-Mandly, Oscar García-Regata (2007)  Complex partial status epilepticus is an unrecognised feature in SESA syndrome: new insights into its pathophysiology.   Epileptic Disord 9: 2. 134-139 Jun  
Abstract: We report a patient diagnosed as having subacute encephalopathy with frequent seizures in alcoholics (SESA syndrome), in which recurrent, non-convulsive seizures of frontal origin contributed significantly to the alteration of the mental state. Our case suggests that the occurrence of episodes of complex partial status epilepticus (CPSE) may contribute greatly to the origin and pathophysiology of the confusional state in this rare, epileptic entity.
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C Valero, M A Alonso, M T Zarrabeitia, C Viadero, J L Hernández, J A Riancho (2007)  MTHFR C677T polymorphism and osteoporotic fractures.   Horm Metab Res 39: 8. 543-547 Aug  
Abstract: The C677T (rs1801133) polymorphism of MTHFR (methylenetetrahydrofolate reductase) has been associated with the risk of cardiovascular events, and also with osteoporosis in some studies. However, the results are controversial. Our objective was to determine the relationship of the polymorphism with osteoporotic fractures by means of a case-control study. C677T was analyzed in 823 subjects (365 controls, 136 with vertebral fractures and 322 with hip fracture) by using a Taqman assay. The distribution of MTHFR genotypes was similar in patients and controls. In comparison with TC/CC genotypes, the age-adjusted OR for hip fractures of the TT genotype was 1.0 (95% confidence interval 0.6-1.7) in women and 0.7 (0.3-1.8) in men. The OR for vertebral fractures was 0.8 (0.4-1.7) in women and 1.7 (0.4-6.7) in men. A meta-analysis combining these data with previous reports confirmed the lack of association between MTHFR and fractures, with an OR of 1.1 (0.7-1.9, p=0.65) for vertebral fractures and 1.2 (0.7-2.0; p=0.45) for peripheral fractures, but there was significant heterogeneity among the results of individual studies, particularly about peripheral fractures. In conclusion, the C677T polymorphism of the MTHFR gene does not appear to be associated with the overall risk of osteoporotic fractures. However, given the heterogeneity of the results of published studies, further investigations are needed to evaluate its influence in specific population subgroups.
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Maria T Zarrabeitia, Jose L Hernandez, Carmen Valero, Ana Zarrabeitia, Jose A Amado, Jesus Gonzalez-Macias, Jose A Riancho (2007)  Adiposity, estradiol, and genetic variants of steroid-metabolizing enzymes as determinants of bone mineral density.   Eur J Endocrinol 156: 1. 117-122 Jan  
Abstract: OBJECTIVES: Bone mineral density (BMD) is a complex trait resulting from the interplay of genetic and acquired factors. The objective of this study was to explore the influence of several anthropometric, lifestyle, genetic, and hormonal factors on BMD and analyze the possible differences in men and women. METHODS: We studied 572 individuals over 50 years of age (381 postmenopausal women and 191 men). Lumbar spine and femoral neck BMD were measured by dual energy x-ray absorptiometry. The free estrogen index (FEI) was calculated as the ratio of serum estradiol to sex hormone binding globulin in 241 individuals. Three polymorphisms in the genes coding for 17-hydroxylase/liase, sulfotransferase, and 5alpha-reductase were studied in DNA isolated from blood cells. RESULTS: Body mass index was strongly correlated to spine and femoral BMD both in women and in men (r = 0.32-0.49; P < 0.001). FEI was also independently correlated with spine BMD in both sexes (r = 0.23 and 0.34, P < 0.01), and with femoral neck in women (r = 0.30). Women with G alleles of the sulfotransferase gene tended to have higher spine BMD than those with C alleles (P = 0.025). No other genotype-related differences in BMD were found. CONCLUSIONS: In conclusion, the results of this study point toward body weight and estradiol levels as major factors determining BMD both in women and in men. A common polymorphism of the sulfotransferase gene also appears to be associated to spine BMD in women.
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José A Riancho, Carmen Valero, José L Hernandez, José M Olmos, Blanca Paule, Ana Zarrabeitia, Jesús Gonzalez-Macias (2007)  Biomechanical indices of the femoral neck estimated from the standard DXA output: age- and sex-related differences.   J Clin Densitom 10: 1. 39-45 Jan/Mar  
Abstract: We explored the feasibility of using routine dual-energy X-ray absorptiometry (DXA) to estimate several parameters of femoral neck geometry related to bone strength and to analyze their changes with age. Bone mineral density (BMD) was measured in 871 control men and women and in 19 women with hip fracture. Volumetric BMD (volBMD) and geometrical parameters were estimated from the DXA output with previously published formulas. In young subjects, areal BMD was higher in men than in women, but volBMD was similar in both sexes. However, it showed a more rapid decline with age in women. The femoral neck width and cortical thickness were also higher in young men than in women. Neck width increased and cortical thickness decreased with age in both sexes. The buckling ratio, an index of local cortical instability, increased more rapidly in women. The compressive strength decreased progressively with age in women, whereas it did not change in men after 50 yr of age. Compressive strength and the buckling ratio showed the largest difference between control and hip fracture women (Z=-1.3). This cross-sectional study suggests that data available in the standard DXA output can easily be used to estimate several geometrical parameters of the femoral neck that evolve in a sex- and age-specific manner. Further studies are needed to elucidate whether they add significant information to BMD in the prediction of fracture risk.
