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Biomedical subjects

J González-Macías

Publications and source records attributed to J González-Macías.

At least 19 recordsLinked to original sources

Factors other than glucocorticoids are involved in the osteoblast activity decrease caused by tissue injury.

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.

Abdomen↗

Bone mass in young adults: relationship with gender, weight and genetic factors.

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.

Absorptiometry, Photon↗

[What is the opinion of Spanish internists on osteoporosis?].

OBJECTIVE: To conduct an opinion survey on osteoporosis in Spanish internists. METHOD: Survey sent by mail and by personal visit to members of the Spanish Internists Society. Collection of data on opinion on the disease, diagnostic and therapeutic attitude and means available (general laboratory analyses, conventional radiology, biochemical markers of bone remodeling, densitometry and ultrasounds) and preference when choosing a certain treatment. RESULTS: A total of 538 internists answered. More than 90% of those surveyed consider that osteoporosis is a disease that should be treated by internists. A total of 93% consider that osteoporosis is a prevalent disease. More than 80% have access to densitometry. CONCLUSIONS: The majority of Spanish internists consider that osteoporosis is a disease that should be treated by internists and that it is a disease that enters into their action scope. In general, they have the means necessary for its study and treatment. Bisphosphonates constitute the drug of choice and calcium and vitamin D supplements are indicated in almost all the cases.

Aged↗

Discriminative capacity of calcaneal quantitative ultrasound and of osteoporosis and fracture risk factors in postmenopausal women with osteoporotic fractures.

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.

Aged↗

Involuntary weight loss without specific symptoms: a clinical prediction score for malignant neoplasm.

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.

Adolescent↗

Quantitative ultrasound calcaneus measurements: normative data and precision in the spanish population.

Quantitative ultrasound (QUS) assessment at the calcaneus has been found to be a safe and reliable method for evaluating skeletal status. In this study we have determined the normative QUS data in the Spanish population for the Sahara Clinical Sonometer (Hologic). Broadband ultrasound attenuation (BUA), speed of sound (SOS), quantitative ultrasound index (QUI) and estimated bone mineral density (BMD) were determined. We also studied the precision in vivo and in vitro. The short-term in vivo precision (CV) was 4.88% for BUA, 0.36% for SOS, 3.45% for QUI and 4.15% for BMD, while in vitro precision was 0.40% for SOS and 2.67% for BUA. Our results are comparable to reference population data previously published in other countries and may serve as reference normative data for both genders in Spain.

Adolescent↗

[Etiologic spectrum of solitary constitutional syndrome].

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.

Adolescent↗

Progressive cardiomyopathy as manifestation of mitochondrial disease.

Cardiomyopathies are a clinically and genetically heterogeneous group of cardiac diseases in which the myocardium is primarily involved. Mitochondrial DNA point mutations have been identified in a broad spectrum of mitochondrial disorders, which are associated with neurological diseases. However, they also have been reported in patients with cardiomyopathy, either alone or as part of a multisystem disorder. A patient who presented with severe heart failure and was diagnosed as having a mitochondrial A3243G mutation is described.

DNA, Mitochondrial↗

Evaluation of the Duke criteria in 93 episodes of prosthetic valve endocarditis: could sensitivity be improved?

BACKGROUND: Since publication of the Duke criteria for diagnosing endocarditis, several articles have confirmed their sensitivity when native and prosthetic valves are considered together. OBJECTIVES: To compare the differences between the older von Reyn criteria and the Duke criteria in prosthetic valve endocarditis only, and to determine if the latter's sensitivity could be improved by adding 2 minor criteria: new-onset heart failure and presence of conduction disturbances. METHODS: We retrospectively evaluated 93 episodes of prosthetic valve endocarditis from January 1986 to January 1998 in a teaching hospital, and then analyzed the 76 surgically confirmed episodes to compare the differences between the von Reyn and Duke diagnostic criteria. RESULTS: The von Reyn criteria rejected the diagnosis in 16 of the confirmed episodes, compared with 1 diagnosis missed by the Duke criteria and 1 missed using our suggested modifications. Definite diagnosis (Duke) was established in 60 episodes, compared with a diagnosis of probable (von Reyn) in 36 episodes (P<.001). Our modifications improved the sensitivity of the Duke criteria, diagnosing 70 episodes as definite (P = .02). CONCLUSIONS: As was the case with native valve endocarditis, the Duke criteria proved to be more sensitive than the von Reyn criteria in prosthetic valve endocarditis. The addition of 2 minor criteria (new-onset heart failure and presence of conduction disturbances) could improve the diagnostic sensitivity of the Duke criteria.

