Decreasing prevalence of disability in activities of daily living, functional limitations and poor self-rated health: a 6-year follow-up study in Spain

BACKGROUND AND AIMS: Forecasting functional status in elderly populations is uncertain. Our aim is to provide evidence of population trends of Activities of Daily Living (ADL) disability, functional limitations and self-rated health. METHODS: Data come from a longitudinal study of aging in Leganés (Spain), collected in 1993, 1995, 1997 and 1999, on a representative sample of 1560 community dwelling people over 65. Response rate at baseline was 82%. ADL disability was defined as needing help in at least one of the following: walking across a small room, taking a shower, toileting, getting out of bed, getting up from a chair, using the toilet, dressing and eating. Functional limitations were based on questions of difficulty with upper and lower limbs. Self-rated health was assessed with a single question. ADL disability, functional limitations and self-rated health were regressed on age, survey year, sex and education. RESULTS: There are significant declines in ADL disability, functional limitations and poor self-rated health at every age and up to very advanced ages. Over 90, the ADL disability trend may be reversed, with the emergence of a very old and disabled population. Women and people with little education have a higher prevalence of disability, functional limitations and poor health, when compared with men and those with higher education. CONCLUSIONS: Results suggest the postponement of severe disability onset in this Spanish population, leading to longer healthy life expectancy, and support the emergence of a very disabled population over 90 years of age.     

Prolonged cholestasis after raloxifene and fenofibrate interaction： A case report

Assigning causality in drug-induced liver injury is challenging particularly when more than one drug could be responsible. We report a woman on long-term therapy with raloxifen who developed acute cholestasis shortly after starting fenofibrate. The picture evolved into chronic cholestasis. We hypothesized that an interaction at the metabolic level could have triggered the presentation of hepatotoxicity after a very short time of exposure to fenofibrate in this patient. The findings of an overexpression of vascular endothelial growth factor in the liver biopsy suggest that angiogenesis might play a role in the persistance of toxic cholestasis.     

The quail mesonephros: a new model for renal senescence?

BACKGROUND/AIMS: Renal senescence during normal aging is associated with specific vascular alterations and tissue degeneration. Although the degenerative program executed during embryonic kidney development is known to include vascular alterations, studies yet have to examine whether it involves replicative senescence. In this study, we assessed the potential of the quail mesonephros, a transitory embryonic kidney, as a model of human renal senescence. METHODS: Quail embryos with developing or degenerating mesonephros were studied on day 6 or day 11 of incubation, respectively. Senescence-associated beta-galactosidase activity, a marker of replicative senescence, was examined on whole mounts and sections. Senescent vascular characterization was performed by the scanning electron-microscopic analysis of vascular corrosion casts. RESULTS: Senescence-associated beta-galactosidase activity was found only in old mesonephros. Moreover, at 11 days of incubation glomerular capillaries showed discontinuities and were thinner and more tortuous than those observed at 6 days, characteristics also reported for the aging human kidney. CONCLUSION: The degenerating quail mesonephros is a potential model of renal senescence, showing biochemical and morphological characteristics of the aging human kidney.     

Beta-myosin heavy-chain gene mutations in patients with hypertrophic cardiomyopathy

INTRODUCTION AND OBJECTIVES. To determine the frequency of mutations in the beta-myosin heavy-chain gene (MYH7) in a cohort of patients with hypertrophic cardiomyopathy (HCM) and their families, and to investigate correlations between genotype and phenotype. METHODS. Single-strand conformation polymorphism analysis and sequencing of fragments with abnormal MYH7 gene mobility were carried out in 128 consecutive index patients with HCM. The phenotypes of patients with and without mutations were compared and the phenotypes of identified families were recorded. RESULTS. A total of 11 mutations were found in 13 families (10%); 7/11 had been previously described. The I736T mutation was found in three families and the A797T in two. One patient had two mutations (i.e., I736T and R787H). Mutations were more frequent in patients with a family history of sudden death (31%) and in those with severe hypertrophy (39% had a thickness > or = 30 mm). Mutations were found in 29 of 42 members of the 13 families, including six family members (20%) who were healthy carriers and aged < or = 36 years. Sudden death had occurred in eight members of four families: four in two families with the I736T mutation, one in a family with A797T, one in a family with R870H, and two in a family with A901P. CONCLUSIONS. MYH7 mutations were present in 10% of our families. Mutations were more frequent in patients with a family history of sudden death and in those with severe hypertrophy. Most mutations had been described previously. Some appeared in several families. For some mutations, the correlation between genotype and phenotype was stable, while for others, there were marked differences between the phenotypes of the index patients and their relatives, suggesting the presence of additional genetic factors that have yet to be identified.     