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M T Zarrabeitia, J L Hernández, C Valero, A L Zarrabeitia, F Ortiz, J Gonzalez-Macias, J A Riancho (2007)  Klotho gene polymorphism and male bone mass.   Calcif Tissue Int 80: 1. 10-14 Jan  
Abstract: The Klotho gene codes for a protein that is thought to influence the homeostasis of several tissues, including bone, as well as the aging process. Although the mechanism of action has not been fully elucidated, some studies in women have associated Klotho allelic variants to bone mineral density (BMD). The objective of this study was to determine the relationship of a common T/G polymorphism, resulting in a phenylalanine (F) to valine (V) substitution, with male bone mass. BMD was measured by dual-energy X-ray absorptiometry in 362 Spanish men aged 19-83 years. Klotho alleles were determined by a Taqman assay. Allele frequencies were 85% and 15% for the F and V alleles, respectively. In comparison with the most common FF genotype, young and middle-aged men (age less than 53 years) with FV/VV genotypes had higher age- and body mass index-adjusted BMD at the lumbar spine (1.059 +/- 0.017 vs. 1.016 +/- 0.011 g/cm(2), P = 0.036), the hip (1.077 +/- 0.017 vs. 1.033 +/- 0.011 g/cm(2), P = 0.028), and the calcaneus (0.599 +/- 0.125 vs. 0.547 +/- 0.108 g/cm(2), P = 0.012). Klotho alleles explained about 2-4% of BMD variance. However, Klotho genotype was not associated to BMD in older men. There were no Klotho-related differences in height, body weight, calcium intake, tobacco or alcohol consumption, or serum testosterone levels. In conclusion, these results suggest that allelic variants of Klotho constitute one of the genetic factors influencing BMD in male adults.
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José A Riancho, Carmen Valero, José L Hernández, Fernando Ortiz, Ana Zarrabeitia, María A Alonso, Nicolás Peña, M Asunción Pascual, Jesús González-Macías, María T Zarrabeitia (2007)  Association of the F352V variant of the Klotho gene with bone mineral density.   Biogerontology 8: 2. 121-127 Apr  
Abstract: Klotho gene codes for a protein with glucuronidase activity and is thought to influence bone and vascular homeostasis. We studied the relationship of a common T/G polymorphism, resulting in a phenylalanine (F) to valine (V) substitution at aminoacid position 352, with bone mineral density (BMD) and osteoporotic fractures. The study group comprised 914 Spanish women, including 438 control subjects, 190 patients with osteoporosis, 198 with hip fractures, and 88 patients with severe osteoarthritis. BMD was measured by DEXA in 540 women from the control and osteoporosis groups. Allele frequencies were 86% and 14%, for the F and V alleles, respectively. In comparison with the most common FF genotype, postmenopausal women with FV/VV genotypes had higher hip BMD (femoral neck: 0.673 +/- 0.011 vs. 0.644 +/- 0.006 g/cm(2); P = 0.02; total hip: 0.807 +/- 0.014 vs. 0.774 +/- 0.008 g/cm(2); P = 0.03). Klotho alleles explained about 1.5% of BMD variance, but were not associated to the risk of osteoporotic spine or hip fractures. The Klotho genotype was not associated to BMD in premenopausal women. In conclusion, the F352V Klotho polymorphism is associated with BMD in postmenopausal women, suggesting that Klotho gene variants influence skeletal aging.
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2006
Marta Martín-Millán, Carmen García-Ibarbia, Manuel Gutiérrez-Cuadra, Mar Gutiérrez-Santiago, Marta Fernández-Sampedro, Jesús González-Macías, José L Hernández-Hernández (2006)  Pyomyositis: retrospective review in a third-level hospital in the north of Spain   Enferm Infecc Microbiol Clin 24: 3. 173-177 Mar  
Abstract: OBJECTIVE: To describe the clinical, radiological and microbiological features of a series of patients diagnosed with pyomyositis in a tertiary care university-affiliated center over a 12-year period. PATIENTS AND METHODS: The medical records of all patients diagnosed with pyomyositis between January 1992 and December 2003 were reviewed. The charts were retrieved from the hospital database. Data were extracted according to a standardized protocol and included clinical, radiological, laboratory and microbiological parameters. RESULTS: A total of 54 patients (mean age, 50 years, 61% men) had pyomyositis. The most frequent predisposing factors were diabetes mellitus (22%) and traumatic injury (20%), followed by neoplasms (9%). Primary pyomyositis was diagnosed in 25 patients (55%), and a contiguous source of infection was detected in the remainder, with skin infection being the most frequent (40%). The most common presentation was isolated inflammatory signs with or without other symptoms (94%). Isolated fever was documented in only one patient. Ultrasonography was the most common diagnostic procedure performed (32%), followed by CT scanning (18%). Forty-five patients underwent a drainage procedure combined with antibiotic therapy. Pyomyositis was monomicrobial in 20 cases, and polymicrobial in 12. The most frequent pathogen was Staphylococcus aureus followed by coagulase-negative staphylococci (6 cases). Sepsis developed in 4 patients, and recurrence was observed in 8 (15%). Mortality was 10% (5 patients). CONCLUSIONS: Pyomyositis is a relatively uncommon infection in temperate climates, and is often considered late in the diagnostic workup. Physicians should bear this disease in mind to avoid diagnostic delays and initiate prompt therapy, in order to improve the prognosis of these patients.
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J M Olmos, J A Amado, C Valero, J L Hernández, J González-Macías (2006)  Factors other than glucocorticoids are involved in the osteoblast activity decrease caused by tissue injury.   Clin Endocrinol (Oxf) 64: 3. 280-283 Mar  
Abstract: OBJECTIVE: Serum osteocalcin is a marker of bone formation. The concentration of osteocalcin is decreased with tissue injury. As glucocorticoids are known both to be increased in this situation and to diminish serum osteocalcin, we have hypothesized that they could be involved in this decrease. DESIGN AND PATIENTS: We compared osteocalcin levels in two groups of patients undergoing abdominal surgery, one receiving thiopental, and the other etomidate, a glucocorticoid synthesis blocker. For comparative reasons, another protein decreased by glucocorticoids (osteoprotegerin) was measured in patients anaesthetized with thiopental. MEASUREMENTS: Serum osteocalcin, cortisol and albumin were determined before and over the 24 h following surgery. Serum concentration of osteoprotegerin (OPG) and receptor activator of the nuclear factor kappaB ligand (RANKL) were also determined before and 24 h after surgery in a third group of nine patients who received thiopental for anaesthetic induction. RESULTS: Cortisol levels were increased in the thiopental group, whereas, as expected, were decreased in etomidate patients. However, serum osteocalcin concentration decreased in a similar way in both groups. Serum OPG and RANKL levels were within the normal range at baseline and did not significantly change after surgery. CONCLUSIONS: The decrease in serum osteocalcin induced by tissue injury is independent of the increase in cortisol secretion triggered by the latter. In addition, another pharmacologically proven effect of cortisol on bone metabolism, OPG inhibition, could not be demonstrated in the first 24 h following surgery, in spite of the physiological increase in endogenous cortisol secretion taking place in this period.