Adult↗

[Multiple genetic typing (vitamin D receptors and estrogens) in the assessment of the risk of fractures].

BACKGROUND: Several studies suggested that some vitamin D receptor (VDR) and estrogen receptor (ER) polymorphisms influence bone mass. However, others did not confirm these results. This study was undertaken to determine if the genotypes revealed by the combined analysis of VDR and ER polymorphisms are associated with clinically significant differences in peak bone mass and the risk of osteoporotic fractures. PATIENTS AND METHODS: Restriction fragment length polymorphisms of VDR were determined with the enzymes Bsml, Apal, Taql, and Fokl. Enzymes Xbal and Pvull were used as polymorphic markers of the ER. The study group comprised 149 young control women (18-34 years), 66 postmenopausal controls, 99 women with hip fracture and 76 women with osteoporotic vertebral fractures. Bone mineral density (BMD) was measured by DEXA. RESULTS: We did not find significant differences in lumbar spine or hip BMD among young women with different genotypes (determined with either single or multiple polymorphic markers). Likewise, there were no differences in the frequency distributions of VDR or ER alleles between control and fractured women. The study had a 77% power to detect a fracture odds ratio of 2 in case of genotypes present in at least 15% of the population. CONCLUSIONS: These results suggest that the polymorphic markers used in this study do not have enough discriminant power to be clinically useful in the assessment of fracture risk.

Adult↗

Prognostic factors for pneumococcal bacteremia in a university hospital.

The records of adult patients with pneumococcal bacteremia who were seen over an 8-year-period at an 1,100-bed university teaching hospital were reviewed in order to revise the clinical and laboratory findings and to identify the risk factors associated with mortality. A total of 156 patients were studied, 101 men and 55 women. The mean age of the patients was 65 years. Eighty-seven percent of the patients had community-acquired bacteremia and 13% had nosocomial pneumococcal bacteremia. The overall mortality was 33.9% and the related mortality was 20.5%. The following factors were associated with an increased risk of adverse outcome in the univariate analysis: mechanical ventilation (risk ratio [RR]=3.40; 95% confidence interval [95% CI]=1.44-8.05), administration of parenteral nutrition (RR=3.40; 95% CI =1.44-8.05), and the presence of an intravenous catheter (RR=2.33; 95% CI=1.27-4.24). In the multivariate analysis, the independent prognostic factors for mortality were as follows: development of clinical complications during the episode of bacteremia, rapidly fatal illness, advanced age and administration of parenteral nutrition. The results suggest that the overall mortality due to pneumococcal bacteremia continues to be high. Four independent risk factors associated with increased mortality were identified. Prevention and immunization with polyvalent pneumococcal polysaccharide vaccine should be practiced more widely.

Adult↗

Multifactorial thrombotic-type microangiopathy with skin ulcers and hepatitis C infection.

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.

Journal Article↗

Expression of opioid receptors in osteoblast-like MG-63 cells, and effects of different opioid agonists on alkaline phosphatase and osteocalcin secretion by these cells.