Utility of NT-proBNP for diagnosing heart failure in a heterogeneous population of patients with dyspnea. Spanish multicenter study

INTRODUCTION AND OBJECTIVES: Recent studies have shown that brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are useful in the diagnosis of heart failure in patients presenting with dyspnea. However, the cutoff values used with these markers vary according to patient characteristics and dyspnea severity. The aim of this study was to investigate the diagnostic accuracy of using the plasma NT-proBNP level for identifying heart failure in a heterogeneous population of patients with dyspnea. METHODS: A multicentre study involving 247 consecutive patients with recent-onset dyspnea was carried out at 12 Spanish hospitals. Patients previously diagnosed with heart failure or any other condition known to cause dyspnea were excluded. RESULTS: Of the 247 patients, 161 (65%) had heart failure. The remaining 86 (35%) presented with dyspnea of non-cardiac origin. Plasma NT-proBNP levels were higher in patients with heart failure (5600 [7988] pg/mL vs 1182 [4406] pg/mL; P=.0001), and increased as functional status deteriorated (P=.036). The area under the receiver operating characteristic curve was 0.87 (0.02) (95% CI, 0.81-0.91) for the optimum cutoff value of 1335 pg/mL. The sensitivity of this cutoff value for diagnosing heart failure was 77% (95% CI, 70%-83%), the specificity was 92% (95% CI, 84%-97%), the positive predictive value was 94%, and the negative predictive value was 68%. CONCLUSIONS: The plasma NT-proBNP concentration provides an accurate means of diagnosing heart failure. However, the negative predictive value found in this study was somewhat lower than the values found in previous studies involving more homogeneous patient populations.     

Angiographic evaluation of high-risk treadmill scores in patients with unstable angina according to sex, age, or use of drugs with a negative chronotropic effect

INTRODUCTION AND OBJECTIVES: The aim of the study is to determine whether age, sex, or the use of drugs with a negative chronotropic effect modifies the sensitivity, specificity, positive or negative predictive value, or positive or negative likelihood ratio of the high-risk criteria used in exercise testing as defined by the Spanish Society of Cardiology (SEC) and the American College of Cardiology/American Heart Association (ACC/AHA), the Duke treadmill score, the Veterans Affairs and West Virginia prognostic score, or the ST/Heart Rate Index at the time when left main coronary artery disease, three-vessel disease or two-vessel disease involving the proximal left anterior descending artery is detected by coronary angiography. METHODS: The study included a cohort of 469 consecutive patients aged 75 years who were admitted to hospital for unstable angina. All patients underwent exercise stress testing and coronary angiography. RESULTS: In all situations, the ACC/AHA high-risk criteria had the highest sensitivity, negative predictive value, and negative likelihood ratio, and the Duke Treadmill Score had the highest specificity and positive predictive value. The diagnostic accuracy of the other treadmill scores was affected by sex, age or the use of drugs with a negative chronotropic effect. CONCLUSIONS: The ACC/AHA high-risk criteria and Duke Treadmill Score provided useful additional information during the assessment of ST-segment depression. These measures could help improve the diagnostic accuracy of conventional ECG exercise testing in women, older individuals, and patients taking beta-blockers or non-dihydropyridine calcium antagonists.     