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C Valero, J M Olmos, F Rivera, J L Hernández, M E Vega, J González Macías (2006)  Osteoprotegerin and bone mass in squamous cell head and neck cancer patients.   Calcif Tissue Int 78: 6. 343-347 Jun  
Abstract: Osteoprotegerin (OPG) is considered one of the main regulators of bone remodeling. Various patterns of serum OPG levels have been described in different types of tumors. We undertook this study to determine serum OPG levels in patients with squamous cell head and neck cancer (SCHNC), analyzing their relationship with other metabolic bone parameters and bone mineral density (BMD), as well as the possible influence of chemotherapy. Forty male patients with localized SCHNC were studied, and their results were compared with those of 40 healthy male controls. The type of treatment followed by each patient was noted. Age, weight, height, and lifestyle habits were recorded; and OPG, Ca(2+), intact parathyroid hormone (iPTH), 25-Hydroxyvitamin D (25OHD) and 1,25-Dihydroxyvitamin D (1,25(OH)(2)D), bone alkaline phosphatase, osteocalcin, and serum C-terminal cross-links telopeptide of type I collagen (ICTP) were determined. Dual-energy X-ray absorptiometry BMD at the lumbar spine, femoral neck, and hip was also measured. Serum OPG was higher in patients than in controls (91.7 +/- 25.8 vs. 77.2 +/- 26.3, P = 0.02). ICTP (a bone resorption marker) was 37% higher in patients (P = 0.007). Bone mass was lower in patients at the lumbar spine, femoral neck, and total hip. Lumbar spine Z-score showed a significant progressive decrease in controls, stage I-III patients, and stage IV patients. Logistic regression analysis showed a significant association between the disease and serum OPG levels, the odds ratio per standard deviation increase of this being 1.9 (95% confidence interval 1.1-3.8, P = 0.04) after adjusting for bone mass and ICTP serum levels, as well as for alcohol and smoking history. Adjustment for alcohol intake and tobacco use did not cancel out BMD differences between patients and controls. Patients with SCHNC show increased OPG serum levels, increased bone resorption, and decreased bone mass. The OPG rise appears to be unrelated to the BMD decrease, and the BMD decrease seems to be, at least in part, independent of smoking and drinking habits. No differences in either OPG or BMD were seen between patients with and without chemotherapy. Further studies are needed to clarify the mechanisms responsible for OPG and BMD changes in SCHNC.
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José L Hernández, José M Olmos, Maria A Alonso, Carmen R González-Fernández, Josefina Martínez, Marcos Pajarón, Javier Llorca, Jesús González-Macías (2006)  Trend in hip fracture epidemiology over a 14-year period in a Spanish population.   Osteoporos Int 17: 3. 464-470 11  
Abstract: Spain lacks detailed data on hip fracture trends despite being the country with the greatest increase in the pensioner-to-provider ratio in Europe. We reproduced a study on hip fracture incidence in a region of northern Spain (Cantabria) carried out 14 years ago to determine whether a secular trend to change is taking place. If such a trend could be found, our objective was to determine whether the effect is solely due to ageing or whether additional variables are involved. We assessed the incidence of hip fracture in patients aged > or =50 years through clinical records from Emergency Units and Orthopedic Surgical Units of all hospitals in the region of Cantabria in 1988 and 2002. A total of 318 new cases of hip fracture were recorded in 1988 and 490 in 2002 (54% increase; p<0.001). No significant changes were noticed following an adjustment for age. Women accounted for the increase in crude hip fracture incidence [246 women and 72 men suffered a hip fracture in 1988 compared to 404 women and 86 men in 2002 (64% increase in women and 19% increase in men; p<0.005 and not significant, respectively)]. The female:male ratio was 3.4 in 1988 versus 4.7 in 2002; following age-adjustment, no significant changes were found (1.8 in 1988 and 1.9 in 2002). The increase in crude hip fracture incidence was greater at cervical (versus trochanteric) sites. Patient residence, time of the year, site of fracture, kind of injury, previous contralateral hip fracture, length of stay, and peri-operative mortality did not differ significantly. In conclusion, a crude hip fracture incidence increase of about 50% in the northern Spanish region of Cantabria has taken place over the last 14 years. This effect does not persist after adjustments have been made for age. The crude rate increase occurred mainly at the expense of women, with a more noticeable rise in cervical fractures as opposed to trochanteric lesions.
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2005
C Valero, M T Zarrabeitia, J L Hernández, A Zarrabeitia, J González-Macías, J A Riancho (2005)  Bone mass in young adults: relationship with gender, weight and genetic factors.   J Intern Med 258: 6. 554-562 Dec  
Abstract: OBJECTIVES: To determine the relationship of the bone mass attained in young adults with anthropometric and genetic factors. DESIGN: Cross-sectional study of normal individuals. METHODS: We studied 341 healthy subjects between 22 and 45 years of age. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) and correlated with body weight, height and nine polymorphisms in six genes involved in sex steroid metabolism (17-hydroxylase, aromatase and 5-reductase) and activity (oestrogen receptors (ER)-alpha and -beta, and androgen receptor). RESULTS: The BMD was higher in men than in women (spine: 1.048 +/- 0.120 vs. 1.034 +/- 0.112; hip: 0.907 +/- 0.131 vs. 0.822 +/- 0.104 g cm(-2), P < 0.001). However, the difference was due, at least in part, to the larger body size in men and diminished markedly after height adjustment. There was a negative correlation between age and hip BMD. Body weight was the single most influential factor on spine and hip BMD in both sexes, explaining 8-9% of BMD variance. Amongst the genetic factors studied, a common CA repeat polymorphism in ER-beta showed a significant association with BMD in women (P = 0.03 at the spine, and 0.008 at the hip). The relationship between ER-beta genotype and BMD persisted after adjustment by body weight and age, explaining a further 2-3% of BMD variance. Allelic variants of other genes studied were not related with BMD. CONCLUSIONS: Body weight and allelic variants of ER-beta are associated with BMD in young adults.