We have previously shown that several stressful situations associated with tissue injury determine a decrease in serum osteocalcin concentration. Since reduced osteocalcin production is a marker of decreased osteoblastic activity, this finding could be related to the pathogenesis of osteoporosis secondary to some diseases. Endogenous opioids are involved in stress response. Proenkephalin-derived peptides have been shown to inhibit alkaline phosphatase activity, another marker of bone formation, in the murine cell line ROS-17/2.8. On the other hand, serum osteocalcin has been reported as being low in heroin abusers. We have therefore thought it of interest to study the presence of opioid receptors in the human osteoblast-like cell line MG-63, and to evaluate the effects of different opioid agonists on the secretion of alkaline phosphatase and osteocalcin by these cells. The presence of opioid receptors was studied by means of RT-PCR and immunohistochemistry. RT-PCR studies suggested the presence of specific mRNA for the three types of receptors, and immunohistochemistry clearly showed their occurrence. Osteocalcin synthesis was significantly inhibited by high concentrations of the mu agonists morphine and (D-Ala(2), N-MePhe(4),Gly(5)-ol)-enkephalin although no changes were seen with the delta agonist (D-Ala(2),D-leu(5))-enkephalin. Morphine-induced osteocalcin inhibition was abolished when osteoblastic cells were incubated simultaneously with naloxone, whereas it was potentiated when cells were preincubated with naloxone. None of the opioid agonists modified the secretion of alkaline phosphatase. In conclusion, human osteoblast-like cells MG-63 express the three types of opioid receptors. Endogenous opioids may be involved in the reduction of osteocalcin observed in stressful situations associated with tissue injury.

Alkaline Phosphatase↗

Diagnostic approach to patients with suspected pulmonary embolism: a report from the real world.

This study was carried out to examine the diagnostic approach to patients with suspected pulmonary embolism (PE) in a university hospital. A retrospective case record review of 251 patients with suspected pulmonary embolism was carried out according to a standard protocol, which looked at the utilisation of imaging techniques and compared clinical diagnoses with a standardised diagnosis established according to current recommendations. Isotopic lung scan was the most commonly used technique (73%), followed by leg vein sonography (36%) and contrast venography (31%). Lung arteriography was done in only 7% of patients. Among the 205 patients with a clinical diagnosis of PE, 115 (56%) would be diagnosed as having PE according to the standard criteria, 84 (41%) would be unclassified, and six (3%) would not be regarded as having PE. Among patients who were diagnosed as having PE and received anticoagulant therapy, 32% did not have the diagnosis confirmed by an imaging technique. Most of these had a non-diagnostic lung scan which, despite evidence to the contrary, seemed to be interpreted as confirmation of PE. We conclude that clinicians do not seem to follow current recommendations when approaching patients with suspected PE. In particular, there is an over-reliance on lung scans, and the significance of non-diagnostic scans was often misinterpreted. Arteriography was underused. These results emphasise the need to take measures to implement practice guidelines and to explore the usefulness of newer non-invasive techniques.

Anticoagulants↗

Etidronate inhibits the production of IL-6 by osteoblast-like cells.

IL-6 is a resorbing cytokine synthesized by osteoblasts and monocytes that has been implicated in the pathogenesis of osteoporosis. Bisphosphonates are well-known antiresorptive drugs, the antiosteoclastic effect of which has been recently suggested to be brought about at least in part through osteoblasts. Based on these facts, we have studied the effect of etidronate on the production of IL-6 by two tumoral cell lines of human osteoblastic phenotype (MG63 and SaOs cells), and by peripheral blood mononuclear cells (PBMC). For comparison, another antiresorptive drug, estradiol, was included in the study. MG63 cells were stimulated with LPS and IL-1 beta, SaOs cells with LPS, IL-1 beta and PMA, and PBMC with LPS and PMA. Etidronate was tested at 10(-7), 10(-6), 10(-5), and 10(-4) M, and 17beta-estradiol was tested at 10(-10), 10(-9), 10(-8), and 10(-7) M. IL-6 was determined in supernatants by an ELISA. No significant effect of either etidronate or estradiol on IL-6 secretion by LPS or PMA-stimulated PBMC was found. However, in osteoblastic-like cells, an inhibition of IL-6 production by etidronate in LPS-stimulated cultures was found. At the highest concentrations tested, IL-6 production values were 58 +/- 9% and 53 +/- 8% of those at base line for MG63 and SaOs cells, respectively. Estradiol did not modify IL-6 secretion under any condition. In conclusion, our study supports the contention that the antiresorptive effect of bisphosphonates may be due in part to a decrease in IL-6 production by osteoblasts.

Cells, Cultured↗