Normative data for adiponectin, resistin, interleukin 6, and leptin/receptor ratio in a healthy Spanish pediatric population: relationship with sex steroids

OBJECTIVES: To investigate the circulating levels of adiponectin, resistin, interleukin 6 (IL-6), and leptin/receptor ratio in healthy Spanish children throughout the different stages of pubertal development. To analyze the relationship between adipokines and sex steroid level changes during puberty. STUDY DESIGN: Serum adiponectin, resistin, IL-6 levels, and leptin/receptor ratio were studied in 160 healthy Spanish children grouped according to their pubertal stage (Tanner I, 23 girls and 22 boys; Tanner II, 19 girls and 16 boys; Tanners III and IV, 21 girls and 20 boys; and Tanner V, 20 girls and 19 boys). In addition, circulating levels of sex hormone-binding globulin (SHBG) were determined in every subject, and testosterone and estradiol levels in boys and girls respectively. RESULTS: Adiponectin levels decreased in boys from mid puberty (P < 0.05) to become significantly lower than in girls (P < 0.001), whereas IL-6 decreased in both sexes (P < 0.05). Resistin levels and leptin/receptor ratio showed no differences between sexes or according to pubertal stage, except in adult females, who had the highest levels of both parameters (P < 0.001). Serum IL-6 levels correlated significantly (P < 0.05) with testosterone and estradiol levels (r=-0.37 and -0.42 respectively), whereas estradiol, but not testosterone, correlated with leptin/receptor ratio (r=0.59; P < 0.001). Furthermore, a positive relationship was found between SHBG and adiponectin and IL-6 (P < 0.001 and P < 0.05 respectively). In addition, a direct correlation between leptin/receptor and body mass index was found in both sexes (P < 0.001). CONCLUSION: Variations in adipokine profiles throughout pubertal development appear to be related with progression of gonadal function.     

Association between physical and echographic fat thickness assessments and a lipodystrophy grading scale in lipodystrophic HIV patients: practical implications

A simple diagnostic method for detecting in clinical routine HAART-associated lipodystrophy in HIV-infected patients is lacking. We studied the relationships between the scores obtained with a subjective lipodystrophy severity grading scale (LSGS) and standard anthropometric and echographic measurements of the subcutaneous and visceral fat thickness of 74 HIV-infected patients. Patients were divided into four groups according to their LSGS score (0, 1-7, 8-14, 15-21). Significant correlations between the LSGS and the anthropometric and echographic measurements of fat thickness, mainly the limb circumferences (brachial: r= -0.43, p < 0.001; thigh: r= -0.41, p < 0.001), and, especially, the echographically assessed perirenal fat diameters either adjusted (r= 0.46, p < 0.001) or nonadjusted to the body mass index (r= 0.35, p < 0.001) were observed. Significant differences in most of these anthropometric parameters between either the lowest (score 0) and the highest (score 15-21) score groups and the remaining groups were found, but not between the two intermediate groups (scores 1-7 vs. 8-14). This suggests that lipodystrophy should be clinically categorized as absent, mild, or marked, and that even minor changes in physical aspect should be considered as indicative of this disorder. The combination of these subjective and objective parameters could be helpful in the early detection of lipodystrophy in clinical practice.     

Transient donor cell-derived myelodysplastic syndrome with monosomy 7 after unrelated cord blood transplantation

Donor cell leukaemia or myelodysplastic syndromes are extremely rare complications that have been observed not only after haematopoietic transplantation with progenitor cells harvested from bone marrow and peripheral blood, but also after cord blood transplantation. We describe the early onset of monosomy 7 in donor cells after cord blood transplantation in a patient diagnosed with myelodysplastic syndrome 3 months after transplantation. Fluorescent in situ hybridisation analysis performed in a cryopreserved aliquot of the cord blood showed 2.5% of nuclei with monosomy 7. The cord blood donor was studied and he showed neither peripheral blood cytopenias nor cytological or cytogenetic features of myelodysplasia. The cell blood counts (CBC) of the girl have improved over 2 yr while decreasing the percentage of monosomic cells. The monosomic clone has finally disappeared and the CBC are finally normal. This case of transient monosomy 7 started very early after engraftment emphasises the relevance of clonal instability of specific progenitor cells in the early engraftment, and host immune status, in cytogenetic abnormalities founded in donor cell-derived MDS and acute leukaemia. Moreover, the clinical follow-up of this patient, recommends a more conservative treatment for this clonal disease early developed after transplantation.