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José Luis Hernández Hernández, José Antonio Riancho Moral, Jesús González Macías (2005)  Intravenous bisphosphonates   Med Clin (Barc) 124: 9. 348-354 Mar  
Abstract: Bisphosphonates possess a fundamental role in the treatment of bone metabolic diseases. Yet their main limitations are poor oral absorption and gastrointestinal side effects, mainly esophageal irritation. Indeed, oral administration is unpleasant for many patients, and it is difficult in bed-confined subjects. Therefore, intravenous administration of these agents can be very useful in several clinical scenarios, especially to improve the compliance. Recently, it has been showed that intravenous bisphosphonates are very useful to control hypercalcemia of malignancy, and to prevent bone complications related to metastases. Their use has also been analyzed in the prevention of bone disease after organ transplantation. Thus, their application to control Paget's disease of bone is well-known, and probably they could have an important role as antiresorptive agents in postmenopausal and steroidal osteoporosis. We present here a state of the art of the use of intravenous bisphosphonates for the aforementioned disorders.
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José L Hernández, Javier Gómez-Román, Ciro Ramos-Estébanez, Daniel Nan, Javier Martín-Oviedo, Jose A Riancho, Jesús González-Macías (2005)  Human herpesvirus 8 and Epstein-Barr virus coinfection in localized Castleman disease during pregnancy.   Haematologica 90 Suppl: Nov  
Abstract: Castleman's disease is a rare disorder characterized by two distinct entities with similar histology but different time course and therapeutic response. Multicentric plasma cell variant is highly associated with infection by human herpesvirus 8 (HHV-8), but the pathogenesis of the hyaline vascular variant is currently unknown. We report a pregnant patient who develops a localized axillary hyaline-type Castleman's disease in which HHV-8 DNA sequences were detected in the lymph node lesions by nested PCR. In addition, the PCR multiplex also showed positivity for EBV. Immunohistochemical studies confirmed the presence of both viruses. Our results provide the first evidence of the presence of HHV-8 and EBV sequences in localized Castleman's disease, suggesting a possible role of the association of these herpes virus in the pathogenesis of this type of disorder. This case highlights that searching for HHV-8 and EBV sequences in cases of localized Castleman's disease is strongly advised.
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José A Riancho, María T Zarrabeitia, Carmen Valero, Carolina Sañudo, José L Hernández, José A Amado, Ana Zarrabeitia, Jesús González-Macías (2005)  Aromatase gene and osteoporosis: relationship of ten polymorphic loci with bone mineral density.   Bone 36: 5. 917-925 May  
Abstract: Aromatase activity appears to be important for bone homeostasis in postmenopausal women. In fact, therapy with aromatase inhibitors is associated with bone loss and fractures. A common biallelic A/G polymorphism in the 3'-untranslated region (UTR) of CYP19-aromatase gene has been associated with differences in gene transcription and the risk of estrogen-responsive tumors. We explored the relationship of such a polymorphism and other 9 polymorphisms situated within or near CYP19 gene with bone mass. The study group comprised 286 postmenopausal women. DNA was isolated from peripheral blood. Biallelic and insertion/deletion polymorphisms were analyzed with exonuclease assays using TaqMan probes. A microsatellite polymorphism in intron 4 was studied by capillary electrophoresis. Bone mineral density (BMD) was determined by DXA. In this cross-sectional study, the postmenopausal decrease in bone mass appeared to be slower in women with AA genotype in the 3'UTR, than in those with AG or GG genotypes. Consequently, there were significant genotype-related differences in BMD. In women after age of 60, hip T-scores were: AA -1.3 +/- 0.1, AG -1.3 +/- 0.2, GG -1.9 +/- 0.1 (P = 0.002). Lumbar spine T-scores were: AA -1.9 +/- 10.2, AG -2.2 +/- 0.1, GG -3.0 +/- 0.2 (P = 0.001). Moreover, GG genotype showed a trend for lower free estrogen levels. This polymorphism was strongly linked to a tetranucleotide repeat in intron 4, as well as to other biallelic polymorphisms situated between 3'UTR and I.2 promoter regions. They all were associated with BMD. However, biallelic polymorphisms in the extreme 5' region of CYP19 and two polymorphisms in neighbor genes were not associated with BMD. In conclusion, common variations of CYP19-aromatase are associated with differences in BMD that seem to be important from an individual as well as from a population perspective.
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Daniel N Nan, Marta Fernández-Ayala, Carmen García-Ibarbia, Mar Gutiérrez-Santiago, José L Hernández (2005)  Henoch-Schönlein purpura after intravesical administration of bacillus Calmette-Guérin.   Scand J Infect Dis 37: 8. 613-615  
Abstract: The administration of intravesical bacille Calmette-Guérin (BCG) in early stages of bladder cancer is usually a safe therapy. Side-effects of BCG immunotherapy can be of both local and systemic nature. We report the first case of Henoch-Schönlein purpura following intravesical administration of BCG.
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2004
Maria T Zarrabeitia, José L Hernández, Carmen Valero, Ana L Zarrabeitia, Mayte García-Unzueta, José A Amado, Jesús González-Macías, José A Riancho (2004)  A common polymorphism in the 5'-untranslated region of the aromatase gene influences bone mass and fracture risk.   Eur J Endocrinol 150: 5. 699-704 May  
Abstract: OBJECTIVE: The aromatization of androgenic precursors in peripheral tissues, including bone, is the main source of estrogens after the menopause. CYP19, the gene encoding aromatase, has a long 5'-untranslated region with several variants of exon I and specific promoters. The aim of this study was to investigate the possible relationship between a common biallelic (C/G) polymorphism located on exon I.2 and bone mineral density (BMD). DESIGN: This was designed to be an association study between CYP19 polymorphism and BMD and the risk of vertebral fractures in women. METHODS: DNA was extracted from the peripheral blood of 299 women (116 premenopausal and 183 postmenopausal). CYP19 alleles were identified by a method based on the exonuclease activity of Taq-polymerase. BMD was determined by dual-energy absorptiometry. RESULTS: In premenopausal women there were no genotype-related differences in BMD. However, postmenopausal women with the CC genotype had lower spine and hip BMD than those with the GG genotype. The association between CYP19 genotypes and BMD was independent of other variables, such as age, height, body weight, calcium intake or years since menopause. The CC genotype was also associated with an increased risk of osteoporotic vertebral fractures (odds ratio 2.0; P=0.03). Serum levels of estrone and estradiol were similar in women with CC and GG alleles. CONCLUSIONS: A common biallelic polymorphism in the 5'-untranslated region of the CYP19-aromatase gene was associated with significant differences in bone mass and the risk of vertebral fractures in postmenopausal women. Given the frequency of allelic variants, genotype-related differences appear to be important from the perspective of the individual as well as the general population. Further studies are needed to elucidate underlying mechanisms that may be dependent on differences in estrogen bioactivity at the bone tissue level.
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J L Hernández, F Marin, J González-Macías, A Díez-Pérez, J Vila, S Giménez, B Galán, M S Arenas, F Suárez, L Gayola, G Guillén, T Sagredo, R Belenguer, A Moron, E Arriaza (2004)  Discriminative capacity of calcaneal quantitative ultrasound and of osteoporosis and fracture risk factors in postmenopausal women with osteoporotic fractures.   Calcif Tissue Int 74: 4. 357-365 Apr  
Abstract: Bone fragility fractures constitute the principal complication of osteoporosis. The identification of individuals at high risk of sustaining osteoporotic fractures is important for implementing preventive measures. The purpose of this study is to analyze the discriminative capacity of a series of osteoporosis and fracture risk factors, and of calcaneal quantitative ultrasound (QUS), in a population of postmenopausal women with a history of osteoporotic fracture. A cross-sectional analysis was made of a cohort of 5195 women aged 65 or older (mean +/- SD: 72.3 +/- 5.4 years) seen in 58 primary care centers in Spain. A total of 1042 women (20.1%) presented with a history of osteoporotic fracture. Most fractures (93%) were non-vertebral. Age-adjusted odds ratios corresponding to each decrease in one standard deviation of the different QUS parameters ranged from 1.47 to 1.55 (P < 0.001) for fractures. The age-adjusted multivariate analysis yielded the following risk factors independently associated with a history of osteoporotic fracture: number of fertile years, a family history of fracture, falls in the previous year, a history of chronic obstructive airway disease, the use of antiarrhythmic drugs, and a low value for any of the QUS parameters. The area under the receiver operating characteristic curve of the best model was 0.656. In summary, a series of easily assessable osteoporotic fracture risk factors has been identified. QUS was shown to discriminate between women with and without a history of fracture, and constitutes a useful tool for assessing fracture risk. Various of the vertebral and hip fracture risk factors frequently cited in North American and British populations showed no discriminative capacity in our series--thus suggesting that such factors may not be fully applicable to our population and/or to the predominant type of fractures included in the present study.
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2003
J L Hernández, P Matorras, J A Riancho, J González-Macías (2003)  Involuntary weight loss without specific symptoms: a clinical prediction score for malignant neoplasm.   QJM 96: 9. 649-655 Sep  
Abstract: BACKGROUND: Involuntary weight loss (IWL) is a non-specific symptom frequently found in the setting of a malignant neoplasm. There is no established diagnostic approach for patients presenting with isolated IWL, i.e. without data suggesting a particular organ involvement or system disorder. AIM: To assess the clinical probability of cancer in patients with isolated IWL by means of a score based on simple clinical and laboratory parameters. DESIGN: Retrospective analysis, followed by prospective model validation. METHODS: We analysed data from 328 patients who were treated at our Internal Medicine Department because of isolated IWL from January 1991 to December 1997. A predictive model for cancer was developed and validated. For use in clinical practice, a prediction score was derived from the regression model. RESULTS: There were 236 in-patients (72%) and 92 out-patients (28%). Malignancies were the most frequent cause of isolated IWL (35%), followed by psychiatric disorders (24%). Age, white blood count, and serum albumin, alkaline phosphatase, and lactate dehydrogenase levels were selected as the best predictors. The regression model discriminated relatively well between patients with or without a malignant neoplasm (area under the ROC curve 0.90, 95%CI 0.88-0.92). Model sensitivity was 69%, specificity 93% and positive likelihood ratio 9.9 (using a cut-off point of 0.5). DISCUSSION: We believe this to be the first study to attempt a systematic approach to the diagnosis of isolated IWL. The approach, based on very simple clinical and laboratory data, should assist the physician in a rational approach to such patients.
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José L Hernández, José A Riancho, Pedro Matorras, Jesús González-Macías (2003)  Clinical evaluation for cancer in patients with involuntary weight loss without specific symptoms.   Am J Med 114: 8. 631-637 Jun  
Abstract: PURPOSE: There is no established diagnostic approach to rule out cancer in patients who present with involuntary weight loss in the absence of other symptoms (isolated involuntary weight loss). We sought to evaluate the efficiency of various diagnostic studies used in these patients. METHODS: We studied 306 patients referred to an urban tertiary care teaching hospital for isolated involuntary weight loss, 276 of whom were followed for at least 1 year or until a final diagnosis was reached. We collected data about the diagnostic approach, the causes of unintentional weight loss, and survival. RESULTS: Of the 276 patients, 104 (38%) had cancer, mainly of the digestive system (54%, n = 56). The first diagnostic clue usually came from routine blood tests (complete blood count, erythrocyte sedimentation rate, and a biochemical profile), which led to a more targeted diagnostic procedure, such as abdominal ultrasonography, computed tomography, and gastrointestinal endoscopy. Only 2 patients with cancer had normal results in all of these tests. Nine of the patients with cancer were not detected during the initial evaluation. Median survival was 2 months among patients with cancer, and only 9 survived longer than 1 year. CONCLUSION: These results suggest that a clinical approach, including routine laboratory tests (complete blood count, erythrocyte sedimentation rate, and serum albumin, aminotransferases, gamma-glutamyl transpeptidase, alkaline phosphatase, and lactate dehydrogenase levels) and abdominal ultrasonography, seems to be appropriate for detecting the majority of cases of cancer among patients with isolated involuntary weight loss.
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O Acha, J L Hernández, S Penado, M Cano, J A Riancho (2003)  Risk factors and stroke among patients of different ages   Rev Clin Esp 203: 4. 189-192 Apr  
Abstract: OBJECTIVE: To determine the frequency of cardiovascular risk factors in patients of different ages with ischemic cerebrovascular accident.Patients and methods. Descriptive, retrospective study of 1,077 patients with stroke or transient ischemic attack. RESULTS: Arterial hypertension (49%-67%) and atrial fibrillation (38%-46%) were the most prevalent risk factors in men and women aged over 65 years. Among individuals aged less than 65 years, smoking in men (58%) and arterial hypertension (64%) and hyperlipidemia (36%) in women predominated. Atrial fibrillation was particularly frequent in patients aged over 80 years (46% in men and 52% in women). CONCLUSION: On the basis of the high prevalence of arterial hypertension and atrial fibrillation in these patients, the appropriate management of these conditions should by a priority for the prevention of cerebrovascular diseases, especially in advanced aged patients.
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Susana Penado, Marta Cano, Olga Acha, José L Hernández, José A Riancho (2003)  Atrial fibrillation as a risk factor for stroke recurrence.   Am J Med 114: 3. 206-210 Feb  
Abstract: BACKGROUND: Although atrial fibrillation is a well-known risk factor for ischemic stroke, the extent to which it increases the risk of stroke recurrence, particularly in elderly patients, is less certain. METHODS: We performed a retrospective cohort study of 915 patients aged 50 to 94 years who were admitted with an ischemic stroke. The rates of recurrent strokes and recurrent severe strokes were estimated with the Kaplan-Meier method. The effects of atrial fibrillation on stroke risk were analyzed with proportional hazards models. RESULTS: Of the 829 patients who survived the initial hospitalization, 163 (20%) had a stroke during follow-up. Of the 203 patients with atrial fibrillation during index hospitalization who were not anticoagulated, 54 (27%) had recurrent strokes, compared with 18% (19/103) among those with atrial fibrillation who were anticoagulated and 17% (90/523) among those without atrial fibrillation. The age-adjusted hazard ratio for recurrent stroke among those with atrial fibrillation who were not treated with anticoagulants was 2.1 (95% confidence interval [CI]: 1.4 to 2.9; P <0.001), whereas the hazard ratio for recurrent severe stroke was 2.4 (95% CI: 1.6 to 3.6; P <0.001). The increased risk was observed even in patients aged > or = 80 years and persisted during the follow-up for more than 5 years. CONCLUSION: Atrial fibrillation was an independent risk factor for stroke recurrence over a wide age range.
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2002
L Iglesias Oliva, E Pérez-Llantada Amunárriz, G Saro Gutiérrez, R Tejido García, J L Hernández Hernández (2002)  Acute hepatic failure in a teaching hospital: a review of 20 cases in the past seven years   An Med Interna 19: 10. 521-523 Oct  
Abstract: Acute liver failure (ALF) is a medical emergency which entails a multisistemic affectation almost always. Twenty cases of ALF have been reviewed in a teaching hospital with active liver transplantation programme. A high percentage of patients with alcohol abuse was observed although these patients did not have previously known hepatic damage. Although microbiological, toxicological and anatomopatological studies were performed in all cases, an important difficulty for establishing the etiologic agent was observed. We observed a worse prognosis in those patients older than 40, those with grade IV encephalophaty and those that did not undergo a liver transplantation. Most patients needed UCI attention and more than half died.
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C Ramos-Estébanez, J L Hernández Hernández, R Muñoz Arrondo, H Alonso Valle (2002)  Binswanger's disease or multi-infarct dementia? Diagnostic keys in vascular dementia   Rev Clin Esp 202: 1. 7-11 Jan  
Abstract: OBJECTIVE: To develop a model that assists in the classification of patients with vascular dementia in two of its most relevant subtypes: multi-infarct dementia (cortical involvement) and Binswanger's disease (subcortical involvement). PATIENTS AND METHODS: Retrospective analysis of 50 consecutive patients with Binswanger's disease and 50 patients with multi-infarct dementia studied throughout a 12-year period (1986-1998) in a tertiary university hospital. The statistical model was obtained by multivariant analysis (logit model) and its accuracy was estimated by means of ROC curve analysis. RESULTS: The variables included in the regression model were: arterial hypertension (p < 0.03), cardioembolic disease (p < 0.05), and presence of cortical (p < 0.01) and lacunar (p < 0.01) infarctions in CAT. The specificity of the model was 90%, the sensitivity near 60%, and the positive likelihood ratio 5.8. The area under the ROC curve was 0.80 (0.73-0.87). CONCLUSIONS: Despite the availability of consensus diagnostic criteria for vascular dementia, their use is very commonly restricted to the research field. We have developed a classification model for patients with vascular dementia in two relevant subgroups: multi-infarct dementia and Binswanger's disease. This model can contribute to make identification of these patients in the daily clinical practice easier.
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J L Hernández Hernández, P Matorras Galán, J A Riancho Moral, J González-Macías (2002)  Etiologic spectrum of solitary constitutional syndrome   Rev Clin Esp 202: 7. 367-374 Jul  
Abstract: OBJECTIVE: To know the spectrum of diseases responsible for the solitary constitutional syndrome in our setting. This syndrome was defined as a clinical picture characterized by the presence of asthenia, anorexia, and weight loss of at least 5% of body weight in the last six months, not associated with any other symptom or sign suggesting the diagnosis of an organ or system disease. PATIENTS AND METHODS: All patients diagnosed of the solitary constitutional syndrome (328) in a tertiary-care level teaching hospital between January 1991 and December 1996. RESULTS: Fifty-two (170) percent of patients with solitary constitutional syndrome were males and 48% (158) females. The mean age was 65.4%, ranging from 15 to 97 years. The average of the monthly estimated weight loss was 3 to 4 kilograms. A total of 115 (35%) malignant neoplasms and 5 (1.5%) benign tumors were diagnosed. The most common malignant tumors corresponded to the digestive tract (51.3% of the total malignant tumors). The second cause in frequency of the solitary constitutional syndrome corresponded to psychiatric diseases, with a total of 80 patients (24.3%). A total of 116 non-neoplastic organic diseases were detected, with digestive tract diseases --mainly peptic disease-- being the most common cause in this group. After follow-up, only in twenty cases were we unable to detect the underlying disease responsible for the syndrome. In nine of these, the solitary constitutional syndrome was self-limited. Forty-four percent of patients had at least another concomitant disease and in 24% of patients more than one associated condition was found. CONCLUSION: The most common diseases responsible for the solitary constitutional syndrome were, by decreasing frequency, malignant tumors, psychiatric disorders, and non-malignant organic diseases located in the digestive tract. A better knowledge of the etiological spectrum of this syndrome might be useful for a more efficient management of these patients.
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José L Hernández, Francisco J Ramos, Jon Infante, Mariano Rebollo, Jesús González-Macías (2002)  Severe serotonin syndrome induced by mirtazapine monotherapy.   Ann Pharmacother 36: 4. 641-643 Apr  
Abstract: OBJECTIVE: To document a case of serotonin syndrome (SS) associated with mirtazapine monotherapy, review the previously reported cases of SS associated with this tetracyclic antidepressant, and discuss the possible pathogenic mechanisms leading to this serious adverse drug reaction. CASE SUMMARY: A 75-year-old man developed agitation, confusion, incoordination, and gait disturbance because of progressive rigidity. Mirtazapine had been started 8 days earlier to control major depression. Physical examination revealed diaphoresis, low-grade fever, hypertension, tachycardia, bilateral cogwheel rigidity, hyperreflexia, tremor, and myoclonus, symptoms and signs that are consistent with severe SS. DISCUSSION: A review of the cases of SS with implication of mirtazapine as the cause was performed. The possible pathogenic mechanisms leading to this adverse reaction in this patient are also discussed, and pathophysiologic hypotheses are formulated. CONCLUSIONS: Although mirtazapine offers clinicians a combination of strong efficacy and good safety, we suggest bearing SS in mind when prescribing this drug, especially in frail, elderly patients with underlying chronic conditions. In these patients, it might be more adequate to start mirtazapine therapy at a lower dose (<15 mg/d).
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2001
J L Hernández, C Ramos (2001)  Pyogenic hepatic abscess: clues for diagnosis in the emergency room.   Clin Microbiol Infect 7: 10. 567-570 Oct  
Abstract: The objective of this paper is to describe the clinical and diagnostic characteristics of patients with pyogenic hepatic abscesses evaluated in the emergency room, and to know whether it is feasible to make an early diagnosis based on any of these characteristics. The setting was an urban, tertiary-care teaching hospital. This was a retrospective study of 63 adult patients admitted to our institution because of pyogenic liver abscesses from January 1991 to December 1998.
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R Muñoz-Arrondo, J L Hernández-Hérnandez, C Ramos-Estébanez, H A Valle (2001)  Alcohol and stroke: a controversial association   Rev Neurol 33: 6. 576-582 Sep  
Abstract: OBJECTIVE: Although an increasing quantity of information concerning risk factors for stroke have been developed lately, the relationship between alcohol consumption and cerebral ischemic infarction, unlike at coronary sites, remains unclear. This review highlights the main pathogenic mechanisms of alcohol in the development of ischemic stroke, as it intends to be an update of this possible association. DEVELOPMENT: A critical literature review has been performed regarding this association to study its pathogenic mechanisms and the possible confounding factors present in the current design of epidemiological reports. CONCLUSIONS: There is an increasing evidence about the effect of light to moderate alcohol consumption and prevention of ischemic stroke. On the other hand it seems that heavy drinking, and particularly binge drinkers, are exposed to a higher risk for cardioembolic stroke. The growing incidence of acute heavy alcohol consumption highlights the necessity of considering a cardioembolic source when managing ischemic stroke, specially in young adults.
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J L Hernández, J Calvo, R Sota, J Agüero, J D García-Palomo, M C Fariñas (2001)  Clinical and microbiological characteristics of 28 patients with Staphylococcus schleiferi infection.   Eur J Clin Microbiol Infect Dis 20: 3. 153-158 Mar  
Abstract: The aim of this study was to analyse the clinical and microbiological characteristics of a series of patients with infection by Staphylococcus schleiferi. Seventy-one isolates were recovered from 36 patients between January 1993 and June 1999 at a tertiary care centre in northern Spain. There were 28 patients with well-documented clinical data. Infection was more frequent in men (89.3%), and more than half of the patients had some degree of immunosuppression, mainly malignant neoplasms. Infection was nosocomial in 22 cases and community-acquired in the remaining cases. Staphylococcus schleiferi was frequently associated with wound infections, mainly surgical-site infections, although unusual types of infections were detected. Infection-related mortality was low. This study highlights the importance of careful identification of Staphylococcus schleiferi in the clinical microbiology laboratory. Due to the documented association of Staphylococcus schleiferi with clinical infections in humans, any isolates of this organism should be assumed to be pathogenic, unless proven otherwise.
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J L Hernández Hernández, I Fidalgo González, M López-Calderón, J M Olmos Martínez, J González Macías (2001)  Diagnosis of osteoporosis by lateral chest X-ray   Med Clin (Barc) 117: 19. 734-736 Dec  
Abstract: BACKGROUND: Lateral chest X-rays may be helpful in the early detection of osteoporotic patients. We studied the proportion of chest X-ray reports in which the radiologist highlighted the presence of vertebral osteoporotic signs, as well as the proportion of patients with such records who were further studied by their physicians in order to confirm the diagnosis of osteoporosis. PATIENTS AND METHOD: We reviewed both lateral chest X-ray records of 3,500 consecutive patients and their medical records with the ultimate diagnosis. RESULTS: Radiology reports referred to the presence of vertebral abnormalities suggestive of osteoporosis in only 20% of potentially expected cases. Final medical records registered a diagnosis of osteoporosis in only one third of positive radiological records (6.3% of expected cases with vertebral abnormalities). Only two thirds of patients diagnosed with vertebral osteoporosis by their physician were adequately treated (4% of positive lateral chest X-ray reports). CONCLUSION: Osteoporosis is a disease overlooked by both radiologists and clinicians. Lateral chest X-ray is a helpful diagnostic tool for osteoporosis but its usefulness is often
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2000
J L Hernández Hernández, J M Olmos Martínez, J Figols Ladrón de Guevara, J A Riancho Moral, J González Macías (2000)  Femoral osteolytic lesions with soft tissue tumors and hypercalcemia as presentation form of a B-cell lymphoma   An Med Interna 17: 5. 264-266 May  
Abstract: Hypercalcemia associated with haematological neoplasms account for 15 to 20% of hipercalcemia in malignancy, and occurs usually in patients with multiple myeloma. However, its incidence in patients with linfoma is low, and it is observed usually in T-cell linfomas. Bone affectation is also uncommon in patients with non-Hodgkin linfoma. It usually is seen as a late manifestation of the disease, and its occurrence as the form of presentation is exceptional. We hereby report a patient with a B-cell non-Hodgkin linfoma presenting with hypercalcemia and femoral osteolytic lesions.
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Hernández, Zarrabeitia, Fernández-Llaca, Hortal, González-Macías (2000)  Multifactorial thrombotic-type microangiopathy with skin ulcers and hepatitis C infection.   Eur J Intern Med 11: 3. 165-167 Jun  
Abstract: The case of a patient with hepatitis C virus infection who presented with symmetric ulcers of the legs is reported. She was found to have type III mixed cryoglobulinemia, high titers of anticardiolipin antibodies, lupus anticoagulant, and a free protein S deficiency. To our knowledge, this is the first reported case of such an association. The role of these factors in the pathogenesis of skin lesions in the setting of hepatitis C virus infection is discussed.
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J Calvo, J L Hernández, M C Fariñas, D García-Palomo, J Agüero (2000)  Osteomyelitis caused by Staphylococcus schleiferi and evidence of misidentification of this Staphylococcus species by an automated bacterial identification system.   J Clin Microbiol 38: 10. 3887-3889 Oct  
Abstract: We report a case of sternal osteomyelitis due to Staphylococcus schleiferi in a patient who underwent thoracic surgery. This constitutes the first documented case of osteomyelitis caused by this Staphylococcus species. We also relate our experience in the utilization of commercially available MicroScan panels for the identification of this microorganism.
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Iglesias, Pérez-Llantada, Saro, Pino, Hernández (2000)  Benign symmetric lipomatosis (Madelung's disease).   Eur J Intern Med 11: 3. 171-173 Jun  
Abstract: We report on a 50-year-old man who presented with benign, symmetric lipomatosis and chronic alcoholic liver disease. The characteristic clinical features and a brief review of the current literature are presented.
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1999
1998
1997
R Tejido García, M Anta Fernández, J L Hernández Hernández, J Bravo González, J González Macías (1997)  Fever of unknown origin as the clinical presentation of malignant peritoneal mesothelioma   An Med Interna 14: 11. 573-575 Nov  
Abstract: Malignant peritoneal mesothelioma is a rare disease. The most frequent initial symptoms are abdominal pain, anorexia, marked weight loss and ascites. Clinical presentation as fever of unknown origin is exceptional. We report three cases diagnosed over a period of twenty years, two cases as fever of unknown origin and the third as prolonged fever. Three patients died within two months after diagnosis and prolonged fever was the clinical manifestation at the onset of the disease. It is important to take malignant peritoneal mesothelioma in the differential diagnosis of fever unknown origin.
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J I Hernández, J Gómez-Román, E Rodrigo, J M Olmos, C González-Vela, J C Ruiz, J F Val, J A Riancho (1997)  Bronchiolitis obliterans and IgA nephropathy. A new cause of pulmonary-renal syndrome.   Am J Respir Crit Care Med 156: 2 Pt 1. 665-668 Aug  
Abstract: IgA nephropathy is a common form of glomerulonephritis, classically manifested by asymptomatic hematuria. Although the exact pathophysiologic mechanism is still unknown, renal damage has been related to mesangial deposition of IgA-containing immune complexes. In recent years, some lung diseases have been associated with IgA nephropathy, including pulmonary hemorrhage and sarcoidosis. We report a patient with idiopathic bronchiolitis obliterans who developed a rapidly progressive glomerulonephritis due to IgA deposits. Extensive deposits of IgA were also found in the lungs, thus suggesting a pathogenetic role for IgA in tissue injury at both organ levels. To our knowledge this association has not been previously described in the literature.
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J L Hernández, L Palacios-Araus, S Echevarría, A Herrán, J F Campo, J A Riancho (1997)  Neuroleptic malignant syndrome in the acquired immunodeficiency syndrome.   Postgrad Med J 73: 866. 779-784 Dec  
Abstract: Patients infected by the human immunodeficiency virus are predisposed to many infectious and noninfectious complications and often receive a variety of drugs. Furthermore, they seem to have a particular susceptibility to idiosyncratic adverse drug reactions. It is therefore surprising that only a few cases of the neuroleptic malignant syndrome have been described in patients with the acquired immunodeficiency syndrome. A high index of suspicion is required to diagnose the neuroleptic malignant syndrome in these patients, as its usual manifestations, including fever and altered consciousness, are frequently attributed to an underlying infection.
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J L Hernández, S Echevarría, A García-Valtuille, F Mazorra, R Salesa (1997)  Atypical coccidioidomycosis in an AIDS patient successfully treated with fluconazole.   Eur J Clin Microbiol Infect Dis 16: 8. 592-594 Aug  
Abstract: Cervical lymphadenopathy due to Coccidioides immitis occurred as the sole opportunistic infection in a Spanish patient with the acquired immunodeficiency syndrome. Twelve years earlier the patient had lived in the desert regions of the southwestern USA. After an initial course of high doses of fluconazole, the patient recovered without any sequelae. This is the first case of coccidioidomycosis in Spain.
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1996
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